Health Meaning

WASHINGTON, DC - Scientists have discovered two mutations that can be major contributors to the development of the lateral sclerosis amyotrophic (ALS), or Lou Gehrig's disease. The discovery, presented here today at the annual meeting of the Society for Neuroscience, may one day lead to a useful diagnostic test and improved treatments.

ALS, which affects around 30,000 people worldwide, causes progressive paralysis which usually results in death. Although scientists have discovered a gene that causes an inherited form of the disease in 1993, the majority of cases - over 0% - are "sporadic", which is not hereditary, and are due to unknown causes

. Jeffrey Rothstein, a neurologist at Johns Hopkins University, found mutations in 10 of 20 patients with sporadic ALS. It was followed earlier observations that many patients have abnormally low levels of EAAT2, a protein that helps turn off and recycling the neurotransmitter glutamate in the brain and spinal cord. Due to excessive glutamate concentrations are toxic to neurons, suggesting paralysis patients could be caused by accumulation of the neurotransmitter and the resulting death of neurons that control muscles.

In the current work, the Hopkins team found a possible explanation for the deficiency EAAT2 in ALS: the mutations they identified are nucleic acids that translate the genetic code into the structure protein. He and his colleagues did not find mutations in healthy subjects or in patients with Alzheimer's disease or Huntington's disease, which are also characterized by the death of neurons.

The work is preliminary, Rothstein said, and he recognizes it leaves many questions unanswered. For example, researchers have found that the modified proteins in the cells of the brain controlling motor function; they can not explain why the changes are limited to those cells. And many experts are not convinced that the metabolism of faulty glutamate is the main culprit in the disease. Rothstein said, however, that the only drug that has shown promise against ALS is Rilutek, which inhibits glutamate production. Although protein mutations do not play a major role in the disease, he said, they could help neurobiologists track down the actual cause.

in an honor that has never been granted to a single scientist, Time magazine named David Ho, head of Aaron diamond AIDS Research Center in New York City (ADARC), its man of the year. The magazine tapped the 44-year-old Ho, he said, for "pioneering treatment which could, could well lead to a cure." But some AIDS researchers fear that the award may further divide a field known for its fierce competition and heated disputes.

> An accompanying profile muses on Ho "genius." And there is no doubt that Ho and his colleagues at the 5-year-old ADARC had a record year, the publication of several papers in high impact in basic and clinical research of AIDS. Clinically, they have been at the forefront of studies that have shown that protease inhibitors, a new class of anti-HIV drugs can lead blood levels of HIV at undetectable levels for more than a year in many patients when used in combination with older drugs like AZT and 3TC. And Ho laboratory also conducted pathbreaking studies on how quickly HIV replicates, how long it takes medication to decimate the virus and how HIV uses receptors for immune system chemicals called chemokines to infect cells.

The Time package emphasizes that the strides AIDS researchers conducted in 1996 in the treatment of people infected with HIV can not fairly be credited to any scientist or institution - a Ho item readily admits . "Our achievements reflect not only the efforts of [ADARC], but also many other scientific and research institutions active in the HIV / AIDS movement," he said in a statement. In addition, as Ho and Time focus, AIDS has not been healed, and many crucial questions remain unanswered. For example, although the addition of proteases to the anti-HIV drug plans has clearly led to marked improvements in many AIDS patients, the magnitude - and especially the duration -. These benefits is still in the air

Despite warnings, some researchers fear that AIDS Ho will be seen to have played a more important role in the fight against AIDS that every person deserves. When asked his reaction to Time 'choice, Duke University researcher AIDS Dani Bolognesi - who says he appreciates the value of working Ho - is a little stunned. "Wow, is all I have to say, wow," says Bolognesi, adding he fears that singling Ho could further polarize a turbulent field. Just a few days before the award was announced, in fact, The Wall Street Journal published a front page article in which critics blamed Ho for what Journal called his "propensity for publicity"

However, as Time first Man 'of the year tribute to a scientist since 1960 -. when he presented 15 scientific a package of different disciplines of the renaissance of scientific discovery - some AIDS researchers undoubtedly will see the credit given to the way Ho time intended: as "an emblem of a key moment, chosen represent the best work of all scientists of AIDS. "

Researchers have isolated a new herpes virus strain from cells of Kaposi's sarcoma, the most common cancer in patients AIDS. The achievement, reported in tomorrow's issue of New England Journal of Medicine , may help researchers explore how the new virus spreads. Preliminary work with the virus already suggested that it plays a role in cancer development.

's sarcoma lesions are comprised of tumor cells, spindle-shaped in the wall of the tiny blood vessels. A team led by virologist Gary Nabel of the University of Michigan Medical Center in Ann Arbor pathologist Brian Nickoloff of Loyola University Medical Center has isolated the new virus from the cells in skin lesions taken from five HIV-positive people. Other groups have isolated unique herpes DNA fragments from injuries sarcoma, but this study is the first to grow live virus from tumor cells. When the group added the virus in embryonic kidney cells, the cells were infected with viral DNA to 20 cell generations.

The discovery is an important step in understanding the transmission of Kaposi's sarcoma, says Parkash Gill, professor of pathology and medicine who studies these tumors at the University of Southern California. It is still unclear whether the virus causes lesions, says Nabel, but the replication of the virus seems to imply in the origin of tumors.

The kidney epithelial cells are infected, Nabel said, may also help explain why Kaposi's sarcoma is common among gay men with AIDS. Indeed, epithelial cells line the rectum - a port of entry for the virus during anal sex - and embryonic kidney cells are closely related to those of the device and the urogenital bladder, which with genital secretions may harbor the virus, he said.

Get herpesvirus replication in the test tube is an important step towards the development of animal models of the new virus and antiviral drugs. Nabel said, "All these possibilities are now."

The dream of many planners of the family is a birth control pill for men, something that would somehow cut production sperm, but leave intact libido and beard. For years, researchers have focused follicle stimulating hormone (FSH) for this delicate task. This hormone ripen eggs in females and was long thought to do the same for sperm - without affecting levels of the male sex hormone testosterone. But now, a pair of papers to be published in this month's issue of Nature Genetics suggests a fatal flaw in any method of birth control that is based on the judgment of the single FSH :. Developing sperm do not need to become powerful

Martin Matzuk, an endocrinologist at Baylor College of Medicine in Houston, began investigating FSH for another reason: to investigate the role of the hormone in ovarian cancer. He and his colleagues created genetically modified mice that lack the gene for FSH. When they mated adult mice, females had no hormones to develop their eggs were infertile. But men - despite having smaller testicles and sperm count lower than normal mice - were clearly fertile and produced offspring. "It was a real surprise to people," said Matzuk. "The dogma was that FSH is needed to make sperm. That's what the textbooks say."

Matzuk results are stored in an accompanying document by a Finnish team of FSH study of mutations in humans. Juha Tapanainen University Hospital of Oulu in Oulu and colleagues at the University of Helsinki studied 15 infertile women brothers who had mutations in the gene encoding the receptor for FSH. Although men with FSH mutant gene products, support cells for sperm-producing cells in their testicles lacked the hormone receptors. Five of the men shared the symptoms of mice - small testicles and reduced sperm count -. But two of the five children had generated

FSH plays a role in making sperm stimulating the Sertoli cells that provide nutrients to growing sperm cells, said Matzuk. Without these helper cells, testicles are smaller and have fewer sperm. But Finnish researchers believe that testosterone itself can partially compensate for the lack, reversing any birth control pill designed to eliminate the FSH. "The moral is, you must come up with something to do a better job of removing the sperm count," says Bill Bremner, a reproductive endocrinologist at the University of Washington. With FSH and contraceptive in a single step for men out of the picture, researchers now need to focus on a more complicated hormonal balance between FSH, testosterone and other reproductive hormones.

For the first time, scientists have discovered a retrovirus that infects swine human cells. The discovery, published in next month's issue of Nature Medicine , raises new questions about whether people could contract diseases if exotic animal organs become regularly transplanted into human patients. It may also force US regulators to tighten their xenotransplantation guidelines.

Critics have long argued that the transplantation of animal tissue in even a small number of immunocompromised patients could allow obscure pathogens to jump from animals to humans. Now a team led by Robin Weiss of the Cancer Research Institute of London reports that the "PK" porcine endogenous retrovirus, which does not seem to affect pigs, can replicate in mink and human cells. In addition, after one round of viral replication, human cells lack a key sugar that flags as cells compromises the immune system to destroy.

Although there is no evidence that PK causes human disease, retroviruses are particularly worrying candidates to cross the species barrier, said virologist Jon Allen Foundation San Antonio Southwest for biomedical research . They thrive in body fluids and tend to be copied repeatedly into gene sequences reception, which can cause genetic havoc sometimes lead to cancer. "We had assumed that the pig tissues were safer than the baboon tissues, but now we see that they can infect human cells," says Allen. The study suggests, he said, "maybe we should reconsider what guidelines we have and what species we use."

The United States shall permit the limited xenotransplantation while the British government last month announced that human clinical trials will not continue until the procedures are shown to be safe (see science NOW, January 17). officials US health now "have reason to pause," says Allen. "I hope they take it." Other experts predict the US will consider stricter guidelines. "I would not be terribly shocked if something was adopted, nor do I think it wrong," said Fritz Bach, a xenotransplantation researcher at Harvard Medical School. "But it is certainly not the time to say forget xenotransplantation. "

uS officials have declined to speculate whether the results would lead to stricter guidelines." This emphasizes the need for caution again, adding some concrete data to help us quantify risks and benefits, "said Amy Patterson, Acting Director of the Division of Food and Drug Administration of cell and gene therapies. The FDA plans to develop new guidelines on xenotransplantation later this year.

scientists have discovered a gene, inactivation of which can help to take the brakes off the development of several major cancers, including those of the brain and prostate. The surprising finding, reported by a team in the issue tomorrow Science and a second in Nature Genetics , may help oncologists neighbor predict months could be at high risk for these cancers and also the brain or prostate tumors are highly malignant -. information that could help clinicians determine how aggressive they should be with surgery, chemotherapy or other treatments

The researchers began their hunt on chromosome 10, because they knew that this chromosome is partially or completely absent in a variety of cancers, particularly aggressive brain tumors called gliomas - a first indication of what he carries a tumor suppressor gene. To refine the location of the suspected gene, a team led by Ramon Parsons College of Columbia University of Physicians and Surgeons and Michael Wigler of Cold Spring Harbor Laboratory on Long Island compared equivalent sections of DNA from cells and normal cells from 65 breast cancers humans. They found that one genetic marker is absent in the two samples of breast cancer, as well as of certain tumor cell lines, prostate and brain. By comparing fragments of the target gene reported by the marker in a DNA database short pieces called expressed sequence tags, the researchers were able to reconstruct the entire gene. Their description of the gene, called PTEN (for phosphatase and tensin homologue deleted on chromosome 10 ), appears in Science .

The other group, led by cell biologist Peter Steck MD Anderson Cancer Center in Houston and Sean Tavtigian biotech firm Myriad Genetics in Salt Lake City, pursued the same gene in brain tumor cells . They called MMAC1 (for mutated in multiple advanced cancers 1 ), and issue a report Nature Genetics . "We started from two different places for two different reasons and we were in the same place at the same time," says Steck.

The new gene joined some 16 other tumors suppressors known. But while it is far from the first such gene discovered, cancer researchers are enthusiastic, because the early data indicate that PTEN could rank in importance with p53 and other tumor suppressors that have been linked to several types of tumors. "[ PTEN ] appears to be a major gene in some very important cancers," says Kenneth Kinzler, a molecular geneticist at Johns Hopkins University. In addition to prostate cancer, which affects approximately 317,000 men each year in the United States, and gliomas, still affecting 15,000 people, these might include breast and kidney cancer.

researchers still have much to do to find how much the loss of the gene could contribute to these cancers, although its sequence provides important clues. the PTEN protein appears to be a phosphatase enzyme that can counteract the work of kinases growth stimulators, which can help make cancer cells when they are mutated in a hyperactive form . Thus, PTEN "of the loss can lead to excessive cell growth. the loss of the gene could also help cancer cells invade other tissues, in which case the assessment PTEN "status could help predict the malignancy of a tumor. Steck said, "If you had a molecular marker that could help a clinician in this decision, it would be very important."

Some smokers may be more sensitive to damage from tobacco smoke DNA and thus more likely to develop lung cancer. Preliminary results of a population study, reported in the April 15 issue of Cancer , identify one of the many long-sought genetic factors that may increase susceptibility to the disease. If the results are confirmed, they could possibly lead to a blood test to screen for sensitive people with lung cancer.

Although 0% of all lung cancers are linked to tobacco smoke, only about 10% of smokers get cancer. To fathom why some smokers are sensitive and others are not, Xifeng Wu and Margaret Spitz at MD Anderson Cancer Center in Houston and colleagues studied alterations in chromosome 9. Other groups have observed that in cells tumor of lung cancer patients, chromosome often lacks a portion of its DNA or has acquired a piece of another chromosome -. a problem attributed to carcinogens DNA damaging agents in tobacco

Wu and Spitz studied the chromosomes of normal cells - in this case, the white blood cells - from 97 Mexican and African Americans newly diagnosed with lung cancer. The researchers asked participants about their lifestyles and family history of cancer, as part of a study on lung cancer risk factors among minorities. The group had 43 sections or other alterations in the missing chromosome 9. People with genetic damage were 8.5 times more likely to have parents suffering from lung cancer than those who had normal copies of chromosome 9. "It suggests that there could be some form of genetic instability" in the chromosome which can be inherited, said Spitz.

results suggest a potential "inherited genetic susceptibility" to smoke tobacco, says molecular biologist dawn Willis of the American cancer Society in Atlanta, which can put some smokers at increased risk of lung cancer. First, however, more rigorous studies are needed to confirm the hypothesis, warns Michael Kelley oncologist from the National Cancer Institute in Bethesda, Maryland. The number of subjects was small and was limited to minority populations; Therefore, he said, the results "may simply be due to chance."

Secretary Energy Federico Peña yesterday said it will terminate the contract with the department the operator of Brookhaven National Laboratory, Associated Universities Inc. . (UAI). During a visit to Upton, New York, laboratory, Peña AUI accused of mismanagement in the long term of the facility, which has been plagued by a host of environmental and safety issues during the last decade - more recently leakage of tritium of a reactor.

Peña's decision marked the first time the Department of Energy (DOE) has canceled a major contract due lab. "The combination of confusion and mismanagement that has been occurring here over the years will end," he said at a meeting of Brookhaven employees. "It is unacceptable, inexcusable, and flat-out wrong . " This is not how AUI Chairman Paul Martin, Dean of Harvard University's engineering school, sees. The decision to Peña, he said Science NOW, is "hasty and probably unwise."

Brookhaven, which has more than 3,000 employees and an annual budget of $ 400 million, is home to several major DOE facilities, including the top Flux Beam Reactor - one of the first neutron scattering centers the nation - and two major synchrotrons that are used for a multitude of materials, biology and medical research experiments. The reactor is now closed while technicians examine the source of the leak of tritium, which is shed in a plume in the ground water under laboratory grounds. DOE officials now believe there was a leak continues for more than a decade, but they say it does not threaten drinking water Long Island. This and other environmental problems have angered community activists, who complain that the Brookhaven managers have induced in error over the years. Peña acknowledged yesterday that the laboratory has lost public confidence, and he also criticized the DOE for not acting on the problems in Brookhaven.

The AUI contract will not be completed until a new contractor is selected, which will probably take six months, said Martha Krebs, head of the DOE energy research. Meanwhile, "we will work aggressively to put Brookhaven on a course towards a new culture," promises Lyle Schwartz, who is both president and AUI interim laboratory director. He declined to say whether UIA plans to bid for the new contract.

Years of intense research to develop treatments against the revolutionary cancer have largely failed to make a dent in the cancer death rate the United States, according to a new report. The study, published in tomorrow New England Journal of Medicine , shows that despite the war against cancer, cancer death rates were 6% higher in 1994 than in 1970. Progress Recent against the disease came largely from improved prevention and detection rather than treatment, the authors claim, and therefore, they call for a change of priorities in the nation's cancer research program .

The study, led by John C. Bailar III, an epidemiologist at the University of Chicago, and his colleague from Chicago, biostatistician Heather Gornik, analyzed the number of deaths from 1970 to 1994 of the National Cancer Center for Health Statistics. They determined the mortality rate adjusted for age for each type of cancer by year, race and sex. Mortality rates were adjusted to compensate for changes in the overall size of the population and changes in the age distribution during the 25 year study period.

As in previous studies, Bailar and Gornik found that overall rates of cancer death increased steadily until the early 190s, but decreased by 1% from 1991 to 1994. Last November, a team from the University of Alabama, Birmingham, reported a 3.1% decline from 190 to 1995. However, Bailar notes that the overall cancer mortality rate continues today to be higher than in 1970. the figures also revealed that the prevalence of certain types of cancer is changing. For example, the prevalence of melanoma and brain and prostate cancers increases, while stomach cancer is declining. Meanwhile, better methods of detection and prevention are the cause of a fall in the colon and rectum cancer mortality rates. At the same time, the authors note that some treatments have been remarkably successful. There have been marked improvements, for example, cancer survival rates, such as Hodgkin's disease, which tends to affect children and young adults. But because the number of these cancers is low, the overall effect is minimal.

The results point to the fact that "much of the research that went into the improvement of cancer treatments does not seem to bear fruit," said Clark Heath, an epidemiologist at the American Cancer Society in Atlanta. Bailar and Gornik therefore propose that more research funding is devoted to methods of prevention and detection, even, if necessary, to the detriment of seeking treatment. Currently, for every $ 5 spent on research of treatment, $ 1 goes to prevention, Bailar said. More money for research is needed to study topics such as cancer effects of food choices and carcinogenic effects of water and air pollution, Bailar said.

"We do not address the treatment of cancer," said Bailar. These treatments almost heal half of all cancer patients and "can do a lot for those who can not be cured," in under help them live longer and more comfortably. "But the 50% cure rate is not enough, because he failed to bring the mortality rate down by cancer, and provides a strong argument for a change orientation of research. "not all agree with this assessment, however." No one is satisfied with a mortality rate of 50%, "says Samuel Broder, former director of the National cancer Institute. But he adds that it would be a "grave mistake of being too pessimistic" about the future prospects for treatment.

Researchers have fingered a virus as the culprit behind a bone marrow tumor called multiple myeloma. Although viruses have been linked to other cancers, the modus operandi of it - sarcoma-associated herpesvirus sarcoma (KSHV) - is unusual: The virus appears to work behind the scenes as the puppet master cell, triggering tumor growth in neighboring countries cells. The discovery, published in tomorrow's issue Science * could guide researchers toward new therapies for multiple myeloma, which strikes 13,000 people each year in the US alone and usually kills its victims within 3 years.

KSHV is already suspected as the cause of Kaposi's sarcoma, a cancer that affects many AIDS patients. But unlike malignant cell sarcoma and other cancers assumed to be caused by viruses, multiple myeloma cells - derived from antibody producing plasma cells in the bone marrow - unnecessary appear to be directly infected. Instead, a research team led by James Berenson oncologists and Matthew Rettig of Veterans Affairs Medical Center West Los Angeles found evidence that KSHV is hiding in the adjacent dendritic cells, a subset of macrophages found in the microenvironment bone marrow.

In these cells, the virus seems to handle its own version of a human protein called interleukin-6 (IL-6) which is known to stimulate the growth of myeloma cells. This, the researchers suggest, is what propels the uncontrolled growth of myeloma tumors, or as Berenson describes, "The soil, the dendritic cell, is to put a lot of fertilizer, which makes the seed, the tumor cell, germinate. "This kind of remote control, said Yuan Chang, who studies KSHV at Columbia University in New York, is a" new mechanism "for the virally caused cancer." This is really exciting, if [the authors] are right. "

Drugs to block IL-6 could be a therapeutic avenue and Berenson also suggests that it might be possible to develop therapies that specifically target the virus-infected dendritic cells themselves. Attacking the virus with drugs or a vaccine could avert multiple myeloma full in about 1 million people who have been diagnosed with an apparent precursor condition called monoclonal gammopathy of undetermined significance. others who would benefit are AIDS patients , particularly gay men, who have a high risk of being infected with KSHV and get Kaposi's sarcoma.

* for details, Science online subscribers can create a link to the full report.

Athletes can live with muscle strains, but a torn ligament or tendon is a serious matter. Every year, surgeons in the US perform about 500,000 operations on tendons and ligaments, which usually recover slowly and incompletely. But faster, better healing may be on the way: A Report Journal of Clinical Investigation today describes proteins that, at least in rats, favor the growth of the connective tissue

results. the emergence of bone repair studies. For years, Vicki Rosen and colleagues at the Institute of Genetics Inc., in Cambridge, Massachusetts, have been experimenting with proteins that induce undifferentiated stem cells to divide and form new bone. They produced factors using recombinant DNA technology and implanted under the skin and in the rat muscle, where they cause new bone to form. Doctors have also successfully used these factors as an experimental treatment for severe bone fractures in over 1,000 human patients worldwide.

During their investigations on rats, Rosen's team was surprised to find that three proteins of the bone inducing growth and differentiation factors --called 5, 6 and 7 - growth of what appeared to be the connective tissue, not bone triggered. Under the electron microscope, for example, they found the induced tissue "showed a very orderly arrangement of collagen bundles," form fibers of the size of those found in tendons and ligaments. "These proteins may have a very large capacity to repair tendons and ligaments injured," says Rosen.

The work has impressed experts, including Marshall Urist at the University of California, Los Angeles, who discovered bone inducing factors there are more than 30 years If confirmed, these new factors of growth and differentiation could lead to great advances in orthopedic surgery, he said. "in the 21st century, surgeons can be used for the repair of tendons and ligaments. "

A protein that accumulates in the brains of patients with Alzheimer's disease may help to cause mass death of neurons by triggering a destructive inflammatory response, a study to be published in number tomorrow Nature suggests. The discovery could finally explain how one of the characteristics of the disease - the deposition of what is known as the amyloid precursor protein - helps with the symptoms. It could also explain the success of anti-inflammatory drugs to delay the onset and progression of Alzheimer's disease.

in the hope of learning what causes inflammation of the brain seen in Alzheimer's disease, Steven Barger, cellular neurobiologist at the University of Arkansas for Medical Sciences, Little Rock, has decided to test whether a secreted form of the amyloid precursor protein known as sAPP, could trigger the reaction. Barger and his student Ashley Harman sAPP added to cultured neurons and microglia - cells that help serve as the immune system of the brain. The enlarged microglia and began pumping the toxins in the framework of the inflammatory response.

After one day, 63% of the neurons died, compared to only 7% of the neurons in control. The researchers also found another link in the human Alzheimer's disease: When the sAPP has been pre-treated with apolipoprotein E3, microglia are activated. But apolipoprotein E4 - a variant associated with a higher risk of developing Alzheimer's disease -. Did not provide this protection

"The bottom line is quite clear," said Zaven Khachaturian, neurobiologist and director of the Alzheimer's Association Ronald and Nancy Reagan Research Institute "sAPP plays an important role in sickness. "But questions remain strong, he said." at what stage in the disease process is it in the image and where it enters the cascade of events do? "

William Paul, who oversees one of the largest budgets at the National Institutes of Health (NIH) as head of its Office of Research on the AIDS (SRO), aa decided to resign. "The time has come for me to give up the responsibilities of this position and return to the science lab as part of my commitment to the search for a vaccine against HIV safe and effective," wrote Paul in a "dear colleague "letter that will be widely distributed tomorrow.

Paul, who could not be reached for comment, did not specify the reasons for its abandonment of his position since February 1994, he did not give a timetable. but it is clearly not to be forced to leave. "Bill has done an excellent job and his departure is a real loss, but I am grateful to him for serving as long as it" , said NIH Director Harold Varmus, in response to a question from Science NOW.

When Paul took over SRO, Congress had redesigned the office, which gives it broad powers to oversee the entire NIH AIDS budget, which now stands at $ 1.5 billion. Under the mandate of Congress, Paul launched an ambitious revision of the gigantic program, which was conducted by more than 100 extramural research conducted by Arnold Levine of Princeton University. The gigantic "Levine Report," which was released in July 1996, "provides a restructuring plan NIH AIDS science program", as Paul noted in his letter to his colleagues.

Paul, a prominent immunologist, also tried to bring more attention and money for vaccine research against AIDS. One of his ideas, a center for research on vaccines intramural NIH, won so much support that President Bill Clinton has announced its formation in a speech last May.

Varmus said NIH now is to set up a "high profile" search committee "will advertise widely, hoping to find someone with talent approaching Bill to continue his good work . " Varmus added that he hopes to find a new director within 6 months, so that the person will be ready to testify at Congressional hearings appropriations next year. No candidate for the post is still on the radar screen.

A brand of fatal cancer is its ability to spread like a windblown fire to other parts of the body. Today, scientists have identified an enzyme that can link the ability of a tumor to spread with an abnormality in the integrated self-destruct mechanism in all cells. The discovery, reported in Nature tomorrow , may help scientists better understand how aggressive the cancer cells reproduce more tumors.

Normal cells divide enough to replace others that have aged. But when a decrepit cell ignores commands the body to self-destruction, it can continue to divide, eventually forming a tumor. But for tumor cells to spread - a process called metastasis - they need more specific skills. After leaving the main tumor, cells must evade the body's defenses and penetrate tissues. Scientists have investigated the genes and proteins that provide cells with these deadly talents; Recently, they began to find evidence that certain enzymes involved in programmed cell death, or apoptosis, can also allow cancer cells to strike on their own.

Now Adi Kimchi molecular geneticist at the Weizmann Institute of Science in Rehovot, Israel, and colleagues identified an enzyme called DAP-kinase, which seems to strengthen this link. When DAP kinase is missing, the cells ignore the molecular signals that control the cells to kill themselves. To better understand how the enzyme is involved in tumor development, Kimchi and his colleagues searched various types of cell lines from mouse lung cancer. They noticed a fascinating pattern: the enzyme is absent in aggressive, spreads rapidly cell lines, and present in the tamer ones. When the team inserted the DAP kinase gene in aggressive cancer cells and injected into healthy mice, the cancer does not spread as easily as it did in mice with cancer cells without enzymes.

The connection makes sense, Kimchi said, since a break of cancer cell ignores a variety of immune signals that should trigger his death. His team is now screening patients for tumor samples with several types of cancer - including breast cancer and leukemia - to see if the enzyme is missing. The discovery, she said, could eventually lead to gene therapy for particularly pernicious cancers. DAP-kinase, is a researcher Eric Stanbridge agreement on the cancer of the University of California, Irvine, perhaps "still a target for testing" for possible gene therapies.

Fractals - objects whose parts resemble the whole - were used to describe all the meandering coastline in the distribution of distant galaxies. Now there may be a very human application - as a tool for the diagnosis of malignant breast cancer. The technique, which appears in January 12 number of Physical Review Letters , gauges the extent of entanglement in the DNA of a cell.

Breast cancer diagnosis often begins with mammography, followed by a biopsy. In a common type of biopsy, a thin needle is used to aspirate some suspicious tissue cells. Although extremely difficult, a trained doctor can eyeball cancer cells in the laboratory, in part because the chromatin - the twisted mass of proteins and DNA that make up chromosomes - appears agglomerated in malignant cells than in benign. To the naked eye, according to a biopsy expert Shahla Masood, a pathologist at the University of Florida, Gainesville, breast cancer diagnosis from a few cells "is like looking through a keyhole and try to see the whole room. "

Indeed, it is often an anguished appeal with only a few cells, said Andrew Einstein, a team member at Mount Sinai School of Medicine in New York. "An upscale cytologist should be diagnosed correctly most of the time," he said.. But with less qualified doctors behind the microscope, cancer cells are sometimes falsely considered healthy

In hope to develop an easier and more reliable approach, Einstein and two colleagues evaluated a variety of mathematical techniques to measure lacunarity - or the size of the spaces between the regions of chromatin - cells, and to extract a "fractal dimension" the core. as a branch usually looks like a whole tree, chromatin close-ups look like larger pictures a large scale. the scale of this "self-similarity" is called fractal dimension.

The team tested the technique on high resolution cell nuclei images from 41 patients, 22 were known to have breast cancer. After scanning images, a computer measured the fractal dimension and lacunarity and made the correct diagnosis in 39 of 41 cases - a success rate that rivals that of the best doctors. Malignant cells tend to have lower fractal dimensions, or less self-similarity, which Einstein said supports the idea that cancer is associated with a "loss of complexity" in a cell structure.

"I really do not understand the math," concedes Alberto Marchevsky, a pathologist at Cedars-Sinai Medical Center, Los Angeles, "but it could be a very useful technique. "Masood agreed, but said more tests are needed before the diagnosis of the computer can be used clinically. Einstein said that these trials are underway and that an improved technique using neural networks is to the horizon.

A new gene therapy technique that seems to exploit own genetics of a cell repair mechanism to rewrite its DNA sequence showed remarkable success in rats. The results, in this month of Nature Medicine , could have a major impact on efforts to cure hemophilia and other incurable genetic diseases.

For over a decade researchers have been trying to find a way to efficiently insert the DNA into the punishment cells. Clifford Steer and his team at the University of Minnesota Medical School in Minneapolis used a technique that mouthwatering results showed previously: so-called chimeric molecules, loops that contain both DNA and of RNA. Genes are made of DNA and cells use RNA - a molecule closely related - to translate the genes into proteins. A chimeric molecule is designed to match the target gene nucleotide for nucleotide bases except to researchers want to change -. In hemophilia, for example, single nucleotide must correct

Although no one really knows how to rewrite chimeric DNA sequences, the researchers suspected that when the chimera binds to the region of corresponding DNA in a cell, the cell's DNA repair mechanism detects the mismatch and - as an overlay key on a typewriter - removes the mutant base in its own DNA and the correct inserts. The RNA in the chimeric resistant enzymes that break down the foreign DNA into the cell and allows the binding molecule to the target gene closely

Although previous efforts to use chimeras were only carried out with cells in culture -. With mixed success with -the new study is the first to test the animals approach. Steer and colleagues injected their molecule, covered with a polymer which has the chimera into the liver cells in the tail veins of rats. In this case, the chimeras were designed not to cure a disease but to induce mutation that causes hemophilia in persons, which occurs when the liver cells can not make a protein essential for blood clotting. Indeed, the blood of treated rats did not coagulate as easily as those that were injected with saline. When researchers inspected the livers of the animals, they found that 40% of the cells were induced mutation. Changing the same DNA in 5% of liver cells would be enough to heal a haemophiliac patient, Steer said. The next step, he said, will be to try the technique in reverse, this time to cure the mutation hemophilia in dogs.

One expert called the experiment a success "incredible". Michael Strauss gene therapy researcher of the Humboldt University in Berlin warns that liver cells may be particularly amenable treatment. However, "if the technique can be reproduced by others in other cell systems and other target genes," he said, "we would have a method that could theoretically provide a cure for genetic diseases."

As the belt in your old favorite pajamas, overworked hearts often lose their elasticity and ability to effectively pump blood - a condition called congestive heart failure. Tired hearts are prone to arrhythmias that cause sudden death. Now, researchers reporting in tomorrow's issue of the Journal Cell found a domestic signaling causing a closely related form of heart failure in mice. The discovery could lead to new drugs to maintain the stressed hearts of sagging.

Hearts attempt to compensate for the abnormal stress on their walls by increasingly large. This works for a while, but eventually the muscle cells get long and thin, and they fail as elastic stretched. fibrous deposits also form and can cause strokes and arrhythmic death. Scientists have long suspected that calcium in heart cells could play a role in this tragic transformation. Then Eric Olson, a biologist at the University of Texas Southwestern Medical Center in Dallas and colleagues were excited when they found a protein called calcium regulating NF-AT3 which seemed to also turn on genes that caused the widening heart.

To see if NF-AT3 could cause heart failure by itself, the researchers created mice that have an enzyme that has kept active NF-AT3 way, whatever the level of calcium . To the surprise of satisfaction group, mice "recapitulate all physiological and pathological aspects of human heart failure," said Olson, including the fibrous growth, arrhythmia, and sudden death.

The researchers warn that there may be other mechanisms that cause hearts to grow and fail in humans, but many are optimistic the finding may lead to new drug treatments. Indeed, the Olsen group gave the even mutant mice immunosuppressive drug (cyclosporine) to block NF-AT3 activity and found that it kept them healthy. Because the way seems specific to the heart, it could also be used to develop drugs for the heart with few side effects, said Stanford University Medical Center researcher Jerry Crabtree. "I would be very surprised if a pharmaceutical company did not jump immediately on this issue."

Women carrying two copies of a variant of p53 gene are seven times more likely to develop cervical cancer uterine patients with one copy. The discovery, published in today's issue of Nature , helps explain the link between the disease and the human papilloma virus (HPV), a common infection of the genital tract in women.

"The importance of this study is that it suggests another risk factor" for cervical cancer, said Kathleen Cho, a gynecological pathologist at the Johns Hopkins University School of Medicine. " this makes sense in the context of what we understand how HPV contributes to cervical cancer. "Cho said the findings could lead to the development of a genetic test that would identify those at high risk of cervical cancer.

cervical cancer kills more women worldwide than any cancer except breast cancer. for over 20 years, researchers have known that millions of women whose number genital tract is infected by certain types of HPV, a few thousand will develop cervical cancer. HPVs produce proteins that inactivate the cellular tumor suppressor proteins. one of these HPV proteins, called E6 inactivate p53 protein, which is as an emergency brake to stop cells that have suffered genetic damage in the division.

In the late 1980s, researchers discovered that the p53 gene that had two different alleles. We used the amino acid arginine, while the other proline used. A team led by Alan Storey of the Imperial Cancer Research Fund in London wondered if the appearance of these forms could affect the susceptibility of an individual to cancer of the cervix.

In test tube experiments, the researchers studied the effect of the HPV E6 protein of the 18 human cells that express the type of p53 protein. They found that although HPV-18 p53 arginine destroyed, it left intact p53 proline. The researchers then compared the frequency of the two alleles in the tumor cells and control and found that a person carries two copies of the form of arginine p53 gene is seven times more susceptible to induced cancer HPV-than those that are not.

Scientists have obtained severed the spinal cord of a rat to push after injection with certain immune cells. The findings, reported in the July Nature Medicine have raised hopes that the technique could help repair the brain and spinal cord trauma in people as well.

In mammals, peripheral nerves can often be repaired, but damage to the brain and spinal cord is usually permanent time. Many researchers have tried to coax these vital tissue healing themselves by treating them with growth factors or nerve helper cells that are thought to secrete restorative chemicals. These techniques have worked in rats, but has not been successfully transferred to humans

Michal Schwartz and colleagues at the Weizmann Institute of Science in Rehovot, Israel, decided to continue the seemed to be an index for the regeneration .: neurons that can repair themselves attract immune cells called macrophages to the site of injury, while nonrepairing cells suffer in silence. Following this observation, the group of Schwartz broke the spinal cords of 22 rats, which paralyzed their hind legs and then injected macrophages in the area surrounding the wound. The researchers monitored the recovery of rats over the next 19 weeks by recording their ability to move their hind legs. The rats not receiving macrophages taken only the slightest tremor in their legs, while most type of macrophage treated rats could move their legs in a sweeping motion and sometimes use them to support some of their weight. "It's a partial recovery but very spectacular," says Schwartz. His team also found that new nerve fibers had increased across the wound area.

"It is a very provocative finding," said Dalton Dietrich, a neuroscientist at the University of Miami School of Medicine in Florida. He noted that scientists thought that macrophages to the wound site may help damaged tissues, as they contribute to inflammation. "But this suggests that macrophages may be releasing substances that promote regeneration," he said. He warned that many other potential treatments for spinal cord showed the same promise at first, but failed to pan in other animal tests.

P ARIS - An international team of AIDS researchers has identified what appears to be a new separate strain HIV-1, AIDS virus, which is sufficiently different from the known strains that can escape the current blood tests. This new strain, isolated from a Cameroonian woman who died of AIDS in 1995, appears to be rare and localized, but experts are urging that tests be modified to pick it up.

The new strain, described in the September issue of Nature Medicine , came to light in a study in Cameroon, led by virologist Simon Francis Hospital Bichat Paris. Testing the blood of an AIDS patient was detected no virus belonging to the two known groups of HIV-1 - called groups ( "outliers") M (the "majority") and O. But a test for a strain of SIV - the simian version of HIV. - isolated earlier from a chimpanzee in neighboring Gabon was positive When the researchers isolated the patient's virus and sequenced its genetic code, they concluded that it a third HIV-1 previously unknown group, which they called the group N.

the new strain, designated YBF30 is genetically closer to chimpanzee SIV that other strains of HIV-1 , suggesting that its evolutionary ancestors could have been transmitted from chimps to humans. the monkeys and other primates are believed to be the source of other HIV strains. Simon Wain-Hobson, an AIDS researcher at the Pasteur Institute paris, warns, however, that because some sequences of chimpanzee SIV are available for comparison, "it is too close to call."

for the moment, does not seem s YBF30 be propagated further: Only three of the 700 blood samples from HIV-1 infected patients living in Cameroon have tested positive for the strain. Wain-Hobson notes, however, that "probably exploded because M group entered urban and got there early. If you introduce viruses N group in New York, you will get an epidemic "For this reason, the authors of the paper recommend that HIV tests be modified to pick up the new strain Said François Simon.". A continuous search for new variants is necessary to ensure the safety of blood donation ... these viruses are waiting, waiting for favorable conditions. "

Scientists have sequenced the entire genome of Chlamydia trachomatis , the enigmatic bacterium that is the leading cause of venereal disease in the US . The work, described in Science tomorrow offers surprising insights into the bug that could lead to better treatments and vaccines perhaps.

Nearly 4 million new cases of Chlamydia are reported each year in the US, says lead author Richard Stephens, a microbial geneticist at the University of California, Berkeley. It can cause pelvic inflammatory disease, ectopic pregnancy and infertility if untreated. In Africa and Asia, where the bacteria is spread by contact hand-eye in children rather than sexual intimacy, it is a major cause of blindness. But efforts to create a vaccine were frustrated by the refusal of the parasite to survive in a petri dish.

Stephens team took 18 months to sequence 1,042,519 base pairs of the bacteria. Surprises include the discovery of about 20 eukaryotic genes; other bacteria that have been sequenced have been few, if any, of such genes. "This paints a picture of an intimate and long evolution with eukaryotic cells," says Stephens The conclusion goes to the question of how it has evolved its parasitic lifestyle Many of these eukaryotic genes resemble plant genes -.. Hinting that Chlamydia microorganisms to plants "of his ancestors may first parasitized. Also intriguing is that Chlamydia can make ATP, the basic fuel for any cell. "We always thought that the reason Chlamydia could live in a eukaryotic host was that the ATP had," says Stephens.

the new genome map "will facilitate and stimulate much more research on Chlamydia " predicts Thomas Hatch, a microbiologist at the University of Tennessee medical school in Memphis. the genetic code also holds clues Chlamydia surface proteins, which Stephens said would give researchers new targets for vaccines, diagnostic tests and medications.

Weighing in on one of the biggest controversies of the health of the decade, a scientific committee appointed by the court concluded this week that, on the basis of available evidence, silicone breast implants do not appear to elicit immune diseases such as lupus.

judge Sam Pointer J. of the US District Court in Alabama, the panel appointed in October 1996 to examine the scientific evidence in lawsuits by women claiming their implants caused debilitating symptoms ranging from fatigue for painful joints. Pointer asked panelists - a toxicologist, an immunologist, an epidemiologist and rheumatologist - to examine whether the expert testimony of applicants "provide [s] reliable and reasonable scientific basis" to conclude that silicone breast implants " cause or aggravate "systemic diseases such as lupus or connective tissue disease, which could explain the reported symptoms. The Committee also reviewed the evidence for "atypical" disease of the connective tissue and immune, the report, which was released on November 30th.

After reviewing 40 studies in their fields and hearing scientists witnesses, experts have concluded that they could find no link between implants and disease. For example, the toxicology report's summary states that "the preponderance of data ... indicate ... that the implants do not alter the incidence or severity of the autoimmune disease." And the data analysis grouped many epidemiological studies found "no association" between implants and connective or immune diseases, the report said.

"We are happy," said Doug Schoettinger, managing trial counsel for Dow Corning, an implant manufacturer. "I think this will help to end this controversy." But everyone does not read the report in this way. "Nowhere where they say breast implants are safe" said Robert Garry, an immunologist at Tulane University in New Orleans who studies women with breast implants. "They have found flaws in almost all science," he said. "They keep the fairly wide open for further research."

Dow Corning, which is in bankruptcy, has proposed a regulation his pursuit of $ 3.2 billion there 3 weeks, although applicants may still choose to go to trial. the panel report "will certainly have an impact" on those and thousands of other pending cases said Professor Margaret Berger Brooklyn Law School. First, however, the judge will ask the panel, and it could end up including the evidence in its decision; Lower court judges then decide to follow the decision in their own cases. "It will take some time to see what the effects are," says Berger.

A detailed analysis of the experience of the first year with the law on assisted suicide Oregon doctor suggests that the worst fears some opponents of the law was not supported outside. the terminally ill patients who choose to end their lives under the law were more concerned about losing their autonomy as suffering unbearable pain or financially ruin their families, according to the analysis, which was published in this week New England Journal of Medicine .

In October 1997, Oregon became the first and only US state to legalize physician-assisted suicide for terminally ill people. At the time, critics have warned the so-called "Death with Dignity Act" would cause a disproportionate number of poor people or patients with fear of extreme pain to commit suicide, while those who could afford good care or had less fear would stay alive longer. To minimize these risks, a number of safeguards were built into law: The patient, not the doctor had administered the fatal dose; two doctors to agree to prescribe the lethal dose of barbiturates; the patient had to ask three times the requirement of 15 days; and the patient should be informed of the hospice and other care options.

One year after the law took effect, epidemiologist Gene Chin and colleagues at the Health Division of the Oregon (agency of the State Public Health) from 15 people who took lethal doses with 43 deaths similar terminal illnesses, to find out why some people choose to end their life and others do not. Detailed questionnaires completed by physicians of patients revealed that both groups were similar in many respects; people who opted for suicide are less educated disproportionately underinsured, on Medicaid, or fear of pain, said Chin. But suicide group had worried addition to being bedridden and incontinent: 80% of them, against 40% of control patients were told their doctors they feared losing control over their lives. "What has been driving this was a strong need for autonomy," says Chin.

But some experts disagree. "This conclusion is not justified by the data," says psychiatrist Herbert Hendin, medical director of the American Foundation for suicide prevention, which maintains that the information provided by doctors could be misleading because patients may not reveal their true motivation. But the pathologist Cyril Wecht of Pittsburgh Duquesne University calls the study "valid and credible." "It highlights several misconceptions," he said.

W ASHINGTON , DC - Marijuana today received the imprimatur of the most August body science of the United States: the drug and its active ingredients can relieve pain, nausea and vomiting associated with chemotherapy and anorexia of AIDS wasting syndrome, according to a report by the Institute of the National Academy of science of Medicine (IOM). The report, released at a news conference here today, also calls for more clinical trials of marijuana and efforts to develop new synthetic drugs that mimic the active ingredients of the pot. For now, the smoke of marijuana for medical use is recommended only in rare circumstances, such as for terminal patients.

Since 1996, voters in seven states have approved ballot initiatives that allow the medical use of marijuana. In response to the often heated debate, the White House Office of National Drug Control Policy there about 2 years commissioned IOM to review the scientific literature on the health effects of marijuana and medical benefits potential. According to Stanley Watson, co-director of the Mental Health Research Institute at the University of Michigan, Ann Arbor, and an author of the report, the panel found no evidence that medical marijuana use leads the abuse of other illicit drugs. Beyond the damage due to smoking, marijuana has no worse side effects than any other approved drug, the panel found. Because the majority of evidence suggests that marijuana is effective in relieving pain, stimulating appetite, and elimination of nausea and vomiting, the report recommends that Watson called "compassionate use of marijuana."

This verdict pleases many patient advocacy groups. "This report clearly shows that there is scientific evidence for medical benefits in good faith for some patients," said Chuck Thomas, spokesman for the Marijuana Policy Project. But others criticize the report to limit recommendations for cases serious and not to recommend ways for patients to take the drug without smoking. "There are ways around smoking marijuana, but the report makes no mention of them," says psychiatrist Lester Grinspoon of Harvard Medical School in Boston, who was one of 13 external experts review the report before the end. for example, delivery into the lungs rapidly acting, Grinspoon said vaporizers already exist that selectively extract vapors cannabinoids without burning the plant material. Adds Thomas "many patients eat ;. marijuana is no more dangerous than eating Valium"

Armed with a bacterial enzyme, tobacco can break down toxic explosive that contaminate the reasons many munitions factories, the scientists report in the issue May of Nature Biotechnology . If the plant is successful in field tests, experts say that the variants can be sicced solvents and other organic pollutants.

According to the Agency for the protection of the US Environmental has 22 Superfund Sites laced with explosive waste, such as nitroglycerin or TNT. soil patches it contains enough TNT to explode when exposed to flame or struck by an earthquake. The most common contaminant, TNT is a more insidious threat to humans and wildlife, too: It can cause liver damage and cancer. The current approach for cleanup crews is to dig and incinerate contaminated soil.

few years, a team led by biotechnologist Neil Bruce of Cambridge University in the UK has come through the fabric of a technical soft. While sifting through the toxic soil, the researchers encountered a bacterium Enterobacter cloacae , which develops on toxic substances. The team isolated the enzyme responsible and found that it could degrade a variety of explosives, not only TNT.

Because it is difficult to control the bacteria spread on land, the researchers transferred the TNT-cracking enzyme in tobacco plants. Seeds, they found, germinated in a growth medium supplemented with TNT or nitroglycerin, an environment that kills normal seeds. The modified seeds survived by absorbing toxic substances and break down into non-toxic substances. Bruce said this is a breakthrough, like other types of waste cleaning plants "were simply the accumulation of toxic substances."

In the young field of the use of plants to clean up toxic substances, the latest work is "the most revolutionary thing so far," said Brian Hooker, a biochemical engineer at the Pacific Northwest National Laboratory in Richland, Washington. The technique to use plants with bacterial enzymes is not limited to the removal of explosives, Hooker notes. "It can be extended to anything for which a track enzymatic degradation is known."

When the Food and Drug Administration of the United States approved the anti-inflammatory drugs Celebrex and Vioxx earlier this year, it marked the beginning a new era of custom Engineered analgesics that target a specific enzyme. But the results in rats, described in Nature Medicine this month , suggest the authors of the study that new drugs can delay the healing of chronic tissue damage in people. A scientist with Searle, which makes Celebrex, disagree, arguing that the enzyme inhibitors are a safe and effective treatment for chronic inflammatory conditions such as rheumatoid arthritis.

reddish and painful swelling around burns, infected wounds, and chronic irritation are signs that the immune system is trying to limit the damage and stimulate healing. Aspirin and related drugs exert their soothing effects by blocking cyclooxygenase-1 (COX-1) and COX-2, a pair of related enzymes which catalyze the production of inflammatory prostaglandins molecules. COX-1 is thought to help supply prostaglandins that maintain the lining of the stomach and salt balance in the kidney; COX-2 is activated only during injury and infection. To avoid side effects of aspirin, such as irritation and ulcers of the stomach, drug developers in recent years, designed compounds which block the COX-2 alone. But sporadic studies, mostly in animals have suggested that this tactic may delay the healing of ulcers.

Paul Colville-Nash, a researcher of inflammation in St. Bartholomew's Hospital in London, and his colleagues wanted to know whether the COX -2 levels decrease as the inflammation decreases. The team induced inflammation in the lining of the lungs of rats, then gave the animals is two COX-2 inhibitors - NS-398, a compound that only inhibits COX-2, or indomethacin, which blocks both cyclooxygenase - or an injection of saline. Researchers measured the severity of inflammation and the levels of COX-2 and prostaglandins that inflammation subsided.

After a start, well known COX-2 boost, the team found a second peak, even more important as COX-2 levels decreased inflammation. In addition, the team noticed a simultaneous increase in a different set of prostaglandins, called PGD ₂ and PGJ ₂ , which appear to play a role in suppressing inflammation. When they blocked the activity of COX-2 2 days after the rat lung irritant, inflammation persists; then, inflammation had cleared in control animals. "This suggests that COX-2 also contributes to the determination inflammation of the body," says Colville-Nash.

Experts differ on what the results might mean for the use of COX-2 to treat people. in rheumatoid arthritis, for example, episodes of acute inflammation are broken by periods of remission, during which COX-2 inhibitors could do more harm than good, says Colville-Nash. James Lefkowith, immunologist at Searle in Skokie, Illinois, disagrees. "There is no evidence in humans that COX-2 inhibition has a detrimental role in rheumatoid arthritis," he said. But the study is "clearly interesting," said Lefkowith because it alludes to a possible role in the inflammation of the enigmatic PGD ₂ and PGJ ₂ .

Merck & Co., a pharmaceutical plant that has abandoned the field of vaccine against HIV in the early 190s, is aggressively re-entering the arena. The company intends to launch two different vaccine testing before the end of the year, Science NOW has learned.

In 1980, Merck had a vaccine program against AIDS High profile Repligen, a Cambridge, Massachusetts biotechnology company. The project aimed to make a vaccine that stimulates the production of antibodies to HIV, preventing the virus from entering cells. But the strategy was ungrateful, and the effort died in 1994. Now, Merck is focusing on the other arm of the immune system: cell-mediated immunity, which rids the body of cells that the virus has already successfully infect

Emilio Emini, a virologist who heads the Merck vaccine program, is sketchy on the plans, but says the company puts a lot of effort in the development of a vaccine against the so-called DNA. In this approach, the HIV genes stitched into a segment of DNA called a plasmid, which can infect cells and produce viral proteins. Merck is also developing a live virus vector, but defective Emini who refuses to discuss publicly. "One of the reasons we have kept a low profile is that we do not want to raise expectations," he said. "The probability of failure is quite high." Then again, he said, Merck puts a lot of resources in the project. "It is a great program for us." In its preliminary, Phase I vaccine trials, the company plans to rely on his own clinical trial system rather than on the vast network of test vaccine against AIDS run by the National Institute of Allergy and Infectious diseases.

HIV vaccine researchers are much encouraged by the news of Merck's interest, some large pharmaceutical companies have shown interest in the continuation of this scientific challenge. "The more [players] we can get with good ideas, plus all the benefits on the ground," said Donald Burke, who heads clinical trials of HIV vaccines at Johns Hopkins. "The momentum is in less optimal time."

T OKAIMURA , J APAN - As life returns to here normal this week after the worst nuclear accident ever in the country, sanded worker with the highest radiation dose is prepared for an experimental therapy that may be his best chance to survive the accident. It is expected to receive a transfusion of blood stem cells from his brother Wednesday.

The September 30th incident in a nuclear fuel processing facility 110 kilometers northeast of Tokyo started when workers accidentally set off a nuclear chain reaction. They overloaded settling pond with 16 kilograms of uranium, seven times the amount approved for the procedure. That was enough to trigger a chain reaction runaway, that plant workers were finally able to end 18 hours later. The first reports of an explosion that released radioactive materials were false, officials said, and the radiation levels quickly returned to normal once the reaction has ceased.

Three workers were hospitalized and more than 60 others, including three rescue workers and seven golfers on a nearby course, were found to have been exposed to high levels of radiation. The sicker workers, Hisashi Ouchi, 35, was exposed to about 17 sievert of radiation, according to Science and the National Institute of Technology Agency of Radiological Sciences in Chiba, near Tokyo. Normal background radiation produced a dose of about 2-4 mSv per year, and doses above 5 Sieverts have generally been fatal.

Radiation destroyed lymphatic cells of Ouchi white cells to the immune system of the body. Ouchi is scheduled to receive blood stem cells donated by his brother, in a first procedure for victims of radiation. Hisamaru Hirai, a specialist in cell transplantation at the University of Tokyo Hospital, where the procedure will take place, said stem cell transplantation promises to restore the ability Ouchi generation blood faster than transplants bone marrow. The treatment was used as a nonsurgical alternative to bone marrow transplants for those undergoing cancer treatment. The donor receives a growth factor for several days before the procedure to increase the number of stem cells in the blood. Hirai said the second victim in hospital, which received 10 Sieverts of radiation, received a transfusion of blood stem cells from umbilical cord of a newborn because of the lack of a suitable donor.

Researchers have a new clue to what causes multiple sclerosis (MS), a disease in which the immune system destroys the protective sheath around nerve cells. A study in the January Nature Medicine suggests that in MS, immune cells never learn properly to avoid a certain protein in the duct. The results can help to pave the way for better treatment strategy.

In MS, which affects about 1 million people worldwide, the immune system eats away the fatty myelin that insulates nerves and helps in the transmission of the signal. The victims cope with episodes of muscle weakness and numbness; in severe cases, MS can lead to paralysis and death

Most of the time the immune system learns to distinguish between "self" proteins and "non-self" :. T cells, for example, going to school in the thymus, where they own baited with body proteins. These T cells that attack are eliminated. Flaws in this educational program could be a means by which autoimmune disorders such as MS might arise, thought immunologists Ludger Klein and Bruno Kyewski the German Research on Cancer in Heidelberg. For example, if there is not enough of a particular protein in the thymus, T cells that are prone to attack it would not be eliminated. To test this hypothesis, the researchers examined the activity of the gene for a protein called PLP - a major component of myelin and one of the main targets of renegade T cells in MS - in the thymus of two different strains of mice, one sensitive and one resistant to a disease similar to MS. They found that the two strains had roughly the same amounts of PLP in their thymus -. Although the version in the thymus was slightly shorter than that produced in the central nervous system (CNS)

When the team took a closer look the parts of the protein that T cells locked on during their attack, they were a surprise: in the MS-resistant strain, the top four all target regions was in the short version of the PLP present in the thymus, but in susceptible mice, a target region fell into short away section in the thymus, but present in the CNS. Like mice, humans are only the shorter version of PLP in the thymus.

To exploit this in therapy for MS, "should restore tolerance against [protein snippets], which are not expressed in the thymus" early in the course of the disease, said Stanford immunologist Lawrence Steinman. If the first results in animal work in humans as well, he added, it might one day be possible to give MS T cells with some remedial training by injecting fragments of artificial proteins.

The Elizabeth Glaser Pediatric AIDS Foundation, which supports research on HIV infection in children, expands its scope considerably. At a Los Angeles press conference today, Paul Glaser, president of the board of the foundation, announced the creation of the Glaser Pediatric Research Network, which hopes to accelerate the testing and development of drugs to treat children with a variety of other serious diseases, including. cancer, asthma and psychiatric diseases

new network address "a problem that has existed for many years," said Philip Pizzo, pediatrics chief at the hospital affiliated with Harvard Boston children: Up to 80% of medicines used on children and infants has not been specifically tested on young people, and there is little information on side effects, appropriate doses or formulations suitable for children . Treating children is not just a matter of smaller doses, says pediatrician Harvey Cohen of the Packard children's Hospital at Stanford, in California, for example, a drug against leukemia that was safe for adults has been found to endanger the heart the development of a child.

Until modernization Act, the Food and drug Administration took effect this year, there was no need drugs to be tested on children, said Pizzo. Now the law requires limited trials to establish the safety, dose, and tolerance. The network, whose research priorities will be determined by a scientific advisory group not yet unnamed, will facilitate and coordinate these tests. It includes institutions of Pizzo and Cohen and the affiliated children's hospitals at the University of California, Los Angeles; Baylor College of Medicine, Houston; and the University of California, San Francisco. The Glaser Foundation is priming the pump with $ 8 million for the first 2 years -. $ 5 million for clinical studies, the rest for clinical fellowships and health policy for the defense of children's rights

The Glaser Pediatric AIDS Foundation was founded in 1988 by Elizabeth Glaser - the wife of actor Paul Glaser - who, having contracted AIDS during a blood transfusion, unknowingly passed the virus to his two small children. Before his death in 1994, Elizabeth Glaser was already thinking about how to expand the scope of the effort. Since its inception, the foundation has raised over $ 85 million.