August 2, 2006, 11:33 PM CT

Mapping System For Skin Cells

Global-positioning system aficionados know that it's possible to precisely define any location in the world with just three geographic coordinates: latitude, longitude and altitude. Now researchers at the Stanford University School of Medicine have discovered that specialized skin cells use a similar mapping system to identify where they belong in the body and how to act once they arrive.

These cellular cornerstones direct embryonic patterning and wound healing by sending vital location cues to their neighbors, and may help in growing tissue for transplant or understanding metastatic cancer.

"There is a logic to the body that we didn't understand before," said John Rinn, PhD, a postdoctoral scholar in the laboratory of Howard Chang, MD, PhD, assistant professor of dermatology. "Our skin is actively maintaining itself throughout our life, and these 'address codes' help the cells know how to respond appropriately." Rinn is the first author of the research, which is reported in the current issue of Public Library of Science-Genetics.

Until now it's been a mystery as to how adult skin, which consists of basically the same components all over the body, knows to grow hair in some areas like the scalp, while manufacturing sweat glands, calluses and fingerprint whorls in others. In 1969, well-known developmental biologist Lewis Wolpert authored a famous treatise that described two possible ways for cells to know where they are in the body: Either they infer their location and adjust their behavior based on interactions with nearby cells, or they deduce their "positional identity" through the use of some type of coordinate system. The findings from the new Stanford study bolster the second possibility.........

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August 2, 2006, 11:29 PM CT

First Treatment For Drug-resistant HIV

Doctors have their first FDA-approved tool to treat drug-resistant HIV thanks to a new molecule created by a Purdue University researcher.

"There are a number of therapys for AIDS on the market, but none are able to combat drug resistance," said Arun Ghosh (pronounced A-rune GO-sh), a professor with a dual appointment in the departments of chemistry and medicinal chemistry and molecular pharmacology. "This is the first therapy that is effective against the growing number of drug-resistant strains of HIV, the virus that causes AIDS. The problem is widespread".

The FDA recently approved the pill-based treatment of Ghosh's molecule, TMC-114, for medical use. The molecule, also known as Darunavir (pronounced DA-rune-a-veer), is the forerunner in a series of molecules under development by Ghosh.

Earlier research shows that almost half of patients with the human immunodeficiency virus (HIV) who initially respond to therapy develop drug-resistant strains and stop responding to therapy within eight to 10 months, he said. An additional 20 percent to 40 percent of patients have drug-resistant strains when they are first diagnosed, suggesting these strains can be transmitted from one person to the next.

This year marks the 25th anniversary of the first reported U.S. cases of AIDS, a disease that claims the lives of more than 15,000 Americans each year, as per the Centers for Disease Control and Prevention. World Health Organization figures estimate more than 40 million people worldwide are infected with HIV.........

Posted by: Mark      Permalink         Source

August 2, 2006, 11:04 PM CT

Uterine Cancer May Yield Clues To Genetics

A new study suggests that women with endometrial cancer should be screened for inherited mutations that could lead to a high risk of several other cancers.

The study showed that 1.8 percent, or about one in 50, of newly diagnosed endometrial cancer patients have mutations for Lynch syndrome, an inherited condition also known as hereditary nonpolyposis colon cancer, or HNPCC.

People with Lynch syndrome mutations are at high risk for colon, endometrial, ovarian and gastric cancer. Endometrial, or uterine, cancer is the most common cancer in women with this condition.

The study, led by scientists at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), is reported in the Aug. 1 issue of Cancer Research.

The study is the first to comprehensively screen a large number of women with uterine cancer for Lynch syndrome mutations, said Heather Hampel, a genetic counselor in the clinical cancer genetics program and first author of the study.

"It's important to identify women with one of these mutations because they have a very high risk for developing colon cancer, and they may not be aware of that risk," said Hampel. "Because this is hereditary, half of her siblings and children may also be at risk for the syndrome.........

Posted by: Emily      Permalink         Source

August 1, 2006, 11:41 PM CT

Evolution At The Tips Of Chromosomes

In terms of their telomeres, mice are more complicated than humans. That's the finding from a recent Rockefeller University study, which shows that mice have two proteins working together to do the job of a single protein in human cells. The findings, published recently in Cell, suggest that the protein complex that protects chromosome ends may have evolved far more rapidly than previously believed.

Acting as caps on the ends of each chromosome, telomeres are composed of repetitive DNA and shelterin, a protective protein complex protects. Titia de Lange's lab has identified a number of of the components of shelterin and studies how its components work together to ensure that chromosome ends are not recognized as DNA breaks.

Prior work from the de Lange lab showed that TRF2, a shelterin protein that binds to the duplex part of the telomere, is crucial for telomere protection. Without TRF2, telomeres activate a DNA damage signal and are repaired by the same pathways that act on DNA breaks. TRF2 brings a second shelterin protein, POT1, to the telomeres. Because POT1 binds to single-stranded telomeric DNA present at the very end of the chromosomes, the de Lange lab asked how POT1 contributes to the protection of telomeres.

"We had previously removed TRF2 from mouse cells and seen a number of dramatic phenotypes," says de Lange, "all of the telomeres ligate together; there is a massive DNA damage response and the cells basically die. We argued that if the function of TRF2 was to bring POT1 to the DNA, then we should observe the same phenotype if we removed POT1".........

Posted by: Scott      Permalink         Source

August 1, 2006, 6:58 AM CT

No Cancer Without Cell Walls

Cancer cells, like houses, need building materials for their walls. And as with a house, the cell wall needs to be built at just the right moment to protect and allow the construction of internal components. A team from the Uppsala Branch of the global Ludwig Institute for Cancer Research (LICR) has not only shown how the cell gets this timing right, but has also conducted proof-of-principle studies that indicate taking away the cell's bricks and mortar is a potential strategy for cancer control.

"New cells are created by the duplication of existing cells through a highly-organized process known as the cell cycle," explains lead author, Dr. Maite Bengoechea Alonso. "Last year we discovered that a protein called SREBP1 that regulates the synthesis of lipids needed for new cell walls was regulated during the cell cycle. Now we show that the SREBP1 protein actually controls the cell cycle".

Senior author, LICR's Dr. Johan Ericsson, realized that disrupting the function of SREBP1 might prevent the lipid synthesis mandatory for new cell walls. "In fact, we literally stopped the cell cycle in its tracks by removing SREBP1 from cells. It seems that if you don't have SREBP1 activity, you can't make lipids, and if you don't have lipids, you can't make new cells".

As per Dr. Ericsson, who is also a Research Fellow of the Royal Swedish Academy of Sciences, this approach might one day form the basis of a new strategy for the long-term control of cancer. "Cancer cells divide uncontrollably, so their need for lipids is more urgent and continuous than normal cells. Treatment with an inhibitor of SREBP1 might reduce the rate of cancer cell proliferation to slow down tumor growth, or might enhance the effect of targeted therapies that aim to actually kill cancer cells".........

Posted by: Janet      Permalink         Source

August 1, 2006, 6:42 AM CT

Human Cytomegalovirus Vaccine

Each year, about 40,000 children are born infected with human cytomegalovirus, or CMV, and about 8,000 of these children suffer permanent disabilities due to the virus almost one an hour. These disabilities can include hearing loss, vision loss, mental disability, a lack of coordination, and seizures. As per the Centers for Disease Control and Prevention, CMV is as common a cause of serious disability as Down syndrome, fetal alcohol syndrome, or neural tube defects.

Because of the dangers posed by the virus to infants, the Institute of Medicine has declared that development of a CMV vaccine should be one of the highest priorities for vaccine makers. Now, in a new study in the August 1 issue of The Journal of Virology, scientists at The Wistar Institute outline an innovative approach that could be used to create such a vaccine.

The Wistar researchers began with the observation that mice harbor a species-specific form of CMV that is unable to sustain an infection in humans and is completely harmless to them. They then asked whether, using recombinant technologies, there might not be a way to shift the mouse-specific virus closer to the human-specific virus to generate a version of the virus able to elicit a protective immune response but not a dangerous infection in humans.........

Posted by: JoAnn      Permalink         Source

July 31, 2006, 6:51 AM CT

Malignant Melanoma Secretes Embryo Protein

A Northwestern University research group has discovered that aggressive melanoma cells secrete Nodal, a protein that is critical to proper embryo formation.

An article describing this research was published recently in the advanced online issue of the journal Nature Medicine.

The scientists identified the potent and highly unstable embryonic growth factor by injecting aggressive melanoma cells into developing zebrafish embryos, which were used as "biosensors" for tumor cell-derived signals, and were consequently able to induce ectopic (abnormal) embryonic skull and backbone (axes) formation.

"This finding highlights the convergence of tumorigenic and embryonic signaling pathways. From a translational perspective, Nodal signaling provides a novel target for therapy of aggressive cancers such as melanomas," said Mary J. C. Hendrix, the corresponding author, of Children's Memorial Research Center where the discovery was made.

Hendrix is president and scientific director of the Children's Memorial Research Center, professor of pediatrics at Northwestern University Feinberg School of Medicine and a member of the executive committee of The Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Jolanta M. Topczewska and Lynne-Marie Postovit, from Children's Memorial Research Center, co-led the study.........

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July 29, 2006, 8:49 PM CT

Genetic Model For Parkinson's Disease

In the mouse model generated by the research team, a gene called TFAM is automatically deleted from the genome in dopamine nerve cells only. Without TFAM, mitochondria cannot function normally. The so called respiratory chain is compromised and energy production decreases severely in the dopamine cells.

The new mice are born healthy from healthy but genetically modified parents and will develop spontaneous disease. Prior studies in the field have been based on scientists delivering neurotoxic substances to kill the dopamine neurons. In the new mice, however, mice develop disease slowly in adulthood, like humans with Parkinson's disease, which may facilitate research aimed at finding novel medical therapys and other therapies.

"We see that the dopamine producing nerve cells in the brain stem slowly degenerate", says Dr. Nils-Gran Larsson. "In the microscope we can see.

that the mitochondria are swollen and that aggregates of a protein, probably alpha-synuclein starts to accumulate in the nerve cell bodies. Inclusions of alpha-synuclein-rich so called Lewy bodies is typical for the human disease".

The causes of Parkinson's disease have long remained a mystery. Genes and environment are both implicated, but recently there has been an increased focus on the roles of genetic factors. It has been observed that mutations in many genes can lead directly to disease, while other mutations may be susceptibility factors, so that carriers have an increased risk of becoming ill. A common denominator for some of the implicated genes is their suggested role for the normal functioning of mitochondria.........

Posted by: Daniel      Permalink         Source

July 28, 2006, 9:31 PM CT

Nanotechnology And Atherosclerosis

In laboratory tests, one very low dose of a drug was enough to show an effect on notoriously tenacious artery-clogging plaques. What kind of drug is that potent?.

It's not so much the drug itself as how it was delivered. Fumagillin - a drug that can inhibit the growth of new blood vessels that feed atherosclerotic plaques - was sent directly to the base of plaques by microscopically small spheres called nanoparticles developed by scientists at Washington University School of Medicine in St. Louis.

"Previously we reported that we can visualize plaques using our nanoparticle technology, but this is the first time we've demonstrated that the nanoparticles can also deliver a drug to a disease site in a living organism," says Patrick Winter, Ph.D., research assistant professor of medicine. "After a single dose in laboratory rabbits, fumagillin nanoparticles markedly reduced the growth of new blood vessels that feed plaques."

The scientists report their findings in the recent issue of the journal Arteriosclerosis, Thrombosis, and Vascular Biology, and the article is now available on line.

An atherosclerosis plaque results when a buildup of cholesterol, inflammatory cells and fibrous tissue forms inside an artery. If a plaque ruptures, it can block blood flow to the heart or brain, causing heart attack or stroke.........

Posted by: Daniel      Permalink         Source

July 28, 2006, 9:26 PM CT

Steroid Osteoporosis Connection

Scientists are closing in on the solution to a persistent medical puzzle: why do high doses of cortisone, widely prescribed for asthma, rheumatoid arthritis and other inflammatory and autoimmune conditions, weaken bones?

Through studies of mice, researchers at Washington University School of Medicine in St. Louis have now identified osteoclasts, cells that dismantle old bone, as the essential link between osteoporosis and cortisone. As scientists flesh out the molecular-level details of this connection, they may be able to identify targets for therapy to prevent cortisone's damaging side effects on bone.

"High-dose cortisone is the second most common cause of osteoporosis, and we currently have no real treatment for this serious side effect," says senior author Steven L. Teitelbaum, M.D., Messing Professor of Pathology and Immunology. "Given how frequently these drugs are used to treat many different conditions, that's a major clinical problem".

Teitelbaum and colleagues including lead author Hyun-Ju Kim, Ph.D., a postdoctoral fellow, publish their results in the recent issue of the Journal of Clinical Investigation.

Cortisone is a steroid produced naturally by the adrenal gland and synthesized by a number of pharmaceutical companies for clinical use. The drug is also used to treat lupus, multiple sclerosis and chronic obstructive pulmonary disease, and it is prescribed to transplant patients to prevent rejection of transplanted organs.........

Posted by: Scott      Permalink         Source