Health Meaning

The researchers found that a diet high in salt causes subtle biochemical changes that can fatally shaking heart rate in rats with high blood pressure. The results, reported in tomorrow's issue of Science * suggest how untreated hypertension in people can lead to chronic heart failure.

Doctors have long thought that in a hypertensive person, the heart adapts to stress by expanding to pump blood more efficiently. Thinking such swelling may not be as benign, W. Jonathan Lederer and colleagues at the University of Maryland School of Medicine in Baltimore probed the mechanism by which the heart muscle cells to absorb calcium, which causes the heart to contract. They fed a high salt diet in a strain of rats bred to have high blood pressure, and analyzed changes in calcium channel moves into a cell to trigger contraction.

The researchers found that the differences between the calcium channels and calcium receptors located just inside the cell membrane had expanded. Initially, however, the rats have overcome this defect by producing additional adrenaline that the increased sensitivity of calcium receptors. But after several weeks of steady expansion, damaged hearts started to contract evil, resulting in heart failure.

Experts are impressed by the study. "What is surprising is that most of the problems seem to be a step between the electrical excitation of the heart and its contraction," says David Yue, a biomedical engineer at the School of the Johns Hopkins University of Medicine in Baltimore . Such a fundamental fatal process is also likely to occur in people, said Lederer. The message for people with high blood pressure, he said, is "Do not wait to treat, because you develop an irreversible failure." In the meantime, Lederer says, pharmaceutical companies should aim to test agents which increase the calcium receptor sensitivity in hypertensive people.

* for details, Science online subscribers can link to the full text of the report.

Researchers have finally been able to make charges stick against a tumor suppressor gene long suspected. The gene, called NF1 , was identified in 190 as the culprit in neurofibromatosis (NF), a disfiguring and potentially fatal disease that affects one in 3500.

in the number of tomorrow the New England Journal of Medicine , researchers from the University of California, San Francisco, and Roche Biomedical Laboratories report convincing evidence that NF1 gene acts as a suppressor tumor in human cancer. Such genes help regulate cell division, and when they are missing or inactivated by mutations, cell division is unleashed, causing tumors. The discovery suggests that therapies under development that target the pathway of cell division may hold great promise for NF1 patients who develop many non-cancerous tumors and have a very high risk for several types of Cancer.

Scientists already had tons of indirect evidence that NF1 was a tumor suppressor. The disease itself, with its multiple tumors, suggests the work of such a gene has gone wrong. And in a few months NF1 discovery of, the researchers found that its sequence was remarkably similar to a gene called GAP , which was known to regulate the signal system tells a cell to divide. Data from mice also suggested that the gene was necessary to prevent tumor development. But it has been difficult to gather strong evidence needed to confirm the role of tumor suppressor.

The best way to prove that a gene is a tumor suppressor is to show that the gene works properly in normal cells, but is absent or inactive in tumor cells. This has been difficult to prove to NF1 , because the large gene could potentially contain thousands of mutations that render inactive, and it is impossible to screen for all of them. But a tip recently developed to examine the protein product of the gene activated Kevin Shannon, a pediatric hematologist and oncologist at the University of California, San Francisco, and colleagues to gather evidence to load. They examined tissue samples of 18 children with NF who also developed leukemia. In eight patients, the normal cells showed mutated NF1 gene and a normal gene, while cancer cells had only the mutated form. "Overwhelming evidence," said Shannon, the NF1 gene is indeed the culprit in cancers.

Other researchers applaud the work. "This is the best example NF1 is a tumor suppressor, "says David Viskochil, a geneticist at the University of Utah, but he warned that the case is not yet closed: There may be still other genes that play a role in tumor development NF. Nevertheless, he says, the finding suggests that drugs that block the path to cell division will be an effective treatment for NF leukemia related and potentially other disease complications.

W ASHINGTON , DC - New therapies and treatments for diseases are compromised by a decline money, time, and training for clinical research, scientists said today at a joint meeting convened by the Institute of Medicine (IOM). Gaps in Clinical Research "will compromise our ability to bring innovation to health care at the bedside," warned Kenneth Shine, IOM President.

Most clinical research is performed in hospitals managed by medical schools. But the rise of managed care, such as health maintenance organizations (HMO), requires training and research hospitals to cut costs and competition. This "irrevocable rapid momentum to control costs ... is rapidly squeezing the time and money of clinical research, "George Lundberg, editor of the Journal of the American Medical Association ( JAMA ), at a press conference.

As evidence of this trend, Lundberg said a report JAMA published today that details how the cost reduction takes a toll on clinical research. a study of 50 university hospitals by Eric Campbell of Massachusetts General Hospital and colleagues, clinical researchers based at hospitals in more competitive markets (defined in part by numerous, large HMO) published on average, 15% fewer articles in peer-reviewed journals that had peers in less competitive markets. Campbell also found that faculty members in competitive hospitals reported more patient care duties and stress department that made them less competitive their colleagues.

To reverse the decline today called Shine a 1% tax on health care premiums and self-insurance plans to support clinical research. Gradually over several years, service estimates the tax could raise up to $ 5 billion per year that could be allocated in the form of peer-reviewed grants.

A vaccine that AIDS has had more success in monkey experiments that any other approach has never been tested in humans. The reason: Many researchers believe the vaccine based on weakened - or attenuated - live virus, would be too risky.

The International based in Chicago Now, a group of doctors involved in AIDS care, convinced that the potential benefits outweigh the risks, leads an unusual campaign to recruit hundreds of volunteers for a study this security approach. Association of Physicians in AIDS Care (IAPAC) uses a live attenuated HIV test in the August issue of his newspaper and posted a registration form for the trial on its website (www.iapac.org) . IAPAC said more than a dozen people have already stepped forward.

Ronald Desrosiers, Central New England Regional Primate Research in Southborough, Massachusetts, first showed the power of live attenuated approach in a monkey study published in science there are nearly 5 years (December 18, 1992, p. 1938). Monkeys who received the vaccine are infected later, when administered a lethal strain of SIV, simian cousin of HIV. Desrosiers has spent the last few years to eliminate various genes of SIV and HIV to find a weakened form that is as safe as possible, but still be able to protect animals against pathogenic isolates of the virus.

A live attenuated vaccine AIDS would have three potential pitfalls, however. The weakened virus is still able to replicate and can cause AIDS after, say, 30 years. It is also possible that the virus could mutate into a virulent form, although Desrosiers think that this risk can be virtually eliminated by removing enough genes. Finally, the weakened HIV would still incorporate the DNA of a host cell, which could theoretically trigger cancer.

Leading the drive to register is voluntary AIDS clinician Charles Farthing, medical director of the AIDS Healthcare Foundation in Los Angeles, California. Farthing said he hopes the trial will show that people, like monkeys, can control the replication of the virus and weakened immune comes to no harm. Yet AIDS experts say a short trial would not answer some key questions of security. "We are really concerned about what happens when you vaccinate 20 million people and 10 years later, 5% or 10% get lymphoma," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "You're not going to know [IAPAC's proposed test]."

A team of researchers immunized mice with proteins derived from their own cancer cells. The treatment, reported in tomorrow Science *, significantly slowed the spread of many types of cancer.

A group of researchers from the University of Connecticut School of Medicine in Farmington made the vaccine by purifying heat shock proteins (HSP), which are released from stressed cells and alert the immune system to destroy it. To test the ability of the vaccine to stop the spread of cancer, the researchers injected cancerous lung cells in the footpads of mice. The tumors were removed when they were 5 mm wide, and half the mice received weekly doses of heat shock proteins purified from the same type of cancer cells that were injected. The mice that received saline all died within 45 days of cancer that spread from tiny remnants of the tumor. But 80% of vaccinated mice survived without cancer lesions for 250 days. The team had similar success with colon cancer and melanoma.

"We proved the HSP vaccines can be used as a general strategy for treating a variety of tumors in mice," said Ping Peng, an immunologist with the team. Research is an important step, says Hans Schreiber, an immunologist and cancer researcher at the University of Chicago. By purifying the heat shock proteins of cancers, "you can get individualized therapies," he said. "This is a major breakthrough."

* For details, Science Online Subscribers can create a link to the full report.

W ASHINGTON DC - After decades of largely be repelled by the American medical establishment, acupuncture appears to be gaining some respectability. Last year, the Food and Drug Administration took the label off of acupuncture needles "experimental" as medical devices. And today, a group of experts convened by the National Institutes of Health (NIH) concluded that acupuncture is an effective treatment for nausea and some forms of pain.

About 1 million people get stuck in the United States each year, mostly for pain relief, the panel said. Some Western researchers say acupuncture triggers the production of many chemicals, including endorphins analgesics, benzodiazepines endogenous painkillers and serotonin with mood lifting. "The challenge in studying acupuncture is to integrate the theory of Chinese medicine in the classic model of Western biomedical research," says the president of the committee David Ramsay, president of the University of Maryland.

The conference, sponsored by the NIH Office of Alternative Medicine (OAM), reviewed research on a host of ailments: nausea and ovulatory problems to paralysis and drug abuse. Although research that most acupuncture studies are lacking for various reasons such as covering too few subjects or lack of control, the panel found "clear evidence" that the acupuncture needle can relieve nausea of operations and chemotherapy, and perhaps morning sickness. They also found "evidence of effectiveness" for postoperative dental pain, and "reasonable studies" showing the pain for other conditions

to penetrate deeper into the mystique of acupuncture, the panel called for more research. - the music to ears of OAM, who sponsored $ 2 million for research on acupuncture in the last 5 years. especially gray areas, the Panel noted include discrimination "reality" from acupuncture points "dummy" for research purposes.

But experts are not invited to address the panel say that there is less mystery than meets the eye. Longtime acupuncture practitioner George Ulett, psychiatrist and neurologist at the Institute of Mental Health of Missouri in St. Louis, said you can forget the Yin and Yang: Electrical stimulation - either with needles or conductive pads - is "a very simple technique" to fan the hormones that affect the nerves.

W ASHINGTON , DC - Scientists have discovered a gene that some cancer cells destined to a period of limited life. Experts hope that the finding, reported this week at the American Society for the Annual Meeting of Cell Biology, could eventually lead to a new type of gene therapy for cancer.

Most adult human cells are at rest, meaning they stopped dividing, after receiving certain biochemical signals. But even without these signals, most cells will eventually stop dividing themselves, to achieve a permanent sort of quiescence called "senescence". signals cancer cells to ignore becoming idle, and many types never reach senescence. They are called immortal, because, in theory, they could continue to divide forever.

By using a careful combination of trial and error and standard genetic techniques, gerontologist Olivia Pereira-Smith and colleagues at Baylor College of Medicine Houston, Texas, have now found a gene that ends in immortality one of the four classes of immortal cells. They used cell lines of brain cancer and cervical cancer. Based on its sequence, the group says the gene may encode a transcription factor, a protein that controls the expression of other genes -. Perhaps those that give the cells of limited life

The conclusion "will give us insight into the entire process of [cellular] immortality," says Harvey Ozer, a molecular biologist and cell at the New Jersey medical school in Newark, because this is the first time that researchers have found a gene involved in the process. the gene could one day be used to treat cancer, Ozer said. "If you should find a way of introducing a normal version of this [gene] in [patient's] cancer cell, you might stop growing. "

P HILADELPHIA - A molecule known for its Texas circumference now appears to be a promising new weapon against cancer . A pilot test of the new metal compound carrying heavy, described here Saturday at the annual meeting of the American Association for the Advancement of Science (which publishes Science NOW), extended the life of people living with brain cancer.

natural pigments called porphyrins, that carry iron in the blood, the home in on the tumors. Jonathan Sessler, a chemist at the University of Texas, Austin, thought that porphyrins could become haul for cancer drugs. Because Sessler said that everything is bigger in Texas, he initially stalled fifth link in the porphyrin molecule, resembling a bracelet of four linked rings. This new molecule "Texas size" - appropriately nicknamed texaphyrin - had a capacity of 20% larger, enough to carry a heavy metal atom of gadolinium. net positive charge of gadolinium would be able to absorb an excess of electrons, which tend to recombine with hydroxyl radicals - corrosive molecules formed during radiation therapy against tumor - and eliminate their carcinogenic killing. Gadolinium, Sessler hoped would prolong the effects of hydroxyl radical and thus increase the power of radiation.

To see if Texaphyrins gravitate to tumors like their cousins ​​are porphyrin, Sessler used magnetic resonance imaging (MRI) to scan cancerous mice before and after an injection of texaphyrin. Gadolinium MRI shows increased sharply. Sessler and colleagues at Pharmacyclics in Sunnyvale, California, found that cancerous cells appeared bright white areas on the MRI, even days after an injection of texaphyrin. When the team irradiated these mice, tumor cells decreased or disappeared and 50% of the mice survived the 140 day study. Only 10% of irradiated mice survived without texaphyrins.

In early clinical trials, Sessler and colleagues treated 39 patients with metastatic brain tumors with Texaphyrins 2 hours before radiotherapy for 10 days. Patients who had a life expectancy of 2 to 4 months, survived an average of 188 days. The patients in the group receiving the highest dose survived an average of 362 days. Although drug studies are not complete, Sessler said, "there are people alive that would normally be dead." The National Cancer Institute has selected Texaphyrins within its network of decision NCI -. A group of what he considers therapies is coming and most promising

In one of the greatest moments in modern medical science, American microbiologist Jonas Salk, April 12, 1955 delivered safely its vaccine against polio newly invented and effective in almost 0% of cases. Salk discovered that injecting a small amount of killed virus induces the body to produce protective antibodies without causing polio, a disease that caused permanent paralysis, particularly in children, since the time of the Ancient Egypt.

Salk identified the three main varieties of poliovirus, developed a killed virus vaccine tested in monkeys and in May 1952 conducted a test on the massive human terrain of over 400,000 children - the most largest medical experiment ever conducted in the United States. After the success was proclaimed in 1955, the Salk vaccine against polio was administered to more than 0 million people in the United States, and the incidence of polio has dropped from 96% in 1961. Salk vaccine finally was replaced by a more effective live oral vaccine developed by Albert Sabin competitor and distributed worldwide. Some 2,000 cases of polio were reported last year, most of which were in the Indian subcontinent and the former Soviet Union

[Source:EmilyMcMurrayEd Notable Twentieth Century scientists (Gale Research Inc., ITP, 1995).]

artificial antibodies can shrink tumors in women with advanced breast cancer, researchers announced yesterday at the American Society of Clinical Oncology meeting (ASCO) in Los Angeles. Experts said it is not yet known if treatment can extend patients' lives, but the news suggests renewed promise for these compounds, which have suffered disappointing clinical results in the late 1980s

antibodies are a first line of the body natural defenses against infection. Each antibody captures a specific target and holds on, alert meanwhile the rest of the immune system to the intruder. Genentech researchers have designed an artificial antibody to a particular molecule, a receptor for a growth factor called HER-2 / neu, which is found in abundance on the surface of recalcitrant breast tumors. Numerous studies have shown that the unlucky 25% to 30% of breast cancer patients whose tumors occur more HER-2 / neu have worse prognoses.

When the antibody was combined with the chemotherapy drug Taxol, 42% of 96 women with metastatic breast cancer have reacted with tumors decreased nearly half. This was much better than the 16% of 92 patients who improved with taxol alone. The addition of the antibody also appears to have extended the four months of time to relapse for up to 11 months. Side effects were minor. "For the marginal additional toxicity [to the patient], you get a huge amount of profit," says project leader Genentech Robert Cohen.

breast cancer patients who have exhausted other treatment options are already calling for the antibody, and the FDA has promised consideration within 6 months. "We estimate that 30,000 to 50,000 women would be eligible" to receive orders for Herceptin if approved, said Cohen.

Although Herceptin slows the progression of the disease, it is too early to say it extends women's lives, simulations radiation oncologist guard Alan Lichter of the University of Michigan Medical School in Ann Arbor and president of ASCO. Lichter calls "modest" response, but significant in that it shows that antibody therapies, considered the best for cancers of the blood, can work against solid tumors as well.

The cracks are widening in the first line of defense against the virus that causes AIDS - drugs that inhibit the essential viral enzymes called proteases and reverse transcriptase. At the World Conference against AIDS 12 in Geneva, Switzerland, separate teams of US and Swiss researchers reported today the first cases in which HIV strains resistant to both classes of drugs were sent to new confirmed victims. While multidrug resistance does not come as a surprise, researchers had hoped that HIV, by mutating to survive exposure to the two classes of compounds will be rendered incapable of infecting new hosts.

The ability of HIV to mutate rapidly -and, of course, hiding in the immune system of its host - was one of the worst AIDS epidemics of infectious diseases worldwide. But the tide began to turn in late 1995 and early 1996, when the US Food and Drug Administration approved the first inhibitors 3 protease that prevent HIV machines clipping viral proteins newly formed just the right size needed to assemble new virus. Used in combination with reverse transcriptase inhibitors, which prevent the HIV genome to be incorporated in infected cells, the drugs have caused new cases of AIDS in the United States to decrease by 15% compared to early 1996 in mid-1997 - the first decline since the beginning of the epidemic in 1981.

The drugs seemed as promising as agents for blocking HIV transmission. Although AIDS patients regularly develop strains of HIV resistant to one or more protease inhibitors, only a handful of unconfirmed reports have suggested that resistant strains - probably less virulent because of mutations that help them survive treatment drug - could be passed on to new victims. "The thought was that the inhibitor resistant virus protease was unlikely to be transmitted to new hosts," says Frederick Hecht epidemiologist at the University of California, San Francisco. At the conference, however, Hecht described a patient who was infected with HIV already resistant strain in six of the 11 approved antiretroviral medicines, including four protease inhibitors. A second study presented by researchers from Geneva University Hospital had three cases of similar-resistant HIV transmission drugs.

These reports represent "the best documentation to date of the multiple drug resistance against HIV," said infectious disease specialist Joel Gallant, director of the Moore HIV Clinic at the Medical School of the Johns Hopkins University. "We do not yet know the implications of resistance to multiple drugs public health, but it will likely be increasingly important," says Gallant, adding that it is a threat that highlights the need to . prevent HIV transmission Hecht agrees: ". While we must continue to develop new drugs against HIV, they are all likely to be prey to resistance "

Scientists have identified a chemical in the blood that can indicate ovarian cancer at an early stage. If confirmed by larger studies, the finding may provide a way to detect ovarian cancer when the disease is most treatable.

Because ovarian cancer usually escapes detection until it has spread beyond the ovaries, it is the deadliest of all gynecological cancers. The survival rate at 5 years with advanced disease is not more than 15%. But if so the cancer can be detected it is still localized, almost 0% of patients live longer than 5 years. A possible early warning sign was on Yan Xu cancer biologist at the Cleveland Clinic Foundation while studying lysophosphatidic acid (LPA), a chemical blood which stimulates the growth of cancer cells of ovary in the laboratory. Because some patients with advanced ovarian cancer have elevated levels of the APL, Xu asked whether women in the early stage of the disease may also have elevated LPA levels.

Xu and colleagues at the Cleveland Clinic Foundation has recruited 84 women with various gynecological cancers and tested their LPA levels. They report in tomorrow's issue of Journal of the American Medical Association that all women with advanced ovarian cancer and 95% of women with other gynecological cancers had blood levels LPA higher than their healthy counterparts. Particularly noteworthy was the finding that nine out of 10 women with early stage ovarian cancer have also documented the high scorer. "If we have a chance to pick up early stages of the disease by 0%, then you can say that would be a good test," said team member Maurie Markman, a medical oncologist. First, however, many more women with cancer of early stage ovarian must be tested to determine whether it would be useful to screen healthy women and people at high risk of developing ovarian cancer .

other experts consider these results with cautious optimism. James Roberts, a gynecologic oncologist at the medical School at Stanford University, would like to see a simple test has tried with more patients. by linking high levels of the APL to gynecological cancers, especially on stage ovarian cancer, "you have a much more treatable disease."

Three US researchers learned yesterday that they will share the Nobel Prize in Physiology or Medicine for his discovery that nitric oxide gas ( NO) acts as a messenger molecule in the body. The discovery led to the development of the drug to the popular impotence Viagra and offered hope of new treatments for blood pressure and tumor.

price $ 975,000 will be divided equally between Robert Furchgott pharmacologists at the University of New York in New York City, Louis Ignarro at the University of California, Los Angeles, and Ferid Murad to University of Texas Medical School, Houston, for their discovery of how the nitric oxide can pass a signal from one cell to another. Because NO is a simple molecule - it is a common pollutant in car exhaust gases -. Scientists were surprised by its sophisticated operation

In 1986, Furchgott and Ignarro presented their work independently showing that NO has worked as a signaling factor in the blood vessels, triggering research worldwide. It was later discovered that NO indicates blood vessels throughout the body to relax, which lowers blood pressure and increases blood flow. Murad, meanwhile, discovered that nitroglycerin, a longtime treatment for heart disease, works by releasing NO from cells. White blood cells also use gas to defend against tumors.

The price has already started. Strict rules prevent the Nobel committee to award the prize to more than three people, but critics say that the committee overlooked key researchers. In particular, the decision not to include pharmacologist Salvador Moncada at University College London drew fire from top scientists. Rudi Busse, a researcher of nitric oxide at the University of Frankfurt, said he was "extremely surprised" that Moncada, who led key experiences when he worked for the Wellcome Foundation in the 1980s, n has not been included.

P ARIS - The controversy erupted on the southern government decision -africain retain the antiviral drug AZT to pregnant women infected with HIV - despite the compound to demonstrate efficacy in preventing HIV transmission to offspring

AIDS officials, doctors and activists say that they are puzzled by the decision, in which the south African government. last month said it would not provide AZT to pregnant women in any health program funded. "We believe that the drug prices unaffordable," said Ian Roberts, Special Adviser to the Minister of Health of South Africa Nkosazana Zuma. But Peter Piot, executive director of UNAIDS, argues that South Africa " clearly [hasn't] done enough "to contain the mother's infection rate to alarming child: in some areas, more than a fifth of pregnant women are HIV-positive, and a hospital based in Soweto delivered nearly 1,000 children infected HIV this year. Overall, nearly 15% of South African adults are home HIV, said Bernhard Schwartländer, senior epidemiologist of UNAIDS.

While Africa is currently the main victim of the epidemic, the latest figures published by the United Nations last week reveal disturbing trends on the other. In India, sampling in rural areas found adult HIV prevalence of infection up to 2%. Even in Western Europe and North America, where AIDS deaths are down thanks to antiviral therapies, the proportion of the population infected with HIV continues to rise; Epidemiologists registered 74,000 new infections on both continents in 1998. Some 5.8 million people worldwide were infected with HIV in 1998, bringing the total number of people infected with HIV to 33.4 million.

Malignant tumors in transplant patients are generally attributed to a weakened immune system by medication. But a study in tomorrow's issue of Nature shows that drugs can play a more direct role: A common immunosuppressive can stimulate tumor cells to divide and spread. The conclusion suggests that it might be possible to design new drugs without the lethal side

For nearly 20 years, doctors have used cyclosporin to reduce the immune response, which would otherwise reject a transplant. - A strategy that carries with it an increase of 100 times the risk of tumors in these patients compared to healthy individuals. Recent experiments have shown, however, that cyclosporine may increase the body's production of TGF b , a growth factor known to promote tumor spread.

To further explore the role of cyclosporine in cancer, Minoru Hojo and colleagues from Tokyo University Medical School tested whether cyclosporine may help cancer cells become more mobile. They bathed a relatively mild strain of lung cancer cells in cyclosporine. Within 72 hours, the drugged cells began to extend pseudopods - appendages that help cell migration. Another experiment showed that the treated cells were in fact move more easily.

When the researchers injected these tumor cells into the tail veins of mice 35, almost twice sprouted new tumors in the lungs of cyclosporine treated mice compared to control animals. Exposed to cyclosporine, "tumor cells become smarter and more invasive" said Hojo. In experiments in both petri dish and the mouse, the effects of cyclosporine can be reversed by adding antibody against TGF b . for Hojo, this suggests that cyclosporine stimulates TGF b production in transplant patients, which in turn spurs cancer cells.

the discovery "sheds monkey wrench in our view of cyclosporine mechanism "for promoting tumor, says Gary Nabel, a molecular biologist at the University of Michigan, Ann Arbor. It can also force people to rethink the role of the immune system in cancer transplant patients, he said. the group of Hojo is now looking for ways to block TGF b 's tumor promoting capacity without reducing its effectiveness in reining in the immune system during transplant operations.

The virus that causes herpes could one day provide relief, rather than misery. In today Proceedings of the National Academy of Sciences , biologists show that the herpes virus can shuttle human genes in nerve cells in mouse pain, increasing their tolerance to pain. If the technique works in people, it could be used to relieve chronic pain.

pharmacologist Steven Wilson at the University of South Carolina, Columbia, and molecular geneticist Joseph Glorioso of the University of Pittsburgh sought to exploit the herpes virus tends to take residence in sensory neurons. First, the duo removed pieces of several genes of the virus to prevent it from causing disease. They also attached to a human gene that produces the pro-enkephalin, a peptide of natural pain blocking, and a second gene that produces a blue dye, to trace the path of the virus under the microscope. They were then infected mice with the modified virus.

To determine how the treatment affected mice, David Yeomans, University of Illinois, Chicago, watched how they reacted to a pain test standard. Mice get their away leg of a heat lamp in about 12 to 15 seconds, but they feel pain and yank back much more quickly after being sensitized by capsaicin, the active ingredient in hot peppers. Capsaicin stimulates the nerve cells that also cause chronic burning pain in humans. The sensitizing effect "was completely abolished by the virus," says Wilson. Infected mice withdrew their paws again - proving that they could feel the normal sensations of pain -., But the hypersensitivity of chronic pain was past

"This is the first evidence that genes neuropeptides delivered in this way can actually have an effect on pain, "says Gudarz Davar, an anesthesiologist at Brigham and Women's hospital in Boston, Massachusetts. Davar is "cautiously optimistic" that gene therapy will eventually be used to control pain in people. Before that happens, he said, researchers need to show it works in animal models that more closely mimic human disease. They must also ensure that the herpes virus mails can not go back to the enemy by friends "recombine" with active herpes virus hides in the body.

Johannes Fibiger, a Danish pathologist and bacteriologist who improved public health and research on cancer revitalized, was born that day

in 1867. early in his career, Fibiger discovered that there are two distinct forms of diphtheria, a disease that caused frequent epidemics in children and remains a problem in parts of the world. Based on the finding, Fibiger developed an antitoxin that was successfully tested in 1897.

At the turn of the century, cancer research has been stagnant because scientists did not know how to provoke cancer in laboratory animals. In 107 Fibiger noticed that some TB rats showed gastric tumors infested with tiny worms called nematodes. Intrigued, he investigated the source of the rats, a sugar refinery. Having collected cockroaches from the refinery, Fibiger fed them to rats that had been trapped elsewhere. When the first dead rat, he found stomach cancer. To create the first reproducible animal model of cancer, Fibiger received the Nobel Prize for medicine in 1926. He died two years later

[Source:EmilyMcMurrayEd Notable Twentieth Century Scientists (Gale Research Inc., ITP, 1995); Tyler Wasson, Ed., Nobel laureates (H. P. Wilson, 1987)]

A new drug taken for a few months prevented monkeys rejecting transplanted kidneys. The drug described in the June Nature Medicine also lack the side effects of immunosuppressive drugs, such as increased susceptibility to infection. Human trials are just beginning in progress, but the results of primates are "really, really incredible," said transplant immunologist Norma Kenyon of the University of Miami in Florida.

The drug is an antibody that binds to a protein called CD154, a signal that the immune system needs to launch an attack against a microbial invader or transplanted tissue. The antibody counteracts attack by binding to CD154 and preventing it from binding to its receptor.

The strategy has far exceeded. Immunologist Allan Kirk and endocrinologist David Harlan of the Naval Medical Research Center in Bethesda, Maryland, and colleagues gave nine monkeys weekly doses of the antibody for the first month after transplant, and monthly doses for 5 months. All treatment was then arrested. More than a year later, eight of the nine are alive and well. The only death was due to complications during a routine blood test; an autopsy revealed that the monkey had normal kidney function when he died. monkeys witnesses who received conventional immunotherapy died in 9 weeks.

No one knows why the immune system in apes accept foreign tissue long after stopping the drug. Some scientists suspect that immune cells activated by the foreign organ, but lacking the CD154 signal die soon after a transplant, although it is not known why the new generation of immune cells would not recognize and attack the tissue. Others suspect that the cells "blocked" can be immune sort of protection

Scientists warn it is too early to know if the acceptance is permanent -. Activated immune cells that scientists have found in the kidneys could still lead to possible rejection. Although Christian Larsen said transplant immunologist from Emory University, "It is spectacular to have a monkey out of immunosuppression with good graft function, for more than a year."

Science now wants a happy 21st birthday of the first test tube baby, Louise Joy Brown, born in England 25 July 1978. Brown debuted through in vitro fertilization technique developed by the gynecologist Patrick Steptoe and physiologist Robert G. Edwards. The success has attracted praise and ethical debates

Steptoe pioneered the use of laparoscopic surgery -. In which a long, thin telescope is inserted through a small incision in the abdominal cavity inflated - and he has developed a method for obtaining eggs from the ovaries. Edwards understood how to fertilize eggs outside the body and got his first success in 1968. In 1972, the pair attempted the first settlement, but had no luck until 1977. Critics have expressed concerns ethical and moral about the falsification of the creation of human life, and Steptoe and Edwards were reluctant to discuss the new procedure. They finally presented their work to the scientific community in 1979.

Brown was the first, but it is hardly the only test tube baby life today. . According to a global survey by the pharmaceutical company Oragnon, by 1994 more than 150,000 babies worldwide were born after in vitro fertilization

[Sources:EmilyMcMurrayEd Notable The Twentieth Century scientists (Gale Research Inc., ITP, 1995).]

W ASHINGTON, DC - A review by recasting program peers national Institutes of health (NIH) takes the intense fire of the AIDS community. Complaints activists patients and scientists have been accumulating for 2 weeks in the scientific review for NIH Center (CSR), which is considering the recommendations of a group led by Bruce Alberts, president of the National Academy of Sciences, to redraft grant applications rank groups ( science , 30 July, p. 666).

The Alberts committee suggested the review committees grouping peer in broad areas of science rather than specific disease categories or methods of research, as many are now grouped. For example, the panel proposed the removal of the existing category "AIDS and AIDS-related research" and moving the sections seven study under this heading in new, more general scientific categories such as immunology or behavioral processes.

One critic Mario Stevenson, a virologist at the University of Massachusetts, Worcester, said: "I am a firm believer in the old saying:" If it is not broke, do not fix it. "... And I think that criticism in the field of AIDS work very well." He and others have approved letters of protest, arguing that the elimination of the specific category dilute expertise AIDS and lower the quality of peer review. Charles Carpenter of Brown University, Chairman of the Board, which advises the NIH Office of Research on AIDS, sent a letter to CSR behalf of the warning that the proposed reform council could expose grant proposals "a review by investigators do not have appropriate AIDS research knowledge. "

CSR director Elvera Ehrenfeld said she was surprised by the angry reaction. She thinks that AIDS researchers may be confused by "an unfortunate misunderstanding" that the existing study items disappear. the AIDS panels would simply be placed into new groups, she said. However, some critics "may be valid," Ehrenfeld said, "and that's why we asked for feedback, "which are due to CSR on 15 October Alberts also wants to dispel concern.". It is clear that we must explore with AIDS researchers exactly what bothers and why "

B ETHESDA , M ARYLAND - Doctors and scientists from University of Pennsylvania defended their clinical judgment today in the case of Jesse Gelsinger, 18, who died September 17 while receiving experimental gene therapy. At a meeting here, the National Institutes of Health, a team leader and gene therapy pioneer James Wilson said he "felt comfortable" with the decision to treat the teenager with a strong dose of virus GM, though it is clear in retrospect that the viral concoction has killed Gelsinger.

Wilson and his co-researchers, Mark Batshaw and Steven Raper, presented data suggesting that unexplained anomaly is Gelsinger in metabolism, genetic makeup, or immune status triggered a toxic reaction to the therapy --a response that could not have been expected, they said, on the basis of earlier data.

Gelsinger had a rare genetic disorder, ornithine transcarbamylase (OTC) deficiency, which can cause a lethal buildup of ammonia in the body. Although he kept his symptoms under control through diet and the ammonia-drugs lowering, he volunteered to join the trial for gene therapy for risk, hoping it would lead to a cure. Gelsinger, 18 patient to be treated in the study died of respiratory failure four days after receiving a high dose of adenovirus genetically crippled (a common cause of human infections) which was equipped with the human gene little by little.

defense team came after gene therapy authorities to the Food and Drug Administration (FDA) yesterday blamed the Penn trial. Kathryn Zoon, director of FDA's Center for Biological evaluation products and research, said a preliminary investigation had found "gaps" to a protocol approved by the FDA agreed. An official at the FDA found that when Gelsinger underwent therapy, the ammonia level in the blood was more than 50% above the maximum permissible level specified in the memorandum, a deviation from the plan that the FDA n has not been notified in advance. Batshaw acknowledged that "we would have called FDA" about the change.

Other researchers say the team took a risky approach by administering high doses of the modified virus. "They pushed the edge of the envelope, "says Thomas Caskey, director of the therapy program and Merck Genome Gene West Point, Pennsylvania.

HIV may well be the most studied virus of all time, but the steps between its introduction into the body through sexual intercourse and an established infection remains mysterious . Now, researchers reported intriguing evidence that a poorly understood protein may allow the virus to sneak behind the defenses of the body. In addition to clarifying the mechanism of the sexual transmission of HIV, the findings identify new targets for vaccines against AIDS.

The new work, presented in two articles in the cell on March 3 , was born studies of dendritic cells, the sentinels that alert the immune system when the violent invading the borders of the body . The researchers reported that a protein called DC-SIGN carries HIV dendritic cells in the mucosa of the cervix or rectum to distant lymph nodes. There, the DC-SIGN hands HIV in CD4 ⁺ T cells, immune cells that the virus easily infects and destroys, eventually leading to AIDS.

The team, led by Yvette van Kooyk, a tumor immunologist at the Medical Center of the St. Radboud University in Nijmegen, the Netherlands, conducted test tube experiments to learn how HIV interacts with DC-SIGN. The protein binds tightly to the virus, they report, stabilize during the trip of the lining to lymph nodes. This stabilization makes a huge difference: No DC-SIGN, HIV has lost its infectivity in less than a day. Protected by the protein, however, the virus could infect CD4 cells after 4 days.

On a practical level, the results can inform vaccine design. To date, many HIV vaccine designers aim to elicit antibodies that disrupt HIV fusion with CD4 its targets. Now, one might seek to induce antibodies that block the binding of DC-SIGN to HIV. "It is a very elegant work," said AIDS researcher Douglas Richman of the University of California, San Diego.

T UCSON , A RIZONA - If the pharmaceutical companies are good at thing, there are tons of new molecules. In recent years they have embraced a technical producer of high-speed drugs known as combinatorial chemistry to multiply the new compounds by the millions. The problem is that few ever work against diseases. But at a meeting on the future of combinatorial chemistry here yesterday, a chemist proposed a new way to increase the chances :. Pair the most promising building blocks to produce compounds whose activity is much greater than the sum of their parts

a popular technique in combinatorial chemistry is to start with a handful of molecular building blocks then connecting in all possible combinations. As expected, the number of compounds quickly becomes unwieldy. Using all currently available building blocks, the researchers could produce a staggering 10 ⁶⁰ small combinations druglike molecules.

To make things more manageable, Jonathan Ellman of the University of California, Berkeley, and his colleagues have focused on the components with the best chance of success. They are turned toward a class of molecular building blocks called oximes which are common components of pharmaceuticals. The researchers screened a library of just over 300 oximes for their ability to bind to a cell-signaling protein called Src, which is considered too active in cancer and osteoporosis. When tested alone oximes, about 10% showed moderate ability to inhibit Src in the test tube. However, when these have been linked to poor binding, the story changed dramatically. The team synthesized Ellman about 4000 pairs of oxime and found a handful of potent inhibitors of Src, a success rate that usually requires much more compounds.

The new approach is powerful because it has the potential to produce drugs that bind to more than one part of a target molecule, said Sheila DeWitt, a combinatorial chemist Arqule, a company Woburn, Massachusetts. This could lead to a new way to make ultra powerful drugs. "If it works, it will have enormous value," she said.

B ETHESDA , M ARYLAND - It is time for bold action to stimulate the development of vaccines for major killers in the world - AIDS, malaria and tuberculosis - according to a panel of experts convened here May 22 to 23 Technically, these vaccines are feasible, the group concluded, but the funding will go up considerably

Scientists believe that new vaccines are the only way to get the great plagues of the world under control. Economists believe that healthy populations could also be a shot in the arm for development, particularly in Africa. But with the exception of AIDS, the pharmaceutical industry has not taken much interest in the development of vaccines against common diseases because they do not expect to make a profit. And there was little political support on Capitol Hill to pass on diseases that afflict some US citizens.

But it seems to change. Recently, the industry leaders have expressed a desire to help, and in January, President Clinton announced his Millennium Vaccine Initiative, in which he proposed a series of measures to boost research on vaccines. Bills introduced in the House and Senate would do the same. The meeting this week was held at the request of Clinton and hosted by the National Institute of Allergy and Infectious Diseases (NIAID), was set up to propose new ways to propel the development of vaccines. With the peaking political interest, "now is your chance, people," said NIAID Director Anthony Fauci them together researchers, experts in public health, and executives from the pharmaceutical and biotechnology industry

In three sessions -. For tuberculosis, malaria and AIDS - participants identified the main obstacles on the road to a vaccine and came with a plethora of ideas to make them disappear. The malaria researchers want the president to launch a "vaccination against malaria aggressive" and increase federal funding of the current $ 25 million to $ 500 million per year; Moreover, the US should commit to buying $ 500 million a year the value of vaccines once they have been developed to ensure the industry with a market. AIDS group called for a funding increase of 10 times, while TB researchers suggested the establishment of a new agency, flexible funding that rewards good scientific ideas quickly. The suggestions will be compiled into a report and sent to the White House.

Get scientists and industry to map out a common strategy "is a very important step," said Malegapuru Makgoba, Chairman of the South Africa Medical Research. And with the current political momentum, the results are handy, Makgoba said: ". I am confident, for example, that we will see a vaccine against AIDS in the next 5 or 6 years "

D URBAN , S OUTH A AFRICA - When the south African president Thabo Mbeki has risen to meet the opening ceremony of the international AIDS Conference XIII yesterday, thousands of researchers in packed Kingsmead Stadium hoped he was going to say three simple words: the causes of HIV AIDS. He did not do it. "He waffled while Rome burns," said Glenda Gray, a pediatrician who co-directs an HIV perinatal clinic in huge Chris Hani Baragwanath Hospital in Soweto.

Mbeki recently convened a panel to help his government develop policies against the growing AIDS crisis, but it has included so-called "dissidents", who insist that HIV does not cause the disease and whether AIDS is a new disease or old diseases collectively given a new name. scientists around the world have rebuked Mbeki to give new vitality to the dissidents, whose community arguments had it a few years ago to licensees background. Many hoped that the President would finally distance themselves from eccentric views.

But Mbeki addressed the issue indirectly. much of his speech quoted a report by the World Health Organization 1995 that fingered "poverty extreme "as" the biggest cause of ill health and suffering across the world. " Mbeki noted, however, that his government would continue to intensify its anti-AIDS campaign promoting condom use, support for research on vaccines against AIDS and HIV medications, and respond humanely "to people with AIDS and HIV. "But he made no mention of its decision not to provide relatively cheap course of anti-HIV drugs to infected, pregnant women, which studies have shown can reduce 50% HIV transmission to their babies.

failure of Mbeki to acknowledge directly that HIV causes AIDS researchers angered against AIDS in South Africa and elsewhere. "it was a good opportunity for him put a closure on the whole, and he did not, "complained virologist Lynn Morris, who works at the Johannesburg National Institute of virology and sat on the panel that Mbeki convened. Indeed, many researchers and activists have left during the speech by Mbeki.

Yet some South African researchers have seen up the speech as a step forward. "Considering all that we experienced in the past months, it is an excellent speech," said Malegapuru William Makgoba, Medical Research Council of the leader of the country and another member of the Mbeki panel. "He had the ability to just about AIDS. But he always talked about HIV-AIDS. Then he connects HIV to AIDS. "What some saw as the exact wording, Makgoba concluded was a" clever way "for Mbeki to disengage from the debate. Those who criticized the speech, Makgoba said, were" surly. "

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pig cells released an ancient virus when transplanted into mice lacking an immune system, according to results published in the August 17 issue of Nature . This transmission is a potential concern for xenotransplantation research, but there is still no evidence that the virus overnight guests or it could trigger an outbreak. "This virus is not very scary," says transplant biologist David Solomon of The Scripps Research Institute in La Jolla, California, who led the study.

All pig cells contain the so- called porcine endogenous retrovirus (PERV), which usually hibernates as a DNA fragment into the genome of the pig But when retroviral genes are activated. - we do not know how it happens - the cell begins churning out viral particles theoretically. these particles could spread to other species. Some scientists fear the virus could sicken transplant patients, or even spread to other people. Solomon and his colleagues decided to study the PERV activity in cells pancreatic islets, which have already been transplanted in pigs in some human diabetics.

the team injected cells of pig islets in mouse kidneys that lack immune system function. These so-called NOD / SCID accept pig tissues as their own (as do the transplant patients receiving immunosuppressive drugs). When the team tested the activity of PERV islands over the next seven weeks, they found signs of an active infection. Because the mouse lived in a sterile environment, the transplant procedure must be "awakened" the pig retroviruses. In addition, they found that the pig cells were scattered throughout the body in 17 of 25 mice, and some of these wandering cells had infected cells near the mouse.

This is not necessarily the cause of the alarm. Nobody has found no evidence that PERV is spreading in people or non-human primates used in research of xenotransplantation notes Khazal Paradis, a doctor of transplantation with Novartis in the UK. "The bottom line," Solomon adds, "is that we do not have sick animals, and we do not have sick patients."

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full text of Nature

a study in this week's issue of science showed that a new AIDS vaccine can protect monkeys from getting sick, providing new avenues for AIDS vaccine human. But experts warn that many barriers remain high, and there are currently no plans to move the experimental vaccine in human trials.

The study, led by Norman Letvin and Dan Barouch of Beth Israel Deaconess Medical Center in Boston, in collaboration with Merck Research Laboratories in West Point, Pennsylvania, combines several high-tech concepts. The heart of the vaccine is a bacterial DNA fragment, called a plasmid, which can carry genes from other organisms. genes contained a plasmid encoding SHIV proteins, a combination of HIV and simian cousin, SIV concocted laboratory. In addition, the researchers created another plasmid encoded a messenger of the immune system, interleukin-2 (IL-2), attached to a piece of an antibody, or immunoglobulin (Ig). This protein, the researchers hoped, would rev the immune response of the vaccine.

When challenged with a relatively high dose of SHIV which rapidly destroys the immune system in apes, animals that received the vaccine developed a fictitious disease or died within 140 days. The monkeys that received the DNA vaccine and IL-2 / Ig plasmid, however, fared better. All had an intact immune system and low levels of SHIV in their blood after 140 days

The researchers also added new fuel to a long-standing debate on the power of antibodies against another warrior, immunological killer T cells. In the early days of vaccine research against AIDS, almost everyone in favor of vaccines aimed to stimulate antibody. More recently, the killer T cells have become the preferred goal. This experiment showed that the killer T cells played the main role in the control of SHIV infection in monkeys.

"The study is very carefully done, and the results are as good or better than anything tried in experimental settings," said Ronald Desrosiers Central New England Regional Primate Research in Southborough, Massachusetts. But no should get their hopes up too high, he added. Desrosiers, whose laboratory first protected monkeys clean with a vaccine against AIDS 11 years ago, said that "we need to be careful to remember that these are optimized laboratory parameters. "

There are other obstacles, too. Interleukin-2 may have serious side effects and if used in the wrong dose, could hinder an effective immune response, says Emilio Emini, head of vaccine against AIDS researcher at Merck. Merck currently has a single DNA vaccine in a small human study and does not intend to test this more complex vaccine in humans.

Furthermore, notes Letvin, experience "challenged" the monkeys with a strain of SHIV that is identical to the DNA vaccine - a very artificial scenario. In the real world, vaccinated people would face a wide range of HIVs. Letvin but stressed that the point of the study is to demonstrate that a vaccine can accomplish if it powerfully stimulates killer T cells. "It is way short of our ultimate goal, but until we reach that, this is a good place to be," says Letvin.

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NIH vaccine against AIDS

the International AIDS vaccine Initiative

a vaccine to protect children against polio have instigated a recent outbreak of the disease in the Dominican Republic and Haiti - the first outbreak of polio in the Western Hemisphere in over 9 years. This is the first reliable report that a polio-strength vaccine strain can be returned to a virulent and contagious spread. A mass vaccination campaign already in the works is expected to contain the epidemic.

The oral polio vaccine is very effective and easy to administer. But because it uses live strains, but weakened virus, it causes associated paralytic polio vaccine in about 1 of every 750 000 people receiving, usually those whose immune system is weakened. There was no evidence that this form of the disease induced by the vaccine is contagious.

Now an epidemic on the island of Hispaniola demonstrates that the vaccine can mutate to a virulent form and spread. Three children in a rural area of ​​the Dominican Republic and another child in a remote area of ​​Haiti came down with paralytic poliomyelitis in July and August. None of the children had been vaccinated against the disease. Laboratory analysis, first by a local laboratory and then by the US Centers for Disease Control and Prevention in Atlanta, found that the children had been infected with a vaccine derived virus that had become virulent. The Pan American Health Organization (PAHO), which announced the results of the December 1, convened a group of scientists to study the data and recommend action.

The World Health Organization, PAHO is a division strives to eradicate polio worldwide by 05. That incident will delay the schedule remains to be seen, said Donald Henderson, an epidemiologist at Johns Hopkins University in Baltimore, Maryland, who led wHO's global eradication of smallpox successful. "We really want to focus on that and check in detail," says Henderson. "This comes as a big surprise for everyone."

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Johns Hopkins University in Baltimore is placing a big bet that the hot field of cell therapies will pay off. The university announced Tuesday it would use a $ 58.5 million gift from an anonymous donor to launch an ambitious cell Engineering Institute. Its researchers will try to reprogram human cells in treatments for a range of diseases, including amyotrophic lateral sclerosis (ALS), diabetes, and spinal cord.

One objective of the work will be on the stem so-called pluripotent cells. At the end of 1998, researchers at Johns Hopkins and John Gearhart Michael Shamblott and colleagues reported that they had isolated the so-called fetal germ cells taken from immature reproductive organs of aborted fetuses, which could become any type of cell in the body. Since then, the team tried to discover how to program the cells to become specific cell types such as neurons. Initial results were promising enough that the team has begun testing the cells in several animal models of the disease

But Gearhart said the fetal cells derived -. the use of which is disputed by some antiabortion groups-- is one area, the new institute will explore. The teams will work on stem cells derived from adults and from basic research into the molecular signals that govern the ability of a cell to make a new destiny. "We are not putting all our eggs in one basket," said Gearhart. The institute will also include immunologists who will try to find ways to make stem cell therapies compatible with the immune systems of patients. Private financing institute researchers will "not invulnerable" to the heated debate on the use of public funds for research on stem cells ( Science NOW, January 30, 01), says Evan Snyder stem cell researcher of children's Hospital Boston.

university has not yet appointed a director of the institute, which will employ 27 full-time researchers and involved 50 "associate researchers' other departments or institutions, Hopkins said Executive Vice Dean Elias Zerhouni. Finally, it will take two floors of a new basic research building, which should be completed in 03.

related site

Johns Hopkins press release about the new institute with information on some of the key researchers involved