The Medi Ultimatum

New Method Takes Aim At Aggressive Cancer Cells

2009-10-01T23:57:00.000-07:00

In a comparison of a control to the chemical identified by the Weinberg/Lander team, called salinomycin, the tumor cells (stained dark purple in the slide above) were unaffected by the control, but salinomycin killed many tumor cells (stained pink)
A multi-institutional team of Boston-area researchers has discovered a chemical that works in mice to kill the rare but aggressive cells within breast cancers that have the ability to seed new tumors.
These cells, known as cancer stem cells, are thought to enable cancers to spread — and to reemerge after seemingly successful treatment. Although further work is needed to determine whether this specific chemical holds therapeutic promise for humans, the study shows that it is possible to find chemicals that selectively kill cancer stem cells. The scientists' findings appear in the August 13 advance online issue of Cell.

"Evidence is accumulating rapidly that cancer stem cells are responsible for the aggressive powers of many tumors," says Robert Weinberg, a Member of Whitehead Institute for Biomedical Research and one of the authors of the study. "The ability to generate such cells in the laboratory, together with the powerful techniques available at the Broad Institute, made it possible to identify this chemical. There surely will be dozens of others with similar properties found over the next several years."

"Many therapies kill the bulk of a tumor only to see it regrow," says Eric Lander, Director of the Broad Institute of MIT and Harvard, and an author of the Cell paper. "This raises the prospect of new kinds of anti-cancer therapies."

An emerging idea in cancer biology is that tumors (breast, prostate, colon, lung, etc.) harbor a group of cells with the unique ability to regenerate cancers. In addition to promoting tumor growth, these so-called cancer stem cells are largely resistant to current cancer therapies. If it were possible to identify chemicals that selectively kill cancer stem cells, such chemicals might become critical candidates for future drug development.

However, researchers have struggled to study cancer stem cells directly in the laboratory. The cells' relative scarcity compared to other tumor cells, combined with a tendency to lose their stem cell-like properties when grown outside of the body, have severely limited the amount of material available for analysis.

To overcome these hurdles, Broad and Whitehead Institute researchers drew upon recent findings from Weinberg and his colleagues that suggested a way to generate in the laboratory large numbers of cancer cells with stem cell-like qualities. The technique works by coaxing adult cells to undergo a critical change (known as an "epithelial-to-mesenchymal transition") that alters their shape and motility. At the same time, the cells also adopt similar properties as stem cells.

"A critical aspect of our work was to generate relatively homogenous and stable populations of cancer stem-like cells that could then be used for screening," says Tamer Onder, a former graduate student in Weinberg's lab and co-first author of the study. (Onder is now a postdoctoral research fellow at Children's Hospital in Boston.) "We were able to achieve this by inducing the cancer cells into an epithelial-to-mesenchymal transition using novel reagents that we had developed in the lab."

With an ample number of stem cells in hand, the Broad-Whitehead team undertook a large-scale analysis of thousands of chemical compounds, applying automated methods to search for ones with activity against breast cancer stem cells. From a pool of more than 30 promising candidates, the researchers identified a compound with surprising potency.

The compound, called salinomycin, kills not only laboratory-created cancer stem cells, but also naturally occurring ones. Compared to a common chemotherapeutic drug prescribed for breast cancer (known as paclitaxel), salinomycin reduced the number of cancer stem cells by more than 100-fold. It also diminished breast tumor growth in mice.

To further dissect the function of salinomycin, the researchers also examined its genetic effects. Previous studies of tumors from breast cancer patients have revealed groups of genes that are highly active in cancer stem cells. Many of these same genes are linked with particularly aggressive tumors and poor patient prognoses. The researchers' studies show that salinomycin (but not paclitaxel) treatment can decrease the activity of these genes, revealing a possible molecular basis for the chemical's biological effects.

"Our work reveals the biological effects of targeting cancer stem cells," says co-first author Piyush Gupta, a researcher at the Broad Institute. "Moreover, it suggests a general approach to finding novel anti-cancer therapies that can be applied to any solid tumor maintained by cancer stem cells."

Although the new findings signal a noteworthy scientific milestone, it is still too early to know whether cancer patients will reap benefits from it. Additional research is needed to determine exactly how salinomycin works to kill cancer stem cells and if it can wield the same tumor-reducing power in humans as it does in mice. These types of analyses generally take several years to complete.

But even with such tempered enthusiasm, there is also cause for optimism. In the current study, just 16,000 chemical compounds were tested, of which a small subset showed toxicity against cancer stem cells. Therefore, deeper investigations of these compounds as well additional tests of broader collections of chemicals may yield other potential additions to the anti-cancer arsenal.

Scientists Develop Nasal Spray That Improves Memory

2009-10-01T23:52:00.000-07:00

Good news for procrastinating students: a nasal spray developed by a team of German scientists promises to give late night cram sessions a major boost, if a good night's sleep follows. In a research report featured as the cover story of the October 2009 print issue of The FASEB Journal, these scientists show that a molecule from the body's immune system (interleukin-6) when administered through the nose helps the brain retain emotional and procedural memories during REM sleep.
"Sleep to remember, a dream or reality?" said Lisa Marshall, co-author of the study, from the Department of Neuroendocrinology at the University of Lubeck in Germany. "Here, we provide the first evidence that the immunoregulatory signal interleukin-6 plays a beneficial role in sleep-dependent formation of long-term memory in humans."

To make this discovery, Marshall and colleagues had 17 healthy young men spend two nights in the laboratory. On each night after reading either an emotional or neutral short story, they sprayed a fluid into their nostrils which contained either interleukin-6 or a placebo fluid. The subsequent sleep and brain electric activity was monitored throughout the night. The next morning subjects wrote down as many words as they could remember from each of the two stories. Those who received the dose of IL-6 could remember more words.

"If a nasal spray can improve memory, perhaps we're on our way to giving some folks a whiff of common sense, such as accepting the realities of evolution," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This is exciting piece of interdisciplinary science, since IL-6 had previously been considered a by-product of inflammation, not an agent that affects cognition."

Scientists Closer To Making Implantable Bone Material

2009-08-01T07:33:00.000-07:00

Calcium in the the bone-like nodules are fluorescent red in this image captured by the Imperial team
Scientists are closer to understanding how to grow replacement bones with stem cell technology, thanks to research published in the journal Nature Materials.
Many scientists are currently trying to create bone-like materials, derived from stem cells, to implant into patients who have damaged or fractured bones, or who have had parts of diseased bones removed. The idea is that, ultimately, these bone-like materials could be inserted into cavities so that real bone could meld with it and repair the bone.

So far, scientists have found they can grow small 'nodules' of what appeared to be bone-like material in the laboratory from different types of bone cells and stem cells. All of these cell types are attracting considerable interest as promising candidates for future implants in people with clinical trials already underway. However, scientists still need to thoroughly explore and understand the in-depth chemical properties and structure of the bone-like materials they are growing.

Now, scientists from Imperial College London have compared the 'bone-like' material grown from three different commonly used clinically relevant cell types and have discovered significant differences between the quality of bone-like material that these can form.

For example, the researchers have discovered that the 'bone-like' materials that were grown from bone cells from mouse skull and mouse bone marrow stem cells successfully mimicked many of the hallmarks of real bone, which include stiffness. However, they found that the 'bone-like' material grown from mouse embryonic stem cells was much less stiff and less complex in its mineral composition when compared to the other materials. The researchers suggest that further research is now needed to explore the implications of these results for different stem cell therapies.

Professor Molly Stevens, from the Department of Materials and the Institute of Biomedical Engineering at Imperial College London, says: "Many patients who have had bone removed because of tumours or accidents live in real pain. By repairing bone defect sites in the body with bone-like material that best mimics the properties of their real bone we could improve their lives immeasurably. Our study provides an important insight into how different cell sources can really influence the quality of bone that we can produce. It brings us one step closer to developing materials that will have the highest chance of success when implanted into patients."

To carry out their analysis, researchers used laser-based raman spectroscopy to understand the detailed chemical make-up of live cells as they grew and multivariate statistical analysis techniques, which enabled them to compare and analyse data about the growth of different cell populations. They also used a nano-indenter and high resolution electron microscopy, which allowed the researchers to probe the samples so that they could understand how stiff the bone-like materials were and what their structure was at a microscopic level.

Discovery Of A Mechanism Controlling The Fate Of Hematopoietic Stem Cells

2009-08-01T07:29:00.000-07:00

Microscopy image of a hematopoietic stem cell (in yellow) surrounded by other cells, in a spleen section.
Hematopoietic stem cells are capable of manufacturing all types of blood cells. But which factors influence the production of a specific type of cell? Until now, it was thought that this was a random process. At the Centre d'Immunologie de Marseille-Luminy (1), a team of CNRS and Inserm researchers led by Michael Sieweke has discovered the factors that determine the type of cells produced. The mechanism they have demonstrated in the mouse involves one factor intrinsic to the cell and one extrinsic factor.
These results were published in the journal Cell on July 24, 2009.

Stem cells are a source of much hope, thanks to their extraordinary ability to produce all types of cell in the body or an organ, depending on their origin. Scientists are now trying to understand the mechanisms that commit stem cells to a particular specialization.

At the Centre d'Immunologie de Marseille-Luminy, CNRS and INSERM researchers have been working on mouse hematopoietic stem cells. They studied the development of myeloid cells, a lineage of white blood cells that combats microorganisms by "eating" them, by releasing toxins or by alerting other specialized immune cells. Until now, it was thought that the production of different specialized cells from a hematopoietic stem cell was a random process. Sieweke's team has discovered that in the case of myeloid cells, it is the combined action of two proteins which is relevant; one protein that is situated inside the cell (transcription factor) and the other outside (a cytokine).

Transcription factors are capable of switching genes on or off. The identity of a cell is the combination of active genes it possesses. Because of this, scientists already suspected that transcription factors played an important role in the orientation of differentiation. They also knew that blood cells can only prosper in an environment containing a particular cytokine, a type of hormone specific to each cell type. But until now, they thought that cytokines assisted the survival and renewal of cells without affecting their "fate". The team in Marseille has now shown that a specific cytokine (M-CSF) places stem cells on a "myeloid pathway", but that these stem cells can only follow this path if levels of a certain transcription factor (MafB) within the cells is low.

These findings help to solve a mystery that has fascinated specialists during the past fifty years. In the longer term, these results may throw new light on the mechanisms of leukemia, where abnormal stem cells remain "undecided" and are still able to escape therapy.

Until now, studies on hematopoietic stem cells had opened the way to research on stem cells in other tissues. In this context, the results achieved and published by Michael Sieweke and his colleagues may provide more general information on how stem cells function (in the brain, muscle or intestine).

Dietary Acrylamide Not Associated With Increased Lung Cancer Risk In Men

2009-07-25T10:59:00.000-07:00

Dietary acrylamide was not associated with an increased risk of lung cancer, according to data from a large prospective case-cohort study
Dietary acrylamide was not associated with an increased risk of lung cancer, according to data from a large prospective case-cohort study.
Acrylamide is formed in some starchy foods, such as potato chips and French fries, during high-temperature cooking. Epidemiological studies have found a positive association between dietary acrylamide intake and the risk of endometrial, ovarian, renal cell, and estrogen-receptor positive breast cancers.

To investigate whether dietary acrylamide intake is associated with lung cancer risk, Janneke G. F. Hogervorst, M.Sc., of Maastricht University in the Netherlands, and colleagues conducted a case-cohort study among 58,279 men and 62,573 women in the Netherlands Cohort Study on Diet and Cancer. Intake of acrylamide was estimated based on food-frequency questionnaires completed upon enrollment in the study.

After a follow-up of 13 years, 1,600 men and 295 women were diagnosed with lung cancer. When the investigators divided participants into five groups based on dietary acrylamide intake, they found no statistically significant difference in lung cancer incidence in men who consumed the highest and lowest amounts of acrylamide-containing foods. By contrast, the researchers found that women who ate the most acrylamide-containing foods had a statistically significant lower incidence of lung cancer compared with those in the group who consumed the least acrylamide-containing foods. All analyses were adjusted for smoking.

"Acrylamide intake was not associated with lung cancer risk in men but was inversely associated in women… This finding suggests that acrylamide is involved in human carcinogenesis through pathways other than genotoxicity," the authors write. They hypothesize that acrylamide may affect hormonal balances, which might explain how it could be associated with a reduction in lung cancer risk but an increase in risk of endometrial and ovarian malignancies.

In an accompanying editorial, Lorelei A. Mucci, ScD. and Hans-Olov Adami, M.D., Ph.D., of the Harvard School of Public Health in Boston, review past studies of dietary acrylamide and cancer, as well as the initial discovery of acrylamide in foods. They note that several studies have found a positive association between dietary acrylamide and some types of cancer. The editorialists also express caution about concluding that dietary acrylamide may have a protective effect in women with respect to lung cancer risk, pointing out the potential for false-positive associations.

"In our view, speculation about the potential mechanisms of the protective effect of acrylamide on lung cancer among women should await confirmation of the association in additional studies," the editorialists conclude. "Perhaps the safer conclusion we can make from the Netherlands study is that the findings do not support a positive association between acrylamide intake from diet and risk of lung cancer."

Activated Stem Cells In Damaged Lungs Could Be First Step Toward Cancer

2009-07-25T10:50:00.000-07:00

Left: This section of a normal chimeric airway shows a patch distribution of mixed green fluorescent protein positive (green) and negative cells. Right: This photo shows the same airway after a severe chemical injury that wipes out the normally present cells and activates stem cell mediated repair (clonal patches).
Stem cells that respond after a severe injury in the lungs of mice may be a source of rapidly dividing cells that lead to lung cancer, according to a team of American and British researchers.
Cambridge Research Institute. "In terms of lung cancer susceptibility, however, our observation that stem cell activation leads to clonal expansion after injury could, in the context of additional mutations, promote the development of cancerous or precancerous lesions from activated stem cells."

The scientists used a chimeric mouse model, part wild-type and part with green fluorescent protein-tagged cells (GFP), so that the behavior of different populations of duplicating lung cells could be evaluated with high-resolution imaging methods. By understanding the extent to which GFP-positive and GFP-negative cells were mixed, the investigators were able to show that the abundant population of progenitor cells that normally maintain the epithelial layer in the lung could be rapidly wiped out with a strong chemical, naphthalene. Then the rare proliferative cells became active and grew into large patches.

The researchers at Duke and Cancer Research UK used a unique whole-lung imaging method to examine and identify the location of stem cells in the lung tissue of mice, and determine the role they play in both healthy and damaged mouse lungs.

They found that, while the stem cells don't appear to be involved in the normal maintenance of healthy or moderately injured lungs, they do play a vital role in repairing severely damaged lungs.

Even though this repair mechanism is important for restoring lung function, it can come at a price. An acquired mutation in that rare cell or its descendants leads to clonal patches of many identical cells. Secondary mutations in any one of these cells may provide the signals needed for unregulated cell growth and tumor progression.

"This work provides a plausible mechanism to account for this type of event that we previously didn't have," Stripp said.

The study was supported by grant funding from the National Institutes of Health, Cancer Research UK, the University of Cambridge and Hutchison Whampoa.

Other authors include Joshua Snyder from the Duke Department of Medicine; Esther Arwet and Fiona Watt of Cancer Research UK's Cambridge Research Institute; and Ian Rosewell with Cancer Research UK at the London Research Institute in South Mimms. Dr. Watt is also with the Wellcome Trust Centre for Stem Cell Research at Cambridge University

Marijuana Damages DNA And May Cause Cancer, New Test Reveals

2009-07-25T10:46:00.000-07:00

Marijuana smoke may increase the risk of cancer, scientists report.
Using a highly sensitive new test, scientists in Europe are reporting "convincing evidence" that marijuana smoke damages the genetic material DNA in ways that could increase the risk of cancer.
Researchers note that toxic substances in tobacco smoke can damage DNA and increase the risk of lung and other cancers. However, there has been uncertainty over whether marijuana smoke has the same effect. Scientists are especially concerned about the toxicity of acetaldehyde, present in both tobacco and marijuana. However, it has been difficult to measure DNA damage from acetaldehyde with conventional tests.

The research was carried out by Rajinder Singh, Jatinderpal Sandhu, Balvinder Kaur, Tina Juren, William P. Steward, Dan Segerback and Peter B. Farmer from the Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine and Karolinska Institute, Sweden.

Raj Singh said: “Parts of the plant Cannabis sativa, also known as marijuana, ganja, and various street names, are commonly smoked as a recreational drug, although its use for such purposes is illegal in many countries.

The scientists describe development and use of a modified mass spectrometry method that showed clear indications that marijuana smoke damages DNA.

“There have been many studies on the toxicity of tobacco smoke. It is known that tobacco smoke contains 4000 chemicals of which 60 are classed as carcinogens. Cannabis in contrast has not been so well studied. It is less combustible than tobacco and is often mixed with tobacco in use. Cannabis smoke contains 400 compounds including 60 cannabinoids. However, because of its lower combustibility it contains 50% more carcinogenic polycyclic aromatic hydrocarbons including naphthalene, benzanthracene, and benzopyrene, than tobacco smoke.”

The authors added: “It is well known that toxic substances in tobacco smoke can damage DNA and increase the risk of lung and other cancers. Scientists were unsure though whether cannabis smoke would have the same effect. Our research has focused on the toxicity of acetaldehyde, which is present in both tobacco and cannabis.”

The researchers add that the ability of cannabis smoke to damage DNA has significant human health implications especially as users tend to inhale more deeply than cigarette smokers, which increases respiratory burden. "The smoking of 3-4 cannabis cigarettes a day is associated with the same degree of damage to bronchial mucus membranes as 20 or more tobacco cigarettes a day," the team adds.

"In conclusion, these results provide evidence for the DNA damaging potential of cannabis [marijuana] smoke, implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development," the article states. "The data obtained from this study suggesting the DNA damaging potential of cannabis smoke highlight the need for stringent regulation of the consumption of cannabis cigarettes, thus limiting the development of adverse health effects such as cancer."

New Lab Test Offers Better Prediction Of HIV Microbicide Safety

2009-07-25T10:43:00.000-07:00

Tight junctions between genital tract epithelial cells provide an anatomic barrier and prevent HIV from reaching submucosal targets. Microbicides that disrupt the barrier increase the risk for HIV infection. This assay may help in predicting the safety of microbicides.
Scientists at Albert Einstein College of Medicine of Yeshiva University have devised a laboratory test for predicting whether microbicides against HIV are safe for human use. The researchers have also discovered why several supposedly "safe" microbicides made women more susceptible to HIV infection.
The study appears in the online version of the Journal of Infectious Diseases.

For years, scientists have been trying to develop a topical vaginal microbicide for preventing transmission of HIV, the virus that causes AIDS. A safe and effective microbicide would help protect women in settings where male condoms are not used — a common situation in many cultures. The need for an HIV microbicide is especially urgent in Africa, where AIDS is the leading cause of death and where women account for six out of ten of those living with HIV.

Several microbicide gels have been assessed in clinical trials after passing laboratory and animal safety tests. But with just one exception, all the microbicides were found to be ineffective against HIV; and two of the gels — nonoxynol-9 and cellulose sulfate — actually increased the risk of HIV infection in women.

"Our goal was to develop assays that are predictive of safety before proceeding to clinical trials that typically cost millions of dollars, involve thousands of women, and take many years," says study leader Betsy C. Herold, M.D., professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women's health at Einstein.

In evaluating a microbicide's safety, researchers look primarily for signs that the chemical inflames cells of the vaginal lining, or epithelium. That could cause more harm than good: When the epithelium becomes inflamed, T cells flock to the damaged area — which might actually encourage HIV infection, since T cells are the main targets of HIV.

Dr. Herold theorized that another mechanism may also compromise a microbicide's safety. The cells of the vaginal epithelium normally are tightly packed together, forming an impermeable barrier to HIV. If a microbicide disrupts the barrier's structural integrity, HIV would be able to slip through the gaps and infect circulating T cells.

To test this theory, Pedro Mesquita, a postdoctoral fellow in Dr. Herold's lab, developed a model that mimicked the genital tract environment. It was composed of two chambers separated by a barrier of cultured human cells that form tight junctions. After treating the epithelial cells with different microbicides, the researchers tested the barrier's permeability to HIV by placing HIV in the upper chamber, T cells in the lower chamber, and then monitoring the infection of the T cells over time.

When the epithelial barrier was treated with placebo, HIV was unable to pass through to the lower chamber, leaving the T cells uninfected. "But when we applied nonoxynol-9, the virus went right through the barrier and infected the T cells," says Dr. Herold. This result was no surprise, since nonoxynol-9 is a detergent, a class of chemicals known to be disruptive to cells. What was surprising, she says, was to observe the same result with cellulose sulfate ─ a sulfated polymer that is not a detergent and was shown to be safe in all of the other bioassays and in early clinical trials. These findings may explain the unanticipated clinical trial results in which use of cellulose sulfate was associated with an increase in HIV transmission.

The researchers later tested their model on two other microbicide candidates now being evaluated in large-scale clinical efficacy trials. Both drugs — tenofovir and PRO 2000 —performed well by not disrupting the epithelial barrier.

"Our findings strongly suggest that microbicides can increase the risk of HIV infection through a mechanism other that inflammation — namely, by disrupting the protective epithelial cell barrier," says Dr. Herold. "If confirmed by further study, this assay should be used early on to screen for microbicide safety before advancing a product to clinical trials involving thousands of women," she adds.

Dr. Herold is also developing animal models for evaluating microbicides. Since these models use actual epithelial tissue, they could offer even better predictions of microbicide safety.

Dr. Herold's paper, "Disruption of tight junctions by cellulose sulfate facilitates HIV infection: Model of microbicide safety," was published July 8, 2009 in the online version of the Journal of Infectious Diseases. All research was conducted at Einstein. Pedro M. M. Mesquita, Ph.D., was the lead author. Other Einstein co-authors were Natalia Cheshenko, Sarah S. Wilson, Mohak Mhatre, Esmeralda Guzman, Esra Fakioglu, and Marla J. Keller.

DNA Not The Same In Every Cell Of Body: Major Genetic Differences Between Blood And Tissue Cells Revealed

2009-07-17T05:35:00.000-07:00

New research calls into question one of the most basic assumptions of human genetics: that when it comes to DNA, every cell in the body is essentially identical to every other cell.
Research by a group of Montreal scientists calls into question one of the most basic assumptions of human genetics: that when it comes to DNA, every cell in the body is essentially identical to every other cell. Their results appear in the July issue of the journal Human Mutation.
This discovery may undercut the rationale behind numerous large-scale genetic studies conducted over the last 15 years, studies which were supposed to isolate the causes of scores of human diseases.

Except for cancer, samples of diseased tissue are difficult or even impossible to take from living patients. Thus, the vast majority of genetic samples used in large-scale studies come in the form of blood. However, if it turns out that blood and tissue cells do not match genetically, these ambitious and expensive genome-wide association studies may prove to have been essentially flawed from the outset.

This discovery sprang from an investigation into the underlying genetic causes of abdominal aortic aneurysms (AAA) led by Dr. Morris Schweitzer, Dr. Bruce Gottlieb, Dr. Lorraine Chalifour and colleagues at McGill University and the affiliated Lady Davis Institute for Medical Research at Montreal's Jewish General Hospital. The researchers focused on BAK, a gene that controls cell death.

What they found surprised them.

AAA is one of the rare vascular diseases where tissue samples are removed as part of patient therapy. When they compared them, the researchers discovered major differences between BAK genes in blood cells and tissue cells coming from the same individuals, with the suspected disease "trigger" residing only in the tissue. Moreover, the same differences were later evident in samples derived from healthy individuals.

"In multi-factorial diseases other than cancer, usually we can only look at the blood," explained Gottlieb, a geneticist with McGill's Centre for Translational Research in Cancer. "Traditionally when we have looked for genetic risk factors for, say, heart disease, we have assumed that the blood will tell us what's happening in the tissue. It now seems this is simply not the case."

"From a genetic perspective, therapeutic implications aside, the observation that not all cells are the same is extremely important. That's the bottom line," he added. "Genome-wide association studies were introduced with enormous hype several years ago, and people expected tremendous breakthroughs. They were going to draw blood samples from thousands or hundreds of thousands of individuals, and find the genes responsible for disease.

"Unfortunately, the reality of these studies has been very disappointing, and our discovery certainly could explain at least one of the reasons why."

AAA is a localized widening and weakening of the abdominal aorta, and primarily affects elderly Caucasian men who smoke, have high blood pressure and high cholesterol levels. It often has no symptoms, but can lead to aortic ruptures which are fatal in 90 per cent of cases.

If the mutations discovered in the tissue cells actually predispose for AAA, they present an ideal target for new therapies, and may have even wider therapeutic implications.

"This will probably have repercussions for vascular disease in general," said Schweitzer, of McGill's Department of Medicine. "We have not yet looked at coronary or cerebral arteries, but I would suspect that this mutation may be present across the board."

Schweitzer is optimistic that this discovery may lead to new treatments for vascular disease in the near to medium term.

"The timeline might be five to 10 years," he said. "We have to do in-vitro cell culture experiments first, prove it in an animal model, and then develop a molecule or protein which will affect the mutated gene product. This is the first step, but it's an important step."

Brain Emotion Circuit Sparks As Teen Girls Size Up Peers

2009-07-15T10:45:00.000-07:00

Hypothalamus, a node of the emotion circuit.
What is going on in teenagers' brains as their drive for peer approval begins to eclipse their family affiliations? Brain scans of teens sizing each other up reveal an emotion circuit activating more in girls as they grow older, but not in boys. The study by Daniel Pine, M.D., of the National Institute of Mental Health (NIMH), part of National Institutes of Health, and colleagues, shows how emotion circuitry diverges in the male and female brain during a developmental stage in which girls are at increased risk for developing mood and anxiety disorders.
"During this time of heightened sensitivity to interpersonal stress and peers' perceptions, girls are becoming increasingly preoccupied with how individual peers view them, while boys tend to become more focused on their status within group pecking orders," explained Pine. "However, in the study, the prospect of interacting with peers activated brain circuitry involved in approaching others, rather than circuitry responsible for withdrawal and fear, which is associated with anxiety and depression."

Pine, Amanda Guyer, Ph.D., Eric Nelson, Ph.D., and colleagues at NIMH and Georgia State University, report on one of the first studies to reveal the workings of the teen brain in a simulated real-world social interaction, in the July, 2009 issue of the Journal Child Development.

Thirty-four psychiatrically healthy males and females, aged 9 to 17, were ostensibly participating in a study of teenagers' communications via Internet chat rooms. They were told that after an fMRI (functional magnetic resonance imaging) scan, which visualizes brain activity, they would chat online with another teen from a collaborating study site. Each participant was asked to rate his or her interest in communicating with each of 40 teens presented on a computer screen, so they could be matched with a high interest participant (see picture below).

Two weeks later, the teens viewed the same faces while in an fMRI scanner. But this time they were asked to instead rate how interested they surmised each of the other prospective chatters would be in interacting with them.

Only after they exited the scanner did they learn that, in fact, the faces were of actors, not study participants, and that there would be no Internet chat. The scenario was intended to keep the teens engaged –– maintain a high level of anticipation/motivation –– during the tasks. This helped to ensure that the scanner would detect contrasts in brain circuit responses to high interest versus low interest peers.

Although the faces were selected by the researchers for their happy expressions, their attractiveness was random, so that they appeared to be a mix of typical peers encountered by teens.

As expected, the teen participants deemed the same faces they initially chose as high interest to be the peers most interested in interacting with them. Older participants tended to choose more faces of the opposite sex than younger ones. When they appraised anticipated interest from peers of high interest compared with low interest, older females showed more brain activity than younger females in circuitry that processes social emotion.

"This developmental shift suggested a change in socio-emotional calculus from avoidance to approach," noted Pine. The circuit is made up of the nucleus accumbens (reward and motivation), hypothalamus (hormonal activation), hippocampus (social memory) and insula (visceral/subjective feelings).

By contrast, males showed little change in the activity of most of these circuit areas with age, except for a decrease in activation of the insula. This may reflect a waning of interpersonal emotional ties over time in teenage males, as they shift their interest to groups, suggest Pine and colleagues.

"In females, absence of activation in areas associated with mood and anxiety disorders, such as the amygdala, suggests that emotional responses to peers may be driven more by a brain network related to approach than to one related to fear and withdrawal," said Pine. "This reflects resilience to psychosocial stress among healthy female adolescents during this vulnerable period."

SAVI Breast Brachytherapy Device

2009-06-21T02:29:00.000-07:00

After a lumpectomy, you may need radiation treatments to kill off any possible remaining cancer cells. Radiation is done to help prevent a recurrence, or return, of breast cancer. Brachytherapy, or internally-delivered radiation, is a technique that spares healthy tissue and treats only the tissue around your tumor cavity.
Fighting Breast Cancer From Outside and Inside
Radiation treatments for breast cancer can be given with external or internal radiation. External radiation, also called whole-breast irradiation (WBI), treats the whole breast from the outside, by aiming highly penetrating x-rays at your tumor cavity. Breast brachytherapy uses special catheters (tiny tubes) to deliver the radiation from within your breast to your tumor cavity and a small margin of surrounding tissue.

Breast Brachytherapy Advantages

Whole-breast irradiation (external radiation) affects healthy tissue as well as cancer cells, and may cause side effects in healthy tissue. These treatments are usually given daily Monday through Friday for about 6 weeks in a cancer clinic. Breast brachytherapy affects a smaller amount of breast tissue, and delivers a targeted dose of radiation to your lumpectomy site. Brachytherapy can be done with a specially designed device that is temporarily implanted in your breast, allowing your radiation oncologist to give you customized treatment over a 5-day period. You can expect minimal side effects and faster recovery from brachytherapy than from external radiation.

SAVI™ Accelerated Partial Breast Irradiation (APBI)

"SAVI Radiation Applicator"SAVI Applicator - Photo © Cianna Medical

The SAVI, which was was FDA approved in 2006, is a breast radiation device that can be custom-fitted to your lumpectomy cavity, regardless of what shape or size it may be. This device is a bundle of soft, tiny catheters. The SAVI is inserted through a small incision, and the catheter bundle expands uniformly, but its unique design allows it to be opened in a way that truly conforms to the size and shape of your tumor cavity. The radiation dose can be individually controlled through each catheter, allowing precise targeting by the radiation oncologist. This device is more customizable than a traditional balloon catheter device, so women with small breasts may be eligible for this type of treatment.

What You Can Expect From A SAVI Applicator

"SAVI Radiation Applicator Placement"Placement - Photo © Cianna Medical
Your surgeon can place a SAVI radiation applicator at the time of your lumpectomy, or it may be inserted during a separate surgery. Only a small incision is needed, to allow the compact catheter bundle to be placed within your breast. The incision area will be secured with a dressing, and part of each catheter line will extend outside your breast, until your treatment is complete. The catheters are very flexible and soft, so they should be comfortable for you during the five days of radiation. Your site dressings will be changed twice a day during treatment, and must be kept dry. To prevent infections, you may be given antibiotics to take.

Radiation Dosing During Treatments

"SAVI Radiation Applicator Dosing"Dosing - Photo © Cianna Medical
You will report to your radiation oncology facility twice a day for five days, to have treatments. Plan on spending about 30 minutes for each visit, about 5-10 minutes of your appointment will be used for the radiation treatment time. Your radiation oncology team will make you comfortable, and connect your SAVI applicator to the radiation source. During each treatment, the radiation source is sent down each catheter one at a time. A different amount of radiation dose will be given at different points along the length of each catheter. This gives you the best dose for the affected tissue, and the most protection for surrounding healthy tissue.

Completing Radiation and Removing Your SAVI Applicator

"SAVI Radiation Applicator Removal"Removal - Photo © Cianna Medical

After your final radiation treatment, your radiation oncologist can remove the SAVI device. It should take about two minutes to remove the device, clean your incision site, and close the skin with adhesive strips. A bandage or dressing be placed on top, and you will be free to go. Be sure to go to your follow-up visits, so your doctor can see that your incision is healing properly.

Is SAVI Available to Me?
SAVI breast brachytherapy is available across America, but it's not in every state yet. It will work for large or small breasts, but other factors may make it unsuitable for some patients. Check with your doctor about this device or email Cianna Medical, to see if SAVI is available in your state or location.

SAVI Breast Brachytherapy Provides Better Dose Control, Study Finds

2009-06-21T02:26:00.000-07:00

SAVI
Physicians at 21st Century Oncology, Inc., a leading developer and
operator of radiation therapy centers, recently presented research on
their use of the SAVI(TM) applicator for breast brachytherapy. The
scientific poster presented at the 25th Annual Miami Breast Cancer
Conference found that SAVI applicator's superior dose control resulted
in a low rate of toxicities, especially skin reactions.

The poster presented by lead researcher Constantine Mantz, M.D., a
radiation oncologist at 21st Century, was recognized as one of the top
three presentations at the conference.

SAVI is a single-entry, multi-catheter device that delivers
radiation as part of breast conservation therapy. It is the only
accelerated partial breast irradiation (APBI) single-entry device that
can customize the dose according to patient-specific anatomy. By
targeting the radiation more precisely, SAVI treats the tissue where
the cancer is most likely to recur, while minimizing the exposure of
healthy tissue such as the skin, chest wall or lungs.

The 21st Century Oncology study examined the toxicity levels
observed in the first 90 days following radiation treatment with SAVI.
Of the 18 patients included in the study, 14 of them experienced no
skin reactions, which are a common side effect of radiation therapy.
Of the four patients who experienced skin reactions, all had just
minor reactions that were quickly resolved, without the need for
additional care.

Researchers rated the overall cosmetic outcomes with SAVI as
"excellent."

"SAVI allows me to pull radiation dose away from the skin and lung
and push it into the breast tissue where it is needed, to destroy
cancer cells and prevent recurrences," said Dr. Mantz. "Our study
demonstrated that SAVI's ability to shape the dose of radiation
results in very low toxicity and allows more women to be treated
safely with breast brachytherapy."

Nearly 60 percent of the patients in the study had tumors located
close to the skin surface. That tumor location excluded them from
treatment with balloon brachytherapy, an older form of breast
brachytherapy.

"Roughly 30 to 40 percent of patients that I see regarding partial
breast brachytherapy would not be good candidates for balloon
brachytherapy because of technical restrictions, such as the tumor
being located too close to the skin or lungs," said Dr. Mantz. "SAVI
allows these patients, who would otherwise not be eligible, to receive
breast brachytherapy because we can deliver the dose much more
precisely."

"SAVI really is the next step in radiation therapy where you can
make the radiation conform to the anatomy of the patient and the
tumor," said Paul Wallner, DO, FACR, FAOCR, Senior Vice President of
21st Century Oncology. "We see it as a better option for clinical care
for our patients. With SAVI, there is a greater potential for more
women to benefit from APBI."

The research poster from Dr. Mantz and colleagues was named one of
the top three presentations by the program committee of the Miami
Breast Cancer Conference. These three posters, out of approximately 40
submissions, were honored based on their outstanding scientific merit,
applicability and impact in breast cancer, and innovation/originality,
according to MBCC course director Debu Tripathy, M.D.

"My main objective in presenting our data to the medical public is
to make physicians aware of this new device for delivering partial
breast irradiation at least as an alternative - and perhaps a
replacement - to MammoSite balloon brachytherapy for patients who have
tumors located close to the skin or lung," said Dr. Mantz.

Breast conservation therapy includes lumpectomy - the surgical
removal of the cancerous tissue within the breast plus tissue
immediately surrounding the tumor - followed by radiation. Typically,
radiation therapy after a lumpectomy has involved treatment of the
entire breast with external beam radiation. Known as whole breast
irradiation (WBI), this approach exposes more healthy tissue and
requires a much longer treatment course, with radiation delivered five
times a week over a six-to-seven week period. Treatment with the SAVI
applicator lasts just five days. Partial breast brachytherapy is
becoming a more widely used alternative to whole breast irradiation.

The SAVI applicator is made by Cianna Medical, Inc., a women's
health company dedicated to the innovative treatment of early-stage
breast cancer. The Miami Breast Conference was held, Feb, 20-23, 2008,
in Orlando, Fla.

About 21st Century Oncology, Inc.

21st Century Oncology, Inc. is a leading developer and operator of
radiation therapy centers. These centers, which are freestanding and
hospital based, provide a full spectrum of radiation therapy services
to cancer patients. In its more than 20 years of operation, the
company has developed an operating model which enables the company's
centers to deliver high quality, cost effective patient care.
Currently, the company operates more than 84 centers in 16 states,
including Alabama, Arizona, California, Delaware, Florida, Kentucky,
Maryland, Massachusetts, Michigan, New Jersey, New York, Nevada, North
Carolina, Pennsylvania, Rhode Island and West Virginia.

Pathway Linked To Breast Cancer Stem Cells

2009-06-21T02:15:00.000-07:00

Tumors generated from normal breast cells and from breast cells in which PTEN has been deleted.
A gene well known to stop or suppress cancer plays a role in cancer stem cells, according to a new study from the University of Michigan Comprehensive Cancer Center. The researchers found that several pathways linked to the gene, called PTEN, also affected the growth of breast cancer stem cells.
Further, by using a drug that interferes with that pathway, the researchers produced an up to 90 percent decrease in the number of cancer stem cells within a tumor.

PTEN is the most frequently inactivated tumor suppressor gene in several cancers, including breast cancer, where it is inactivated in about 40 percent of patients. PTEN is linked to poor outcomes and is associated with aggressive cancers resistant to chemotherapy and current targeted therapies.

The U-M researchers deleted PTEN in tumors grown in cell cultures and in mice, and found an increase in the number of stem cells. They also looked at pathways associated with PTEN and reported that a pathway called PI3-K/Akt regulated the cancer stem cell population by activating another stem cell pathway, Wnt, which is also implicated in multiple cancer types.

“Although there has been considerable progress in identifying cancer stem cells in a variety of tumor types, the pathways that drive the transformation of these cells are not well understood,” says lead study author Hasan Korkaya, D.V.M., Ph.D., research investigator in internal medicine at the U-M Medical School.

Researchers at U-M were the first to identify stem cells in breast cancer. These cells represent fewer than 5 percent of the cells in a tumor but are believed to be responsible for fueling a tumor’s growth and spread. Researchers believe that the ultimate cure of cancer will require killing these cancer stem cells.

In the current study, researchers looked at a drug called perifosine, which inhibits the Akt pathway. Tumors in mice were treated with perifosine or docetaxel, a standard chemotherapy drug. The docetaxel alone showed no effect on the number of cancer stem cells in the tumor. But adding perifosine reduced the cancer stem cell population by up to 90 percent.

What’s more, the cells treated with perifosine – either with or without docetaxel – were less likely to grow a secondary tumor, compared to the cells treated with just docetaxel.

“This is most exciting since perifosine and other drugs that target this pathway are currently in clinical development. If cancer stem cells do contribute to tumor relapse, then adding drugs that target these cells may help to make our current therapies more effective,” says study senior author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

Additional authors include Amanda Paulson, Christophe Ginestier, Marty Brown, Julie Dutcher and Shawn G. Clouthier, all from the U-M Comprehensive Cancer Center; and Emmanuelle Charafe-Jauffret from the Laboratory of Molecular Oncology at the Marseille Cancer Research Institute in France.

Funding was provided by the National Institutes of Health and the A. Alfred Taubman Medical Research Institute at U-M.

Breast cancer statistics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society.

Portable Device Can Detect Viruses In Minutes

2009-06-16T23:00:00.000-07:00

Schematic representation of the sensor: light from a laser is directed onto a wave-guide structure (chip) on which several measuring and reference channels are located. Different types of antibodies that are specific to certain micro-organisms (or types of micro-organism) are first immobilized onto each measuring channel. The liquid from the sample enters a particular channel on the chip via a micro-fluid system (not shown on the diagram above) that is connected to the measuring and reference channels on the chip. When a micro-organism, such as a virus that is present in the sample being analyzed, binds to the relevant antibody on the chip, the interference pattern of the light changes -- this is recorded on a CCD camera. An accurate analysis of the change in the interference pattern also provides information about the quantity of virus particles that are specifically bound in a given channel on the chip, and this means the concentration of a micro-organism in a sample can be determined. The method is fast and simple, and yet very sensitive
Imagine being able to detect in just a few minutes whether someone is infected with a virus. This has now become a reality, thanks to a new ultra-sensitive detector that has been developed by Ostendum, a spin-off company of the University of Twente.

The company has just completed the first prototype and expects to be able to introduce the first version of the detector onto the market in late 2010. Not only does the detector carry out measurements many times faster than do standard techniques, it is also portable, so it can be used anywhere.

Ostendum’s Aurel Ymeti (R&D director), Alma Dudia (Senior Researcher) and Paul Nederkoorn (CEO) claim that if they had the right antibodies to the swine flu at their disposal, they would be able to highlight the presence of the virus within five minutes. In addition to viruses, the device is also able to pick up bacteria, proteins and DNA molecules.

Following the outbreak of swine flu, the issue of finding a means of detecting quickly and simply whether someone is infected with a virus is again very much on the agenda. It is important to be able to do so as soon as possible in order to prevent the virus from spreading further. However, the techniques that are currently available do not yield results for several hours or even days. Moreover, the tests cannot be carried out without a laboratory or trained personnel.

Researchers at Ostendum, a spin-off company of the University of Twente, have developed a portable device that can show in five minutes whether or not a person is infected with a particular virus. The system is able to detect not only viruses, but also specific bacteria, proteins and DNA molecules, an increased or reduced concentration of which in a person’s saliva may be an indication that they have one illness or another.

The only thing needed by the Ostendum detection method is a sample of saliva, blood or another body fluid from the person being tested and the availability of a specific receptor (i.e. a substance that binds with a specific micro-organism or biological substance). For example, in the case of a virus, a specific antibody served as a receptor on the chip and such antibody to that virus has to be available in order to be able to apply the underlying detection method.

Prototype

Ymeti demonstrated during his doctoral research in 2007 that the principle behind the detector worked. At the time, he used a fairly sizeable laboratory set-up. The Ostendum company was subsequently founded, in 2008, in order to develop the principle into a marketable product.

The company has just completed the first prototype of the device, and it is presently working on two others. The three prototypes are undergoing practical tests, in a collaboration involving the Laboratorium Microbiologie Twente Achterhoek and the Zwanenberg Food Group. Ostendum will then make further improvements to the design of the device on the basis of the test results, and expects to have the first device ready for introduction to the marketplace in late 2010.

How it works

The device consists of two parts: a lab-on-a-chip-system and a portable detector. A lab-on-a-chip is a miniature laboratory the size of a chip. The chip contains tiny channels that are coated with receptors. The blood or saliva sample is transported to the channels with the help of a fluid system. Substances from the saliva or blood can then bind with the receptors on the chip. Light from a laser is guided through the channels. If any of the substances binds with the receptors in any of the channels, this will alter the phase of the light. Such a change will manifest itself in the interference pattern, and is a fingerprint of any viruses present, for example, or biomarkers. The method is highly sensitive: it is possible to measure the binding of a single virus particle.

Swine Flu Hits India..... country on Alert!!!!!!!

2009-06-14T02:06:00.000-07:00

H1N1 virus attacks India
17 swine flu cases in India, ministry warns of escalation

Read more about Swine Flu in Medicalworldofmine :: swine flu

NEW DELHI: The number of swine flu cases across the country climbed upto 17 on Saturday as the Union health ministry warned of a spurt in number
of cases after monsoon.

"They say that the H1N1 group of viruses proliferate more when the weather is slightly cooler," health secretary Naresh Dayal said.

"We are happy that this time it is not proliferating so much because the temperature is high. But after the monsoon there is a chance that it can come again," he added.

Meanwhile, the latest case in the country was that of one-and-a-half-year old boy who tested positive a day after his six-year-old sister tested the same for swine flu.

The siblings had reached India along with their parents from New York on June 10.

Since they are too young to be quarantined, the sister-brother duo are being accompanied in hospital by their grandfather, who was put on anti-viral drugs and has tested negative for H1N1 virus.

The family members are also being tested and their samples have been sent to the National Institute for Communicable Diseases (NICD) for tests.

A 24-year-old student, who came to Hyderabad from Austin (US) via Dubai-Mumbai, was admitted to hospital for showing swine flu like symptoms.

In Tamil Nadu, a family of five, including a six- month-old infant, was quarantined at the airport with suspected symptoms after they arrived from the US

Swine Flu Update: WHO Declares Pandemic In Response To Ongoing Global Spread Of Novel Influenza A (H1N1) Virus

2009-06-14T02:05:00.000-07:00

CDC developed PCR diagnostic test to detect novel H1N1 virus.

Read more about Swine Flu :: SWINE FLU
On June 11, 2009, the World Health Organization (WHO) raised the worldwide pandemic alert level to Phase 6 in response to the ongoing global spread of the novel influenza A (H1N1) virus, which causes swine flu. A Phase 6 designation indicates that a global pandemic is underway.

More than 70 countries are now reporting cases of human infection with novel H1N1 flu. This number has been increasing over the past few weeks, but many of the cases reportedly had links to travel or were localized outbreaks without community spread. The WHO designation of a pandemic alert Phase 6 reflects the fact that there are now ongoing community level outbreaks in multiple parts of world.

WHO’s decision to raise the pandemic alert level to Phase 6 is a reflection of the spread of the virus, not the severity of illness caused by the virus. It’s uncertain at this time how serious or severe this novel H1N1 pandemic will be in terms of how many people infected will develop serious complications or die from novel H1N1 infection. Experience with this virus so far is limited and influenza is unpredictable. However, because novel H1N1 is a new virus, many people may have little or no immunity against it, and illness may be more severe and widespread as a result. In addition, currently there is no vaccine to protect against novel H1N1 virus.

In the United States, most people who have become ill with the newly declared pandemic virus have recovered without requiring medical treatment, however, CDC anticipates that there will be more cases, more hospitalizations and more deaths associated with this pandemic in the coming days and weeks. In addition, this virus could cause significant illness with associated hospitalizations and deaths in the fall and winter during the U.S. influenza season.

Background

Novel influenza A (H1N1) is a new flu virus of swine origin that first caused illness in Mexico and the United States in March and April, 2009. It’s thought that novel influenza A (H1N1) flu spreads in the same way that regular seasonal influenza viruses spread, mainly through the coughs and sneezes of people who are sick with the virus, but it may also be spread by touching infected objects and then touching your nose or mouth. Novel H1N1 infection has been reported to cause a wide range of flu-like symptoms, including fever, cough, sore throat, body aches, headache, chills and fatigue. In addition, many people also have reported nausea, vomiting and/or diarrhea.

The first novel H1N1 patient in the United States was confirmed by laboratory testing at CDC on April 15, 2009. The second patient was confirmed on April 17, 2009. It was quickly determined that the virus was spreading from person-to-person. On April 22, CDC activated its Emergency Operations Center to better coordinate the public health response. On April 26, 2009, the United States Government declared a public health emergency and has been actively and aggressively implementing the nation’s pandemic response plan.

Since the outbreak was first detected, an increasing number of U.S. states have reported cases of novel H1N1 influenza with associated hospitalizations and deaths. By June 3, 2009, all 50 states in the United States and the District of Columbia and Puerto Rico were reporting cases of novel H1N1 infection. While nationwide U.S. influenza surveillance systems indicate that overall influenza activity is decreasing in the country at this time, novel H1N1 outbreaks are ongoing in parts of the U.S., in some cases with intense activity.

CDC is continuing to watch the situation carefully, to support the public health response and to gather information about this virus and its characteristics. The Southern Hemisphere is just beginning its influenza season and the experience there may provide valuable clues about what may occur in the Northern Hemisphere this fall and winter.

CDC Response

CDC continues to take aggressive action to respond to the outbreak. CDC’s response goals are to reduce the spread and severity of illness, and to provide information to help health care providers, public health officials and the public address the challenges posed by this new public health threat.

CDC is issuing updated interim guidance in response to the rapidly evolving situation (see: http://www.cdc.gov/h1n1flu/recommendations.htm).

Clinician Guidance

CDC has issued interim guidance for clinicians on identifying and caring for patients with novel H1N1 (see: http://www.cdc.gov/h1n1flu/identifyingpatients.htm), in addition to providing interim guidance on the use of antiviral drugs (see: http://www.cdc.gov/h1n1flu/recommendations.htm). Influenza antiviral drugs are prescription medicines (pills, liquid or an inhaled powder) with activity against influenza viruses, including novel influenza H1N1 viruses. The priority use for influenza antiviral drugs during this outbreak is to treat people hospitalized with influenza illness, and to treat people at increased risk of severe illness, including pregnant women, young children, and people with chronic health conditions like asthma, diabetes and other metabolic diseases, heart or lung disease, kidney disease, weakened immune systems, and persons with neurologic or neuromuscular disease.

Public Guidance

CDC has provided guidance for the public on what to do if they become sick with flu-like symptoms, including infection with novel H1N1 (see: http://www.cdc.gov/h1n1flu/sick.htm). CDC also has issued instructions on taking care of a sick person at home (see: http://www.cdc.gov/h1n1flu/guidance_homecare.htm) and the use of facemasks and respirators to reduce novel influenza A (H1n1) transmission (see: http://www.cdc.gov/h1n1flu/masks.htm). Everyone should take everyday preventive actions to stop the spread of germs, including frequent hand washing and people who are sick should stay home and avoid contact with others in order to limit further spread of the disease.

Testing

CDC has developed a PCR diagnostic test kit to detect this novel H1N1 virus and has now distributed test kits to all states in the U.S. and the District of Columbia and Puerto Rico. The test kits are being shipped internationally as well. This will allow states and other countries to test for this new virus.

Vaccine

Vaccines are a very important part of a response to pandemic influenza and the U.S. Government is aggressively taking early steps in the process to manufacture a novel H1N1 vaccine, working closely with manufacturers. CDC has isolated the new H1N1 virus, made a candidate vaccine virus that can be used to create vaccine, and has provided this virus to industry so they can begin scaling up for production of a vaccine, if necessary. Making vaccine is a long multi-step process requiring several months to complete.

Stockpile Deployment

CDC has deployed 25 percent of the supplies in the Strategic National Stockpile (SNS) to all states in the continental United States and U.S. territories. This included antiviral drugs, personal protective equipment, and respiratory protection devices. The influenza A (H1N1) virus is susceptible to the prescription antiviral drugs oseltamivir and zanamivir. These supplies and medicines will help states and U.S. territories respond to novel H1N1 virus.

Surveillance

Novel influenza A (H1N1) activity is now being detected through CDC’s routine influenza surveillance systems and reported weekly in FluView. CDC tracks U.S. influenza activity through multiple systems across five categories. While our influenza surveillance systems indicate that overall influenza activity is decreasing in the United States, novel H1N1 outbreaks are ongoing in different parts of the U.S., in some cases with intense influenza-like activity. Most of the influenza viruses being detected now are novel H1N1 viruses.

Shared Responsibility

Individuals have an important role in protecting themselves and their families.

* Stay informed. Health officials will provide additional information as it becomes available.
* Everyone should take these everyday steps to protect your health and lessen the spread of this new virus:
o Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it.
o Wash your hands often with soap and water, especially after you cough or sneeze. Alcohol-based hand cleaners are also effective.
o Avoid touching your eyes, nose or mouth. Germs spread this way.
o Try to avoid close contact with sick people.
o If you are sick with a flu-like illness, stay home for 7 days after your symptoms begin or until you have been symptom-free for 24 hours, whichever is longer. This is to keep from infecting others and spreading the virus further.
o Follow public health advice regarding school closures, avoiding crowds and other social distancing measures.

Swine Flu Origins Revealed

2009-06-14T01:56:00.000-07:00

The flu virus: tracking its origin
A new analysis of the current swine-origin H1N1 influenza A virus suggests that transmission to humans occurred several months before recognition of the existing outbreak.
The work, published online in Nature June 10, highlights the need for systematic surveillance of influenza in swine, and provides evidence that new genetic elements in swine can result in the emergence of viruses with pandemic potential in humans.

'Using computational methods, developed over the last ten years at Oxford, we were able to reconstruct the origins and timescale of this new pandemic,' said Dr Oliver Pybus of Oxford University's Department of Zoology, an author of the paper. 'Our results show that this strain has been circulating among pigs, possibly among multiple continents, for many years prior to its transmission to humans.'

Dr Pybus, along with Andrew Rambaut from the University of Edinburgh and colleagues, used evolutionary analysis to estimate the timescale of the origins and the early development of the epidemic. They believe that it was derived from several viruses circulating in swine, and that the initial transmission to humans occurred several months before recognition of the outbreak.

The team conclude that 'despite widespread influenza surveillance in humans, the lack of systematic swine surveillance allowed for the undetected persistence and evolution of this potentially pandemic strain for many years.'

The team included researchers from Oxford, the University of Edinburgh, the University of Hong Kong and the University of Arizona.

New Antibiotics Could Come From A DNA Binding Compound That Kills Bacteria In 2 Minutes

2009-06-12T04:00:00.000-07:00

Dr Adair Richards.
A synthetic DNA binding compound has proved surprisingly effective at binding to the DNA of bacteria and killing all the bacteria it touched within two minutes. The DNA binding properties of the compound were first discovered in the Department of Chemistry at the University of Warwick by Professor Mike Hannon and Professor Alison Rodger (Professor Mike Hannon is now at the University of Birmingham). However the strength of its antibiotic powers have now made it a compound of high interest for University of Warwick researchers working on the development of novel antibiotics.
Dr Adair Richards from the University of Warwick said: "This research will assist the design of new compounds that can attack bacteria in a highly effective way which gets around the methods bacteria have developed to resist our current antibacterial drugs. As this antibiotic compound operates by targeting DNA, it should avoid all current resistance mechanisms of multi-resistant bacteria such as MRSA."

The compound [Fe2L3]4+ is an iron triple helicate with three organic strands wrapped around two iron centres to give a helix which looks cylindrical in shape and neatly fits within the major groove of a DNA helix. It is about the same size as the parts of a protein that recognise and bind with particular sequences of DNA. The high positive charge of the compound enhances its ability to bind to DNA which is negatively charged.

When the iron-helicate binds to the major groove of DNA it coils the DNA so that it is no longer available to bind to anything else and is not able to drive biological or chemical processes. Initially the researchers focused on the application of this useful property for targeting the DNA of cancer cells as it could bind to, coil up and shut down the cancer cell's DNA either killing the cell or stopping it replicate. However the team quickly realised that it might also be a very clever way of targeting drug-resistant bacteria.

New research at the University of Warwick, led by Dr Adair Richards and Dr Albert Bolhuis, has now found that the [Fe2L3]4+ does indeed have a powerful effect on bacteria. When introduced to two test bacteria Bacillus subtilis and E. coli they found that it quickly bound to the bacteria's DNA and killed virtually every cell within two minutes of being introduced - though the concentration required for this is high.

Professor Alison Rodger, Professor of Biophysical Chemistry at the University of Warwick, said: "We were surprised at how quickly this compound killed bacteria and these results make this compound a key lead compound for researchers working on the development of novel antibiotics to target drug resistant bacteria."

The researchers will next try and understand how and why the compound can cross the bacteria cell wall and membranes. They plan to test a wide range of compounds to look for relatives of the iron helicate that have the same mechanism for action in collaboration with researchers around the world.

New 'Idol' Grabs The Spotlight: Enzyme That Controls 'Bad' Cholesterol Discovered

2009-06-12T03:56:00.000-07:00

The above figure shows the LDL receptor in green (at left) and how it degrades after coming into contact with Idol (at right).
Low-density lipoprotein (LDL) is the so-called "bad cholesterol" often linked to medical problems like heart disease and clogged arteries. Cells in the liver produce a specific receptor that sticks to LDL and removes it from the blood, lowering cholesterol levels. Statin drugs also reduce LDL cholesterol levels by boosting cells' production of the receptor.
Using a mouse model, UCLA scientists discovered a new mechanism that controls cells' production of LDL receptor. The team identified an enzyme called Idol that destroys the receptor, permitting more LDL cholesterol to circulate in the blood. In blocking Idol's activity, the researchers triggered cells to make more receptor and absorb more cholesterol from the body.

"We only know of three pathways that regulate the LDL receptor. The first two are already targeted by existing drugs," explained Dr. Peter Tontonoz, professor of pathology and laboratory medicine at the David Geffen School of Medicine at UCLA and an investigator at the Howard Hughes Medical Institute. "Idol is the first mechanism discovered in several years that may lead to a new medication designed to control cholesterol levels."

The findings suggest that development of a drug that interferes with Idol's activity could influence cholesterol metabolism and lower levels of bad cholesterol. Doctors could prescribe the new medication in conjunction with statin drugs, which also cut cholesterol levels by targeting a different enzyme linked to the LDL receptor. This could benefit patients that cannot tolerate statin-related side effects.

Tontonoz collaborated with Noam Zelcer, Cynthia Hong and Rima Boyadjian. The research was funded by the Howard Hughes Medical Institute and the National Heart, Lung and Blood Institute. Tontonoz and Zelcer have filed a patent related to the research findings.

The research appears in the June 11 online edition of the journal Science.

How Tumor Cells Move

2009-05-27T10:12:00.000-07:00

Breast cancer cells move through a three-dimensional matrix gel. Top: "Normal tumor cells" Bottom: Tumor cells in which the signal factor SCAI is disrupted move much more effectively.
Researchers in Heidelberg discover new protein that is suppressed in particularly aggressive cancer cell.
If cancer cells lack a certain protein, it could be much easier for them to penetrate healthy body tissue, the first step towards forming metastases. Scientists at the Pharmacology Institute of the University of Heidelberg have discovered the previously unknown cell signal factor SCAI (suppressor of cancer cell invasion), which inhibits the movement and spread of tumor cells in laboratory tests. When the factor’s functioning was disrupted, the cancer cells moved much more effectively in what are known as three-dimensional matrix systems, which imitate some of the tissue properties of the human body.

“The protein is apparently suppressed in many types of tumors, e.g. breast, lung, or thyroid,” explains Dr. Robert Grosse, head of the Emmy Noether Junior Research Group funded by the German Research Association (DFG) at the Pharmacology Institute. The new factor could be an interesting starting point for research into new mechanisms for fighting cancer. The research team’s results have now been published online in the prestigious international journal Nature Cell Biology.

Focus on particularly aggressive cancers

Tumor cells are extremely mobile and “adept” at penetrating healthy tissue to form metastases. They adapt to the consistency of the respective tissue by changing their shapes constantly and attach flexibly to surrounding tissues during movement with the help of special surface structures (receptors).

One of these receptors is what is known as b1-integrin, which is frequently formed in many tumors such as metastasizing breast cancer. “The cell signal factor SCAI controls the formation and function of b1-integrin,” says Dr. Robert Grosse. “If there is too little SCAI in tumor cells, then b1-integrin is overactive, so to speak. The cell can change more rapidly to a more aggressive form and penetrate surrounding tissue, a crucial step toward increased spreading of the tumor and the possible formation of metastases.”

In their recently published study, the Heidelberg researchers examined cells from skin cancer (melanoma) and breast cancer. In other projects, Dr. Robert Grosse’s team would like to study the function of the signal factor SCAI more closely in an animal model. “If the function of SCAI is confirmed to be decisive in the formation of especially aggressive tumor cells, this could be a promising starting point for developing new diagnostic methods or medication,” says the pharmacologist. It could also be possible to develop an agent that prevents the genetic suppression of the signal factor in cancer cells. But first the researchers need to better understand how the signal factor itself is regulated in the cell.

Swine Flu: To Panic Or Not -- That Is The Question

2009-05-17T10:11:00.000-07:00

Thanks to the 24-hour media coverage about swine flu, we’re all aware that a potential flu pandemic could be high. But before you stock up on face masks and hand sanitizer, it’s important to put some things in perspective.
William Sutker, M.D., chief of infectious diseases at Baylor University Medical Center at Dallas says that first and foremost, we should remain calm.

“As of now, there is no need for people to panic. So far, there have been very few cases reported,” says Dr. Sutker. “At this point, it is unclear if the swine flu outbreak will develop in to a full blown pandemic.”

Although there are many myths and misconceptions floating around, Dr. Sutker says the facts about swine flu are these:

1. Swine flu or H1N1, is a particular strain of Type A flu (Type A and Type B are the usual strains seen every year). Swine flu is typically associated with pigs and usually contracted by those who have close contact with the animals. However, this strain can be spread from person to person.
2. Swine flu is treatable. “Although the type of flu we saw this season was not sensitive to some of the common antivirals that were available, swine flu is,” says Dr. Sutker. He says it can be treated with Tamiflu and Relenza, available by prescription. However, Dr. Sutker adds that these medications should be used carefully as overuse could lead to drug-resistant strains of the virus.
3. So far, 40 people in the United States have been diagnosed with swine flu. In comparison, anywhere from 5 to 20 percent of the population in the United States is diagnosed with human strains of the flu every year, according to the Centers for Disease Control and Prevention (CDC).
4. The symptoms of swine flu are mild. Although the symptoms for swine flu are similar to those of the regular flu, such as fever, chills, body aches and coughing, they are no worse than regular flu symptoms. “However, there seems to be an increase in nausea and vomiting amongst those infected with swine flu. Again, these symptoms can be associated with regular strains of the flu as well.”
5. You can not get swine flu from pork products. According to the U.S. Department of Agriculture scientists you can not catch swine flu from food products.

Dr. Sutker adds that the most powerful weapon in our defense against swine flu is basic flu prevention protocol. Just like any other strain of the flu, swine flu is spread by coughing, sneezing, etc. so in order to protect yourself—or to avoid spreading it if you are infected—practice good respiratory etiquette. Follow these tips:

1. Wash your hands. “Hand hygiene can not be stressed enough,” advises Dr. Sutker. “Wash your hands regularly with soap and water or an alcohol-based sanitizer. As always, this is the single most important prevention technique that we have available.”
2. Cover your cough or sneeze. “Flu, like any other contagious respiratory disease, is spread by contact with infected droplets such as those released during a cough or sneeze.” Cough or sneeze in to a tissue and throw it away. If you don’t have a tissue, use your shirt sleeve or hand, but make sure to wash your hands thoroughly afterwards.
3. Avoid public places if you have been exposed. “Any crowded area is the last place you should be if you think you have been exposed,” says Dr. Sutker. “Do your friends, family and co-workers a favor and stay home. You will not only spare them becoming infected too, but you’ll need the rest in order to get better.”
4. If you think you are infected, see your doctor. “We are advising people to avoid going to their local emergency room if they are feeling sick as they can easily become overwhelmed,” adds Dr. Sutker. “Instead, make an appointment to see your family physician so they can start treatment immediately.”

Scientists Race To Deliver DNA Swine Flu Test

2009-05-17T10:03:00.000-07:00

A team of genetics experts in Southampton is working against the clock to produce the world's first DNA test for the Mexican strain of swine flu.
University of Southampton spin-out company PrimerDesign specialises in producing high-tech DNA detection kits. The technology detects results faster and more accurately than traditional diagnosis techniques. The company was founded by University of Southampton scientists and is part of the University's SETsquared Business Incubation programme.

Staff at the PrimerDesign laboratories realised they were ideally positioned to create the first DNA swine flu test when the US Centre for Disease Control published the genetic data for the killer virus this week.

Coordinator of the swine flu DNA project, Dr Rob Powell said, "With the release of the unique genetic code for this dangerous virus strain we're able to develop the ultimate diagnosis tool within the next few days.

"At PrimerDesign we're able to produce synthetic DNA that matches the virus exactly, without ever having to come into contact with the flu itself. The test can identify the presence of swine flu within two hours."

The high-tech production methods of the kits mean that the Southampton team could very quickly produce enough test kits for hospitals across Europe if needed. The kits will be fully developed and ready to go within two weeks.

PrimerDesign Ltd already produces genetic detection kits for numerous other viruses and conditions; it is possible that this could be the first DNA diagnosis for the Mexican swine flu anywhere in the world.

Swine Flu: Public Health Emergency Declared, Investigation Continues

2009-05-17T09:59:00.000-07:00

Swine flu is a respiratory disease of pigs caused by type A influenza that regularly causes outbreaks of influenza among pigs. Swine flu viruses do not normally infect humans; however, human infections with swine flu do occur, and cases of human-to-human spread of swine flu viruses have been documented.
As new human cases of swine influenza A (H1N1) virus infection are identified in the United States and internationally, health officials around the world are continuing their investigation and response effort surrounding the outbreak of swine flu.
The World Health Organization (WHO) reports that the current situation regarding the outbreak of swine flu is evolving rapidly. As of April 27, 2009, the United States Government has reported 40 laboratory confirmed human cases of swine influenza A (H1N1), with no deaths. Mexico has reported 26 confirmed human cases of infection with the same virus, including seven deaths. Canada has reported six cases, with no deaths, while Spain has reported one case, with no deaths.

For its part, the U.S. Centers for Disease Control and Prevention (CDC) reports that it is working very closely with officials in states where human cases of swine influenza A (H1N1) have been identified, as well as with health officials in Mexico, Canada and the World Health Organization. This includes deploying staff domestically and internationally to provide guidance and technical support.

The CDC activated its Emergency Operations Center to coordinate the agency's response to this emerging health threat, and yesterday the Secretary of the Department Homeland Security, Janet Napolitano, declared a public health emergency in the United States. This will allow funds to be released to support the public health response. CDC's goals during this public health emergency are to reduce transmission and illness severity, and provide information to assist health care providers, public health officials and the public in addressing the challenges posed by this newly identified influenza virus. To this end, CDC has issued a number of interim guidance documents in the past 24 hours.

In addition, CDC's Division of the Strategic National Stockpile (SNS) is releasing one-quarter of its antiviral drugs, personal protective equipment, and respiratory protection devices to help states respond to the outbreak. Laboratory testing has found the swine influenza A (H1N1) virus susceptible to the prescription antiviral drugs oseltamivir and zanamivir. This is a rapidly evolving situation and CDC will provide updated guidance and new information as it becomes available.

CDC is recommending everyday actions that people can take to stay healthy:

* Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it.
* Wash your hands often with soap and water, especially after you cough or sneeze. Alcohol-based hands cleaners are also effective.
* Avoid touching your eyes, nose or mouth. Germs spread that way.
* Try to avoid close contact with sick people. Influenza is thought to spread mainly person-to-person through coughing or sneezing of infected people.

If you get sick, CDC recommends that you stay home from work or school and limit contact with others to keep from infecting them.

Swine flu is a respiratory disease of pigs caused by type A influenza that regularly causes outbreaks of influenza among pigs. Swine flu viruses do not normally infect humans; however, human infections with swine flu do occur, and cases of human-to-human spread of swine flu viruses have been documented.

The public health emergency declaration is available at http://www.hhs.gov/secretary/phe_swh1n1.html. For information on swine flu, visit http://www.cdc.gov/swineflu.

WHO advises no restriction of regular travel or closure of borders. It is considered prudent for people who are ill to delay international travel and for people developing symptoms following international travel to seek medical attention, in line with guidance from national authorities.

There is also no risk of infection from this virus from consumption of well-cooked pork and pork products. Individuals are advised to wash hands thoroughly with soap and water on a regular basis and should seek medical attention if they develop any symptoms of influenza-like illness.

Swine Flu Outbreak Illuminated By Avian Flu Research

2009-05-17T09:58:00.000-07:00

This graphic shows why the Type A virus can't be eradicated.
A new study by University of Maryland researchers suggests that the potential for an avian influenza virus to cause a human flu pandemic is greater than previously thought. Results also illustrate how the current swine flu outbreak likely came about.
As of now, avian flu viruses can infect humans who have contact with birds, but these viruses tend not to transmit easily between humans. However, in research recently published in the Proceedings of the National Academy of Sciences, Associate Professor Daniel Perez from the University of Maryland showed that after reassortment with a human influenza virus, a process that usually takes place in intermediary species like pigs, an avian flu virus requires relatively few mutations to spread rapidly between mammals by respiratory droplets.

"This is similar to the method by which the current swine influenza strain likely formed," said Perez, program director of the University of Maryland-based Prevention and Control of Avian Influenza Coordinated Agricultural Project, AICAP. "The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus. After mutating to be able to spread by respiratory droplets and infect humans, it is now spreading between humans by sneezing and coughing."

In his study, Perez used the avian H9N2 influenza virus, one that is on the list of candidates for human pandemic potential. Using reverse genetics, a technique whereby individual genes from viruses are separated, selected, and put back together, Perez and his team created a hybrid human-avian virus. Their research hybrid has internal human flu genes and surface avian flu genes from the H9N2 virus. Though it comes from a different strain of avian flu than the one that contributed to the hybrid virus now causing the swine flu outbreak, Perez's research virus is similar in origin to the swine flu virus, in that both involved a combination of avian and human influenza viruses.

Perez infected ferrets (considered a good model for human influenza transmission) with the virus he created, and allowed the virus to mutate in the species. Before long, healthy ferrets that shared air space but not physical space with the infected ferret had the virus, showing that the virus had mutated to spread by respiratory droplets.

When the genetic sequences of the mutant virus and original hybrid virus were compared, the only differences were five amino acid mutations, three on the surface, and two internally. Two of the surface mutations were determined to be solely responsible for supporting respiratory droplet transmission. Because so few mutations were necessary to make the hybrid H9N2 transmissible this way, they concluded that after an animal-human hybrid influenza virus forms in nature, a human pandemic of this virus is potentially just a few mutations away.

"We do not know if the mutations we saw in the lab are the same that have made the H1N1 swine flu transmissible by respiratory droplets," Perez said. "We will be doing more research on the current swine flu strain to study its specific genetic mutations."

Perez found that one of the two of the genetic mutations in his lab strain that enabled respiratory transmission between mammals was on the tip of the HA surface protein, one of the sites where human antibodies created in response to current vaccines would bind.

"Because the binding site of the mutant virus is different from the virus upon which the vaccine is modeled, it may mean that current vaccine stocks would not be as effective against the H9N2 mutant strain as previously anticipated," said Perez. "We should keep this in mind when designing vaccines for an avian flu pandemic in humans."

However, scientists cannot predict what the actual mutations will look like if and when they occur in nature, or even which strain of avian influenza will mutate to infect mammals.

"This is just the tip of the iceberg," said Perez. "Many more studies have to be done to see which combinations of mutations cause this type of transmission before we can design the appropriate vaccines."

Perez will be talking this week with the NIH and the CDC to discuss his team's role in researching the current swine flu virus strain. Perez will likely do studies related to vaccine development, virus transmission between humans and animals, and the pathogenesis of the virus.

A virus vaccine is derived from the virus itself. The vaccine consists of virus components or killed viruses that mimic the presence of the virus without causing disease. These prime the body's immune system to recognize and fight against the virus. The immune system produces antibodies against the vaccine that remain in the system until they are needed. If that virus, or in some cases a closely similar one is later introduced into the system, those antibodies attach to viral particles and remove them before they have time to replicate, preventing or lessening symptoms of the virus.

The immune system also retains antibodies to a virus after being infected with it, so humans have general immunity to human strains of avian influenza strains. But humans do not generally have immunity to avian flu strains because they have not been infected by them before. The surface proteins are sufficiently different to escape the human immune response. Avian flu strains are therefore more dangerous for humans because the human immune system cannot recognize the virus or protect against it.

Swine Flu Update: At Least 18 Countries Affected; Human-to-Pig Infection Reported In Canada

2009-05-17T09:55:00.000-07:00

Map of the spread of influenza A(H1N1).
The World Health Organization (WHO) reports that as of 1600 GMT, 3 May 2009, 18 countries have officially reported 898 cases of influenza A(H1N1) infection.
Mexico has reported 506 confirmed human cases of infection, including 19 deaths. The higher number of cases from Mexico in the past 48 hours reflects ongoing testing of previously collected specimens. The United States Government has reported 226 laboratory confirmed human cases, including one death.

The following countries have reported laboratory confirmed cases with no deaths: Austria (1), Canada (85), China, Hong Kong Special Administrative Region (1), Costa Rica (1), Denmark (1), France (2), Germany (8), Ireland (1), Israel (3), Italy (1), Netherlands (1), New Zealand (4), Republic of Korea (1), Spain (40), Switzerland (1) and the United Kingdom (15).

WHO advises no restriction of regular travel or closure of borders. It is considered prudent, WHO officials state, for people who are ill to delay international travel and for people developing symptoms following international travel to seek medical attention, in line with guidance from national authorities.

Canada on 2 May reported the identification of the A(H1N1) virus in a swine herd in Alberta. It is highly probable that the pigs were exposed to the virus from a Canadian farm worker recently returned from Mexico, who had exhibited flu-like symptoms and had contact with the pigs. There is no indication of virus adaptation through transfer from human to pigs at this time.

WHO officials stress that there is no risk of infection from this virus from consumption of well-cooked pork and pork products.

Individuals are advised to wash hands thoroughly with soap and water on a regular basis and should seek medical attention if they develop any symptoms of influenza-like illness.

Who provides daily updates at their Influenza A(H1N1) web site, available at: http://www.who.int/entity/csr/disease/swineflu/

Swine Flu Data 'Very Consistent' With Early Stages Of A Pandemic

2009-05-17T09:53:00.000-07:00

Swine flu data so far is very consistent with what researchers would expect to find in the early stages of a pandemic
Early findings about the emerging pandemic of a new strain of influenza A (H1N1) in Mexico are published in the journal Science.
Researchers from the MRC Centre for Outbreak Analysis and Modelling at Imperial College London, working in collaboration with the World Health Organisation and public health agencies in Mexico, have assessed the epidemic using data to the end of April. Their key findings are as follows:

* The data so far is very consistent with what researchers would expect to find in the early stages of a pandemic.
* The researchers' best estimate is that in Mexico, influenza A (H1N1) is fatal in around 4 in 1,000 cases, which would make this strain of influenza as lethal as the one found in the 1957 pandemic. The researchers stress that healthcare has greatly improved in most countries since 1957 and the world is now better prepared.
* The epidemic of influenza A (H1N1) is thought to have started in Mexico on 15 February 2009. The data suggests that by the end of April, around 23,000 people were infected with the virus in Mexico and 91 of these died as a result of infection. However, the figures are uncertain – for example, some mild cases may have gone unreported. The numbers infected could be as low as 6,000 people or as high as 32,000 people.
* The uncertainty around the numbers of people who have been infected with influenza A (H1N1) in Mexico means that the case fatality ratio (CFR) of 0.4% (4 deaths per 1000) cannot be definitely established. The CFR is in the range of 0.3% to 1.5%, but at this stage the researchers believe that 0.4% is the most likely.
* For every person infected, it is likely that there will be between 1.2 and 1.6 secondary cases. This is high compared to normal seasonal influenza, where around 10-15 percent of the population are likely to become infected. However, it is lower than would be expected for pandemic influenza, where 20-30 percent of the population are likely to become infected.
* In an outbreak in an isolated village called La Gloria, Mexico, children were twice as likely to become infected as adults, with 61% of those aged under 15 becoming infected, compared with 29% of those over 15. This may suggest that adults have some degree of immunity against infection, because of having been previously infected with a related strain of influenza, or it may mean that children are more susceptible to infection because they interact much more closely together, for example in school, than adults.

Professor Neil Ferguson, the corresponding author of the new research from the MRC Centre for Outbreak Analysis and Modelling at Imperial College London, said: "Our study shows that this virus is spreading just as we would expect for the early stages of a flu pandemic. So far, it has been following a very similar pattern to the flu pandemic in 1957, in terms of the proportion of people who are becoming infected and the percentage of potentially fatal cases that we are seeing.

"What we're seeing is not the same as seasonal flu and there is still cause for concern – we would expect this pandemic to at least double the burden on our healthcare systems. However, this initial modelling suggests that the H1N1 virus is not as easily transmitted or as lethal as that found in the flu pandemic in 1918," added Professor Ferguson.

Ginger Quells Cancer Patients' Nausea From Chemotherapy

2009-05-16T10:05:00.000-07:00

People with cancer can reduce post-chemotherapy nausea by 40 percent by using ginger supplements, along with standard anti-vomiting drugs, before undergoing treatment, according to scientists at the University of Rochester Medical Center.
About 70 percent of cancer patients who receive chemotherapy complain of nausea and vomiting. "There are effective drugs to control vomiting, but the nausea is often worse because it lingers," said lead author Julie L. Ryan, Ph.D., M.P.H., assistant professor of Dermatology and Radiation Oncology at Rochester's James P. Wilmot Cancer Center. The research will be presented at the American Society of Clinical Oncology meeting in the Patient and Survivor Care Session on Saturday, May 30, in Orlando, Fla.

"Nausea is a major problem for people who undergo chemotherapy and it's been a challenge for scientists and doctors to understand how to control it," said Ryan, a member of Rochester's Community Clinical Oncology Program Research Base at the Wilmot Cancer Center. Her research is the largest randomized study to demonstrate the effectiveness of ginger supplements to ease the nausea. Previous small studies have been inconsistent and never focused on taking the common spice before chemotherapy.

The Phase II/III placebo-controlled, double-blind study included 644 cancer patients who would receive at least three chemotherapy treatments. They were divided into four arms that received placebos, 0.5 gram of ginger, 1 gram of ginger, or 1.5 grams of ginger along with antiemetics (anti-vomiting drugs such as Zofran®, Kytril®, Novaban®, and Anzemet®.)

Patients took the ginger supplements three days prior to chemotherapy and three days following treatment. Patients reported nausea levels at various times of day during following their chemotherapy and those who took the lower doses had a 40 percent reduction.

Ginger is readily absorbed in the body and has long been considered a remedy for stomach aches. "By taking the ginger prior to chemotherapy treatment, the National Cancer Institute-funded study suggests its earlier absorption into the body may have anti-inflammatory properties," Ryan said.

Rochester's Community Clinical Oncology Program Research Base is a national cooperative research group funded by the National Cancer Institute. The Wilmot Cancer Center team specializes in improving the quality of life of people who have cancer.

Implantable Device Offers Continuous Cancer Monitoring

2009-05-16T10:01:00.000-07:00

MIT researchers have developed a device, right, that can be implanted into a tumor to monitor how it responds to treatment.
Surgical removal of a tissue sample is now the standard for diagnosing cancer. Such procedures, known as biopsies, are accurate but only offer a snapshot of the tumor at a single moment in time.
Monitoring a tumor for weeks or months after the biopsy, tracking its growth and how it responds to treatment, would be much more valuable, says Michael Cima, MIT professor of materials science and engineering, who has developed the first implantable device that can do just that.

Cima and his colleagues recently reported that their device successfully tracked a tumor marker in mice for one month. The work is described in a paper published online in the journal Biosensors & Bioelectronics in April.

Such implants could one day provide up-to-the-minute information about what a tumor is doing -- whether it is growing or shrinking, how it's responding to treatment, and whether it has metastasized or is about to do so.

"What this does is basically take the lab and put it in the patient," said Cima, who is also an investigator at the David H. Koch Institute for Integrative Cancer Research at MIT.

The devices, which could be implanted at the time of biopsy, could also be tailored to monitor chemotherapy agents, allowing doctors to determine whether cancer drugs are reaching the tumors. They can also be designed to measure pH (acidity) or oxygen levels, which reveal tumor metabolism and how it is responding to therapy.

With current tools for detecting whether a tumor has spread, such as biopsy, by the time you have test results it's too late to prevent metastasis, said Cima.

"This is one of the tools we're going to need if we're going to turn cancer from a death sentence to a manageable disease," he said.

In the Biosensors & Bioelectronics study, human tumors were transplanted into the mice, and the researchers then used the implants to track levels of human chorionic gonadotropin, a hormone produced by human tumor cells.

The cylindrical, 5-millimeter implant contains magnetic nanoparticles coated with antibodies specific to the target molecules. Target molecules enter the implant through a semipermeable membrane, bind to the particles and cause them to clump together. That clumping can be detected by MRI (magnetic resonance imaging).

The device is made of a polymer called polyethylene, which is commonly used in orthopedic implants. The semipermeable membrane, which allows target molecules to enter but keeps the magnetic nanoparticles trapped inside, is made of polycarbonate, a compound used in many plastics.

Cima said he believes an implant to test for pH levels could be commercially available in a few years, followed by devices to test for complex chemicals such as hormones and drugs.

Lead author of the paper is Karen Daniel, a recent MIT PhD recipient. Other authors are recent PhD recipients Grace Kim and Christophoros Vassiliou; Marilyn Galindo, research affiliate in the Harvard-MIT Division of Health Sciences and Technology; Alexander Guimares, a radiologist at Massachusetts General Hospital; Ralph Weissleder, a professor of radiology at Harvard Medical School; Al Charest, visiting assistant professor of biology at MIT; and Institute Professor Robert Langer.

The research was funded by the National Cancer Institute Centers of Cancer Nanotechnology Excellence and the National Science Foundation.

Even In Our Genome, Good Fences Make Good Neighbors

2009-05-16T09:39:00.000-07:00

CTCF and Tumor Suppressor Gene Silencing
Our genome is a patchwork of neighborhoods that couldn't be more different: Some areas are hustling and bustling with gene activity, while others are sparsely populated and in perpetual lock-down. Breaking down just a few of the molecular fences that separate them blurs the lines and leads to the inactivation of at least two tumor suppressor genes, according to researchers at the Salk Institute for Biological Studies.

Their findings, published in the May 15, 2009 issue of Molecular Cell, explain how a single event can put a cell well ahead on the road to becoming a tumor cell. "Selectively removing a couple of fence posts jumpstarts a cascade of global changes all over the genome that may eventually lead to cancer," says Beverly Emerson, Ph.D., a professor in the Regulatory Biology Laboratory, who led the study.

Normally, a complex network of accelerators (growth factors) and brakes (tumor suppressors) keeps a tight lid on cell proliferation. Tumors result when changes in the genome activate cancer-causing genes or inactivate tumor suppressor genes that tip this delicate balance in favor of uncontrolled cell growth.

"For a really long time people have been trying to understand how tumor suppressor genes get silenced in cancer," says postdoctoral researcher and first author Michael Witcher. "Now that we have figured out one of the key events that leads to their inactivation, we might be able to exploit this mechanism to develop novel therapies."

If stretched out, the DNA of a single human cell would form a very thin thread about 6 feet in length. To fit such a long molecule inside a cell's nucleus and keep everything neatly organized, the DNA is threaded around histone proteins and coiled up in a highly condensed structure called heterochromatin. In areas of gene activity, the tightly packed chromatin is unfurled just enough to make the DNA accessible to regulatory proteins.

In many different types of cancers, however, including breast, lung, liver, and pancreatic tumors, as well as multiple myeloma and lymphoma, the tumor suppressor p16 gets buried deep inside heterochromatin. As a result, it cannot be read by the transcription machinery and is unable keep watch over cell growth.

Researchers had known for a long time that sometimes p16 is silenced long before a cell turns cancerous, yet why that particular stretch of DNA was flagged with chemical marks and became wound up so tightly that it became inaccessible had remained a mystery.

Most people looked for clues within the immediate vicinity of the gene but came up empty-handed. When Witcher extended his search further upstream, however, he discovered a binding site for CTCF, short for CCCTC-binding factor, which forms the centerpiece of the molecular fence posts that separate heterochromatin from the rest of the genome. "We found that the binding of this protein is lost from several binding sites in numerous types of cancer cells, leading to the collapse of the molecular boundary," he says. "Once the boundary was gone, the adjacent heterochromatin encroached and silenced the nearest gene."

Further experiments revealed that CTCF was missing because it lacked a chemical modification known as "PARlation," lab lingo for poly(ADP-ribosyl)ation, which allows the protein to bind to select sites in the genome. "Without PARlation, CTCF fails to form the complex necessary to regulate p16 and the tumor suppressor RASSF1A and possibly others, explaining why breast cancer cells always contain both silenced p16 and silenced RASSF1A," says Witcher.

"We believe that destabilization of specific chromosomal boundaries or loss of molecular fences through aberrant CTCF function may be a general mechanism to inactivate tumor suppressor genes and initiate tumorigenesis in numerous forms of human cancers," says Emerson.

This work was supported by the Samuel Waxman Cancer Research Foundation and the Canadian Institute of Health Research.

Radiation Device In The Breast Reduces Complications For Early Stage Breast Cancer Patients

2009-05-10T10:21:00.000-07:00

A new study shows that the SAVI™ applicator, a small, expandable device inserted inside the breast to deliver partial breast irradiation, carries a low infection risk, a potential complication of such devices. The research, led by radiation oncologists and surgeons at the Moores UCSD Cancer Center and Fort Myers, Florida-based 21st Century Oncology, also indicates that other complications – such as seromas, pockets of fluid that build with the use of internal radiation devices – are unlikely to occur.
That's good news for those women with early-stage breast cancer who opt to have such devices inserted for their radiation therapy after breast-sparing lumpectomy surgery, said Cate Yashar, MD, associate professor of radiation oncology at the UC San Diego School of Medicine and chief of breast and gynecological radiation services at the Moores UCSD Cancer Center. Their use is increasing, she added, noting that the Moores UCSD Cancer Center was one of the first medical facilities in the country to offer SAVI.

SAVI, which consists of flexible catheters through which radiation is given, provides customized radiation therapy and minimizes exposure to healthy tissue after a woman has undergone a lumpectomy to remove a cancerous tumor. Radiation specialists sometimes decide to give women internal radiation – a process called brachytherapy – with the goal of giving concentrated doses of radiation to areas of concern while avoiding healthy tissue.

In the study, researchers examined one-year follow-up data on 63 patients treated with the Food and Drug Administration-approved SAVI device. They found an infection rate that is less than half of the published rates associated with balloon brachytherapy methods, and rated overall cosmetic outcomes with SAVI as "excellent."

The results will be presented at the American Society of Breast Surgeon's annual meeting in San Diego, April 24, 2009.

In addition, physicians were able to use the device's many catheters to customize the radiation dose based on the woman's needs, greatly minimizing radiation to the heart, lungs, ribs and skin, likely resulting in fewer complications, Yashar said. To date, there have been no recurrences or formation of persistent seromas.

"With a full year of follow-up, our research confirms previous findings that this device is safe and effective for radiation delivery, especially compared to other brachytherapy methods," said Yashar. "Without the ability to customize the dose, other devices can lead to complications, like persistent seroma and skin burns. This applicator was created to overcome these problems, and our research shows it has been successful."

Breast brachytherapy is a form of Accelerated Partial Breast Irradiation (APBI). Lasting just five days, APBI offers a shorter course of radiation compared to the six weeks required with traditional whole breast irradiation.

"SAVI has the most flexible dose modulation for single-entry APBI applicators and can sculpt the radiation dose to the size and shape of the tumor cavity and the patient's anatomy, even when only one to two millimeters from normal tissues," Yashar said.

Without the technical limitations of other methods such as balloon brachytherapy, SAVI substantially increases the number of women who qualify for the benefits of APBI, she noted.

Targeting Tumors Using Tiny Gold Particles

2009-05-09T00:22:00.000-07:00

MIT researchers developed these gold nanorods that absorb energy from near-infrared light and emit it as heat, destroying cancer cells
It has long been known that heat is an effective weapon against tumor cells. However, it's difficult to heat patients' tumors without damaging nearby tissues.
Now, MIT researchers have developed tiny gold particles that can home in on tumors, and then, by absorbing energy from near-infrared light and emitting it as heat, destroy tumors with minimal side effects.

Such particles, known as gold nanorods, could diagnose as well as treat tumors, says MIT graduate student Geoffrey von Maltzahn, who developed the tumor-homing particles with Sangeeta Bhatia, professor in the Harvard-MIT Division of Health Sciences and Technology (HST) and in the Department of Electrical Engineering and Computer Science, a member of the David H. Koch Institute for Integrative Cancer Research at MIT and a Howard Hughes Medical Institute Investigator.

Von Maltzahn and Bhatia describe their gold nanorods in two papers recently published in Cancer Research and Advanced Materials. In March, von Maltzahn won the Lemelson-MIT Student Prize, in part for his work with the nanorods.

Cancer affects about seven million people worldwide, and that number is projected to grow to 15 million by 2020. Most of those patients are treated with chemotherapy and/or radiation, which are often effective but can have debilitating side effects because it's difficult to target tumor tissue.

With chemotherapy treatment, 99 percent of drugs administered typically don't reach the tumor, said von Maltzahn. In contrast, the gold nanorods can specifically focus heat on tumors.

"This class of particles provides the most efficient method of specifically depositing energy in tumors," he said.

Wiping out tumors

Gold nanoparticles can absorb different frequencies of light, depending on their shape. Rod-shaped particles, such as those used by von Maltzahn and Bhatia, absorb light at near-infrared frequency; this light heats the rods but passes harmlessly through human tissue.

In a study reported in the team's Cancer Research paper, tumors in mice that received an intravenous injection of nanorods plus near-infrared laser treatment disappeared within 15 days. Those mice survived for three months with no evidence of reoccurrence, until the end of the study, while mice that received no treatment or only the nanorods or laser, did not.

Once the nanorods are injected, they disperse uniformly throughout the bloodstream. Bhatia's team developed a polymer coating for the particles that allows them to survive in the bloodstream longer than any other gold nanoparticles (the half-life is greater than 17 hours).

In designing the particles, the researchers took advantage of the fact that blood vessels located near tumors have tiny pores just large enough for the nanorods to enter. Nanorods accumulate in the tumors, and within three days, the liver and spleen clear any that don't reach the tumor.

During a single exposure to a near-infrared laser, the nanorods heat up to 70 degree Celsius, hot enough to kill tumor cells. Additionally, heating them to a lower temperature weakens tumor cells enough to enhance the effectiveness of existing chemotherapy treatments, raising the possibility of using the nanorods as a supplement to those treatments.

The nanorods could also be used to kill tumor cells left behind after surgery. The nanorods can be more than 1,000 times more precise than a surgeon's scalpel, says von Maltzahn, so they could potentially remove residual cells the surgeon can't get.

Finding tumors

The nanorods' homing abilities also make them a promising tool for diagnosing tumors. After the particles are injected, they can be imaged using a technique known as Raman scattering. Any tissue that lights up, other than the liver or spleen, could harbor an invasive tumor.

In the Advanced Materials paper, the researchers showed they could enhance the nanorods' imaging abilities by adding molecules that absorb near-infrared light to their surface. Because of this surface-enhanced Raman scattering, very low concentrations of nanorods - to only a few parts per trillion in water [gf1]- can be detected.

Another advantage of the nanorods is that by coating them with different types of light-scattering molecules, they can be designed to simultaneously gather multiple types of information - not only whether there is a tumor, but whether it is at risk of invading other tissues, whether it's a primary or secondary tumor, or where it originated.

Bhatia and von Maltzahn are looking into commercializing the technology. Before the gold nanorods can be used in humans, they must undergo clinical trials and be approved by the FDA, which von Maltzahn says will be a multi-year process.

Other authors of the Advanced Materials paper are Andrea Centrone, postdoctoral associate in chemical engineering; Renuka Ramanathan, undergraduate in biological engineering; Alan Hatton, the Ralph Landau Professor of Chemical Engineering; and Michael Sailor and Ji-Ho Park of the University of California at San Diego.

Park and Sailor are also authors of the Cancer Research paper, along with Amit Agrawal, former postdoctoral associate in HST; and Nanda Kishor Bandaru and Sarit Das of the Indian Institute of Technology Madras.

The research was funded by the National Institutes of Health, the Whitaker Foundation and the National Science Foundation. Nanopartz Inc. supplied gold nanoparticles, gold nanowires and the precursor gold nanorods used in this work.

Using Night Vision Technology To Learn More About Lymphatic System

2009-05-09T00:18:00.000-07:00

The director of the new Center for Molecular Imaging at The University of Texas Health Science Center at Houston is using near-infrared night vision technology made famous by American soldiers in the First Gulf War to shed light on the lymphatic system.
While much is known about the blood system, Eva Sevick, Ph.D., who leads the 20-person research team in the university’s Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), said that until recently comparatively little was known about the lymphatic system, which is a network of vessels that act as the body’s sewer system picking up excess debris and fluid from tissues.

Unlike blood, lymphatic fluid is clear, which makes it hard to see. In addition, lymphatic vessels are so small that it is difficult to inject the amount of contrast agents needed for traditional Magnetic Resonance Imaging or X-rays. While lymphatic fluid can be seen with nuclear techniques, actual fluid movement is hard to observe because it typically takes several minutes to acquire an image.

Sevick’s solution to these medical imaging issues was to inject micro amounts of fluorescent dye below the skin where the lymphatic system would sweep it up. Then with the aid of a small laser and a night vision camera designed to pick up small amounts of light, Sevick’s team was able to observe the dye move through the lymph system below the surface of the skin. This was possible because the night vision camera can acquire images in less than one second.

“No one had ever watched this before,” said Caroline Fife, M.D., clinical associate professor of medicine at The University of Texas Medical School at Houston and director of clinical research for the Memorial Hermann - TMC Wound and Lymphedema Center. “This was like Christopher Columbus discovering America. Until now, we’ve never had a good way to study the lymph system. It felt like being a doctor before antibiotics.”

When the lymphatic system is functioning properly, it picks up fluids that leak from blood vessels into the spaces between cells. As this fluid passes between cells it gathers cell waste and debris. The fluid is subsequently taken up by tiny lymphatic capillaries and propelled through lymphatic ducts and nodes until it is returned to the blood.

The lymphatic system also contains immune cells named lymphocytes, which guard the body against invading viruses and bacteria. The lymphatic system is of particular interest to cancer specialists because malignant cells will often end up in lymphatic filters. “Lymph nodes filter out bacteria and tumor cells,” said Fife, noting that the lymphatic system processes six liters of fluid every day.

Much like plumbing when it backs up, lymphatic drainage problems can cause fluid retention or swelling, which results in a condition called lymphedema. About one in 200 are born with lymphedema, according to the Lymphatic Research Foundation (LRF); however, most in the United States acquire it as result of surgery, infection or trauma that interferes with the lymphatic system. About 30 percent of breast cancer survivors develop lymphedema, the LRF states.

While there is no cure, lymphedema symptoms can sometimes be treated with massage and compression bandaging.

“The Center for Molecular Imaging is poised to develop and translate molecular imaging agents, instruments and computer algorithms for improving patient care in a variety of diseases,” Sevick said. “With our optical technologies, we could image disease before the onset of symptoms. We also investigate the impact of breast cancer therapy on lymphatic function in order to evaluate how long-term treatments impact quality of life for cancer survivors.”

Sevick is working to translate her bench discoveries into patient care. With the approval of the U. S. Food & Drug Administration, the researchers in her lab have begun patient trials using this medical imaging technique, which could aid in the diagnosis and treatment of many diseases including those of the lymphatic system.

In one trial, Sevick’s team is recruiting 18 subjects for a clinical study to determine the effect of an automated massage device on lymphatic flow in persons with lymphedema of either one arm or one leg. In a second study, her research team is evaluating the effect of genetic makeup in persons with hereditary lymphedema and acquired lymphedema. More information is available at 713.500.3561.

Sevick is professor and Cullen Chair in Molecular Medicine at the IMM. Her research is supported in part by the National Institutes of Health and the Longaberger Foundation through the American Cancer Society. Prior to joining the IMM faculty in 2008, Sevick served as a professor of radiology at Baylor College of Medicine and led that department’s division of molecular imaging.

Sevick earned her Ph.D. at Carnegie Mellon University and did postdoctoral work at the University of Pennsylvania. Her honors include the American Cancer Society Research Scholar, Sylvia Sorkin Greenfield Award, Fellow of the American Institute of Medical and Biomedical Engineering and DuPont Young Faculty Award.

New Target For Maintaining Healthy Blood Pressure Discovered

2009-04-26T08:12:00.000-07:00

In trying to understand the role of prostaglandins – a family of fatty compounds key to the cardiovascular system – in blood pressure maintenance, researchers at the University of Pennsylvania School of Medicine and colleagues discovered that mice that lack the receptor for one type of prostaglandin have lower blood pressure and less atherosclerosis than their non-mutant brethren.
The results indicate that the normal role for the type of prostaglandin studied, PGF2α, is to increase blood pressure and accelerate atherosclerosis, at least in rodents, and suggest that targeting this pathway could represent a novel therapeutic approach to cardiovascular disease.

The results appeared this week in the Proceedings of the National Academy of Sciences.

“Blocking this prostaglandin receptor may provide a strategy for controlling blood pressure and its attendant vascular disease,” notes senior author Garret A. FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at Penn.

To address prostaglandins’ role in maintaining blood pressure, FitzGerald and his team, including researchers from the University of Southern Denmark, created strains of mice in which both the maternal and paternal copies of the gene for the PGF2α receptor were deleted. They did this in mice with a normal genetic background and in ones that contained an additional mutation in the low-density lipoprotein receptor gene. These manipulations effectively rendered the mice unable to respond to the prostaglandins.

The delicate balance the body maintains to keep blood pressure stable involves not only the prostaglandin system, but another biological pathway, the renin-angiotensin-aldosterone system, or RAAS. Under conditions of low blood pressure, the liver secretes a protein called angiotensiogen. Renin, an enzyme produced by the kidneys, cleaves angiotensiogen into a peptide called angiotensin I. Angiotensin I is cleaved again to form angiotensin II, which stimulates blood vessels to narrow, thereby increasing blood pressure. At the same time, angiotensin II induces the release of the hormone aldosterone, which further elevates blood pressure by promoting retention of water and sodium in the kidneys.

Many conventional therapies for high blood pressure target components of the RAAS pathway. For instance, ACE inhibitors such as captopril (Capoten) target the formation of angiotensin II, while aliskiren (Tekturna) targets renin.

The team assessed the impact of the PGF2α receptor mutations on both blood pressure and RAAS activity. They found that under a variety of circumstances deletion of the PGF2α receptor lowered blood pressure coincident with suppression of RAAS activity.

“Precisely how these two observations are connected is the focus of our current research,” says FitzGerald.

Blood pressure was reduced in both types of genetically engineered mice relative to control littermates. The RAAS molecules renin, angiotensin I, and aldosterone were also reduced, a biological situation leading to lower blood pressure.

The team found that the PGF2α receptor is expressed in the smooth muscle surrounding arteries in the kidneys. However, it was absent in the muscle surrounding the aorta, in the atherosclerotic lesions of mice with their PGF2α receptors knocked out, as well as in the macrophages that inhabit those lesions. Importantly, these atherosclerotic lesions were smaller and less abundant in mice that had both the low-density lipoprotein and PGF2α receptors knocked out, as was macrophage infiltration and inflammatory cytokine production, both of which are indicators of the inflammatory response that marks these plaques.

Prostaglandins are produced during the oxidation of certain cell molecules by cyclooxygenases, the COX enzymes targeted by COX inhibitors, but how remains unclear. FitzGerald’s group had previously shown that blockading cyclooxygenase 1 and its major prostaglandin product, thromboxane, also lowers blood pressure, slowing atherosclerosis, but in this previous study, the relevant genes are present in the aorta and its atherosclerotic lesions. PGF2α, by contrast, acts via the kidney and represents a distinct therapeutic opportunity.

“The picture is emerging that PGF2α controls blood pressure by a mechanism unique among the prostaglandins,” says FitzGerald. “Besides the case of thromboxane, two other types of prostaglandins, PGI2 and PGE2, stimulate renin secretion, which is part of the RAAS pathway.”

Assuming these findings can be translated to humans, targeting the PGF2α pathway could represent a novel opportunity for therapeutic control of blood pressure in cardiovascular patients.

The research was funded by the National Heart, Lung, and Blood Institute and the American Heart Association.

Best Treatment For Multiple Sclerosis May Depend On Disease Subtype

2009-04-14T10:45:00.001-07:00

Animal studies by University of Michigan scientists suggest that people who experience the same clinical signs of multiple sclerosis (MS) may have different forms of the disease that require different kinds of treatment.
The results, if borne out in further studies, point to a time when doctors will be able to target specific inflammatory processes in the body and more effectively help MS patients, using available drugs and new ones in the pipeline.

Since the 1990s, the treatment picture has brightened for people with multiple sclerosis in its most common form, relapsing-remitting MS. Beta interferon drugs and glatiramer acetate (marketed as Copaxone) have proved effective at decreasing the attack rate and suppressing inflammatory plaque development in many patients with MS. Yet why the drugs help some patients, but not others, has remained a mystery.

The U-M research team conducted the studies in mice that have a disease similar to MS: experimental autoimmune encephalomyelitis or EAE. The team found that different inflammatory chemicals, whose activity is linked to two different types of immune system T cells, could bring on the same paralysis and other MS-like signs. They also showed that drugs that block one of the inflammation pathways were not effective at blocking the other.

"These two forms of disease differ in the specific anti-inflammatory agents that they are responsive to," says Benjamin Segal, M.D., the study's senior author and the director of the Multiple Sclerosis Center at the U-M Health System.

"We already know that some people respond better to the drugs beta interferon or Copaxone than others. Now we've shown proof that you can cause MS-like syndrome in mice due to qualitatively different types of inflammatory damage. As a result, these two kinds of inflammation likely require different approaches to treatment," says Segal. He directs the Holtom-Garrett Program in Neuroimmunology and is the Holtom-Garrett Family Professor of Neurology at the U-M Medical School.

Context

MS is an inflammatory disease of the central nervous system believed to be autoimmune in nature. Certain cells in the body's immune system mount an inappropriate response against proteins in the nervous system, in particular myelin, the fatty substance that covers nerve axons. MS affects an estimated 2.5 million people worldwide. Symptoms, which vary widely, include numbness and weakness, incontinence, double vision, tremor, imbalance and pain.

In 85 percent of MS cases, patients begin with what is called a relapsing-remitting form of the disease. Initially, they have attacks in which they experience symptoms for a time, return to normal, then have attacks again. In the last 15 years, several beta interferon drugs and Copaxone have been effective in many patients at limiting the number of attacks. These drugs also can also decrease damage in the brain as visualized on MRI scans.

Research details

Segal's research team injected one group of mice with an immune system T helper cell, Th1, long believed to play a role in MS, and another group with a T helper cell, Th17, whose potential role in MS has recently come to light. They measured the activity of specific inflammatory agents that are induced by each type of T cell as the immune system mounts its misguided attack on the myelin sheaths of nerve cells.

Both groups of mice developed similarly severe and rapid paralysis. But the researchers found clear differences in the inflammatory agents involved, called cytokines and chemokines, and in the resulting damage to the central nervous system.

Mice injected with Th1 cells showed a pattern of central nervous system inflammation that resembled that of common MS, with lesions filled with macrophages, a type of immune system defender cell. Mice injected with Th17 cells, however, had lesions filled with another immune cell type, neutrophils. In these mice, inflammation reached deep in central nervous system tissues and in the optic nerve.

In both groups of mice, the scientists tested the effects of neutralizing antibody drugs similar to drugs being developed against autoimmune diseases in humans. Some of the drugs inhibited disease in the Th17 mice, but not in the mice receiving Th1 cells. Other drugs were effective against both types of disease.

"That's our proof that these really are different mechanisms of disease," says Mark Kroenke, the study's first author and a Ph.D. student in immunology at U-M.

Implications

It's not yet known whether the same differences will prove true in people with MS. But the study suggests the need to develop drugs tailored to affect distinct inflammation pathways that might drive different forms of relapsing-remitting MS.

"We speculate at some point being able to identify and measure active inflammatory agents in patients, and to develop customized profiles that would help predict what treatments will be effective," Segal says.

In addition, Segal says, the findings may aid the search for effective drugs for two difficult-to-treat diseases closely related to MS: neuromyelitis optica, which affects the optic nerve and spinal cord, and opticospinal MS, most common in Asia. The pattern of inflammation the team saw in the Th17-injected mice resembled the pattern in these variants of MS.

Other authors include: Anuska V. Andjelkovic, Ph.D., U-M Department of Pathology; and Thaddeus J. Carlson, Ph.D., University of Rochester School of Medicine and Dentistry. Segal is on the scientific advisory board of the National MS Society.

Disease Diagnosis In Just 15 Minutes? Biosensor Technology Uses Antibodies To Detect Biomarkers Much Faster

2009-04-14T10:41:00.000-07:00

Testing for diseases such as cancer and multiple sclerosis could soon be as simple as using a pregnancy testing kit.
A team led by scientists at the University of Leeds has developed a biosensor technology that uses antibodies to detect biomarkers – molecules in the human body which are often a marker for disease – much faster than current testing methods.

The technology could be used in doctors' surgeries for more accurate referral to consultants, and in hospitals for rapid diagnosis. Tests have shown that the biosensors can detect a wide range of analytes (substances being measured), including biomarkers present in prostate and ovarian cancer, stroke, multiple sclerosis, heart disease and fungal infections. The team also believes that the biosensors are versatile enough to test for diseases such as tuberculosis and HIV.

The technology was developed through a European collaboration of researchers and commercial partners in a 2.7 million Euro project called ELISHA. It features new techniques for attaching antibodies to innovative surfaces, and novel electronic measurement methods that need no reagents or labels.

ELISHA was co-ordinated by Dr Paul Millner from the Faculty of Biological Sciences at the University of Leeds, and managed by colleague Dr Tim Gibson. Says Dr Millner: "We believe this to be the next generation diagnostic testing. We can now detect almost any analyte faster, cheaper and more easily than the current accepted testing methodology."

Currently blood and urine are tested for disease markers using a method called ELISA (Enzyme Linked Immunosorbant Assay). Developed in the 1970s, the process takes an average of two hours to complete, is costly and can only be performed by highly trained staff.

The Leeds team are confident their new technology – which provides results in 15 minutes or less - could be developed into a small device the size of a mobile phone into which different sensor chips could be inserted, depending on the disease being tested for.

"We've designed simple instrumentation to make the biosensors easy to use and understand," says Dr Millner. "They'll work in a format similar to the glucose biosensor testing kits that diabetics currently use."

Professor Séamus Higson, Dean of the Faculty of Medicine and Biosciences, Cranfield Health, and one of the partners within the ELISHA programme, says: "The speed of response this technology offers will be of great benefit to early diagnosis and treatment of many diseases, and will permit testing in de-localised environments such as GP's surgeries."

A spinout company – ELISHA Systems Ltd – has been set up by Dr Gibson, commercial partners Uniscan Instruments Ltd and Technology Translators Ltd to bring the technology to market.

Says Dr Gibson: "The analytes used in our research only scratch the surface of the potential applications. We've also shown that it can be used in environmental applications, for example to test for herbicides or pesticides in water and antibiotics in milk."

Link Found Between Crohn's Disease And E. Coli Bacteria

2009-04-14T10:38:00.000-07:00

A team of Cornell University scientists from the College of Veterinary Medicine, Weill Cornell Medical College and the College of Agriculture and Life Sciences have discovered that a novel group of E. coli bacteria -- containing genes similar to those described in uropathogenic and avian pathogenic E. coli and enteropathogenic bacteria such as salmonella, cholera, bubonic plague -- is associated with intestinal inflammation in patients with Crohn's disease.
Crohn's disease, an incurable inflammatory disorder of the intestine -- most commonly found in the lower part of the small intestine called the ileum -- affects 1-in-1,000 people in Europe and North America. Thus far, gut bacteria have long been suspected in playing a pivotal role in the development of Crohn's disease, but the specific bacterial characteristics that drive the inflammatory response have remained elusive.

Researchers at Cornell examined possible causes for the disease in patients with Crohn's restricted to the ileum and the colon versus healthy individuals.

"Given that only about 20 percent of fecal bacteria can be cultured, our group adopted a broad culture-independent approach to target specific subgroups of bacteria for quantitative in situ analysis and culture based characterization," said Kenneth Simpson, professor of small animal medicine at the College of Veterinary Medicine.

"Our findings raise the possibility that a novel group of E. coli contains opportunistic pathogens that may be causally related to chronic intestinal inflammation in susceptible individuals. They suggest that an integrated approach that considers an individual's mucosa-associated flora in addition to disease phenotype and genotype may improve outcome."

The study found an increased level of E. coli bacteria in more inflamed areas of the small intestines instead of MAP, a bacterium related to tubercle bacillus that has been more commonly associated with Crohn's.

Reference: "Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum" The ISME Journal: Multidisciplinary Journal of Microbial Ecology, July 12, 2007

The study was supported by an Ithaca Cornell-Weill Cornell Seed Grant.

Could Arthritis Wonder Drugs Provide Clues For Other Diseases?

2009-04-14T10:35:00.000-07:00

Drugs that have helped treat millions of rheumatoid arthritis sufferers may hold the key to many more medical conditions, including atherosclerosis -- a leading cause of heart disease -- says the researcher who jointly invented and developed them.
Professor Marc Feldmann will tell scientists attending the 2008 Congress of European Pharmacological Societies (EPHAR) -- hosted by the British Pharmacological Society -- that drugs he and colleagues helped develop have already proved successful against other autoimmune diseases.

The drugs target proteins called cytokines, which are protein messaging molecules released by immune cells to alert the immune and other systems that the body is under attack from a pathogen and to initiate a protective counter-response against the infection.

"In autoimmune diseases, such as arthritis, we discovered that cytokines are over-produced causing the immune system to fight itself, resulting in inflammation and tissue destruction," said Professor Feldmann, from Imperial College London, who is speaking at the EPHAR 2008 conference at The University of Manchester the week of July 18.

"We further found that by blocking just one cytokine -- Tumor Necrosis Factor (TNF) alpha -- we were able to block all the cytokines involved in the inflammation, with remarkable clinical results."

The team's research led to the development of three anti-TNF alpha drugs -- infliximab, etanercept and adalimumab -- which have had a dramatic effect on the symptoms of rheumatoid arthritis patients, protecting the joints from further deterioration in the vast majority of cases.

Blocking TNF alpha has had further success in treating several more chronic inflammatory conditions, including Crohn's disease, psoriasis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis.

But Professor Feldmann, Head of the Kennedy Institute of Rheumatology, believes similar drugs have the potential to treat many other medical conditions and will also tell the conference about his work on atherosclerosis, a disease affecting the arterial blood vessels, commonly known as 'hardening of the arteries', with his colleague Dr Claudia Monaco.

Their work, which has won a number of awards, has resulted in the emergence of a new branch of medicine -- anti-cytokine therapy -- and research elsewhere has showed promise in yet more conditions, including the potentially fatal acute alcoholic hepatitis.

Professor Feldmann said: "During the conference I will be discussing the potential therapeutic targets in tissue affected by atherosclerosis, which is caused by a chronic inflammatory response in the walls of the arteries, in large part, caused by an excessive immune response to cholesterol.

"I will also discuss whether it is possible -- even likely -- that cytokines play a critical role in all diseases involving multiple biological processes, thus providing therapeutic targets for all unmet medical needs."

Of Mice And Men: New Male Contraceptives Successful In Rodents And Humans

2009-04-10T12:23:00.000-07:00

Pills, sponges, IUDs, diaphragms -- women have many options for planning their fertility, none of them quite perfect. But what if men want to help out? They have only two options -- vasectomy, which is usually permanent, and condoms, which are crucial for dating but get old in long-term relationships. Will men ever have a way to reliably make sure that nobody is every calling them "Daddy" before they are ready?
For decades, pundits have predicted new contraceptives for men within the next 5 to 10 years. But judging from work presented today at the second "Future of Male Contraception" conference, we may finally be getting closer.

Some highlights from the second day of the conference:
- Researchers from the University of Washington tried a hormone regimen based on two products already available on the market. They used testosterone gel, which is marketed for men with low testosterone, plus a progestin shot used as a female contraceptive under the name "DepoProvera." The men got a shot once every 3 months and rubbed on a gel every day, and it worked well at knocking out sperm in 90% of them. However, men's opinions of the method varied widely: 6 dropped out, and of the remaining 38, half of them were satisfied or very satisfied, a third were dissatisfied or very dissatisfied, and the rest were undecided or had mixed feelings.

- Shepherd Medical Company announced the results of their very first U.S. study in men of the "Intra Vas Device" (a vasectomy alternative): after 6 months, 92% of the men had no sperm or almost no sperm. The Intra Vas Device blocks sperm in the vas deferens, the tube sperm swim through (the same tube that is cut in vasectomy). The set of plugs can be removed if a man changes his mind, so it is much easier to get sperm flowing again than after vasectomy. Animal studies have shown that fertility returns if the IVD is removed after short-term use, but that doesn't guarantee successful pregnancy after long-term use. The next step will be to find funding for long-term studies of effectiveness and fertility return.

- Columbia University researchers took advantage of the importance of vitamin A to design a new contraceptive approach. Men who are extremely low in vitamin A lose their fertility-- but they also become extremely sick, so avoiding vitamin A doesn't work as a contraceptive. Instead, Professor Debra Wolgemuth discovered a drug that had been abandoned by a pharmaceutical company precisely because it interfered with vitamin A receptors in the testes. Her team tested it in mice, and it worked with no health effects. "The receptors are everywhere, but the testis is exquisitely sensitive to the drug. So we can use a dose that is so low it has no effect on the rest of the body."

So the drug doesn't harm mice-- but will it be fine in men? Dr. Wolgemuth thinks the chances are good. "There's extensive toxicology data in rats and rabbits -- and at much higher doses-- because industry is developing it for other uses. So we're optimistic that there would be no adverse side effects in humans as well."

So how long must we wait? Advocates say it all depends on men speaking up. "We've seen today that the pipeline is full-- everything from new targets to actual human trials," explains Kirsten Thompson, director of the International Male Contraception Coalition. "And the demand is there-- hundreds of men have voiced their opinion on our website MaleContraceptives.org and in surveys. So it's just a question of whether policymakers act on that demand." Elaine Lissner, director of the Male Contraception Information Project, concurs. "We could have something like the IVD on the market in 4-5 years, if we make an all-out effort with funding and focus. But if we continue with just a study here and a study there, it could be an eternity."

Birth Control Pill Gives Long-lasting Protection Against Ovarian Cancer, Study Shows

2009-04-10T12:21:00.000-07:00

The contraceptive Pill gives women substantial and long-lasting protection against ovarian cancer, according to a new report led by Oxford scientists published in The Lancet.
The researchers found that the protection against ovarian cancer lasted for more than 30 years after women had stopped taking the Pill. They also found that the longer the Pill was used the greater the protection and that taking the Pill for 15 years halved the risk of ovarian cancer.

Researchers estimated that, in high income countries, using oral contraceptives for ten years reduces the risk of developing ovarian cancer before the age of 75 from 12 down to 8 per 1000 women, and reduces the risk of death from ovarian cancer before age 75 from 7 down to 5 per 1000 women.

The new report brings together worldwide evidence from 45 epidemiological studies of ovarian cancer in 21 countries. These include 23,257 women with ovarian cancer of whom 7,308 (31 per cent) had used oral contraceptives and 87,303 women without ovarian cancer of whom 32,717 (37 per cent) had used oral contraceptives.

Lead author Professor Valerie Beral, director of the Cancer Research UK Epidemiology Unit at Oxford University, said: ‘Worldwide, the Pill has already prevented 200,000 women from developing cancer of the ovary and has prevented 100,000 deaths from the disease. More than 100 million women are now taking the Pill, so the number of ovarian cancers prevented will rise over the next few decades to about 30,000 per year.’

The Pill also causes long-lasting protection against endometrial cancer (cancer or the lining of the womb) but causes a short-lived increase in breast cancer and in cervical cancer (cancer of the neck of the womb). Co-author Sir Richard Peto, Professor of Epidemiology at Oxford University, said: ‘Young women don’t have to worry about cancer from taking the Pill because the eventual reduction in ovarian cancer is bigger than any increase in other types of cancer caused by the Pill.’

Young women take the Pill mostly for contraceptive purposes. There are known to be some definite health risks among current or recent users. But these are outweighed by the long-term protective effects against ovarian cancer – one of the most dangerous types of cancer.

The study, led by Oxford University researchers, was conducted by the Collaborative Group on Epidemiological Studies of Ovarian Cancer, a collaboration involving 120 researchers from around the world. The work was suppo

Review Compares Latest Birth Control Options

2009-04-10T11:06:00.000-07:00

With many women still searching for the perfect birth control method, a systematic review analyzes a host of studies comparing the contraceptive skin patch or vaginal ring to the pill. Although perfection remains elusive and choices are equally effective, the review authors were able to pinpoint some preferences.
“Basically, all of these methods were similar in preventing pregnancy,” said lead investigator Laureen Lopez, Ph.D., research associate at Family Health International in Research Triangle Park, N.C.

Recently, the U.S. Food and Drug Administration added warning data to the drug label for the contraceptive skin patch, advising users that the women using the patch have a greater risk of blood clots than pill users. The study prompting the FDA action was not part of the review.

For the review, the researchers looked at 11 randomized controlled trials — three comparing the patch to the pill, and eight comparing the ring to the pill — comprising more than 6,000 women.

Women using the patch were more likely to use the medication as prescribed than those on the pill were. However, patch users experienced more side effects and were more likely to abandon their method eventually than pill users were.

Ring users generally had fewer serious side effects than pill users, but had more vaginal irritation and discharge. Despite this, vaginal ring users tended to stick with their approach longer than the pill group.

The patch is a small adhesive square that dispenses hormones and which a woman must replace every week for three weeks, and then leave off for a week. The Ortho Evra contraceptive patch is the only patch approved for use to date.

The NuvaRing, which Organon manufactures, releases hormones into the vaginal cavity. A woman inserts the ring, a flexible piece of plastic tubing, where it remains for three weeks; she then removes it for one week. Many consider the ring and patch easier to use than birth control pills because women do not have to attend to them every day.

Compared with pill users, patch users had more bleeding breakthroughs, breast discomfort, painful periods, and nausea and vomiting. Rings users, on the other hand, had more vaginal irritation and discharge. Of the two, patch users tended to discontinue the method more readily.

The contraceptive review updates one done in the past, for which only two studies of the patch versus the pill were available. The ring data are new. For all methods, several studies had women drop out, which can limit the value of the results according to the researchers.

“Women who used the ring had fewer bleeding problems than those on the pill, but they did have irritation,” Lopez said. “But discontinuation was similar for the ring and the pill in most of the studies.”

Clinicians have seen the ring increase in popularity, Lopez added.

Mitchell Creinin, M.D., professor and director of gynecological specialties at the University of Pittsburgh, is familiar with all of the review studies. “It all comes back to compliance.” Creinin said. “Once a week versus once a day, twice as much hormone entering the body (with the patch), or half as much (with the ring).”

Creinin, who was not involved with the review, said it is important to understand the people who would enter these studies: “These studies were done primarily when only the pill was available. Women who were unhappy with their present method of birth control were the ones likely to enter them.” He noted that the results differ among studies between European and American women. “North American women tend to have more complaints and are less compliant,” he said.

Overall, Creinin said, women are happy with their birth control because they are not getting pregnant.

Lopez said that women have to consider many issues when choosing a method of birth control. Ease of use, side effects and life situation are each important. For a contraceptive to be effective, the woman must be willing and able to follow the prescribed regimen.

“Women are finally beginning to understand that taking a pill every day is difficult.” Creinin said. He is working on an upcoming study comparing the ring to the patch.

Toward A Long-sought Saliva Test For Autism

2009-04-08T10:24:00.000-07:00

Researchers in Italy are reporting discovery of abnormal proteins in the saliva of autism patients that could eventually provide a clue for the molecular basis of this severe developmental disorder and could be used as a biomarker for a subgroup of patients with autism spectrum disorders (ASD).
Autism involves social withdrawal, impaired emotional responses and communication skills, and other symptoms. With no laboratory test available, scientists are searching for biomarkers such as abnormal proteins that appear in the body fluids of individuals with autism that may provide a way to accurately diagnose autism and track its response to potential treatments.

Massimo Castagnola, Irene Messana, Maria Giulia Torrioli and Fiorella Gurrieri, compared proteins in the saliva of 27 children with ASD to those in a control group without ASD. They discovered that at least one of four proteins in 19 children in the ASD group had significantly lower levels of phosphorylation. That key body process activates proteins so that they can work normally.

The results suggest that these abnormal proteins might be the clue for anomalies in the phosphorylation of proteins involved in development of central nervous system in early infancy that are involved in ASD.

Robot Playmates Monitor Emotional State Of Children With Autism

2009-04-08T10:22:00.000-07:00

The day that robot playmates help children with autism learn the social skills that they naturally lack has come a step closer with the development of a system that allows a robot to monitor a child's emotional state.
"There is a lot of research going on around the world today trying to use robots to treat children with autism spectrum disorders (ASD). It has shown that the children are attracted to robots, raising the promise that appropriately designed robots could play an important role in their treatment," says Nilanjan Sarkar, associate professor of mechanical engineering at Vanderbilt University. "However, the efforts so far have been quite limited because they haven't had a way to monitor the emotional state of the children, which would allow the robot to respond automatically to their reactions."

If these limitations can be overcome, the use of robots to treat children with ASD could have a significant social and financial impact. One baby in every 150 born today in the United States is diagnosed with ASD, making it more common than pediatric cancer, diabetes and AIDS combined. Currently, treatment of these children involves a combination of behavioral, educational, physical, occupational and speech therapies, sometimes accompanied by medication for co-occurring conditions such as anxiety, irritability, bi-polar and other disorders. The average cost of caring for one person with autism for life is $3.2 million. In total, autism currently costs the U.S. more than $90 billion per year, and that cost is projected to double by 2017 due to the growing population of those affected.

Over the last five years, Sarkar has developed a method that uses physiological measurements, including heart rate, galvanic skin response, temperature and muscle response, to monitor the emotional state of individuals. His original motivation was to improve human-robot interactions. When his nephew was diagnosed with autism, however, Sarkar got the idea of applying the technique to aid children with ASD. So he sought out one of the leading authorities on the subject, Wendy Stone, professor of pediatrics and investigator at Vanderbilt's Kennedy Center, and they formed a partnership to develop this new approach.

"I'm always interested in creative ways to study and treat autism, so, when Nilanjan approached me, I was willing to listen," says Stone. "He had clearly done his homework and his proposal sounded like a great idea."

This fall, Sarkar and Stone published two papers – one in the IEEE Transactions on Robotics and one in the International Journal of Human-Computer Studies – that describe the results of their first set of experiments, which were conducted with six children ranging in age from 13 to 16 years who had been diagnosed with ASD. A battery of physiological sensors were attached to the participants and they were asked to play two games. One was the computer game Pong. The other was a variant of Nerf basketball with the hoop and backboard attached to the end of a robotic arm that moves it back and forth or up and down. Graduate students Changchun Liu and Karla Conn participated in the studies.

The researchers report that the physiological data they gathered can be used to develop an affective model for each individual that can predict his or her emotional states of liking, anxiety and engagement with an accuracy of better than 80 percent. Furthermore, they showed that this information can be used in real time to alter the game configuration in ways that significantly increase the children's degree of engagement.

"That's the part that really nailed me," says Stone, "that the robot can read the physiological cues of the person playing the game, control the distance and angle of the hoop, and that the person reported a more positive mood when the computer was responsive to his needs."

The ability to accurately monitor a child's emotional state is particularly important in treating ASD, Stone says: "Children with autism are not necessarily giving the kind of emotional cues that we know how to read. They are not necessarily good reporters of their inner feelings. If we know that the child is becoming upset or anxious, then we can help the child identify his or her own emotional state and implement strategies for monitoring and control. It is a concrete way to help them identify their own feelings."

One of the most encouraging results of their preliminary research was discovering that the affective model works accurately in different settings. The model was based on the readings they took as the children played Pong. The game was changed in several ways: Ball and paddle speeds were varied, and computer-based opponents of different skill levels were introduced. This allowed the researchers to induce emotions of interest, boredom, anxiety and engagement in each of the participants. The model was then used to predict how each child would react to changes in the computer game. When they switched to robot basketball, they found that the model's predictions were equally accurate.

"The model is about as good at identifying a child's emotional state as an experienced therapist. When a child gets a new therapist, as often happens, there is a learning curve as the new therapist gets to know the child, whereas the accuracy of the model should continue to improve over time," Sarkar points out.

A robot's ability to provide consistent and predictable responses should be particularly useful for treating ASD. Each child has individual triggers. For example, one child may not like direct eye contact. Another might be upset by loud voices and sounds. Yet another may react when people get too close. Once a particular trigger is identified, a robot could be programmed to increase the stimulus at such a gradual rate that the child doesn't notice it. The robot could also be programmed to back off when it senses that its responses are beginning to bother the child. In this fashion, it could build up the child's tolerance to the problem stimulus. "Robots can be programmed to respond with a consistency that is difficult for humans to achieve," Sarkar points out.

According to the autism expert, something that robots lack may also be an advantage in this setting. "I've always been interested in the idea of teaching social skills in a non-social situation that is less threatening. The children can be distracted by a lot of sensory stimuli coming at them. Social stimuli are particularly complex and can confuse them. So alternative methods of teaching that can subtract the social component could be very helpful as a beginning step," Stone says.

In the future, the researchers foresee technologies like robots and virtual reality environments as taking over some of the burden of the behavioral therapy that is one of the most time-consuming and expensive aspects of ASD treatment.

"This approach holds great promise," says Stone. "It will involve many steps and this is just the beginning. There are lots of different possible applications. So it is just a matter of finding the resources to explore them all."

The research was supported by a grant from the Marino Autism Research Institute.

Why We Have Difficulty Recognizing Faces In Photo Negatives

2009-04-08T10:20:00.000-07:00

Humans excel at recognizing faces, but how we do this has been an abiding mystery in neuroscience and psychology. In an effort to explain our success in this area, researchers are taking a closer look at how and why we fail.
A new study from MIT looks at a particularly striking instance of failure: our impaired ability to recognize faces in photographic negatives. The study, which appears in the Proceedings of the National Academy of Sciences this week, suggests that a large part of the answer might lie in the brain's reliance on a certain kind of image feature.

The work could potentially lead to computer vision systems, for settings as diverse as industrial quality control or object and face detection. On a different front, the results and methodologies could help researchers probe face-perception skills in children with autism, who are often reported to experience difficulties analyzing facial information.

Anyone who remembers the days before digital photography has probably noticed that it's much harder to identify people in photographic negatives than in normal photographs. "You have not taken away any information, but somehow these faces are much harder to recognize," says Pawan Sinha, an associate professor of brain and cognitive sciences and senior author of the PNAS study.

Sinha has previously studied light and dark relationships between different parts of the face, and found that in nearly every normal lighting condition, a person's eyes appear darker than the forehead and cheeks. He theorized that photo negatives are hard to recognize because they disrupt these very strong regularities around the eyes.

To test this idea, Sinha and his colleagues asked subjects to identify photographs of famous people in not only positive and negative images, but also in a third type of image in which the celebrities' eyes were restored to their original levels of luminance, while the rest of the photo remained in negative.

Subjects had a much easier time recognizing these "contrast chimera" images. According to Sinha, that's because the light/dark relationships between the eyes and surrounding areas are the same as they would be in a normal image.

Similar contrast relationships can be found in other parts of the face, primarily the mouth, but those relationships are not as consistent. "The relationships around the eyes seem to be particularly significant," says Sinha.

Other studies have shown that people with autism tend to focus on the mouths of people they are looking at, rather than the eyes, so the new findings could help explain why autistic people have such difficulty recognizing faces, says Sinha.

The findings also suggest that neuronal responses in the brain may be based on these relationships between different parts of the face. The team found that when they scanned the brains of people performing the recognition task, regions associated with facial processing (the fusiform face areas) were far more active when looking at the contrast chimeras than when looking at pure negatives.

Other authors of the paper are Sharon Gilad of the Weizmann Institute of Science in Israel and MIT postdoctoral associate Ming Meng, both of whom contributed equally to the work..

The research was funded by the Alfred P. Sloan Foundation and the Jim and Marilyn Simons Foundation.

New Theory Of Autism Suggests Symptoms Or Disorder May Be Reversible

2009-04-08T10:17:00.001-07:00

Scientists at Albert Einstein College of Medicine of Yeshiva University have proposed a sweeping new theory of autism that suggests that the brains of people with autism are structurally normal but dysregulated, meaning symptoms of the disorder might be reversible
The central tenet of the theory, published in the March issue of Brain Research Reviews, is that autism is a developmental disorder caused by impaired regulation of the locus coeruleus, a bundle of neurons in the brain stem that processes sensory signals from all areas of the body.

The new theory stems from decades of anecdotal observations that some autistic children seem to improve when they have a fever, only to regress when the fever ebbs. A 2007 study in the journal Pediatrics took a more rigorous look at fever and autism, observing autistic children during and after fever episodes and comparing their behavior with autistic children who didn't have fevers. This study documented that autistic children experience behavior changes during fever.

"On a positive note, we are talking about a brain region that is not irrevocably altered. It gives us hope that, with novel therapies, we will eventually be able to help people with autism," says theory co-author Mark F. Mehler, M.D., chairman of neurology and director of the Institute for Brain Disorders and Neural Regeneration at Einstein.

Autism is a complex developmental disability that affects a person's ability to communicate and interact with others. It usually appears during the first three years of life. Autism is called a "spectrum disorder" since it affects individuals differently and to varying degrees. It is estimated that one in every 150 American children has some degree of autism.

Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. "The LC-NA system is the only brain system involved both in producing fever and controlling behavior," says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.

The locus coeruleus has widespread connections to brain regions that process sensory information. It secretes most of the brain's noradrenaline, a neurotransmitter that plays a key role in arousal mechanisms, such as the "fight or flight" response. It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another). Poor attentional focusing is a defining characteristic of autism.

"What is unique about the locus coeruleus is that it activates almost all higher-order brain centers that are involved in complex cognitive tasks," says Dr. Mehler.

Drs. Purpura and Mehler hypothesize that in autism, the LC-NA system is dysregulated by the interplay of environment, genetic, and epigenetic factors (chemical substances both within as well as outside the genome that regulate the expression of genes). They believe that stress plays a central role in dysregulation of the LC-NA system, especially in the latter stages of prenatal development when the fetal brain is particularly vulnerable.

As evidence, the researchers point to a 2008 study, published in the Journal of Autism and Developmental Disorders, that found a higher incidence of autism among children whose mothers had been exposed to hurricanes and tropical storms during pregnancy. Maternal exposure to severe storms at mid-gestation resulted in the highest prevalence of autism.

Drs. Purpura and Mehler believe that, in autistic children, fever stimulates the LC-NA system, temporarily restoring its normal regulatory function. "This could not happen if autism was caused by a lesion or some structural abnormality of the brain," says Dr. Purpura.

"This gives us hope that we will eventually be able to do something for people with autism," he adds.

The researchers do not advocate fever therapy (fever induced by artificial means), which would be an overly broad, and perhaps even dangerous, remedy. Instead, they say, the future of autism treatment probably lies in drugs that selectively target certain types of noradrenergic brain receptors or, more likely, in epigenetic therapies targeting genes of the LC-NA system.

"If the locus coeruleus is impaired in autism, it is probably because tens or hundreds, maybe even thousands, of genes are dysregulated in subtle and complex ways," says Dr. Mehler. "The only way you can reverse this process is with epigenetic therapies, which, we are beginning to learn, have the ability to coordinate very large integrated gene networks."

"The message here is one of hope but also one of caution," Dr. Mehler adds. "You can't take a complex neuropsychiatric disease that has escaped our understanding for 50 years and in one fell swoop have a therapy that is going to reverse it — that's folly. On the other hand, we now have clues to the neurobiology, the genetics, and the epigenetics of autism. To move forward, we need to invest more money in basic science to look at the genome and the epigenome in a more focused way."

Poultry And Diabetics At Risk From Gas Gangrene Bug

2009-04-07T00:45:00.000-07:00

Gas gangrene, the notorious infectious disease of two world wars can still be a problem today.
Professor Richard Titball of the University of Exeter, told the Society of General Microbiology Meeting at the International Centre, Harrogate March 30 that Clostridium perfringens, the bacterium responsible for gas gangrene in people, can also cause necrotic enteritis in intensively raised chickens. This frequently fatal disease has significant financial implications for the poultry industry.

Intensive study of C. perfringens during World War 2 showed that the bacterium produces a potent toxin. Recent work using modern molecular genetic approaches have provided an insight into the role of this toxin in disease. It works in three ways: by promoting a reduction in blood supply to infected tissues; by increasing inflammation; and by having a toxic effect on the heart.

"Gas gangrene is not just a historical curiosity", said Professor Titball. "In the past it has been a major cause of death and disability in servicemen injured on the battlefield, although it is rarely a problem now because of the prompt treatment that casualties receive. However it does occasionally occur in the civilian population with diabetes patients, with the elderly being most at risk. In the future, the incidence of gangrene infection may rise in line with the increase in this age group in the general population. It is essential to understand how the toxin works to prevent future disease not only in diabetes sufferers but also in intensively reared animals."

Nutritious New Low-sugar Juice Targeted For Diabetics, Individuals With High Blood Sugar

2009-04-07T00:40:00.002-07:00

Scientists in China are reporting development of a low-calorie, low-sugar vegetable juice custom-designed for millions of individuals with diabetes and pre-diabetic conditions that involve abnormally high blood sugar. They reported on the new drink at the 237th National Meeting of the American Chemical Society in Salt Lake City, Utah on March 26.
Heqin Xing, Ph.D., and Xiuqi Liu of Jilin University in Changchun, China, described a cost-effective method of preparing a special type of vegetable drink using lactic acid-producing bacteria (LAB) to remove carbohydrates while retaining good taste, vitamins and other nutrients.

"This is an exciting development," Liu said. "The process significantly removes sugar but retains the nutritional content of the juice's raw materials." To develop the juice — made from pumpkin, balsam pear, onion and carrots — Xing and Liu turned to an age-old technique in the art of food production. For thousands of years, people have cultured food — including everyday eats such as yogurt, cheeses and sausage — by using the same LAB.

LAB microbes produce a compound commonly found in sour milk products called lactic acid. Because of LAB's healthy link to food production, this class of bacteria is also referred to as probiotics.

In the study, LAB reduced sugar content of the vegetable juice by transforming carbohydrates into lactic acid by a routine conversion process called fermentation. As this process increases the juice's acidity, it extends its shelf life as it inhibits growth of other bacteria. Compared to other microorganisms, LAB are known for their ability to withstand acidic environments. In addition to the lactic acid's protection against contamination, the acidity from fermentation could enhance flavors in the beverage.

Xing's and Liu's use of Lactobacillus acidophilus and L. plantarum in the vegetable juice increased its acidity by about 10-fold after 12 hours of fermentation. "The viable cell counts of L. plantarum in the fermented mixed vegetable juice still remained at up to 5 billion colony forming units per teaspoon after four weeks of cold storage," Xing said.

Traditional purification methods are more expensive and highly complex compared to the LAB process, Liu said. "This improves the preparation method of the diabetic-friendly vegetable drinks, but it also simplifies the method over existing ones."

And the taste of the low-sugar vegetable juice? Thanks to the addition of sugar, and a diabetic-friendly sugar substitute called xylitol, Xing said that the juice has a good mix of sweet and sour. "It has a good taste with reduced calories due to lower carbohydrates," said Xing. "I believe we can put it on the market possibly in one year after a few more tests."

Difference In Fat Storage May Explain Lower Rate Of Liver Disease In African-Americans

2009-04-07T00:28:00.000-07:00

Where different ethnic groups store fat in their bodies may account for differences in the likelihood they'll develop insulin resistance and non-alcoholic fatty liver disease, researchers at UT Southwestern Medical Center have found.
According to research reported in the online edition and the March issue of Hepatology, African-Americans with insulin resistance might harbor factors that protect them from this form of metabolic liver disease.

Despite similarly high rates of associated risk factors such as insulin resistance, obesity and diabetes among African-Americans and Hispanics, African-Americans are less likely than Hispanics to develop non-alcoholic fatty liver disease, or NAFLD. The disease is characterized by high levels of triglycerides in the liver and affects as many as one-third of American adults.

"If we can identify the factors that protect African-Americans from this liver disease, we may be able to extrapolate those to other populations and perhaps develop targeted therapies to help populations prone to NAFLD," said Dr. Jeffrey Browning, assistant professor of internal medicine in the UT Southwestern Advanced Imaging Research Center and the study's senior author.

Previous research has shown that when African-Americans do develop NAFLD, they're less likely to reach the later stages of liver disease. Prior work by Dr. Browning and other UT Southwestern scientists has revealed that NAFLD is more prevalent among Hispanics than African-Americans or Caucasians.

For the current study, Dr. Browning and his colleagues analyzed data gathered in the multi-ethnic, population-based Dallas Heart Study. Starting in the year 2000, more than 2,100 participants provided blood samples and underwent multiple body scans with magnetic resonance imaging and computed tomography to examine the liver, heart and other organs. Body composition, including fat distribution, also was scrutinized.

The study found that African-Americans and Hispanics both have obesity rates of about 48 percent among their respective populations, as well as diabetes rates of about 21 percent. Only 23 percent of African-Americans, however, have NAFLD, compared with 45 percent of Hispanics.

Similarly, African-Americans are less likely to have high levels of triglycerides and abdominal fat – both characteristics of insulin resistance – when compared with Hispanics or Caucasians, even though overall rates of insulin resistance among all groups are the same, researchers found.

"This presents something of a paradox," Dr. Browning said.

The explanation might lie in where different ethnic groups typically store fat.

Obese Hispanics tend to deposit fat in the liver and visceral adipose tissue – the area around the belly. Obese African-Americans deposit fat predominantly in subcutaneous adipose tissues – the area around the hips and thighs, Dr. Browning said.

"This may be protective," Dr. Browning said. "In animal studies, if subcutaneous fat is increased as opposed to visceral fat, you can actually reverse fatty liver disease."

Scientists aren't sure why the location of fat storage matters.

"This seems to argue that there is a fundamental difference in the lipid metabolism between African-Americans and Hispanics or Caucasians, and this difference is maintained even when insulin resistance is present," Dr. Browning said.

Differences in liver-fat content in Caucasians seem to be based on gender. Caucasian males are at the highest risk for NAFLD, on par with the risk faced by Hispanics in general. Caucasian females are on par with the African-American population, at about 23 percent. Caucasian females, like African-Americans, might benefit from the greater predilection to store fat in lower extremities.

"Research studies traditionally have been based on examining Caucasian males, but this information suggests that there are sometimes ethnic and gender differences that need to be studied individually to determine if there are important clues we're missing because we're lumping everybody together," Dr. Browning said.

Researchers next will study how differences in metabolism affect fatty liver disease.

Other researchers from UT Southwestern involved in the study were lead author Dr. Richard Guerrero, a postdoctoral trainee clinician in internal medicine; Dr. Gloria Vega, professor of clinical nutrition; and Dr. Scott M. Grundy, director of the Center for Human Nutrition.

The study was funded by the Donald W. Reynolds Foundation and the National Institutes of Health.

New Test May Predict Spread Of Breast Cancer

2009-04-03T01:09:00.000-07:00

Scientists at Albert Einstein College of Medicine of Yeshiva University have previously shown that the co-mingling of three cell types can predict whether localized breast cancer will spread throughout the body. Now, a collaborative study led by investigators at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, has produced a test for metastasis that could help doctors precisely identify which patients should receive aggressive therapy.
This might spare many women at low risk for metastatic disease from undergoing unnecessary and potentially dangerous treatment.

“This is the first marker that could reliably predict metastatic outcome in a case-controlled study,” says study co-author John S. Condeelis, Ph.D., professor and co-chair of anatomy and structural biology and co-director of the Gruss Lipper Biophotonics Center at Einstein. “It could dramatically change the way we approach the care of women with breast cancer.”

The test, which most pathology labs could carry out, was developed by scientists at NewYork-Presbyterian/Weill Cornell based on the intravital imaging observations of researchers from Einstein.

Breast cancer is the most common cancer among women in the United States. Last year, approximately 182,000 women were diagnosed with breast cancer and more than 40,000 died from the disease.

Tumors in breast cancer patients are graded for degree of differentiation and staged for the extent of disease. Surgery is the first line of defense for most patients with breast cancer. For patients with higher grade tumors, additional treatment with chemotherapy or radiation is typically recommended to decrease the risk that the disease will spread. However, studies show that only 40 percent of these patients actually do develop metastatic disease. “What this means is that most of these patients are unnecessarily exposed to chemotherapy or radiation, which can have significant side effects or even worsen the disease,” says Dr. Condeelis.

Recently, Dr. Condeelis found that breast cancer spreads only when a specific trio of cells are present together in the same microanatomic site: an endothelial cell (a type of cell that lines the blood vessels), a perivascular macrophage (a type of immune cell found near blood vessels), and a tumor cell that produces Mena. The protein Mena was shown to enhance a cancer cell’s invasiveness in a collaborative study from Dr. Condeelis and Frank Gertler at the Koch Institute for Integrative Cancer Research at MIT published in Developmental Cell in December. A site with these three cells constitutes what is called a tumor microenvironment of metastasis, or TMEM.

The NewYork-Presbyterian/Weill Cornell investigators, aided by the Einstein and MIT scientists, then developed a tissue test to detect the presence and density of TMEMs. The test consists of a triple immunostain containing antibodies to the three cell types. A high number of TMEMs in a tissue sample means that the tumor is likely to metastasize or has already done so. In the current study, the immunostain was tested on breast tissue biopsy samples taken from 30 patients with advanced metastatic breast cancer and 30 patients with localized breast cancer, all of whom had been followed for at least five years. The resulting immunostains were evaluated by two pathologists who were not aware of the patients’ clinical outcomes.

Their analysis confirmed that TMEM density was significantly higher in patients who had developed metastatic breast cancer than in those who had localized disease. For every ten-unit increase in TMEM density, the risk for metastatic disease doubled. The density of any of three TMEM components alone was not sufficient to predict clinical outcome.

The study also showed that the ability of the TMEM density test to predict metastatic disease was independent of other currently used predictors, including lymph node metastasis, tumor size, presence of lymphovascular invasion, and tumor grade.

While the new test promises to reduce overtreatment of breast cancer, it could reduce undertreatment as well. “There are some patients with Grade 1 breast cancer who ultimately develop metastatic disease,” says Dr. Condeelis. “By measuring TMEM counts, we could identify those people and treat them appropriately.”

The researchers are currently working on a blood test for predicting metastatic breast cancer. In theory, such a test could predict the risk of metastatic disease even before a tumor forms. “It could be part of a routine checkup, especially for women with a strong family history of the disease,” says Dr. Condeelis. Before such a blood test could be developed for commercial use, researchers will need to conduct a population study.

In addition to Dr. Condeelis, the co-authors of the paper include: Brian D. Robinson, Gabriel L. Sica, Yi-Fang Liu, Joan G. Jones of NewYork-Presbyterian Hospital/Weill Cornell Medical Center; Frank B. Gertler of Massachusetts Institute of Technology; and Thomas E. Rohan, professor of epidemiology and population health at Einstein.

New Risk Factor For Melanoma In Younger Women

2009-04-03T01:06:00.000-07:00

Researchers may have found a more potent risk factor for melanoma than blistering sunburns, freckling, or family history of the deadly skin disease. In a new study, scientists at NYU Langone Medical Center report that a genetic variation leads to a nearly four-fold increase of melanoma in women under the age of 50.
"If this number turns out to be reproducible, it is higher than a lot of the other clinical risk factors that we know, such as blistering sunburns, freckling, and family history," said David Polsky, M.D., Ph.D., associate professor of dermatology and director of the Pigmented Lesion Section of the Ronald O. Perelman Department of Dermatology at NYU School of Medicine, and the study's lead author.

"Potentially, we have a genetic test that might identify pre-menopausal women who are at higher risk for melanoma," said Dr. Polsky. "And if that's the case, then we might want to have increased surveillance of those patients including more frequent visits to the doctor, more rigorous teaching of skin self-examination, and other preventive steps."

Melanoma, the most deadly form of skin cancer, was expected last year to strike 62,480 Americans, and kill an estimated 8,420 diagnosed patients, according to the American Cancer Society.

For largely unknown reasons, melanoma is more common among women than men under the age of 40. Between 40 and 50 the incidence is about equal in both sexes, and over the age of 50, melanoma incidence skews markedly toward men. Polsky and his co-authors suspect the difference may be linked to the activity of estrogen, mediated in part by a genetic variant in a gene called MDM2.

When estrogen binds to this gene, it turns on production of MDM2, a potential oncogene (cancer promoting gene) in cells. In the presence of the genetic variation in MDM2, originally identified by the laboratory of Dr. Arnold Levine at the Institute for Advanced Study, Princeton, the estrogen binds more strongly, resulting in far greater production of the MDM2 protein.

Women with higher estrogen levels and who also have the genetic variation would be expected to have higher estrogen-related MDM2 protein that could increase their melanoma risk, explains Dr. Polsky.

The MDM2 genetic variant appears in the gene's promoter, a power switch that determines when the gene is turned on and how many copies are produced within a cell. This promoter region is normally regulated by p53, a tumor suppressor gene implicated in as many of 50 percent of all cancers. Part of MDM2's normal function is to inhibit p53 when its levels get too high in a cell. If MDM2 is turned on independently of p53, it can keep p53 levels low, reducing the cell's protection against turning into a cancer cell.

Scientists have shown that the substitution of a single letter of DNA at a specific point in the MDM2 promoter can significantly ramp up gene production. The new study evaluated the effects of this natural genetic variation in 227 melanoma patients enrolled in NYU's Interdisciplinary Melanoma Cooperative Group between August 2002 and November 2006. Dr. Polsky and colleagues from NYU School of Medicine recorded each patient's MDM2 and p53 genetic variations, as well as age, sex, personal and family history of melanoma, and tumor thickness.

The results showed that more than 40 percent of women diagnosed with melanoma under the age of 50 had the genetic variation in the MDM2 gene promoter. In contrast, only about 16 percent of women diagnosed after the age of 50 had the variation.

The difference in the frequency of the variation corresponded to a 3.89-fold increase in melanoma risk for women under the age of 50—an elevated risk over background levels that increased more among even younger women, according to the study. When the researchers compared the MDM2 genotypes to patients' ages at diagnosis, they found that about 38 percent of women with the variation had been diagnosed between the relatively young ages of 30 to 39—a much higher melanoma incidence than among older women patients with the variation.

Beyond validating the risk in a larger group of patients, Dr. Polsky hopes to begin formulating a stronger model of cancer risk that incorporates genetic information and other factors. "Can we look at people's sun exposure history, hormonal status and a panel of genetic markers in addition to MDM2 and ask, 'Does this help identify more high-risk people?'" he said.

The new study was released online March 24, 2009, in the journal Clinical Cancer Research and will be published in the April 1, 2009, issue of the journal.

Among the study investigators are Elnaz F. Firoz, a medical student from the College of Physicians and Surgeons at Columbia University; and Richard Shapiro, Russell Berman, Anna Pavlick, Prashiela Manga, Harry Ostrer, Hideko Kamino, Farbod Darvishian, Linda Rolnitzky, Judith D. Goldberg, and Iman Osman from NYU Langone Medical Center.

The study was supported by a grant from the Marc Jacobs Campaign to Support Melanoma Research, with partial support by a grant from the National Cancer Institute to Linda Rolnitzky and Judith D. Goldberg. The NYU Interdisciplinary Melanoma Cooperative Group is supported by the NYU Cancer Institute and NYU School of Medicine's Ronald O. Perelman Department of Dermatology.

Numerous CT Scans Over Lifetime May Increase Cancer Risk

2009-04-03T00:54:00.000-07:00

Patients who undergo numerous CT scans over their lifetime may be at increased risk for cancer, according to a new study.
"We found that while most patients accrue small cumulative cancer risks, 7 percent of the patients in our study had enough recurrent CT imaging to raise their estimated cancer risk by 1 percent or more above baseline levels," said Aaron Sodickson, M.D., Ph.D., assistant director of Emergency Radiology at Brigham and Women's Hospital and researcher at the Center for Evidence-Based Imaging in Boston. "The techniques implemented in our study can be used to identify higher risk patients who might benefit from enhanced radiation protection efforts."

CT has proven to be a valuable clinical tool, and its use has grown rapidly. According to a 2008 IMV Medical Information Division report, approximately 68.7 million CT exams were performed in the U.S. in 2007, up from 62 million in 2006. CT provides detailed images of internal organs and is a common technique used to make medical diagnoses and help guide medical treatment decisions. However, CT uses a higher radiation dose than most other imaging exams.

For the study, the researchers developed new methodology to estimate cumulative CT radiation doses and associated radiation-induced cancer risks at the level of the individual patient, by extracting each patient's CT history from the electronic medical record and applying standard risk-estimation models that incorporate patient gender and age at exposure.

The study group was comprised of 31,462 adult patients who had diagnostic CT scans at Brigham and Women's Hospital or the Dana-Farber Cancer Center in 2007 and had undergone a total of 190,712 CT exams over the prior 22 years. Approximately 33 percent of the patients underwent five or more lifetime CT exams, 5 percent underwent more than 22 exams, and 1 percent underwent more than 38 exams. Fifteen percent received estimated cumulative effective radiation doses of more than 100 millisieverts (mSv), equivalent to the dose one would receive from 1,000 chest x-rays. Four percent received over 250 mSv, and 1 percent received over 399 mSv.

The researchers used the BEIR-VII (Biological Effects of Ionizing Radiation) risk model to estimate lifetime attributable risk (LAR) of cancer for each patient, based on their CT exposures. Approximately 7.3 percent of the study group had an estimated LAR of greater than 1 percent, meaning that due to cumulative CT radiation exposure, their risk of developing cancer increased by 1 percent above the baseline US cancer risk rate of 42 percent. Among the 315 patients in the top percentile of cumulative LAR, risk increased by 2.7 to 12 percent.

"CT is an excellent diagnostic tool of tremendous clinical value in many situations," Dr. Sodickson said. "Individual decisions about its use should balance the expected clinical benefits against the potential cumulative risks of recurrent imaging."

Dr. Sodickson points out that for patients who have not undergone a large number of CT scans, the benefits of appropriate CT exams typically outweigh the potential risks.

"However, we feel that a higher clinical threshold is warranted in patients undergoing a large amount of recurrent CT imaging," Dr. Sodickson said, "particularly if many of their prior CT scans have been negative. This scenario may result in a combination of high cumulative risk with low clinical benefit."

Dr. Sodickson hopes that these findings will raise awareness of cumulative radiation exposure concerns, so that physicians will be better able to incorporate patient-specific radiation risk estimates into the CT decision-making process.

Goodbye Needle, Hello Smoothie: New Generation Oral Vaccine Uses Dairy Probiotics To Protect Against Disease

2009-03-29T04:18:00.000-07:00

Instead of a dreaded injection with a needle, someday getting vaccinated against disease may be as pleasant as drinking a yogurt smoothie.
A researcher from the Northwestern University Feinberg School of Medicine has developed a new oral vaccine using probiotics, the healthy bacteria that are found in dairy products like yogurt and cheese. He has successfully used the approach in a preclinical study to create immunity to anthrax exposure. He also is using the method to develop a breast cancer vaccine and vaccines for various infectious diseases.

This new generation vaccine has big benefits beyond eliminating the "Ouch!" factor. Delivering the vaccine to the gut -- rather than injecting it into a muscle -- harnesses the full power of the body's primary immune force, which is located in the small intestine.

"This is potentially a great advance in the way we give vaccines to people," said Mansour Mohamadzadeh, the lead author and an associate professor of medicine in gastroenterology at the Feinberg School.

"You swallow the vaccine, and the bacteria colonize your intestine and start to produce the vaccine in your gut," Mohamadzadeh said. "Then it's quickly dispatched throughout your body. If you can activate the immune system in your gut, you get a much more powerful immune response than by injecting it. The pathogenic bacteria will be eliminated faster."

Most vaccines consist of protein and won't maintain their effectiveness after being digested by the stomach. However, the lactobacillus protects the vaccine until it is in the small intestine.

The Northwestern study was reported in a recent issue of the Proceedings of the National Academy of Science.

There are other advantages to the new oral vaccine. Probiotics, which are natural immune stimulators, eliminate the need for a chemical in traditional vaccines that inflames the immune system and triggers a local immune response. The chemical, called an adjuant, may cause side effects such as dizziness, arm swelling and vomiting. Probiotic vaccines also are inexpensive to produce.

The specially engineered vaccine gives more immune bang for the buck than an injected one because it induces a local and a systemic immune response. The vaccine targets the first line of gut immune cells called dendritic cells -- the commanders-in-chiefs of the immune system. They engulf the vaccine then instruct the immune system's foot soldiers -- killer T-cells and B-cells -- to seek out and destroy any cells in the body infected with a particular bacterium or virus.

In the study, Mohamadzadeh fed mice the new oral anthrax vaccine, and then exposed them to anthrax bacteria. Eighty percent of the mice survived, which is comparable to the results when mice were injected with anthrax vaccine, he said.

"Their immune response was higher and more robust than with the injected vaccine," Mohamadzadeh said. The mice generated a much higher T and B immunity against the pathogenic bacteria.

Mohamadzadeh's vaccine technology can be applied to many other diseases. He is developing an oral vaccine for breast cancer using probiotics. The vaccine would use the Her2/neu breast cancer antigen, a protein highly produced by breast tumor cells, and train the immune system to destroy any cells producing Her2/neu, he said.

In addition, Mohamadzadeh has developed a "multi-tasking" cancer vaccine against breast, colon and pancreatic cancer that soon will be tested in mouse models.

The technology also can be used to develop a probiotic vaccine for HIV, hepatitis C and the flu, he said.

Terrence Barrrett, M.D., chief and professor of gastroenterology at the Feinberg School, said delivering a vaccine to the gut is the most logical route.

"Nature isn't used to seeing antigens injected into a muscle," said Barrett, who also is a physician at Northwestern Memorial Hospital. "The place where your immune system is designed to encounter and mount a defense against antigens is your gut."

The study was funded by the National Institutes of Health and the North Carolina Dairy Foundation.

No More Cold Sores? Scientists Find Cellular Process That Fights Herpes Virus

2009-03-29T04:16:00.001-07:00

Scientists have discovered a new way for our immune system to combat the elusive virus responsible for cold sores: Type 1 herpes simplex (HSV-1). As reported in the advance online edition of Nature Immunology, a group of virus hunters from the Université de Montréal, in collaboration with American colleagues, have identified a cellular process that seeks out and fights herpes.
The five-year study, partially supported by the Canadian Institutes of Health Research, was a joint project with Washington University and Pennsylvania State University.

"Once human cells are infected with Type 1 herpes simplex, the virus comes back because it hides and blocks protection from our immune system," says Luc English, the study's lead author and a doctoral student at the Université de Montréal's Department of Pathology and Cell Biology. "For the first time, our research team has indentified a combative cellular mechanism in this game of hide-and-seek."

"We've found that the nuclear membrane of an infected cell can unmask Type 1 herpes simplex and stimulate the immune system to disintegrate the virus," says English.

The team made its discovery while conducting various tests in HSV-1 infected mice cells. They replicated environments when Type 1 herpes simplex thrives, namely periods of low-grade fever between 38.5 to 39 degrees, and found that herpes-fighting mechanisms were unleashed.

The research team now plans to study how activation of the herpes-combating cellular process could be applied to other illnesses. The outcome could hasten the development of therapies to prevent other immune-evading bacteria, parasites and viruses. "Our goal is to further study the molecules implicated in this mechanism to eventually develop therapies against diseases such as HIV or even cancer," says English.

According to Dr. Michel Desjardins, senior author and a professor in the Department of Pathology and Cell Biology at the Université de Montréal, treatment options might be imaginable in a decade.

"Now that we've identified the novel mechanism in cells that activate immune response to Type 1 herpes simplex, scientists are one step closer to creating new treatments that can activate the defence against this and other viruses," says Dr. Desjardins. "While it may not be possible to completely eradicate Type 1 herpes simplex in people who are already infected, at the very least, future therapies may be able to keep the virus in its dormant state."

This study was funded by the Canadian Institutes of Health Research, the Natural Science and Engineering Research Council of Canada, the Fonds de la Recherche en Santé du Québec, the U.S. National Institutes of Health and the foundation Research to Prevent Blindness.

About Herpes

There are two types of herpes viruses: Type 1 herpes simplex causes facial cold sores and Type 2 causes genital herpes. Both types of herpes affect an estimated 80 million people in America alone and there is currently no cure for the condition

Genomic Fossils In Lemurs Shed Light On Origin And Evolution Of HIV And Other Primate Lentiviruses

2009-03-29T04:12:00.000-07:00

A retrovirus related to HIV became stably integrated into the genome of several lemurs around 4.2 million years ago, according to research led by Dr. Cédric Feschotte at the University of Texas, Arlington. The new analysis of prosimian immunodeficiency virus (pSIV) offers new insights into the evolution of lentiviruses.
During replication, retroviruses integrate within the chromosomes of their host cells. If germ cells are infected, the integrated viral DNA can be transmitted from parent to offspring and may eventually become assimilated as part of the genetic material of the host species. This 'endogenization' process has occurred repeatedly during evolution, and has involved diverse retroviruses, giving rise to a sizeable portion of the genome of many vertebrate species – for example, ~8% of the human genome. Until now, the process was believed to be extremely rare for lentiviruses, an evolutionarily elusive group of retroviruses that infect diverse mammals, including humans (in the form of human immunodeficiency virus [HIV]).

Based on 'fossil' sequences collected from different lemur species, the researchers computationally reconstructed an apparently intact and complete DNA sequence for the ancestral prosimian lentivirus. The discovery that two different species of lemurs endemic to Madagascar suffered, independently and quasi-simultaneously, multiple germline infections of pSIV provides evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species.

These findings should allow future functional analysis of the extinct virus and advance our understanding of the biology of lentiviruses, including HIV. In addition, the characterization of this ancient lentivirus in lemurs raises the possibility that HIV-like retroviruses are still circulating today in the mammalian fauna of Madagascar.

Gene Mutations Increase Risk For Aggressive Prostate Cancer

2009-03-22T01:54:00.000-07:00

Men who develop prostate cancer face an increased risk of having an aggressive tumor if they carry a so-called breast cancer gene mutation, scientists from the Albert Einstein College of Medicine of Yeshiva University report in the January 29 issue of Clinical Cancer Research. The findings could help to guide prostate-cancer patients and their physicians in choosing treatment options.
The study, involving 979 men with prostate cancer and 1251 men without the disease, looked at whether participants carried mutations for either of two genes, BRCA1 and BRCA2. Women carrying mutations in either gene face an increased risk of developing breast cancer, ovarian cancer, or both.

All the people enrolled in the Einstein study were of Ashkenazi Jewish descent. The study focused on them because they are five times likelier than people in the general population to carry a mutation of any kind in the BRCA1 or BRCA2 genes. The researchers looked for the presence of three particular mutations–two in BRCA1 and one in BRCA2. Scientists believe that genetic discoveries among the Ashkenazi can benefit society as a whole in terms of preventing and treating major diseases.

Having any of the three mutations did not increase a man's risk of developing prostate cancer, the study found. But for those men who did develop prostate cancer, two of the mutations–BRCA1-185delAG and the mutated BRCA2 gene–increased the risk that tumors would be aggressive or high-grade, as defined by a Gleason score of 7 or above. The Gleason score, based on the microscopic appearance of prostate tissue removed during a biopsy or surgery, assesses the aggressiveness of a prostate tumor on a scale from 2 (least aggressive) to 10 (most aggressive).

Specifically, prostate cancer patients with high-grade, aggressive tumors (Gleason scores of 7 or above) were 3.2 times more likely to carry the BRCA2 gene mutation than were men in the control group. Carriers of the BRCA1-185delAG mutation were also at increased risk of having an aggressive prostate cancer.

Previous investigations into a possible link between prostate-cancer risk and the BRCA1 and BRCA2 genes have yielded conflicting results–perhaps because they involved small numbers of subjects and lacked well-matched control groups. "Our large study shows conclusively that prostate cancer patients with either the BRCA2 gene mutation or the BRCA1-185delAG mutation are more susceptible to aggressive cancers than people without that mutation," says Robert Burk, M.D., professor of pediatrics (genetics) at Einstein and senior author of the study.

Routine genetic testing for BRCA mutations–done by analyzing blood samples or cells swabbed from the inside of one's cheeks–wouldn't be justified for most men, says Dr. Burk: the prevalence of the mutations in the general population is very low; and men with high Gleason scores already know that their prostate cancer is aggressive. But, notes Dr. Burk, "our findings might have practical implications for some men diagnosed with early-stage (low Gleason score) prostate cancers–particularly Ashkenazi Jewish men, who are much more likely to have these mutations."

"One of the biggest problems with early-stage prostate cancer is being able to distinguish between tumors with the potential to become aggressive and those that may persist for many years without enlarging or spreading," notes Dr. Burk. For that reason, he says, Ashkenazi men diagnosed with early-stage prostate cancer might want to consider getting tested for the BRCA2 and BRCA1-185delAG mutations.

Knowing they have the mutation—and that their tumor may become aggressive—may influence treatment options that patients pursue. For example, a prostate cancer patient who has the BRCA2 mutation might vote against 'watchful waiting'—in which the growth of the cancer is monitored and treatment is held in abeyance—and instead opt for surgery or radiation treatments with or without hormone blockade therapy.

For early-stage prostate cancer patients in the general population, knowing they carry the BRCA1 or BRCA2 mutation would also be useful, says Dr. Burk. But these mutations are so rare in the general population—a prevalence of far less than one percent—that testing is unlikely to reveal their presence.

Other Einstein researchers involved in the study were Dr. Ilir Agalliu and Suzanne Leanza. The authors have no potential conflicts of interest relevant to this article.

New Prostate Cancer Marker In Urine Indicates Whether Cancer Is Spreading

2009-03-22T01:52:00.000-07:00

Howard Hughes Medical Institute researchers have identified a new biological marker present in the urine of patients with prostate cancer that indicates whether the cancer is progressing and spreading.
In experiments reported in the journal Nature, the scientists identified 10 metabolites that become more abundant in prostate cells as cancer progresses. Their studies showed that one of these chemicals, sarcosine, helps prostate cancer cells invade surrounding tissue.

"One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up overtreating our patients because physicians don't know which tumors will be slow-growing. With this research, we have identified a potential marker for the aggressive tumors," says senior study author Arul Chinnaiyan, M.D., Ph.D. director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School.

HHMI investigator Arul Chinnaiyan and colleagues at the University of Michigan showed that as prostate cancer develops and progresses, sarcosine levels increase in both tumor cells and urine samples, suggesting that measurements of the metabolite could aid in non-invasively diagnosing the disease. Researchers might also be able to inhibit prostate cancer's spread by designing drugs that manipulate the sarcosine pathway.

The study is the first to analyze the levels of more than 1,000 different metabolites in human tumors. Scientists know that cells undergo complex changes as cancer develops and progresses to metastatic disease. Chinnaiyan's lab, which has extensively analyzed how genes and proteins in prostate cancer cells reflect these changes, thought that profiling cells' metabolites would offer an even more "holistic picture of the molecular alterations that occur," he said.

"This allows us to have more of a systems perspective of cancer development," he noted. "We are also looking at gene and protein markers, for therapeutic consideration, biomarker consideration, and just understanding the biology. We are not sure yet how it's going to sort out, so we're being non-discriminatory with what types of technologies we use."

In the experiments reported in Nature, the scientists used mass spectrometry, a technique that identifies chemicals based on the size and electrical charge of their components, to compare the levels of 1,126 metabolites in healthy prostate tissue, clinically localized prostate cancer, and metastatic prostate cancer. Sixty metabolites were present in tumor cells, but not in benign tissue. Of these, there were about 10 molecules whose levels increased dramatically during cancer progression. "This is proof-of-principle that we can identify metabolites, or panels of metabolites, that might be correlated with aggressive prostate cancer versus slower-growing prostate cancer," Chinnaiyan said.

Having demonstrated that "metabolomic" profiles change in predictable ways as cancer progresses, the group began more focused analyses. "We began to mine the data to look for metabolites that might serve as biomarkers or as therapeutic targets," Chinnaiyan explained. They chose to focus on sarcosine because it was elevated in clinically localized disease and very highly elevated in metastatic cancer.

They confirmed these dramatic increases in a new set of tissue samples, and also found that there was more sarcosine in the urine of patients with prostate cancer than in healthy individuals.

The team went on to test how sarcosine affected the behavior of cancer cells grown in the laboratory. Adding the chemical to prostate cells or manipulating cells' biochemical pathways so they produced more sarcosine on their own caused benign prostate cells to become cancerous and invasive. Conversely, shutting down sarcosine production in cancer cells blocked invasion.

"This really told us that sarcosine is involved biologically in some of the processes of a cancer cell," Chinnaiyan said. The results suggest that drugs that alter sarcosine metabolism might be useful in treating prostate cancer, but Chinnaiyan cautions that these Petri-dish findings still need further validation in animal models.

An important next step, he says, will be to do similar experiments on the other nine potential biomarkers they identified in this study. For reliable diagnosis of aggressive disease, he said, "we need to have panels, not just rely on a single metabolite."

New Lab Evidence Suggests Preventive Effect Of Herbal Supplement In Prostate Cancer

2009-03-22T01:49:00.000-07:00

DHEA is a natural circulating hormone and the body's production of it decreases with age. Men take DHEA as an over-the-counter supplement because it has been suggested that DHEA can reverse aging or have anabolic effects since it can be metabolized in the body to androgens. Increased consumption of dietary isoflavones is associated with a decreased risk of prostate cancer.
Red clover (Trifolium pretense) is one source of isoflavones. Both supplements may have hormonal effects in the prostate and little is known about the safety of these supplements.

In a recent report in Cancer Prevention Research, a journal of the American Association for Cancer Research, researchers report that DHEA levels can be manipulated in cells in the laboratory to understand its effects.

Julia Arnold, Ph.D., a staff scientist at the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health, said more research is necessary in an environment where men and women concerned about health problems tend to self-prescribe based on information they find on the Internet.

Towards this end, the NCCAM laboratory is studying signaling between human prostate cancer cells and their supporting stromal cells as they grow together in laboratory culture. "DHEA effects in the prostate tissues may depend on how these two cells types 'talk to each other' and further, it may be potentially harmful in tissues containing inflammation or with early cancer lesions because the cells can induce DHEA to become more androgenic," said Arnold.

Combining DHEA with transforming growth factor beta-1 increased testosterone production in the stromal cells and prostate specific antigen protein secretion two to four-fold and gene expression up to 50-fold in the cancer cells. When these cell cultures were treated with red clover isoflavones, the androgenic effects of DHEA were reversed.

"Something is happening in the prostate tissue microenvironment that is illustrating a potential cancer prevention effect from this supplement," said Arnold.

Red clover isoflavones may modify androgenic effects in the prostate but much more work in the laboratory and clinic is needed to validate these effects.

This sort of laboratory manipulation will allow scientists to understand the basic prostate biology as well as learn cellular and molecular mechanisms of over-the-counter supplements and other botanical or herbal agents. Arnold said NCCAM will continue to study DHEA with other supplements to determine any cancer preventive effects.

Pollution-related Asthma May Start In The Womb

2009-03-14T22:01:00.001-07:00

Children born in areas with increased traffic-related pollution may be at greater risk of developing asthma due to genetic changes acquired in the womb, according to new research from the University of Cincinnati (UC) and Columbia University Mailman School of Public Health.
In a study of umbilical cord blood from New York City children, researchers have discovered evidence of a possible new biomarker—an epigenetic alteration in the gene ACSL3—associated with prenatal exposure to polycyclic aromatic hydrocarbons (PAHs). These chemical compounds are created as byproducts of incomplete combustion from carbon-containing fuels, resulting in high levels in heavy-traffic areas. Exposure to PAHs has been linked to diseases such as cancer and childhood asthma.

Researchers say this finding provides a potential clue for predicting environmentally related asthma in children—particularly those born to mothers who live in high-traffic areas like Northern Manhattan and South Bronx when pregnant.

This is the first study to examine the effects of prenatal ambient air pollutant exposure on epigenetic changes linked to asthma. Epigenetic changes may disrupt the normal functioning of genes by affecting their expression but do not cause structural changes or mutations in the genes.

The team reports its findings in the Feb. 16, 2009, issue of PLoS One.

For this study, UC researchers teamed with Columbia's Mailman School of Public Health to study the relationship between prenatal PAH exposure and childhood asthma, hypothesizing that transplacental exposure to PAHs could "reprogram" fetal genes and lead to airway inflammation or asthma during childhood. Epigenetic reprogramming is the result of an organism's genes interacting with the environment.

"Our data support the concept that environmental exposures can interact with genes during key developmental periods to trigger disease onset later in life, and that tissues are being reprogrammed to become abnormal later," says Shuk-mei Ho, PhD, senior author of the paper, chair of UC's Department of Environmental Health and the director of the Center for Environmental Genetics.

"This research is aimed at detecting early signs of asthma risk so that we can better prevent this chronic disease that affects as many as 25 percent of children in Northern Manhattan and elsewhere," adds Frederica Perera, DrPH, professor of environmental health sciences and director of the Columbia Center for Children's Environmental Health (CCCEH) at the Mailman School of Public Health and co- first author on the paper.

Using biological specimens from the CCCEH birth cohort of mothers and children living in Northern Manhattan and the South Bronx, UC scientists analyzed umbilical cord white blood cell samples from 56 children for epigenetic alterations related to prenatal PAH exposure. (The mothers' exposure to PAHs was monitored during pregnancy using backpack air monitors).

The researchers found a significant association between changes in ACSL3 methylation—a gene expressed in the lung—and maternal PAH exposure. ACSL3 also was associated with a parental report of asthma symptoms in the children prior to age 5.

With confirmation in further studies, researchers say changes in the ACSL3 gene could serve as a novel biomarker for early diagnosis of pollution-related asthma.

"This study provides a blueprint for the discovery of epigenetic biomarkers relevant to other investigations of exposure-disease relationships in birth cohorts," says Wan-yee Tang, PhD, a UC research scientist and a co-first author on the paper.

"Understanding early predictors of asthma is an important area of investigation," adds Rachel Miller, MD, director of the CCCEH asthma project and study co-author, "because they represent potential clinical targets for intervention."

The CCCEH birth cohort was launched in 1998 to study the effects of prenatal exposure to common urban pollutants on the health of mothers and their children. Children in the cohort were born to non-smoking Dominican and African-American women in Northern Manhattan or the South Bronx and follow-up is ongoing.

Funding for the multi-institutional study comes from the National Institute of Environmental Health Sciences (NIEHS), the U.S. Environmental Protection Agency (EPA) and private foundations. UC's Linda Levin, PhD and Columbia University Mailman School's Julie Herbstman, PhD, and Deliang Tang, MD, DrPH, were also co-authors of the study.

Best Human Embryos Selected For IVF Using Mathematical Model

2009-03-14T21:58:00.000-07:00

A team of researchers from the University of the Basque Country (UPV-EHU) have developed a mathematical classification which makes it possible to select human embryos for use in assisted reproduction treatments. Scientists have used the morphology of embryos to select the best candidates for implantation in the woman's uterus.
"Up to now experts working in in vitro fertilisation have selected the best embryos subjectively, based on their training and experience", so SINC was informed by Dinora A. Morales, from the Intelligent Systems Group at the UPV-EHU. However, in two studies carried out by researchers from this team the use of mathematical classifiers to help embryologists with that task was looked at.

In the first work, published in the journal Computer Methods and Programs in Biomedicine, the scientists presented an "intelligent system" of support for infertility treatments. For this they used information from 63 cases from the infertility programme at Clínica del Pilar in San Sebastian (Guipúzcoa), and analysed the evolution of trios of embryos (Spanish law allows for the transfer of up to three embryos to a woman's uterus).

To prepare the study, the researchers focused on the case history of infertile couples (age, type of infertility, quality of sperm, etc), as well as the morphological characteristics of the zygote (the resulting cell from the fusion of two gametes) and the embryos.

From the images taken with the microscope, the scientists were able to measure and classify the zygotes and embryos, as well as the blastomeres (undifferentiated animal cells produced by the division of the zygote), their degree of fragmentation and the thickness of the ‘zona pellucida', a membrane that surrounds them.

All this information was processed with Bayesian classifiers, so-called due to the application of Bayes rules, which make it possible to calculate the probability of implanting an embryo in a woman's uterus if transferred there. "What's more, these types of mathematical classifiers provide experts with evidence on what embryo characteristics enable the identification of the most ideal embryos, through the selection of variables", explained Morales.

The results of this study indicate that the size and degree of fragmentation of the blastomeres, thickness of the zona pellucida and the fact that they might have various nuclei are some of the aspects embryologists should concentrate on.

The Basque research group also carried out a second study, published in the journal Computers in Biology and Medicine to check the effectiveness of different Bayesian classifiers as a tool for choosing the best embryo.

The researchers analysed 249 photographs of embryos from the database at the Genesis Centre in Rome (Italy) and discovered that the "wrapper-TAN" classifier had a success rate of over 90%.

The team's next lines of work will concentrate on perfecting these techniques for selecting the best embryo in infertility treatments and in predicting multiple pregnancies, due to the risk they pose to women. The scientists will try to collaborate with other hospitals in this task.

Humans Can Sense 'Smell Of Fear' In Sweat, Psychologist Says

2009-03-08T21:18:00.000-07:00

When threatened, many animals release chemicals as a warning signal to members of their own species, who in turn react to the signals and take action. Research by Rice University psychologist Denise Chen suggests a similar phenomenon occurs in humans.
Given that more than one sense is typically involved when humans perceive information, Chen studied whether the smell of fear facilitates humans’ other stronger senses.

Chen and graduate student Wen Zhou collected “fearful sweat” samples from male volunteers. The volunteers kept gauze pads in their armpits while they were shown films that dealt with topics known to inspire fear.

Later, female volunteers were exposed to chemicals from the "fearful sweat” when they were fitted with a piece of gauze under their nostrils. They then viewed images of faces that morphed from happy to ambiguous to fearful. They were asked to indicate whether the face was happy or fearful by pressing buttons on a computer.

Exposure to the smell of fear biased women toward interpreting facial expressions as more fearful, but only when the expressions were ambiguous. It had no effect when the facial emotions were more discernable.

Chen’s conclusion is consistent with what’s been found with processing emotions in both the face and the voice. There, an emotion from one sense modulates how the same emotion is perceived in another sense, especially when the signal to the latter sense is ambiguous.

“Our findings provide direct behavioral evidence that human sweat contains emotional meanings,” Chen said. “They also demonstrate that social smells modulate vision in an emotion-specific way."

Smell is a prevalent form of social communication in many animals, but its function in humans is enigmatic. Humans have highly developed senses of sight and hearing. Why do we still need olfaction? Findings by Chen and Zhou offer insight on this topic. “The sense of smell guides our social perception when the more-dominant senses are weak,” Chen said.

Diagnosis Of 'War-zone Disorder' To Help Stroke Victims

2009-02-28T22:12:00.000-08:00

The recovery of some stroke victims, those who suffer brain haemorrhage, could be vastly improved if they were tested and treated for post-traumatic stress disorder, a distressing psychological condition more commonly known to affect soldiers who have fought in war zones.
A study of over 100 brain haemorrhage survivors, led by Durham University and funded by the Clarke Lister Brain Haemorrhage Foundation, found more than one third tested positive for the disorder, displaying symptoms such as painful memories and flashbacks of their haemorrhage, extreme anxiety and chronic fatigue.

Researchers found that post-traumatic stress disorder impacted greatly on the stroke patients' recovery and their ability to resume a normal life, even if the actual brain damage caused by their type of stroke, called subarachnoid haemorrhage, was minor.

Subarachnoid haemorrhage affects about 8,000 people in the UK each year and is a sudden leak of blood over the surface of the brain.

The scientists say this type of stroke has a high cost for society because it afflicts much younger people than other types of stroke – most patients are around 55 – and a large proportion of these do not return to work following the haemorrhage.

Tests for post-traumatic stress disorder are currently not part of the usual care of subarachnoid haemorrhage victims.

But researchers say the findings of the study, published in the academic journal Neurosurgery, point to the need for greater awareness of the condition following a haemorrhage and early testing using simple questionnaires.

The findings could lead to significant improvements in the recovery of subarachnoid haemorrhage patients, according to the research team. They say doctors can identify those stroke victims most at risk by assessing how they deal with stress, with denial, self-distraction and self-blame as some of the key signs of 'poor' coping. These patients could be offered pre-emptive treatment to teach them effective coping strategies, say the scientists.

The team from Durham and Newcastle University, James Cook University Hospital in Middlesbrough and Newcastle General Hospital twice examined 105 patients who had suffered a subarachnoid haemorrhage, three months and thirteen months after their episode. Thirty seven per cent of the participants were diagnosed with post-traumatic stress disorder. This is four times higher than the rate normally found in the general population and a similar level to that found in soldiers returning from war zones and amongst victims of sexual assault, say the scientists.

Post-traumatic stress disorder is a psychiatric condition that follows experience of a traumatic event which poses a threat to someone's life or their physical integrity. In the case of subarachnoid bleeding, the researchers believe that many patients struggle to cope with the harrowing nature of their type of stroke – such as its spontaneous and extremely painful onset, the need to undergo invasive medical examinations, such as brain scans, lumbar puncture and surgery to the brain, as well as dealing with the fact that they have had a life-threatening illness.

Lead author Mr Adam Noble, a research assistant in Durham University's Psychology Department said: "This is the first study to show the profound consequences which post-traumatic stress disorder has for patients who have suffered from a subarachnoid brain haemorrhage.

"It highlights a need to address this through more tailored treatment such as group therapy and, where possible, prevention through teaching patients more appropriate stress-coping strategies after they suffer a stroke.

"The findings could have wider implications for the treatment of neurological diseases in general. Brain damage is often seen as the cause of difficulties after a neurological illness but for all these conditions, psychological problems may well be a vital element in the patients' poor recovery. This is something which needs further research."

The research was commissioned by the Clarke Lister Brain Haemorrhage Foundation following the tragedy and sudden death of ten year old Clarke Lister, who died of a subarachnoid haemorrhage in June 1996. Based in Peterlee, County Durham, his parents Carole and Brian Lister, and sister Michelle vowed to raise funds for research.

Co-author Professor David Mendelow is a professor of neurosurgery at Newcastle University and a consultant neurosurgeon at Newcastle General Hospital. He commented: "The study highlights the need for a multidisciplinary approach that begins with the early recognition of the warning signs of stroke, or 'brain attack', and extends throughout the acute care environment and back into the community with ongoing support for patients and their carers.

Newcastle United goalkeeper Steve Harper, who is a patron of the Clarke Lister Foundation, has seen the effects of subarachnoid brain haemorrhage among some of his close family and friends. He said: "I am delighted that this research into the recovery of haemorrhage patients is now complete and I hope the knowledge we have from it will benefit survivors and their families. I am proud to be patron of the charity and will continue to fully support the work they do."

Case study - Peter Chapman from Hartlepool

Peter Chapman, who is married with three grown-up children, suffered a subarachnoid brain haemorrhage at the age of 45 in 2001. Before discharge from hospital, he was not tested for post-traumatic stress disorder. Peter was psychologically very ill after his haemorrhage and he was finally diagnosed with post-traumatic stress disorder in 2003, two years after he had the brain haemorrhage.

Peter returned to work part-time three years after his haemorrhage and now runs his own mortgage advice company. He remains on medication to keep his psychiatric disorder under control.

Peter said: "The haemorrhage happened at home and I just felt this sudden rush of blood to my head. I then lost consciousness and was violently sick. Luckily, my wife was there at the time.

"Before I was sent home from hospital, I wasn't given any real idea of what might happen. The first six months were the worst and I lost over four stone. I was so worried that it might happen again and I have never shed as many tears in my life.

"It was only looking for help myself and finding it in the Clarke Lister Foundation that got me to where I am today. Simply being able to share my experiences with others in the same situation really helped me and improved my condition tremendously.

"But if I had been tested and treated for post-traumatic stress disorder right from the beginning, my life would have been 500 per cent better than what it has been, and would have made the world of difference to my recovery. The information that has come out of this research is so important for the recovery of haemorrhage patients."

Predicting Risk Of Stroke From One's Genetic Blueprint

2009-02-28T22:08:00.000-08:00

A new statistical model could be used to predict an individual's lifetime risk of stroke, finds a study from the Children's Hospital Informatics Program (CHIP). Using genetic information from 569 hospital patients, the researchers showed that their predictive model could estimate an individual's overall risk of cardioembolic stroke -- the most common form of stroke -- with 86 percent accuracy. The findings are reported in the March issue of Stroke.
"For complex diseases like stroke, it's not just a single mutation that will kill you," explains CHIP researcher Marco Ramoni, PhD, the study's senior author, who is also an Associate Professor at Harvard Medical School. "More likely it is an interaction of many factors."

Ramoni, in collaboration with Karen Furie, MD, the director of the stroke unit at Massachusetts General Hospital (MGH), and Rachel Ramoni, DMD, ScD, of the Harvard School of Dental Medicine, identified 569 patients that had presented to MGH's emergency department and outpatient neurology clinics between 2002 and 2005 with symptoms of suspected stroke. They collected genetic information from the 146 patients with confirmed cardioembolic stroke, and 423 controls who were followed and found not to have stroke, and looked for 1,313 genetic variants (called single nucleotide polymorphisms or SNPs) known to correlate with stroke. The SNPs that each patient had were then entered into the model -- known as a Bayesian network -- which not only identified the genetic variants that correlated with stroke, but also determined how these factors interplayed and the strength of these interactions.

"The model looks for factors, combines them and finds out which are the best predictive factors," explains Ramoni. "It's never one factor at a time, it's always more than one factor. What this technology allows you to do is to generate a network of factors that contribute to stroke."

The researchers found that the model was able to predict an individual's risk of cardioembolic stroke with an accuracy of 86 percent. Ultimately, Ramoni envisions doctors using it as a diagnostic tool: a patient's genetic information would simply be entered into the model, which would correlate and analyze the data and output an overall probability of stroke, based on the stroke-related SNPs in the patient's genome. "It sounds like magic," says Ramoni. "But it's just a piece of technology. It gives hope that we will be able to predict early on whether someone is at risk of getting stroke, and allow you to convince them to make life changes."

"The next step is to get more SNPs," Ramoni adds. "These analyses looked at only 1,313 out of 3.3 million known SNPs. Even a million SNPs would cover the vast majority of the genome. We would get much better predictions."

Ramoni also says that by identifying all the genetic variants that modulate the risk of stroke, it could provide insight into its mechanisms and provide targets for future drugs. He is currently refining the model and believes that this technology could be used to predict inherited risk of many other conditions.

Michele Sale, PhD of the University of Virginia, and Blanca Himes, PhD, of CHIP, were coauthors on the paper. This research was supported by the National Institutes of Health (National Human Genome Research Institute, National Institute of Dental and Craniofacial Research, National Institute of Neurological Diseases and Stroke, and National Center for Research Resources), the Mallinckrodt GCRC at Massachusetts General Hospital and the Deane Institute of Integrative Research in Stroke and Atrial Fibrillation.

Researchers Use Human Embryonic Stem Cells To Kill Cancer Cells

2009-02-22T08:52:00.000-08:00

For the first time, stem cell researchers at the University of Minnesota have coaxed human embryonic stem cells to create cancer-killing cells in the laboratory, paving the way for future treatments for various types of cancers (or tumors). The research will be published in the Oct. 15 issue of the Journal of Immunology.
Researchers generated "natural killer" cells from the human embryonic stem cells. As part of the immune system, natural killer cells normally are present in the blood stream and are play a role in defending the body against infection and against some cancers.

"This is the first published research to show the ability to make cells from human embryonic stem cells that are able to treat and fight cancer, especially leukemias and lymphomas," said Dan Kaufman, M.D., Ph.D., assistant professor of medicine in the Stem Cell Institute and Department of Medicine at the University of Minnesota and lead author of the study.

"We hear a lot about the potential of stem cells to treat conditions such as Parkinson's disease, diabetes, and Alzheimer's disease. This research suggests it is possible that we could use human embryonic stem cells as a source for immune cells that could better target and destroy cancer cells and potentially treat infections," Kaufman added.

The results also provided the researchers with a model of how the immune system develops.

Next, the researchers will test whether the human embryonic stem cell-derived natural killer cells can target cancer cells in animal models.

This research was done on two of the federally approved embryonic stem cell lines. Kaufman said, however, that if the research would lead to a treatment for people, new lines would have to be developed. The research was funded by the National Institutes of Health and the American Society of Hematology.

Elasticity Of Tissue Environment Plays Role In Determining Stem Cell Growth

2009-02-22T08:51:00.001-08:00

Researchers at the University of Pennsylvania have shown that the elasticity of a stem cell's environment is a major determinant of what type of tissue the stem cell becomes.

In laboratory tests, Dennis Discher and Adam Engler grew mesenchymal stem cells (derived from adult bone marrow) in polymer hydrogels with either soft, medium or rigid elasticity.

Based on resulting cell shapes as well as messenger RNA and protein markers, stem cells grown in softer environments -- such as brain tissue -- tended to produce nerve-like cells; those grown in environments with medium elasticity -- similar to muscle -- produced muscle-like cells

The stem cells grown in more rigid environments -- like bone -- produced bone-like cells.

The study provides new clues on how chemical and mechanical factors interact to influence stem cell growth, the researchers say.

Stem Cells In Hair Follicles Point To General Model Of Organ Regeneration

2009-02-22T08:48:00.000-08:00

Most people consider hair as a purely cosmetic part of their lives. To others, it may help uncover one of nature’s best-kept secrets: the body’s ability to regenerate organs. Now, new research from Rockefeller University gets to the root of the problem, revealing that a structure at the base of each strand of hair, the hair follicle, uses a two-step mechanism to activate its stem cells and order them to divide.
The mechanism provides insights into how repositories of stem cells may be organized in other body tissues for the purpose of supporting organ regeneration.

“The hair follicle is like a mini-dispensable organ,” says Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development. “Throughout our lifetime, each hair follicle undergoes cyclical bouts of growth, destruction and rest through an intrinsic stem cell population. It provides an excellent opportunity to investigate the molecular process of tissue regeneration and stem cell self-renewal.”

For a new round of hair growth to begin, stem cells in the hair follicle must receive a signal to divide. In response to this signal, the hair follicle regenerates first by growing downward through the skin’s middle layer, the dermis, and then producing the specialized cells that form the hair. After a period during which the hair grows longer, stem cells stop dividing, and the hair follicle gradually retracts again. There is then a period of rest and the cycle repeats.

Fuchs and her team have for several years been exploring the infrequently dividing stem cells located near the base of the hair follicle in a compartment known as the bulge. This time they focused on a much smaller cluster of often-ignored cells called the hair germ, located at the very bottom of this structure. Although little is known about the hair germ, scientists postulate that it emerges from the bulge at the end of the destructive phase of the hair cycle.

In their work, to be highlighted in the February 6 issue of Cell Stem Cell, Fuchs and her team scrutinized the hair cycle through the resting phase and discovered that during most of this time, both the bulge and the hair germ remain dormant. By isolating cells from both the hair germ and the bulge, they also confirmed that the two are molecularly very similar, suggesting that the germ does indeed originate from the bulge. The researchers believe, however, that toward the end of the resting phase, the hair germ gets activated to proliferate before the bulge. Moreover, the team showed that the activating signal comes from a structure known as the dermal papilla.

“We discovered that the dynamics of the hair follicle regeneration is a two-step process,” says Valentina Greco, a visiting postdoctoral fellow who, along with postdoctoral associate Ting Chen, spearheaded the project. “The hair germ, which is in constant contact with the dermal papilla, gets activated first and the bulge is then called to contribute later during growth.”

“Because the germ is in closer proximity to the dermal papilla, it may achieve a threshold of stimulatory signals sooner than the bulge,” explains Fuchs, who is also a Howard Hughes Medical Institute investigator. Previous work by her team has shown that two inhibitory signals, known as Wnts and BMP, are needed for hair follicle stem cells to activate. They have now identified an additional activation signal, a growth factor called FGF7, that is made by the dermal papilla and steadily increases throughout the resting phase. “We think that FGF7 might contribute, along with the Wnts and BMP inhibitory signals, to coax the hair germ to divide and proliferate,” says Fuchs.

The dual organization makes sense, explains Greco, since unlike the bulge stem cells, hair germ cells respond and proliferate quickly but soon exhaust their proliferative potential. “This organization prevents depletion of the bulge stem cells, which are long-lived,” says Greco. “It also allows a rapid initial proliferation of the hair follicles.”

Fuchs and her team believe that this dual organization of the stem cell niche could apply to other organs. “It could be that the two-step process we’ve identified is needed to achieve optimal organ regeneration, not only in the skin but also in the blood and intestine,” says Greco. “These organs have slow- and fast-cycling cells — much like the hair germ and the bulge — and have the capacity to self-renew and regenerate.”

Don’t Go Changing: New Chemical Keeps Stem Cells Young

2009-02-12T20:16:00.001-08:00

Scientists at the Universities of Bath and Leeds have discovered a chemical that stops stem cells from turning into other cell types, allowing researchers to use these cells to develop new medical treatments more easily.
Stem cells have the ability to develop into many other cell types in the body, and scientists believe they have huge potential to treat diseases or injuries that don’t currently have a cure.

Professor Melanie Welham’s team at the University of Bath’s Department of Pharmacy & Pharmacology, collaborating with Professor Adam Nelson at the University of Leeds, have discovered a chemical that can be added to embryonic stem cells grown in the lab, allowing them to multiply without changing into other cell types.

This breakthrough will help scientists produce large stocks of cells that are needed for developing new medical therapies.

Professor Welham, who is co-director of the University of Bath’s Centre for Regenerative Medicine, explained: “Stem cells have great potential for treating spinal injuries and diseases like type I diabetes because they can change into a range of specialised cell types including nerve or pancreatic cells, which could be used to repair damaged tissues.

“Unfortunately, when you grow stem cells in the lab, they can spontaneously develop into specialised cells, making it difficult to grow large enough stocks to use for medical research.

“We’ve identified a chemical that will put this process on hold for several weeks so that we can grow large numbers of them in their unspecialised state. This is reversible, so when you take it away from the cells, they still have the ability to change into specialised cells.”

Professor Adam Nelson’s team, at the Astbury Centre for Structural Molecular Biology, made more than 50 chemical compounds that were tested for activity in the stem cells.The researchers found that the chemicals worked by blocking an enzyme, called GSK3, that can control when the stem cell switches to a more specialised cell type.

Professor Nelson, who is Director of the Astbury Centre at the University of Leeds, said: “This research is a great example of how small molecules can be used as tools to understand biological mechanisms.”

The research, supported by funding from the Biotechnology & Biological Sciences Research Council.

Even Natural Perfumes May Cause Allergies

2009-02-12T20:15:00.003-08:00

Hypersensitivity to perfumes is the most common contact allergy in adults. Research at the University of Gothenburg has demonstrated that even natural aromatic oils, which many deem harmless compared to synthetic perfumes, may cause allergic reactions.
Roughly one in five adults in northern Europe is believed to suffer from contact allergy to one or more chemicals. The most common is nickel allergy, but many people also suffer from contact allergy to perfumes – even perfume substances that at first glance appear to be harmless can cause allergic reactions. New eczema-provoking allergens are formed by reaction with acid in the ambient air (known as autoxidation) or with skin enzymes.

Modern society commonly regards anything that comes from nature as being healthier and less dangerous. Where it concerns natural aromas, known as essential oils, many manufacturers believe that natural antioxidants in these oils offer protection against autoxidation thus making them safer and longer lasting than artificial perfumes. Research at the University of Gothenburg shows this is not the case.

Lina Hagvall, a researcher at the University of Gothenburg's Department of Chemistry, has examined natural lavender oil in her thesis. Her results show that essential oils do not prevent the formation of allergenic substances through reactions with acid; something which had not previously been possible to confirm. Hagvall's thesis also examines geraniol, a common constituent of perfumes such as rose oil. The study shows geraniol by itself to be only slightly allergenic. However through autoxidation and reaction with skin enzymes, the substance is activated and becomes the closely related allergen geranial. This is the first time these activation pathways have been demonstrated for the substance.

It is important to investigate how perfumes react with air or on skin. Lina Hagvall's thesis concludes that such risks must be factored into health risk assessments of chemicals relating to contact allergy. The thesis also demonstrates that more perfumes than previously believed can be activated into allergens, and that more studies should be done to increase knowledge within the field and thus reduce the number of eczema cases.

Hagvall's thesis, Formation of Skin Sensitizers from Fragrance Terpenes via Oxidative Activation Routes. Chemical analysis, Structure Elucidation and Experimental Sensitization Studies was defended on the January 30th. The supervisor was Ann-Therese Karlberg, professor of dermatochemistry and head of the research platform Göteborg Science Centre for Molecular Skin Research at the University of Gothenburg, Sweden

Rare Skin Tumor Responds Better To Treatment Than Melanoma

2009-02-12T20:13:00.001-08:00

University of Michigan Health System researchers have published new data to help answer two dreaded questions: "Is it cancer?" and "What type of treatment should I have?"
Cancer is the primary concern when abnormal skin lesions are detected. Macroscopic and microscopic features of a lesion usually provide clues about whether it is benign or malignant. However, the distinction is not always clear-cut, and doctors are faced with the question of how to best treat such patients.

The quandary is especially pronounced in atypical spitzoid tumors (ASTs), a rare proliferation of pigmented skin cells. ASTs have many features of melanoma, a potentially deadly form of skin cancer. ASTs tend to appear in patients who are much younger than the age when skin cancer traditionally occurs, which makes determining whether the lesion is malignant or benign even more difficult.

The new research, led by the University of Michigan Multidisciplinary Melanoma Program and published in the journal Cancer, suggests that ASTs behave differently from other types of melanoma. This finding could eventually lead to fundamental changes in the way ASTs are treated.

"As patients with AST appear to do better than conventional melanoma after similar treatment, we are now able to provide some reassurance to concerned parents and loved ones about the implications of the diagnosis," says lead study author Mathew Ludgate, MBChB, FRACP, assistant professor in the U-M Multidisciplinary Melanoma Program.

Although ASTs are rare, the U-M Multidisciplinary Melanoma Program has considerable experience as a preeminent national referral center. ASTs are an increasing challenge for physicians, as the number of ASTs diagnosed throughout the country appears to be increasing for unknown reasons. The researchers focused on long-term outcomes of ASTs to formulate improved evidence-based treatment guidelines.

Doctors generally treat patients with AST similar to malignant melanoma by surgically removing the lesion and in many cases also with a sentinel lymph node biopsy. The sentinel lymph node biopsy involves the removal and evaluation of one or a few lymph nodes nearest the skin lesion to determine whether the skin lesion has spread to the lymph nodes.

Ludgate and his team analyzed U-M's unique comprehensive melanoma database that has been collecting data for almost two decades for all cases of ASTs of uncertain biological potential between 1994 and 2007. Data were examined to learn the clinical features of a patient, whether the patient underwent a lymph node biopsy and the histological features of the tumor.

Of the 67 patients in the study, 57 had undergone wide excision and sentinel lymph node biopsy, and 27 biopsies were positive.

All 27 of AST patients with positive sentinel node biopsy are alive and disease-free at an average of about 44 months follow-up, researchers note.

"If AST were a form of melanoma, we would expect that at least some of the patients would have had the AST recur throughout the body by this time" Ludgate explains. "This study provides evidence that although ASTs have some features of melanoma microscopically, they do not behave as aggressively."

These findings can be interpreted in three ways, Ludgate says. "The first is that AST is not cancer at all, but has some ability to spread. The second possibility is that because ASTs often occur in younger people with intact immune systems, the body is able to successfully fight off the beginnings of metastatic disease. The third possibility is that AST is potentially deadly but removal of the primary AST lesion and the sentinel lymph node biopsy is curative."

Each of these possibilities is considered in the treatment strategy developed collectively as a result of this study. One result of this new strategy is that not every patient with AST must undergo a complete lymph node dissection or treatment with interferon-alpha after a positive sentinel lymph node biopsy, depending on the degree of lymph node involvement and the age of the patient. This is important as complete lymph node dissection is a more extensive surgery than a sentinel lymph node biopsy alone, and has considerable more risk of long term side effects.

Given the difficulty determining whether AST is benign or malignant, Ludgate notes, the melanoma team plans to "identify the molecular profile of ASTs to further characterize the true behavior of these tumors."

In addition to Ludgate, authors of the study are senior author Timothy M. Johnson, M.D., as well as Douglas R. Fullen, M.D., Julia Lee, M.P.H., M.S., Lori Lowe, M.D., Carol Bradford, M.D., James Geiger, M.D., and Jennifer Schwartz, M.D. The authors are affiliated with the U-M Department of Dermatology, Department of Pathology, Comprehensive Cancer Center, Department of Statistics, Department of Otolaryngology

Wrinkles Removed With Protein RHAMM, Study Shows

2009-02-12T20:12:00.001-08:00

Hollywood stars of a certain age take note: Research at Berkeley Lab suggests that a protein linked to the spread of several major human cancers may also hold great potential for the elimination of wrinkles and the rejuvenation of the skin. If this promise bears fruit, controlling concentrations of the RHAMM protein could one day replace surgical procedures or injections with neurotoxins that carry such unpleasant side-effects as muscle paralysis and loss of facial expressions.
RHAMM stands for Receptor for Hyaluronan Mediated Motility. Mina Bissell, a cell biologist with Berkeley Lab’s Life Sciences Division and a leading authority on breast cancer, was collaborating with Eva Turley, an oncology professor at the University of Western Ontario and leading authority on tissue polysaccharides, on a study of the role that RHAMM plays in regulating the signaling of adipocytes (fat cells) during the repairing of tissue wounds from injuries such as skin cuts, heart attacks and stroke. Earlier research by Turley, who discovered RHAMM, had shown that over-expression of this protein points to a poor patient outcome for such human cancers as breast, colon, rectal and stomach.

In the course of their collaborative study, Bissell and Turley, working with mice, discovered that blocking the expression of the RHAMM protein - either by deleting its gene, or through the introduction of a blocking reagent - can be used to selectively induce the generation of fat cells to replace those lost in the aging process. At the same time blocking RHAMM expression also reduces deposits of unhealthy visceral fat.

“This technique could be developed as a means of providing a non-surgical approach for normalizing skin appearance after reconstructive surgery, for wrinkle reduction, and for face lifts and figure enhancement,” said Bissell.

Said Turley, “Unlike neurotoxin agents, which have to be injected periodically, a localized injection of a RHAMM inhibitor should produce long-lasting skin volumizing effects and would not involve muscle paralysis, which means there would be no loss of expression if it were to be injected into the face.”

There are compounds now on the market that promote the production of adipocyte cells and result in increased subcutaneous fat, however, these adipocyte-promoting factors also increase the production of visceral fat. The mouse studies led by Bissell and Turley have shown that blocking RHAMM expression significantly increases subcutaneous fat while decreasing visceral fat. This suggests that blocking RHAMM should also have a beneficial effect on patients with obesity-related diseases, cardiovascular disease or diabetes. Another unique advantage of RHAMM is that its expression in normal adult human tissues is restricted.

“Therefore, anti-RHAMM agents should have low toxicity and according to preliminary animal studies, could be beneficial to patients with a tumor or inflammation-related disease,” said Turley.

Potential applications of RHAMM modulation in addition to wrinkle reduction include normalizing skin appearance after reconstructive or cosmetic surgery, e.g., grafted tissue on burn victims. It has also been shown to have a beneficial effect on tumors and inflammatory diseases in mice.

Stem Cells From Skin Cells Can Make Beating Heart Muscle Cells

2009-02-12T20:08:00.000-08:00

A little more than a year after University of Wisconsin-Madison scientists showed they could turn skin cells back into stem cells, they have pulsating proof that these "induced" stem cells can indeed form the specialized cells that make up heart muscle.
In a study published online Feb. 12 in Circulation Research, UW-Madison School of Medicine and Public Health professor of medicine Tim Kamp and his research team showed that they were able to grow working heart-muscle cells (cardiomyocytes) from induced pluripotent stem cells, known as iPS cells.

The heart cells were originally reprogrammed from human skin cells by James Thomson and Junying Yu, two of Kamp's co-authors on the study.

"It's an encouraging result because it shows that those cells will be useful for research and may someday be useful in therapy,'' said Kamp, who is also a cardiologist with UW Health. "If you have a heart failure patient who is in dire straits — and there are never enough donor hearts for transplantation — we may be able to make heart cells from the patient's skin cells, and use them to repair heart muscle. That's pretty exciting."

It's also a few more discoveries away. The researchers used a virus to insert four transcription factors into the genes of the skin cell, reprogramming it back to an embryo-like state. Because the virus is taken up by the new cell, there is a possibility it eventually could cause cancer, so therapies from reprogrammed skin cells will likely have to wait until new methods are perfected.

Still, the iPS cardiomyocytes should prove immediately useful for research. And Kamp said the speed at which knowledge is progressing is very encouraging.

Jianhua Zhang, lead author on the study, noted that it took 17 years, from when a mouse embryonic stem cells were first created in 1981, to 1998, when Thomson created the first human embryonic stem cells. In contrast, the first mouse iPS stem cells were created in 2006, and Thomson and Yu published their paper in November 2007, announcing the creation of human iPS stem cells that began as a skin cells.

While research on embryonic stem cells is controversial, because it destroys a human embryo, lessons learned through such research apply to current work with iPS cells made from adult cells.

"That's one of the important things that have come out of the research with embryonic stem cells, it taught us how human pluripotent stem cells behave and how to work with them,'' Kamp says. "Things are able to progress much more quickly thanks to all the research already done with embryonic stem cells."

Many types of heart disease have known genetic causes, so creating cardiomyocytes grown from patients who have those diseases will likely be some of the next steps in the research. One of Kamp's colleagues, Clive Svendsen, a UW-Madison School of Medicine and Public Health professor of neurology and anatomy, has grown the iPS cells into disease-specific neural cells. Kamp and Svendsen are also on the faculty of the Waisman Center and the Stem Cell and Regenerative Medicine Center.

Kamp's latest research, proving that iPS cells can become functional heart cells, is just one step along the way to better understanding and treatment of disease.

"We're excited about it, because it's the some of the first research to show it can be done, but in the future, we'll probably say, 'Well, of course it can be done,'" he says. "But you don't know until you do it. It's a very mysterious and complicated dance to get these cells to go from skin cells to stem cells to heart cells."

Headway In Understanding Alzheimer's Disease

2009-02-05T20:09:00.000-08:00

Scientists at UC Santa Barbara have discovered that a protein called BAG2 is important for understanding Alzheimer's disease and may open up new targets for drug discovery. They are ready to move from studying these proteins in culture to finding out how they work with mice.
In a recently paper published in the Journal of Neuroscience, the scientists describe important activities of BAG2 in cleaning up brain cells. The protein tau is normally found in brain cells, but scientists don't know why it clumps into tangles in people with Alzheimer's disease.

Senior author Kenneth S. Kosik, co-director of UCSB's Neuroscience Research Institute, and Harriman Chair in Neuroscience, has been involved in the study of neurons that develop neurofibrillary tangles, one of the hallmarks of the disease, since he was a postdoctoral fellow. "Early on in my career, we were one of several labs to discover that tau was in the neurofibrillary tangles," said Kosik.

Kosik's team recently started to work on BAG2 to find out how it may be involved in the removal of tangled tau. "It turns out that when you put this protein into the cell, it clears away the damaged tau very nicely," said Kosik. It doesn't clear away all the tau; it goes for the damaged tau protein and removes it.

For unknown reasons, when tau accumulates in a neurofibrillary tangle, the cell can't get rid of it. "All cells including neurons have an elaborate, sophisticated, elegant system for disposing of proteins," said Kosik. "Proteins have a certain turnover; sometimes they get damaged. The cell has its own trash can called the proteosome, and damaged proteins are deposited there.

"We've done this experiment many ways," said Kosik. "We've discovered a bit about how BAG2 works. We've turned it on to remove tau. We've turned it off to increase tau. We've really done a lot of manipulations using cell culture." So BAG2 is a new player, a new protein that may be a good target for study in the research of Alzheimer's disease.

"There is nothing about a drug or a treatment in any of these findings; however, the first step in fighting any illness is finding what you want to target the drug to," said Kosik. "This is a protein that is involved in neurofibrillary tangles, so now we have a new target for drug discovery. This is not a drug or a treatment, just a new target. The new target is BAG2." Kosik is looking forward to studying BAG2 in mice.

Kosik explained that we all have these proteins in our cells; however, they can go awry. Their levels can be off, or they may malfunction in another way. The same normal protein can begin to malfunction.

"It may be that BAG2 is not doing its job right; it may be that BAG2 is overwhelmed, because sometimes tau is building up, and there is not enough BAG2 there," said Kosik. "We cannot conclude from this that BAG2 is the fundamental problem in the disease state. It is only a possible target that can help us find our way out of the disease."

However, as Kosik explained, the current project started when he and his team suspected that one of the problems in Alzheimer's disease is to find out why the cell fails to dispose of tau and degrade it. They knew, even before starting the project, that the cell has marked the tau protein in Alzheimer's disease for degradation. There is a marker on the tau protein in the neurofibrillary tangles, which indicates that this is a protein that should go to the trash. The marker is called ubiquitin.

Previously, Kosik's team found a protein that is involved in the decision to throw away tau. That protein is called CHIP, and Kosik's team published information on that about four years ago.

"We knew something was going on there," said Kosik. "CHIP has a dual function. It calls out to the cell and says there is a protein here that is at a critical juncture. If the protein is salvaged, then CHIP goes off tau, and tau goes back to being a normal protein. But if the protein cannot be salvaged because it is so badly damaged, then CHIP goes into action and marks the tau for degradation by putting on several ubiquitins, and that's the signal to go to the trash."

The first two co-authors are Daniel C. Carretiero, postdoctoral fellow, and Israel Hernandez, graduate student. Both are molecular biologists. Co-author Pierre Neveu works in Kosik's lab, as well as UCSB's Kavli Institute for Theoretical Physics. Neveu brought in a number of computational insights that enhanced the findings.

Fungus Lessens Serious Grapefruit-Drug Reaction

2009-02-05T20:06:00.000-08:00

Scientists in Florida report that adding an edible mushroom-like fungus to grapefruit juice may help to reduce the serious side effects that can occur when people taking certain prescription drugs drink grapefruit juice.
In the study, Kyung Myung and colleagues explain that furanocoumarins (FCs) — chemicals found in grapefruit and some other citrus — block a key enzyme critical for metabolizing, or breaking down, certain prescription medications. This “grapefruit/drug” interaction — sometimes called the “grapefruit effect” — can turn normal drug doses into toxic overdoses. Researchers have tried to remove FCs using chemical, physical and microbiological methods. Myung and colleagues, for example, had previously discovered that an inedible fungus can be used to remove most of the FCs from grapefruit juice.

Now they report that the edible fungus Morchella esculenta, which is from the same major fungal group as the previously tested inedible fungus, removed most of the furanocoumarins from the grapefruit juice. It also reduced grapefruit juice’s inhibition of the enzyme by 60 percent.

Dried M. esculenta also worked, leading the researchers to suggest that it could be useful in removing the compound from grapefruit juice and identifying the specific components in the fungi that bind to furanocoumarins.

New Technique Images Tumor Vessel Leakiness To Predict Breast Cancer Chemotherapy Outcome

2009-02-02T08:48:00.000-08:00

Chemotherapy is an integral part of modern cancer treatment, but it's not always effective. Successful chemotherapy depends on the ability of anticancer drugs to escape from the bloodstream through the leaky blood vessels that often surround tumors.
Predicting chemotherapy's efficacy could save thousands of individuals from unnecessary toxicity and the often difficult side effects of the treatments.

In a study published in the February issue of the journal Radiology, researchers describe a technique for determining the "leakiness" of tumor blood vessels using a simple digital mammography unit. The researchers designed nanometer-sized capsules containing a contrast agent that could only leak into tumors with blood vessels that were growing and therefore leaky. The digital mammography-based quantification of "leakiness" is closely correlated to the ability of a clinically approved chemotherapy agent to enter the tumor, allowing the researchers to predict the agent's therapeutic efficacy.

"We developed a quantitative way to measure the leakiness of the blood vessels, which is directly linked to the amount of drug that gets to the cancer and in turn determines effectiveness," said Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "By simply measuring how much contrast agent reaches the tumor, we can predict how much of a clinically approved chemotherapeutic will reach the tumor, allowing physicians to personalize the dose and predict effectiveness."

In some cases, one chemotherapy drug may not be effective in treating the tumor, but this new technique allows oncologists to investigate other drugs sooner since they know the drug is reaching the tumor. Studies are currently underway to determine if mammography can predict the optimal dose of a wide range of breast cancer chemotherapeutics.

Bellamkonda and Coulter Department postdoctoral fellow Efstathios Karathanasis collaborated on this study with Ioannis Sechopoulos, an assistant professor in radiology at Emory University; Andrew Karellas, a former professor in the Emory University Winship Cancer Institute currently at the University of Massachusetts Medical School; and Ananth Annapragada, an associate professor of health information sciences at the University of Texas, Houston. The project was funded by the National Science Foundation and Georgia Cancer Coalition.

For the study, a long-circulating nanometer-scale liposomal capsule filled with iodinated contrast agent was injected into rats with six-day-old breast cancer tumors. For the next three days, the researchers collected digital mammography images of the animals and compared the pre- and post-injection grayscale intensity values to study the dynamics of how the contrast agent accumulated in the tumor over time.

"During the three-day time course, some tumors exhibited a rapid and significant increase in image brightness, meaning the contrast agent was accumulating in the tumor, whereas other tumors showed a slow and low increase," said Bellamkonda, who is also a Georgia Cancer Coalition Distinguished Scholar.

While the brightness of the tumors in the images changed significantly, no variations were observed in non-tumor areas or in the tumors of animals that did not receive the contrast agent. Immediately after the imaging was completed and the leakiness of each individual cancer vessel was quantified, the animals were intravenously injected with a clinically approved chemotherapy drug, liposomal doxorubicin.

Results showed that the chemotherapeutic drug slowed the progress of the tumor. The variability in uptake of the contrast agent by the tumors, as measured during the three-day imaging sessions, provided an accurate prognosis of the effect of liposomal doxorubicin on tumor growth rate.

"When we plotted the post-treatment tumor growth rate versus the intensity of leakiness, there was a significant and strong correlation," noted Bellamkonda. "The tumors in which the nanocarrier leaked out and accumulated the most in the tumors during the initial three-day test were the ones that responded best to the treatment."

To verify that the intensity changes in the images were caused by the nanocarrier and not endogenous changes in the tumor tissue, liposomal probes tagged with a fluorescent dye were injected into the animals. By looking at histological tumor sections, the researchers showed that the location of the increased image brightness and the fluorescent dye were the same.

"This study showed that higher uptake of the probe by the tumor related to leakier vasculature and suggested a better therapeutic outcome of liposomal doxorubicin," said Bellamkonda. "Imaging the integrity of the tumor vasculature like this may allow cancer treatment to be more patient-specific and potentially spare patients from chemotherapy if it is not going to be effective."

While the goal of the study reported in the journal was not to induce tumor regression, the researchers plan to investigate whether the liposomal probes can be used for this purpose in the future. To further develop and commercialize these multifunctional probes, Bellamkonda and Annapragada founded a start-up company called Marval Biosciences, Inc.

The researchers also want to investigate whether the leakiness of tumor vasculature represents a parameter that is useful for clinical diagnosis or tumor characterization.

"We want to study the molecular basis for blood vessel leakiness," said Bellamkonda. "We want to understand why there is variation in leakiness and chemotherapy effectiveness among individuals with tumors of the same type, size and stage."

Acupuncture Used For Animal Ailments

2009-01-14T22:55:00.000-08:00

Needles are often equated with pain and discomfort; however, for a horse named Gypsy the tiny sharp objects brought about much needed relief as Dr. Mark Crisman, a professor in the Department of Large Animal Clinical Sciences in the Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech, administered acupuncture therapy.
Gypsy had an infection in her ankle and Crisman was using acupuncture -- along with traditional therapy -- to help strengthen her bones and immune system, and provide pain relief.

Acupuncture, which has its roots in eastern countries, is a technique of inserting and manipulating very fine needles into specific points on the body with the intention of relieving pain and other therapeutic purposes. This ancient practice has long been used among human patients and, over the past few decades, has gained popularity and recognition in veterinary medicine.

“Acupuncture has proven to be a safe and relatively painless treatment for a variety of illnesses in animals,” said Crisman who has been practicing the therapy for over a decade on equine patients and now teaches others who desire certification.

The Virginia-Maryland Regional College of Veterinary Medicine’s Veterinary Teaching Hospital offers this therapy to both large and small animals. Conditions that respond well to acupuncture range from skin disorders to musculoskeletal issues to neurological problems.

"While pain and osteoarthritis are common conditions we treat with acupuncture in small animals,” said Dr. Bess Pierce, an associate professor in the Department of Small Animal Clinical Sciences, who is leading the hospital’s community practice, “we certainly provide therapy for a multitude of problems."

Veterinarians who wish to practice acupuncture most undergo an additional training process. With the recent completion of her certification, Dr. Beverley Purswell, a professor in the Department of Large Animal Clinical Sciences, brings the total of certified veterinary acupuncturists in the college to four.

"Acupuncture certainly does not replace traditional veterinary medicine," said Purswell who plans to use the therapy in her work in theriogenology, the specialized field of veterinary medicine that focuses on reproduction. "It can, however, compliment the therapies we already use."

In addition to Crisman, Pierce, and Purswell, Dr. Scott Pleasant, associate professor in the Department of Large Animal Clinical Sciences, is also a certified acupuncturist.

Drink Brewed Tea To Avoid Tooth Erosion, Study Suggests

2009-01-14T22:53:00.000-08:00

Today, the average size soft drink is 20 ounces and contains 17 teaspoons of sugar. More startling is that some citric acids found in fruit drinks are more erosive than hydrochloric or sulfuric acid—which is also known as battery acid. These refined sugars and acids found in soda and citrus juice promote tooth erosion, which wears away the hard part of the teeth, or the enamel. Once tooth enamel is lost, it's gone forever.
There is a beverage that does not produce such irreversible results. When deciding between the many options available, the best thing to drink to avoid tooth erosion is brewed tea, according to a study in the July/August issue of General Dentistry, the clinical, peer-reviewed journal of the Academy of General Dentistry (AGD).

Apart from tasting good, brewed tea has many health benefits. Tea is loaded with natural antioxidants, which are thought to decrease incidence of cancer, cardiovascular disease, and diabetes.

Mohamed A. Bassiouny, DMD, BDS, MSc, PhD, the lead author of the study, compared green and black tea to soda and orange juice in terms of their short- and long-term erosive effect on human teeth. The study found that the erosive effect of tea was similar to that of water, which has no erosive effect. And, when comparing green versus black, he discovered that there is a better option among those as well.

Dr. Bassiouny says that "when we look at tea and read about the benefits, it's amazing—not because green tea is 'the in thing'—but because there are advantages." He adds that much research done overseas, in countries such as Japan and Europe, found that green tea was identified to being superior over black due to its natural flavonoids (plant nutrients) and antioxidants.

But, if you do drink tea, experts suggest avoiding additives such as milk, lemon, or sugar because they combine with tea's natural flavonoids and decrease the benefits. In addition, stay away from prepackaged iced teas because they contain citric acid and high amounts of sugars. It does not matter whether the tea is warm or cold—as long as it is home brewed without additives.

Kenton Ross, DMD, FAGD, AGD spokesperson, sees patients' erosion problems on a daily basis in his practice. "Severe cases of erosion occur monthly and are frequently associated with high rates of soft drink consumption," he says. "This study clearly shows that brewed teas resulted in dramatically less enamel loss than soft drinks and acidic juices," says Dr. Ross. "I would highly recommend patients choose tea as an alternative to more erosive drinks like soda and fruit juice."

Tips to decrease erosion:

* Reduce or eliminate carbonated beverages. Instead, drink water, milk, or tea
* Skip the additives such as sugar, lemon, and milk
* Drink acidic drinks quickly and through a straw
* Chew sugar-free gum to increase saliva flow in your mouth
* Rinse with water to neutralize the acids, and wait an hour before brushing

High Caffeine Intake Linked To Hallucination Proneness

2009-01-14T22:48:00.000-08:00

High caffeine consumption could be linked to a greater tendency to hallucinate, a new research study suggests.
People with a higher caffeine intake, from sources such as coffee, tea and caffeinated energy drinks, are more likely to report hallucinatory experiences such as hearing voices and seeing things that are not there, according to the Durham University study.

‘High caffeine users’ – those who consumed more than the equivalent of seven cups of instant coffee a day - were three times more likely to have heard a person’s voice when there was no one there compared with ‘low caffeine users’ who consumed less than the equivalent of one cup of instant coffee a day. With ninety per cent of North Americans consuming some of form caffeine every day, it is the world's most widely used drug.

The researchers say the findings will contribute to the beginnings of a better understanding of the effect of nutrition on hallucinations. Changes in food and drink consumption, including caffeine intake, could place people in a better position to cope with hallucinations or possibly impact on how frequently they occur, say the scientists.

In the study, funded by the Economic and Social Research Council and the Medical Research Council, 200 students were asked about their typical intake of caffeine containing products, such as coffee, tea and energy drinks as well as chocolate bars and caffeine tablets. Their proneness to hallucinatory experiences, and their stress levels, were also assessed. Seeing things that were not there, hearing voices, and sensing the presence of dead people were amongst the experiences reported by some of the participants.

The researchers, whose paper is published in the academic journal Personality and Individual Differences, say their finding could be down to the fact that caffeine has been found to exacerbate the physiological effects of stress. When under stress, the body releases a stress hormone called cortisol. More of this stress hormone is released in response to stress when people have recently had caffeine. It is this extra boost of cortisol which may link caffeine intake with an increased tendency to hallucinate, say the scientists.

Lead author, Simon Jones, a PhD student at Durham University’s Psychology Department, said: “This is a first step towards looking at the wider factors associated with hallucinations. Previous research has highlighted a number of important factors, such as childhood trauma, which may lead to clinically relevant hallucinations. Many such factors are thought to be linked to hallucinations in part because of their impact on the body’s reaction to stress. Given the link between food and mood, and particularly between caffeine and the body’s response to stress, it seems sensible to examine what a nutritional perspective may add.”

Co–author Dr Charles Fernyhough, also from Durham University’s Psychology Department, noted “Our study shows an association between caffeine intake and hallucination-proneness in students. However, one interpretation may be that those students who were more prone to hallucinations used caffeine to help cope with their experiences. More work is needed to establish whether caffeine consumption, and nutrition in general, has an impact on those kinds of hallucination that cause distress.”

Mr Jones added: “Hallucinations are not necessarily a sign of mental illness. Most people will have had brief experiences of hearing voices when there is no one there, and around three per cent of people regularly hear such voices. Many of these people cope well with this and live normal lives. There are, however, a number of organisations, such as the Hearing Voices Network, who can offer support and advice to those distressed by these experiences.”

Caffeine use can lead to a condition called caffeine intoxication. Symptoms include nervousness, irritability, anxiety, muscle twitching, insomnia, headaches, and heart palpitations. This is not commonly seen when daily caffeine intake is less than 250mg.

Drinking Milk To Ease Milk Allergy? Oral Immunotherapy Study Shows Promise -- But Do Not Try This At Home

2009-01-10T21:21:00.001-08:00

Giving children with milk allergies increasingly higher doses of milk over time may ease, and even help them completely overcome, their allergic reactions, according to the results of a study led by the Johns Hopkins Children's Center and conducted jointly with Duke University. Researchers emphasize the findings require further research and warn parents and caregivers not to try this approach without medical supervision.
Despite the small number of patients in the trial – 19 – the findings are illuminating and encouraging, investigators say, because this is the first-ever double-blinded and placebo-controlled study of milk immunotherapy. In the study, the researchers compared a group of children receiving milk powder to a group of children receiving placebo identical in appearance and taste to real milk powder. Neither the patients nor the investigators knew which child received which powder, a rigorous research setup that minimizes the chance for error and bias.

"Our findings suggest that oral immunotherapy gradually retrains the immune system to completely disregard or to better tolerate the allergens in milk that previously caused allergic reactions," says Robert Wood, M.D., senior investigator on the study and director of Allergy & Immunology at Hopkins Children's. "Albeit preliminary and requiring further study, these results suggest that oral immunotherapy may be the closest thing yet to a 'true' treatment for food allergy."

Currently, food allergy management involves complete avoidance of the trigger foods, waiting for the child to outgrow the allergy or treating allergic reactions if and when they occur. The latter could be dangerous, investigators say, because these common foods are difficult to avoid and some reactions can be severe and even life-threatening.

In a report released Oct. 22, the Centers for Disease Control and Prevention estimates that food allergies are on the rise with three million children in the United States now having at least one food allergy, an 18 percent jump from 10 years ago. Milk allergy is the most prevalent type of food allergy.

"Given that the quality of life of a child with a food allergy is comparable to the quality of life of a child with diabetes, we urgently need therapies that go beyond strict food avoidance or waiting for the child to outgrow the allergy," Wood says.

Researchers followed allergic reactions over four months among 19 children with severe and persistent milk allergy, 6 to 17 years of age. Of the 19 patients, 12 received progressively higher doses of milk protein, and seven received placebo. At the beginning of the study, the children were able to tolerate on average only 40 mg (.04 ounces or a quarter of a teaspoon) of milk.

At the end of the four-month study, both groups were given milk powder as a "challenge" to see what dose would cause reaction after the treatment. The children who had been receiving increasingly higher doses of milk protein over a few months were able to tolerate a median dose of 5, 140 mg (over 5 ounces) of milk without having any allergic reaction or with mild symptoms, such as mouth itching and minor abdominal discomfort. Those who had been getting the placebo remained unable to tolerate doses higher than the 40 mg of milk powder without having an allergic reaction. In the group receiving milk protein, the lowest tolerance dose was 2, 540 mg (2.5 ounces) and the highest was 8,140 mg (8 ounces). Lab tests showed the children who regularly drank or ate milk had more antibodies to milk in their blood, yet were able to better tolerate milk than those who took the placebo. Researchers say, tolerance in children treated with milk continued to build over time, and recommend that these children continue to consume milk daily to maintain their resistance. The researchers caution that it remains unclear whether the children would maintain their tolerance once they stop consuming milk regularly. "It may very well be that this tolerance is lost once the immune system is no longer exposed to the allergen daily," Wood says.

The Hopkins group is currently studying oral immunotherapy in children with egg allergy to determine whether increasingly higher doses of egg protein can help resolve their allergy, and have recently started another study of milk immunotherapy.

Wood emphasizes the findings require further research and advises parents and caregivers not to try oral immunotherapy without medical supervision.

Other Hopkins investigators in the study: Justin Skripak, M.D., Hannah Rowley, R.D., Nga Brereton, R.D., Susan Oh, R.D., Robert Hamilton, M.D., Elizabeth Matsui, M.D. M.H.S. Duke University co-investigators: Scott Nash, M.D., and A. Wesley Burks, M.D.

The research was funded by the National Institutes of Health and The Eudowood Foundation.

People With Peanut Allergy Can React To Lupin

2009-01-10T21:14:00.000-08:00

Lupin is a legume belonging to the same plant family as the peanut. Lupin seeds are used for flour production and in various types of commercial foods. People afflicted with peanut allergy may also react to lupin, and the EU has recently introduced compulsory labelling of all products containing lupin.
During her doctoral work, Lise Holden developed a method of identifying lupin protein in food products. She also investigated the incidence of lupin allergy among children with food allergy and studied the proteins in lupin responsible for allergy production.

Several hundred species of lupin exist. Lupin seed, rich in protein and fibre, has formed part of the diet of some southern European and south American countries for centuries. Many are cultivated as house plants, but these are inedible. Selective breeding has given us the sweet lupin, which tastes good and has a lower content of alkaloids than previous variants.

During recent years, the use of sweet lupin has become more widespread throughout Europe. Lupin-based ingredients improve both the nutritional value and baking qualities of food, and they are commonly added to wheaten flour. Another use is as a replacement for soya, since many consumers associate soya with gene manipulation. In addition, lupin seed is gluten-free and can therefore be safely eaten by people afflicted with coeliac disease. New studies indicate that lupin protein can have cholesterol-reducing properties.

The increased use of lupin in food has led to several reported cases of allergic reactions against lupin, including in Norway. Lupin may produce allergy either by primary sensitisation or through cross-reaction with other legumes, especially peanut. People with peanut allergy should therefore be aware that they can react to food labelled as containing lupin.

Authorities, producers and sufferers all need a reliable way of identifying even small amounts of allergens in food. For her doctorate, Lise Holden developed a quantitative and sensitive immunological method for demonstrating lupin protein. The method, the first of its kind, now forms the basis of a commercial kit developed in co-operation with an English firm, HAVen. This method was utilised in a comprehensive investigation of lupin in food for the Norwegian market in 2006 - 2007, which showed that lupin is used in many different types of food such as bread, biscuits, cakes, pasta and chocolate spreads. Even though consumers are exposed to lupin in their food, lupin allergy remains a relatively rare form of allergy in Norway today.

Holden and her colleagues have in clinical studies of children conducted provocation testing with lupin. Many of the children had lupin-specific antibody in their blood without showing clinical allergy, demonstrating just how important provocation testing is for accurate diagnosis of lupin allergy.

In addition, Lise Holden worked with the identification of specific proteins in lupin that may produce allergy. Mapping such proteins may lead to a better understanding of allergy in its entirety.

Cand. scient. Lise Holden defended her thesis for Ph. D. degree, entitled "Lupin - a new food allergen: studies on the detection, antigenicity and allergenicity of lupin proteins", on October 17, 2008.

Nothing To Sneeze At: Real-time Pollen Forecasts

2009-01-07T23:18:00.000-08:00

Researchers in Germany are reporting an advance toward development of technology that could make life easier for millions of people allergic to plant pollen. It could underpin the first automated, real-time systems for identifying specific kinds of allergy-inducing plant pollen circulating in the air.
In the study, Janina Kneipp and colleagues explain that current pollen counts and allergy warnings are based on visual identification of the specific kind of pollen by examining pollen grains under a microscope. That procedure takes time, making it impossible for allergy-sufferers to know the kinds of pollen that are airborne on an hour-by-hour basis.

The researchers describe using a common laboratory procedure to identify chemical structures in pollen grains that distinguish oak and maple pollen, for instance, from maple and other kinds. They obtained these chemical "signatures" for 15 different kinds of tree pollen with the procedure, termed Raman spectroscopy. The researchers say that it could provide the basis for a real-time pollen detection and warning system to help allergy sufferers.

Avian Flu Becoming More Resistant To Antiviral Drugs

2009-01-07T23:15:00.000-08:00

A new University of Colorado at Boulder study shows the resistance of the avian flu virus to a major class of antiviral drugs is increasing through positive evolutionary selection, with researchers documenting the trend in more than 30 percent of the samples tested.
The avian flu, an Influenza A subtype dubbed H5N1, is evolving a resistance to a group of antiviral drugs known as adamantanes, one of two classes of antiviral drugs used to prevent and treat flu symptoms, said CU-Boulder doctoral student Andrew Hill, lead study author. The rise of resistance to adamantanes -- which include the nonprescription drugs amantadine and rimantadane -- appears to be linked to Chinese farmers adding the drugs to chicken feed as a flu preventative, according to a 2008 paper by researchers from China Agricultural University, said Hill.

In contrast, resistance of the avian flu virus to the second, newer class of antiviral drugs that includes oseltamivir -- a prescription drug marketed under the brand name Tamiflu -- is present, but is not yet prevalent or under positive genetic selection, said Hill of CU-Boulder's ecology and evolutionary biology department. The CU findings should help health administrators around the world plan for the possibility of an avian flu pandemic.

The CU-Boulder study is the first to show H5N1 drug resistance to adamantanes arose through novel genetic mutations rather than an exchange of RNA segments within cells, a process known as re-assortment, said Hill. The research on the mutations, combined with molecular evolution tests and a geographic visualization technique using Google Earth, "provides a framework for analysis of globally distributed data to monitor the evolution of drug resistance," said Hill.

The CU-Boulder-led study appears online in the journal Infection, Genetics and Evolution. Co-authors included CU-Boulder Associate Professor Robert Guralnick, recent CU-Boulder graduate Meredith Wilson, Farhat Habib of Kansas State University and Daniel Janies of Ohio State University.

"As these adamantanes have gotten into nonhuman vectors like birds, the positive selection for resistance to avian flu is rising," said Hill. "If Tamiflu is ever used in the manner of adamantanes, we could conceivably see a similar resistance developing through positive selection."

The research team used an interactive "supermap" using Google Earth technology that portrays the individual gene mutations and spread of the avian flu around the globe, said Guralnick of CU-Boulder's ecology and evolutionary biology department. By projecting genetic and geographic information onto the interactive globe, users can "fly" around the planet to see where resistant H5N1 strains are occurring, said Guralnick, also Hill's doctoral adviser.

For the study, the researchers analyzed 676 whole genomes of Influenza A/H5N1 from National Institutes of Health databases of viruses isolated between 1996 and 2007. The team is comparing how often amino acid sequence changes in genes lead to mutations that affect drug resistance in the H5N1 virus and how often such changes evolve into random mutations that don't affect resistance, Hill said.

The next step is to analyze 2008 data, he said.

First detected in China in 1996, the avian flu has spread throughout Asia and to India, Russia, Pakistan, the Middle East, Africa and Europe by various carriers, including poultry and migratory waterfowl, Hill said. While H5N1 is not highly communicable to humans from birds or between humans, experts are concerned future evolution of this subtype or other subtypes, or genetic re-assortment between subtypes, could make an avian influenza strain more contagious with the potential to cause a pandemic.

"Even if H5N1 is not the flu subtype that develops into the next pandemic, this technique can help us understand the properties of flu viruses and we can use these methods to track mutations in other viruses," said Guralnick. "We can harvest genetic influenza data and monitor it in near real-time, which should give this project some traction to help governments make decisions on managing potential pandemics."

Like the legend of a road map, colors and symbols on the supermap indicate which types of hosts carry the virus or the distribution of genotypes of interest, said Hill. A click by users on viral "isolates" generates computer windows revealing H5N1 mutations linked to positive genetic selection resulting from the spread and use of adamantanes.

The information is linked by computer to the National Institutes of Health's GenBank, a database with more than 75 million sequence records.

According to the Centers for Disease Control in Atlanta, an avian flu pandemic could kill millions of people in America, infect 15 percent to 35 percent of the population and cost well over $100 billion.

Common Cold Virus Came From Birds About 200 Years Ago, Study Suggests

2009-01-02T00:06:00.000-08:00

A virus that causes cold-like symptoms in humans originated in birds and may have crossed the species barrier around 200 years ago, according to a new article published in the Journal of General Virology. Scientists hope their findings will help us understand how potentially deadly viruses emerge in humans.
"Human metapneumovirus may be the second most common cause of lower respiratory infection in young children. Studies have shown that by the age of five, virtually all children have been exposed to the virus and re-infections appear to be common," said Professor Dr Fouchier. "We have identified sites on some virus proteins that we can monitor to help identify future dominant strains of the virus."

Human metapneumovirus is related to the respiratory syncytial virus, measles, mumps and parainfluenza viruses. It infects people of all ages but is most common in children under five. Symptoms include runny nose, cough, sore throat and fever. Infection can also lead to more severe illnesses such as bronchitis and pneumonia, which can result in hospitalisation, especially in infants and immunocompromised patients. HMPV infection is most common during the winter and it is believed to cause up to 10% of respiratory illnesses in children.

"HMPV was first discovered in 2001, but studies have shown that the virus has been circulating in humans for at least 50 years," said Professor Dr Ron Fouchier from ErasmusMC in Rotterdam, The Netherlands. "HMPV is closely related to Avian metapneumovirus C (AMPV-C), which infects birds. Because of the similarity, scientists have suggested that HMPV emerged from a bird virus that crossed the species barrier to infect humans."

Metapneumoviruses have high evolutionary rates, similar to those of other RNA viruses such as influenza, hepatitis C and SARS. By understanding the evolution and emergence of these viruses the scientists hope to develop ways of monitoring and predicting the emergence of new pathogenic viruses.

"We investigated the evolutionary history of metapneumoviruses using genetic information available for numerous strains of HMPV and AMPV-C circulating in humans and birds," said Professor Dr Fouchier. "We calculated that the moment of divergence between HMPV and AMPV-C occurred approximately 200 years ago. Therefore, HMPV probably originates from an AMPV-C like virus that crossed the species barrier to infect humans around that time."

"Besides the evolutionary history of metapneumoviruses, we also investigated the mutation rates and the selection pressures of these viruses. An understanding of how viruses evolve and how they adapt to new hosts and their immune systems is important, especially if we are to prepare for new, potentially pandemic diseases."