June 21, 2006, 11:36 PM CT

Microchannels Aid Drug Discovery

tiny fluid-filled channel on a microchip that allows single cells to be treated and analyzed could lead to advances in drug and gene screening and early disease diagnosis.

The tool breaks down cell membranes to allow drug and gene delivery and permits examination of intracellular materials by establishing an electrical current across a microscale channel, said Chang Lu, a Purdue University biological engineer. The Purdue system is different from current techniques that use electricity for drug delivery and cell analysis. The new technique handles one cell at a time and uses a common DC power supply rather than a costly pulse generator.

"Normally when you do testing, you need a lot of cells, and the properties that you record are the average of that cell population," Lu said. "If you carry out the test based on single cells, you have access to a more detailed picture of the cell population and can pinpoint abnormalities more quickly and exactly".

The size of the channel, while small enough to accommodate only one cell at its narrowest diameter, varies in width so that the electric field intensity differs depending on the cell's location in the device, Lu said. The flow rate controls how much time the cell spends in the high electrical field, where a process called electroporation occurs. Controlling the length of time in the high electrical field without turning the voltage on and off helps maintain the cell's viability.........

Posted by: Scott      Permalink         Source

June 21, 2006, 10:11 PM CT

Herbal Therapies For Cancer

Whether herbal supplements can help cancer patients avoid common problems such as fatigue and sleeplessness is under study at the Medical College of Georgia.

Ginseng, a perennial found in North America and eastern Asia touted as a safe way to improve the body's stress resistance, is being tested for its potential in battling common fatigue.

Valerian, a flowering perennial from Eurasia widely used as a sedative, is being studied for its potential in helping cancer patients sleep.

"These are some of our quality of life trials to help cancer patients with side effects of their disease and therapy," says Dr. Daron G. Ferris, director of the MCG Gynecologic Cancer Prevention Center and a principal investigator. "Almost every cancer patient has fatigue, for some reason. Both cancer and its therapy can have an effect on blood count and patients may become anemic. Others battle depression, which can also make them feel tired".

Thirty to 50 percent of cancer patients also have trouble getting to sleep and staying asleep, a common side effect of chemotherapy, says Darlene Gibson, research nurse.

While anecdotal evidence abounds about the effectiveness of these herbal therapies, scientific studies in animals or humans, especially those with cancer, are sparse, Dr. Ferris says. "A number of cancer patients look for 'natural,' non-traditional therapys. We are delighted to offer alternatives that a number of patients desire in a way that ensures the quality of the supplement and does not interfere with the patient's cancer therapy".........

Posted by: Janet      Permalink         Source

June 21, 2006, 8:25 PM CT

The BARD1 Cys557Ser Variant and Breast Cancer Risk in Iceland

Background

Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer.



Methods and Findings

The Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.11–3.01, p = 0.014). The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22–4.75, p = 0.015). Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16–8.40, p = 0.046) in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas were overrepresented amongst Cys557Ser carriers. We found that an excess of ancestors of contemporary carriers lived in a single county in the southeast of Iceland and that all carriers shared a SNP haplotype, which is suggestive of a founder event. Cys557Ser was found on the same SNP haplotype background in the HapMap Project CEPH sample of Utah residents.........

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June 19, 2006, 9:24 PM CT

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Posted by: Janet      Permalink

June 19, 2006, 8:21 PM CT

Creation Of Patient-specific Embryonic Stem Cells

Scientists at Children's Hospital Boston have begun attempts to create human embryonic stem cells using nuclear transfer with human eggs and embryos, after receiving approval from the Institutional Review Boards and ESCRO (Embryonic Stem Cell Research Oversight) committees of Children's Hospital Boston and Partners HealthCare. The work is underway in the Children's Hospital laboratory of George Daley, MD, PhD, Associate Director of the Children's Hospital Stem Cell Program and a member of the Executive Committee of the Harvard Stem Cell Institute. Daley is an internationally recognized expert in diseases of the blood.

Because of Federal funding restrictions on human embryonic stem cell research, these studies are being funded through private philanthropy donated to Children's Hospital Boston and the Harvard Stem Cell Institute (HSCI), a collaborative effort that brings together researchers across Harvard University and all its affiliated hospitals to address the promise of stem cell biology as the basis for cures and therapy for a wide range of chronic medical conditions. HSCI funds research, operates core facilities, conducts undergraduate and graduate education, and coordinates the efforts of hundreds of stem cell researchers and clinicians throughout the Harvard community. Two other HSCI researchers at Harvard University, Doug Melton, PhD, and Kevin Eggan, PhD, have likewise received approval to begin similar experiments aimed at producing disease-specific embryonic stem cells.........

Posted by: Scott      Permalink         Source

June 18, 2006, 11:08 AM CT

New Drug Target In Tuberculosis

Tuberculosis remains one of the deadliest threats to public health. Every year 2 million people die of the disease, which is caused by the microorganism Mycobacterium tuberculosis. Roughly one third of the world's population is infected and more and more bacterial strains have developed resistance to drugs. Scientists from the Hamburg Outstation of the European Molecular Biology Laboratory (EMBL) and the Max Planck Institute for Infection Biology (MPIIB) in Berlin have now obtained a structural image of a protein that the bacterium needs for survival in human cells. This image reveals features of the molecule that could be targeted by new antibiotic drugs. The results appear in this week's issue of the Proceedings of the National Academy of Sciences (PNAS online, 29 May 2006).

M. tuberculosis is dangerous because it hides and persists in the immune cells of our bodies. "It can only persist there because of the activity of key molecules," says Matthias Wilmanns, Head of EMBL Hamburg. "We are investigating the functions of tuberculosis proteins and determining their atomic structures, in hopes of finding weak points and new inhibitors".

A protein called LipB is essential for the organism because it activates cellular machines that drive the bacterium's metabolism. Stefan Kaufmann's department at the MPIIB has specialized in the biology of M. tuberculosis infection and its ability to survive in immune cells. They discovered that LipB is highly active in acutely infected cells, especially in patients infected by multidrug-resistant forms of M. tuberculosis.........

Posted by: Mark      Permalink         Source

June 18, 2006, 11:05 AM CT

Neuronal Inhibitions

A computer - or any digital system which processes and stores information - knows only two states: "on" and "off". While our brain may not be a computer, the signals of nerve cells can also represent "on" or "off" states, causing the receiving - "post-synaptic" - cells to either propagate the signal or to terminate signal transmission. The orchestrated interplay of stimulating and inhibitory signals is central to the development and functioning of the entire nervous system. If inhibitory neurons are prevented from carrying out their function, this causes major defects early in embryonal development - and these defects can even occur outside the nervous system. These are the results of a study recently published by researchers from the Max Planck Institute for Experimental Medicine in Gottingen (Neuron, May 18, 2006).

The most common inhibitory transmitters in the mammalian central nervous system are GABA and glycine. Nerve cells can release GABA or glycine where they contact other nerve cells at junctions called synapses. This typically prevents further signal transmission by the post-synaptic cell.

Most inhibitory nerve cells release either GABA or glycine. However, some inhibitory nerve cells appear to be "bilingual", releasing a mixture of GABA and glycine. These mixed-release cells are most common during nervous system development and seem to be crucial for normal spinal cord growth. For brain researchers, however, they have proven mysterious. Most nerve cells specialise in releasing only one type of neurotransmitter. They use transport proteins to pump the neurotransmitter into vesicles surrounded by a membrane and store it there until release is triggered.........

Posted by: Daniel      Permalink         Source

June 15, 2006, 10:39 PM CT

Gut Microbes' Partnership

Scientists studying mutually beneficial interactions between members of our vast community of friendly gut microorganisms have shown that two common organisms collude and collaborate to increase the amount of calories harvested from a class of carbohydrates found in food sweeteners.

In the study, conducted in previously germ-free mice, colonization with two prominent human gut microbes led to fatter mice. Researchers at Washington University School of Medicine in St. Louis called the results an illustration of how understanding the menagerie of microorganisms that live in our guts can provide new insights into health. The study is published online this week by the Proceedings of the National Academy of Sciences.

To one day consider manipulating gut microbes for medical benefits, such as weight loss or gain, researchers need to know who's living in our digestive systems and how they form strategic alliances with one another to benefit themselves and us. They also have to learn how much this cast of microbial characters varies in different human individuals.

"We are superorganisms containing a mixture of not just human cells but also bacterial cells and cells of another microscopic domain of life known as Archaea," says senior author Jeffrey Gordon, M.D., the Dr. Robert J. Glaser Distinguished University Professor. "As adults, the number of these bacterial and archaeal microbial cells exceeds the number of our human cells by tenfold. The genes present in this community of 10-100 trillion bugs vastly outnumber our own genes and are a key part of our genetic landscape, providing us with attributes we have not had to evolve on our own."........

Posted by: Sue      Permalink         Source

June 12, 2006, 11:50 PM CT

Why That Cold Sore Keep Coming Back?

Scientists at the University of Pennsylvania School of Medicine have discovered part of the reason why cold sores, caused by a herpes virus, come back again and again. The new study, published online last month in Nature, points to a small RNA molecule, called a microRNA (miRNA) as the culprit that keeps the latent virus-infected cell alive. These findings could one day lead to a new way to fight the virus and offers the first target for intervention in the latent infection.

A research team led by Nigel W. Fraser, PhD, Professor of Microbiology, has found that herpes simplex virus-1 (HSV-1), the virus that causes cold sores and ocular keratitis, produces an miRNA molecule. This miRNA is encoded by the Latency-Associated Transcript gene (LAT) in the viral genome and works through a process called RNA interference to prevent normal cell death or apoptosis. Thus, the latent viral infection is maintained for the lifetime of the individual because the latently infected cell does not die.

"Eventhough miRNAs encoded by cellular genes are known to be an important mechanism for controlling gene expression, this is one of the first miRNA found to be encoded by a viral genome," says Fraser. "Our study helps show how HSV-1 can maintain a latent infection for the lifetime of an infected individual."........

Posted by: Mark      Permalink         Source

June 10, 2006, 6:43 PM CT

New Insights On Survival in AIDS

New insights into how a subpopulation of helper T-cells provides immunity and promotes survival following infection with an AIDS-like virus offer a new means of predicting an AIDS vaccine's effectiveness, a discovery that could help researchers as they test these vaccines in clinical trials.

Led by scientists at Beth Israel Deaconess Medical Center (BIDMC) and the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, these findings appear in the June 9 issue of the journal Science.

"Over the last decade, we have created AIDS vaccines that generate T-cell populations that can combat HIV," explains lead author Norman Letvin, M.D., chief of the Division of Viral Pathogenesis at BIDMC, professor of Medicine at Harvard Medical School, and investigator at the NIAID VRC. "These latest findings now provide us with an important new way of looking at subpopulations of CD4 helper T-cells and suggest how they may be used as a marker to gauge the efficacy of these vaccines."

The work was spearheaded by Letvin and colleagues at the VRC, which is dedicated to improving global human health through the rigorous pursuit of effective vaccines for human diseases such as AIDS. Since it was first identified 25 years ago, the human immunodeficiency virus (HIV) has proven extraordinarily difficult to control. Attempts to develop an HIV vaccine that triggers the production of antibodies -- the mechanism responsible for vaccine protection against other viruses including polio and hepatitis B -- have been unsuccessful.........

Posted by: Mark      Permalink         Source