Health Meaning

Eleven prominent AIDS researchers, primatologists and animal advocates urge vaccine developers not to inject chimpanzees with stem HIV that can cause diseases like AIDS in animals. In a letter published in Science tomorrow , they raise ethical and scientific objections to these experiences.

Until recently, chimpanzees have been considered poor models for testing vaccines, because HIV does not replicate well in animals or seem to make them sick. But that changed when researchers at the Yerkes Primate Research University Regional Centre Emory in Atlanta, Georgia, found a strain of HIV that causes a sharp decline in CD4 cells of animals and an increase of virus in their blood. In a study published in the June 19, 1998 Science , Norman Letvin Medical Center Beth Israel Deaconess Harvard in Boston noted that the strain might be useful for candidates Test vaccines, and many researchers on the AIDS agreed.

But not virologist Alfred Prince Of Blood Center of New York, who runs a chimpanzee colony in Liberia, and his colleague Linda Andrus. "The prospect of causing a rapidly progressive and fatal disease in this near-human species is abhorrent," they wrote in a letter to 18 December 1998 Science . A more acceptable to test vaccine candidates, they say, is whether it can prevent a virus to establish a chronic infection; where applicable, the disease does not occur. And several non-virulent strains seem to reproduce fairly well in chimpanzees to provide a realistic challenge, they wrote

In the new letter, Prince, Andrus, and nine others, including defender chimpanzees Jane Goodall, raise new objection .: the virulent strain of HIV may be too "hot". It destroys the immune system of a chimpanzee in a few weeks, while in men the same process generally takes years. This could "seriously compromise the vaccine effort against HIV" excluding vaccines do not protect against this strain, but but could be effective against wild-type HIV, they write.

But Patricia Fultz from the University of Alabama at Birmingham does not believe that the Emory HIV strains are too hot, noting that the infected animals have lived up to 4 years. and Letvin said that focusing only on the ability of a vaccine to ward off chronic infection rather than its effect on the disease process, may lead researchers to overlook a useful vaccine: "If we have a vaccine that can make people live decades longer, we need to know ".

A sometimes fatal heart enlargement can be inherited or acquired through infection. In this month's issue of Nature Medicine , the scientists show that the virus causes symptoms in the same way as genes are faulty, suggesting that a single therapy could work against the disease.

Dilated cardiomyopathy, which can cause shortness of breath and the result of heart failure and death, affects about 50,000 people in the United States each year. For several years, researchers know that up to a third of patients suffering from viral infections, most of them with the Coxsackie B virus infections swell and irritates the heart, sometimes leading to chronic inflammation which can lead to cardiomyopathy. Cardiomyopathy but can also be caused by genetic diseases such as muscular dystrophy, which causes abnormalities in a protein called dystrophin. Dystrophin is responsible for binding of the cell membrane to contractile proteins such as actin and allows the force of contraction in the cells to be transmitted outside.

Cardiologist Kirk Knowlton San Diego University and his colleagues wanted to know if the Coxsackie B virus also affected dystrophin. The researchers showed that in test tubes, proteins produced by the virus Coxsackie B virus separated dystrophin, but not to other proteins present in cardiac cells. After the rat heart cells in culture were infected with Coxsackie virus B virus, the amount of normal dystrophin decreased within 3 days. Finally, the researchers injected immunodeficient mice with Coxsackie B virus when they killed animals a week later, they found that the virus had broken dystrophin in their hearts and that the membranes of heart cells infected with Coxsackie virus B were more permeable to blue dye than uninfected cells. This implies that the distribution of dystrophin damaged cell membranes, said Knowlton; this weakening of cell membranes allows the virus to spread, but damages the heart, as it makes the cells less resistant and less able to contract effectively. In an attempt to keep pumping enough blood, the heart starts getting larger.

The study is the first to show that the damaged dystrophin underlies both genetic and acquired cardiomyopathy, said Jeffrey A. Towbin, a cardiologist with the Baylor College of Medicine and Children's Hospital of Texas in Houston. This similarity suggests that researchers should target the underlying process in different varieties of the disease, he says, for example by developing a drug to prevent the dystrophin breaking down.

A new artificial kidney consists of living kidney cells on a plastic scaffold restored the main functions of the organ during the test in dogs. If the device, described in the May issue of Nature Biotechnology , can replace kidneys in humans, it could save the lives of thousands of patients who suffer from sudden kidney failure each year.

More than half of those whose kidneys fail during or after major surgery die, usually within 2 weeks. Indeed, the standard treatment for kidney failure, pumping blood through a dialysis machine, do filter metabolic waste from the blood, says nephrologist David Humes of the University of Michigan, Ann Arbor. A kidney, in comparison, pumps hormones such as activated vitamin D can increase the capabilities against the body of the infection subsides and the salts and nutrients from the liquid become urine. To create a better replacement kidney, Humes and his colleagues enlisted the real experts -. Kidney cells themselves

First, the team extracted primitive kidney cells called renal tubular cells from adult pigs and inject them into plastic tubes. These tubes form a hemofiltration cartridge, a blood filtering device already used by a handful of patients with kidney failure. The cells can collect on the tubes with small holes to allow the dissolved molecules to slip through. The cells then come together to form a fabric sheet, as they do in a normal kidney. When the blood of dogs that had just had their kidneys removed was passed through the device, it filters the blood more effectively than standard dialysis machine. In addition, devices with better maintained cells control blood pH and actively secreted hormones to fight against infection and glutathione activated vitamin D in the blood of animals compared to devices without cells. The group is seeking regulatory approval to begin clinical trials for patients with acute renal failure later this year, said Humes. And a variant of the device for chronic renal failure is scheduled for tests on animals.

The new system "should provide much normal kidney function as possible with conventional dialysis," says biomedical engineer Barry Solomon Circe Biomedical Inc. in Lexington, Massachusetts, which produced similar devices fill for failing livers. the device also shows the promise of bioartificial organs plastic compounds and living tissue, said biomedical engineer Clark Colton Massachusetts Institute of Technology. "I think it is a big step forward for the field. "

American geneticist Barbara McClintock, who challenged the prevailing theory that genes are stable elements of chromosomes with his discovery of "jumping genes", was born in date 102. McClintock studied inheritance in corn, examining patterns of color appearing in the nuclei and leaves.

in 1931, McClintock and a graduate student Harriet Creighton proved that the physical mixing of chromosomes could lead to the exchange of genetic material. In 1944, McClintock observed that certain genes cell hopped cell developed as a core. Four years later, she discovered that the controlled breaking of chromosomes was that allowed genes to move. When McClintock published the surprising discovery in 1950, the scientific community was skeptical, but in 1983 she received the Nobel Prize in physiology or medicine. His work was then used to explain the inheritance patterns that follow the rules of Mendel based on dominant and recessive characters. McClintock died in 1992.

A potential AIDS drug called azodicarbonamide suppresses not only HIV, but also the human immune system, the scientists report in the August issue Nature Medicine . Although some scientists believe that the discovery casts doubt on the future of the drug in the treatment of AIDS, it points to its possible use to prevent the body from rejecting organ transplants.

In 1996, azodicarbonamide has been found to inhibit HIV replication in cell cultures by interfering with "zinc fingers" - elongated members comprising a zinc atom - a crucial viral protein. it has been shown to work in both the early and late stages of AIDS and is currently in clinical trials. researchers at the University of Brussels, Belgium, wonders, however, if the drug could also affect on the immune system -. More particularly, on CD4 cells, the class of white blood cells infected with HIV

the researchers used monoclonal antibodies to activate the human CD4 cells in test tubes They. then measured azodicarbonamide effect on the production of cytokines, proteins which signal other cells to mount defenses of cells. "We were surprised that this drug has a drastic effect," said a member of the Jamila Ismaili team. In most tested human samples, the drug reduced cytokine production by 80% to 0% within 72 hours

The result led the researchers to think about a completely different use for azodicarbonamide: . As a drug that could stop the immune system from attacking the transplanted organs. Thus, in a second experiment, they gave a daily dose to mice that received a skin graft rejection and controlled. Without the drug, the skin grafts survived only 12 days; on average, doubled it azodicarbonamide. This suggests that azodicarbonamide can be added to the arsenal of immunosuppressive drugs, said Ismaili.

But the study raises questions about the use of azodicarbonamide as anti-HIV agent. "You could worry additional immunosuppressive effects with AIDS," says Stephen Desiderio, a molecular biologist at the School of Medicine at Johns Hopkins University. He stressed that the drug could still be useful in the early stages of infection when it will be more important than maintaining the immune system in the form containing the replication. "This is really a first look at the issue," says Desiderio.

"Nobels of America," the annual awards - light on money, but heavy prestige - the Albert and Mary Lasker Foundation, will this year six biomedical researchers. They include neuroscientist Seymour Kety, 84, pioneer explorer in the biological roots of schizophrenia, who works at McLean Hospital in Belmont, Massachusetts.

The winners of the basic price of medical research, for work on the architecture of ion-channel proteins are physiology Clay Armstrong professors from the University of Pennsylvania, Philadelphia, and Bertil Hille, University of Washington, Seattle; and neurobiologist Roderick MacKinnon of Rockefeller University in New York City. The medical clinic Research Award goes to David W. Cushman and Miguel A. Ondetti two Bristol-Myers Squibb researchers have designed ACE inhibitors, cardiovascular drugs. The $ 10,000 awards will be presented in New York on October 1st.

Sometimes called the "genome guardian" protein known p53 responds to DNA damage or by halting cell division or causing the cell to commit suicide. Anyway, p53 action helps the formation of short-circuit preventing tumor cells that have undergone malignant mutations continue to grow. However, the p53 gene itself may be damaged, which is thought to contribute to the development of half of all cancers. In tomorrow Science , the researchers describe a drug that may be able to restore the normal function of certain mutated p53 proteins and could therefore open the way for a new type of cancer treatment.

To stop cell division or trigger cell suicide, p53 needs to regulate the activity of various genes, which requires that the first bind to DNA regulatory sequences of genes. The researchers found that many mutations that inactivate p53 cause the protein to misfold, producing a three-dimensional conformation without rigid molecule needed for this connection.

Before searching for a molecule capable of bracing aberrant p53 in the proper position to attach to DNA, biologists Farzan Rastinejad cancer and Barbara Foster Pfizer Central Research in Groton, Connecticut, needed to a quick way to tell if a compound worked. They hit on the idea of ​​using a known antibody that recognizes a part of p53 that is exposed only when the protein is in the right conformation. Ultimately, they examined more than 100,000 compounds with antibodies, initially to identify compounds that could increase its binding to p53 normal, then testing them successfully compounds on the mutant p53 in the tube test. Compounds that have taken this test then went to the next phase, in which the group Rastinejad looked to see who could correct a mutant p53 protein in tumor cells in culture. After winnowing the pack further, they showed that the drugs remaining candidates slowed cancer growth in mice.

The results are a first step on the long road to the manufacture of a drug that can be used in humans. Nevertheless, they represent "an exciting proof of principle of what promises to be a new form of therapy," says Bert Vogelstein, a cancer biologist at Johns Hopkins University School of Medicine in Baltimore, Maryland. In addition, Rastinejad adds, because misfolded proteins are involved in other diseases, including Alzheimer's disease, cystic fibrosis and diseases of the brain thought to be caused by infectious proteins called prions, "this approach may relate to a large number of diseases. "

Shining some light on the skin lesions and the extent of reflection can help dermatologist to identify the most dangerous form of cancer skin more easily, according to a new study. The technique could help pick up the cancer early and save patients from unnecessary biopsies.

Melanoma, the most aggressive form of skin cancer, shows first as a dark pigmentation patches on the skin, but it is difficult to say such a malignancy a harmless mole or freckle . Dermatologists can have a computer compare the following images and search for mysterious reasons, they usually rely on signs, like irregular edges or more colors. Even specialists can have trouble detecting melanoma, however, and most would like to spare patients the stress of a biopsy when possible.

In 1991, an Italian team developed a new technique. When they shine a beam of light on the lesions of the skin, they found that the spectra of the reflected light are different for melanoma and benign skin lesions. Now, a research team from the Institute of Cancer and the Royal Marsden Hospital, UK, took this a step further technique.

Physicist Vincent Wallace and colleagues first measured the spectra of 121 "worrisome lesions," which were then removed and diagnosed in the laboratory. They found seven main differences between the spectra of benign lesions and melanomas, they used to develop software that analyzes the signal and determines whether the lesion is likely to be a melanoma or not. they integrated it in an experimental scanner, they tested of 47 lesions. As reports team in the March Physics in Medicine and Biology , they could change the system so that he can choose each malignant tumor, but produce few false alarms. the system has outperformed the analysis current computerized image, and as good as the visual inspection by most dermatologists, says physicist and member of the Jeffrey Bamber team. the process is also faster and can consider smaller lesions. And because it is fully automated, it could be used by nondermatologists such as GPs, said Bamber.

But Ronald Barr, a dermatologist at the University of California, Irvine, said he would be wary of using the technique to systematically screen patients - at least in the US - because he is afraid , it may not detect certain malignancies. "We have a litigious society," said Barr. Instead, he said the system could be helpful to detect many lesions on one patient known to have a melanoma, or for monitoring patients after treatment.

Smoking or inhaling secondhand smoke can increase the risk of breast cancer, according to a large study, published in the current number of Causes and control [cancer. The work may help explain why previous studies of the link between smoking and breast cancer has come up with conflicting results.

Researchers have long puzzled over the blurred relationship between cigarettes and breast cancer. Some studies have suggested that smoking may actually protect women, a finding the researchers attributed to the removal of nicotine from estrogen, often linked to breast cancer hormone. But most follow-up studies found no relationship between smoking and breast cancer; and others have shown that smoking and secondhand smoke in particular, increased the risk.

Kenneth Johnson and colleagues at the Laboratory of the Canadian government for Disease Control in Ottawa glean information on 2317 women with breast cancer and 2438 healthy women from a Canadian study monitoring Cancer. Participants answered questions about risk factors such as alcohol consumption, physical activity and age at menarche, and their lifetime exposure to tobacco smoke at home and at work. For premenopausal women, smoking or regular exposure to secondhand smoke doubled the risk of breast cancer; for postmenopausal women, these factors have increased the risk of 50% and 30% respectively

Johnson said the study may explain why studies consistently show that secondhand smoke increases the risk of breast cancer -. his is the seventh to do - while others that examined smokers have had mixed results. Maybe, he says, it is because smoking and passive smoking are almost the same risk. Most previous studies have compared active smokers to people who had never smoked; but most women in the latter group were exposed to passive smoke "so that you are really exposed to compare exposed," Johnson said. In fact, when smokers in the new study were compared to all non-smoking - regardless of whether they were exposed to secondhand smoke or not - the risk of breast cancer was equal, as in studies previous. The results suggest that some women develop breast cancer when they were exposed to a certain amount of smoke, Johnson said - no matter how it gets into their bodies

Support for this theory came in 1996, when Christine. Ambrosone, biologist at the National Center for Toxicological Research in Jefferson, Arkansas, reported that women with a slow form of an enzyme that metabolizes carcinogenic tobacco had an increased risk of breast cancer. Ambrosone Johnson said the study is solid, but cautions that researchers still need to work on many details about the link between smoking and breast cancer. "My feeling is that breast cancer is a very heterogeneous disease, so that this relationship will be complicated."

Chafing at the slow pace of commercial development of the drug, a disease advocacy group made last week to fund new drugs for his district . Last week, cystic fibrosis (CF) Foundation Bethesda, Maryland, has announced it will invest at least $ 30 million in a small biotech company, Aurora Biosciences of San Diego, to identify compounds that could be useful in treating CF. The project, initially fed by a gift of $ 20 million from the Bill and Melinda Gates Foundation, marks a new departure in the growing trend of patient groups that support biomedical research.

The plan calls for Aurora to several one hundred thousand molecules display in his library over the next five years and identify two or three that could be candidate drugs for CF. If this approach gives promising results "," CF Foundation plans to pay an additional amount of $ 16.9 million Aurora to prepare candidates for clinical trials. Carry drugs through the final approval, however, would require co-investment by a major pharmaceutical company. The benefits would be shared between the CF Foundation and its business partners, but the foundation would immediately plow all its own charges directly in research on new therapies.

President Robert Beall CF Foundation believes that this new society "virtual drug," a hybrid business, non-profit, is unique in the pharmaceutical industry. Her group decided to take the plunge into the drug R & D because he did not wait for drug manufacturers to small molecules to take an interest in the FC

Large pharmaceutical companies have not been drawn on the ground, Beall notes, because the number of cystic fibrosis patients that could buy a drug is relatively small - only about 30,000 in the United States. And he said that "when we tried to involve them" in the search for new compounds of interest, "they did not return our calls." Thus, the foundation has hired a consultant veterinarian for innovative small businesses; they have settled quickly Aurora, which maintains a library of 400,000 small molecules that can be screened at high speed for medical applications.

Francis Collins, director of the National Institute for Research on the human genome and co-discoverer of the CF gene, said, "This roll-up-your sleeves partnership" between an advocacy group for the disease and a drug discovery company's new "The CF Foundation is taking an interesting step. this obviously has a high risk, but could also have a strong gain if it works." By providing early support for drug discovery, Collins said, the foundation ensures that the disease "will get more attention and approaches more advanced than it would otherwise."