Health Meaning

As a mark of death, the modified proteins called monoclonal antibodies are expected to stick to cancer cells and flag down immune fighters to destroy a tumor. But such a strategy, for whatever reason, have generally failed. Now scientists may have found a way to turn monoclonal antibodies into killing machines, after all: by linking them together. The results, reported in the current issue of Proceedings of the National Academy of Sciences , suggest that antibody dimers could be a promising new approach to the development of treatments against cancer.

These rare monoclonal antibodies are capable of killing cultured tumor cells seem to make it through an unexpected mechanism: instead attract other immune cells, antibodies trigger the tumor cell to stop dividing or undergo apoptosis, or programmed cell death. A team led by Ellen Vitetta of the University of Texas Southwestern Medical Center at Dallas has undertaken to examine this phenomenon in cells of Burkitt lymphoma, a disease in which a type of white blood cell called B cells divide uncontrollably, resulting tumors anywhere in the body. Monoclonal antibodies for latching to several different receptors on lymphoma cells were almost powerless. In large quantities, however, an antibody against a CD19 receptor showed poor ability to inhibit cell growth. Some of these antibodies, the researchers found, had formed pairs; when separated and tested alone, these dimers packed a powerful punch.

Researchers then tested dimers of monoclonal antibodies against other receptors lymphoma. All were better to stop the growth of tumor cells or promoting cell death. The researchers also tested the anti-CD19 antibody in mice with human Burkitt lymphoma tumors. Mice receiving the dimers, they found, lived up to 80% longer than the mice given the monomers. "It is an interesting observation," says immunologist Martin Glennie of Southampton University, U.K., "but the mechanism remains unclear." Vitetta The team will try to understand that in other tests in mice.

Nerve cells threatened by stroke or degenerative diseases can have a surprising new ally - microscopic spheres of carbon called buckyballs. A study published in Proceedings of the American Academy of Sciences tomorrow describes how buckyballs modified - that absorb nerve-destroying chemicals -. Delaying the onset of symptoms in mice suffering from Lou Gehrig's disease

standard buckyballs do not since they dissolve only work in highly toxic compounds such as benzene. Instead, Dugan used fullerenes modified by six pairs of soluble molecules in the carboxylic acid from water. Dugan and her colleagues added these antioxidant buckyballs to cultured neurons that have been deprived of oxygen and glucose (which occurs after a stroke) for one hour. Buckyballs cut neuronal death by 75%.

Dugan also buckyballs pumped into the cavity of mice bred to mimic the stomach to Lou Gehrig's disease. Untreated, these mice became progressively weaker in the doe and forelegs. They end up losing all muscle control, and die after about 130 days. The mice that received the modified buckyballs had their symptoms delayed 10 days and survived 8-10 days longer than untreated mice.

The discovery shows that buckyballs "act as an effective antioxidant," sweeping free radicals, said Jonathan Gitlin, a pediatric neurologist at the University of Washington. As free radicals have been implicated in many diseases, he says that modified buckyballs have broad therapeutic potential.

The program "AIDS United Nations, UNAIDS, next week plans to hold a closed meeting in Geneva which will begin new sort thorny questions about the ethics of conducting vaccine trials against HIV. A similar ethical dilemma is also discussed in today's New England Journal of Medicine ( NEJM ): if anti-HIV drugs considered standard care in the world developed should be available to people in developing countries who participate in clinical trials.

Peter Lurie and Sidney Wolfe of the advocacy organization focused on public health Citizen Research Group several trials around the world comparing placebo to various schemes of anti-HIV drug AZT to reduce HIV transmission of an infected pregnant mother to her child. The tests are designed to test patterns that are more affordable in poor countries. But Lurie and Wolfe - and NEJM editor Marcia Angell in an accompanying editorial. - Argue that because research has already shown that intensive treatment with AZT can reduce transmission by almost 70%, these trials are unethical

the issue is also critical for testing vaccines against AIDS, because ethics demands that people who are infected during a trial be given the best treatment available. Yet if everyone in a vaccine trial that becomes infected offered powerful anti-HIV drugs, it is extremely difficult - if not impossible - to detect whether the vaccine can delay or prevent the disease. Barry Bloom of the Albert Einstein College of Medicine in New York, who heads the UNAIDS Vaccine subcommittee, made this point at a congressional hearing last spring. Some researchers also claim that it is morally acceptable to use placebos to test treatments in countries where new HIV treatments are not available.

At the meeting of the UNAIDS subcommittee, scheduled for September 23 and 24, the panel will discuss "a framework for formulating these questions, and after a consultation period to try to reach a global consensus that protects the rights of everyone, "says Bloom. Lurie Public Citizen says that there should be one standard of care, but said," agreeably, it is a difficult situation. "Bloom hopes UNAIDS will hold a public meeting on the issue next spring.

The largest study yet to examine whether certain "environmental estrogens" - synthetic chemicals that can act like hormones in the body - could contribute to cancer breast cancer found no evidence of such a link. the research, to be published tomorrow in the New England Journal of Medicine , deals a blow to a popular theory to explain the recent increase breast cancer.

breast cancer rates are the highest in the developed countries, leading some researchers to believe that industrial pollution could be a major factor. the main suspects are two types 'environmental estrogens present in the adipose tissue of everybody. - polychlorinated biphenyls (PCBs) and DDE, a metabolic product of the pesticide DDT There are four years, a US study of 58 women with breast cancer patients seem to confirm the hypothesis: He suggested that women with high blood levels of DDE had a four times greater risk of breast cancer than women with normal levels. But a study over a year later found no link between breast cancer and DDE or PCBs.

Now a team led by epidemiologist David Hunter of the Harvard School of Public Health analyzed 240 cases of breast cancer occurring in a group of nearly 33,000 women after they gave samples blood in 1989 and 190 as part of the health study of nurses and nursing Harvard. Comparison of DDE and PCBs levels in the blood of 240 women with those of a control group of women without cancer, researchers found women with higher levels were at no greater risk for breast cancer. While "no epidemiological studies" can answer the question once and for all, Hunter said, "the weight of evidence is now strongly against the hypothesis" of a DDE or PCB-breast cancer link.

the Harvard findings and "other recent studies should reassure the public that weakly estrogenic organochlorine compounds such as PCBs, DDT and DDE are not a breast cancer cause," wrote Stephen Safe, a toxicologist at Texas a & M University, College station, an editorial in the same issue of NEJM . But all researchers are not willing to exempt the chemicals. Epidemiologist Devra Davis of the world resources Institute in Washington, DC, notes that older women tend to have higher levels of DDE as nurses, whose median age was 59. as a result, she said, the effects of chemical products may have been masked by stronger factors risk -. such as smoking and radiation nurses were exposed in their work

A new study in India shows that people newly infected experience fever of the AIDS virus, joint pain and night sweats weeks before conventional blood tests can detect infection. The study, published in the tomorrow of Journal of the American Medical Association , points to two other early denunciations to possible HIV infection :. genital and sexual recent ulcerations not protected with prostitutes

the global AIDS epidemic rages more furiously in India than in any other country, with as many as 5 million people infected, according to the World Health Organization Health. A team of three organizations - the National Institute of Allergy and Infectious Diseases (NIAID), the School of Hygiene at Johns Hopkins University and Public Health, and the National Institute for Research on AIDS in Pune India - studied 3874 people in India to identify HIV in the early warning signs and get a close examination of behaviors that spread the disease.

patients were tested for p24 antigen, an HIV core protein in a test that is much more expensive than standard antibody tests. According to Thomas Quinn laboratory immunoregulatory NIAID is the lead author of the study, the p24 antigen can be detected in blood infected by HIV 2 to 3 weeks after infection - several weeks before HIV antibodies first appear. "With the p24-antigen testing, we can identify HIV infections much sooner after they occur and get a more accurate picture of the risk factors and symptoms of acute HIV infection," he said .

the p24 positive patients had regularly from a collection of symptoms - fever, night sweats, joint pain and other symptoms, such as enlarged lymph nodes, oral thrush, diarrhea. and rash, which previous studies had linked to acute infection were rare in people with p24. Two other features stand out in the p24 positive patients. They were 50% more likely than uninfected people to have had of unprotected sex with a prostitute, and they were almost twice as likely to have an active genital ulcer

research provides a valuable look at the first signs of HIV infection, said Rod Hoff , an epidemiologist in the Division of AIDS at NIAID. Early detection means regimens may start earlier. Hoff cautions, however, that the symptoms observed in study participants could be nonrepresentative, because studies have been done on a small group of people seeking treatment for sexually transmitted diseases and subtype HIV can be unique.

Controversy ethical one year in clinical trials of AIDS seemed headed toward a resolution today, the government US unveiled data from Thailand show that the short-term treatment with the antiviral drug AZT halved the rate at which HIV, the AIDS virus is transmitted from mother to child at birth. This statement was released by the US Centers for Disease Control and Prevention (CDC) in Atlanta, which sponsored the trial in Thailand.

The results suggest that it may be possible to reduce the rate of HIV infection in infants in poor countries with a cheap version of AZT therapy more elaborate currently used in the United States and Europe . "This is very important," says epidemiologist Ken Nelson of Johns Hopkins University in Baltimore. " Is about to become real "" This means that the ability to deliver this kind of therapy "in the developing world

The new Thailand can also provide relief of another kind - ending debate emotional that raged in the public health community. critics, led by Sidney Wolfe public Citizen Inc. Ralph Nader Washington attacked CDC-sponsored studies in Thailand and Africa because some participants received only placebo while others have received AZT. Because the long-term AZT treatment is known to reduce the transmission rate in the United States and Europe, Wolfe argues, it is unethical to refuse such processing study participants in the developing world. the researchers have devised protocols that way, however, because they feared the effects of AZT therapy in the short term might be obscured unless they were compared directly with the results of an untreated group.

This debate is now moot. According to the official CDC Phillip Nieburg, Thai data show that HIV-positive pregnant women who received a daily dose of AZT for only 3 to 4 weeks before delivery were significantly less likely to transmit the deadly virus to their child than the were those who received no medication. The HIV transmission rate for women who received AZT was 9.2%, according to CDC, compared to 18.6% for the placebo group. For this reason, Nieburg said, the CDC decided that placebos should not be used in such tests, and Thai researchers have agreed not to include more women in the placebo group. Nieburg confirms that other leaders AZT studies sponsored by the United States, the United Nations and France also decided to give placebos.

Most pharmaceutical companies seeking to apply the wealth of data on the human genome in search of new drugs have turned to startups specialized help ( science , February 7, 1997, p. 767). But pharmaceutical giant is bucking that trend. Today, Novartis Pharma in Basel, Switzerland, has announced it is committing $ 250 million to create its own research institute dedicated to track the functions of many genes being discovered.

The Novartis Institute for Functional Genomics, to be based in La Jolla, California, is expected to be operational in 2 years and will be home to some 100 researchers, says neurobiologist Paul Herrling, Director of Research Novartis. The company decided to set up the institute, he adds, because it expects to achieve "a competitive edge" if it can effectively translate genetic information in drug targets. Other biotechnology experts wonder if the Novartis approach is better than the link with small businesses, however.

the Institute will bring together under one roof the various types of expertise to conduct studies of the function of large scale gene . This functional genomics, as it is called, includes bioinformatics, microarray technology, animal models, and other approaches to identify genes that cause human diseases and are therefore prime targets for development medication. "what we want is to create an institute that integrates these technologies," said Herrling. In addition, its scientists "will help develop high-capacity methods" that will speed up and simplify the determination not only of the functions of individual genes, but also of how these genes and their protein products interact.

Few companies have tried to build this vast expertise in-house, because "this model has not been successful overall," said G. Steven Burrill, head of Burrill and Associates, a private investment bank in San Francisco that specializes in the life sciences. In his experience, the best minds in functional genomics are much more likely to start their own businesses, where they can be owners and entrepreneurs, not just employees.

A virus is as a smart bomb, its protein shell a warhead containing DNA or RNA which can subvert genetic machinery of a cell. Now researchers describe in today's issue of Nature how this vehicle could be put to peaceful use, deliver drugs into cells.

Trevor Douglas, a materials scientist at Temple University, has spent years assembling molecules that could be cradled inside ferritin, a protein that carries iron around the body . The problem with ferritin, he says, is that it comes in one size. then a few years ago, Douglas saw a cartoon of a hollow virus coat and realized it could be used as a versatile container for molecules. With hundreds of known viruses, he said, "we have a whole library of shapes and sizes." Douglas teamed up with virologist Mark Young of Montana State University in Bozeman tinkering with making empty shells cowpea chlorotic mottle virus (CCMV).

CCMV, which normally mottled leaves of cowpea plants, is a polyhedron, or a ball multifaceted. When the solution pH is greater than 6, 5, VCC coating swell by 10%, the opening of 60 holes of about 2 nanometers in diameter. researchers have empty virus heads, called virions, and particles of a molecule called a tungstate well known in solution to pH above 6.5, and the tiny orbs tungstate flowed inside. After lowering the pH below 6.5, the holes in the closed virions, trapping inside tungstate. researcher who wants to use the virus head for transporting a drug could adapt the virion to meet the needs of the molecule, said Douglas.

Using virions for delivery of drugs "is an own concept," says Paul Robbins, a molecular geneticist at the University of Pittsburgh Medical School, however, he noted, several obstacles remain -. It including how to work with viruses that do swell and contract in changing the pH and how to trick the immune system to attack not virions. "the work is almost a proof of concept at this point," Douglas said .

educate individuals at high risk of HIV infection manages to get them to engage in safe sex. Experts say the discovery, reported in tomorrow's issue Science , bodes well for reducing rates of sexually transmitted diseases (STDs), especially in developing countries.

U.S. populations present the greatest risk of HIV infection are minority groups in urban low-income areas. African Americans, for example, accounted for 45% of new AIDS cases in 1997 and contract AIDS at about eight times the rate of whites. Hispanics accounted for 21% of new AIDS cases. Investigators from the HIV prevention trial multisite at the National Institute of Mental Health in Rockville, Maryland, wanted to see if the education programs could reduce infection rates.

The team recruited 3706 men and women in health centers in the inner city over five cities. Almost all participants were African-American or Hispanic; all were treated in the past for STDs. Half the subjects were randomly assigned to attend seven meetings in small groups, each of at least 1.5 hours, where they received counseling on sexual risk behaviors. Others attended a single session, which included a one hour video on the subject. All were asked to fill out survey forms every 0 days describing their behavior and symptoms of STDs. The team is based on questionnaires because, say the researchers, they feared that the blood or to require HIV tests cause many subjects to give up.

A year later, participants in longer programs reported having unprotected sex at least half as often as they had before the sessions and seemed to have an STD rates lower than the group short session. The clinical records of the study period showed that patients with long-session were half as likely as other subjects to be infected with gonorrhea. STD symptoms reported on the questionnaires subjects jibed with symptoms recorded by clinicians in the study. "We have a sense that data is reported accurately," says Ellen Stover, head of the NIMH Division supporting the study.

"This is an exciting development," said Michael Merson School of Public Health Yale University. Merson, who formerly ran the World Programme of the World Health Organization AIDS, says study has implications for AIDS programs abroad because it demonstrates that the sex safety education can help stem the spread of STDs in populations with inadequate health care.

W ASHINGTON , DC - In a move that dismayed and primatologists activists for animal rights, the US Air Force announced today that it is most of the chimpanzee colony at a research organization rather than remove chimpanzees. The chimpanzee colony, which includes more than 140 animals, has been used for research ranging from the effects of heat and acceleration of hepatitis and HIV. Over 0 chimpanzees infected with HIV or hepatitis.

Although the Air Force has abandoned his own research on chimpanzees in the 1970s, it has since allowed the Coulston Private Foundation, the new guardian of 111 chimpanzees, to conduct experiments on animals. The foundation plans to continue to study the effects of aging and HIV on chimpanzees, now housed at Holloman Air Force Base in Alamogordo, New Mexico. 30 other chimpanzees, who are not infected, will be donated to Primarily Primates, a sanctuary for retired Texas.

To determine who should get custody of chimpanzees, the Air Force said he considered factors such as financial resources and past experience in the treatment of animals. But "the Air Force has no preference as to whether the animals have been removed or used for other research," said Col. Jack Blackhurst, Associate Deputy Minister Assistant Secretary for Science, technology and engineering.

the decision has angered some experts chimpanzees. Twice, they note, the Coulston Foundation was quoted by the Department of Agriculture (USDA) of the United States . for violation of the Act on the protection of animals and causing chimpanzee deaths the first incident, a 1993 overheat accident that killed three animals, resulting in a fine and renovation of Coulston facilities; the second is still under investigation, said Ed Curlette, a spokesman for the government of the USDA.

This file should have triggered "alarm bells" said Roger Fouts, co-director of the Institute Chimpanzee and human communication at Central Washington University in Ellensburg. It is time, Fouts said, to "start treating [chimpanzees] other beings rather than fur test tubes." The Coulston Foundation replied that treats its neighborhoods with care and dignity. "We take our care chimp very, very seriously, "said spokesman Don McKinney Coulston.

In plying rats with cocaine, researchers have come together to define the boundary between drug use and addiction. Their study, published in tomorrow's issue of Science , shows that rats are looking more and more cocaine that if offered the drug for several hours.

George Koob, Professor of Neuropharmacology at The Scripps Research Institute in La Jolla, California, was intrigued by a study showing that some rats --- when offered as much cocaine they wanted for 3:00 - gradually increased their doses, while others remained stable. Seeking to crystallize the difference in doping styles and question the importance of the availability of cocaine, Koob and postdoctoral Serge Ahmed divided dozens of rats into two groups: one that could receive cocaine for 6 hours per day, another who had only an hour to get high. The rats had a lever they could support to receive a cocaine infusion painless intravenously.

Over a period of about 2 weeks, the rats of Group 6 hours gradually escalating cocaine use, until they are themselves both doses as often - about every 3 minutes - the rats of group 1 hour were. The results suggest that rats with restricted access to the drug were better able to control their use of it, while those with freer access abused. "There is a biological change that occurs somewhere in an animal that has access to the drug for a long period of time," says Koob, who believes that his animal model accurately describes the transition from drug use addiction

experts applaud the study while warning that the results may not apply to people. "I'm very impressed," said Klaus Miczek, professor of pharmacology at Tufts University in Medford, Massachusetts. However, he adds, "this is a rat model, not a primate model."

P ARIS - The number of people infected with HIV has increased 10% this year, according to estimates , 33.4 million worldwide, according to a report released today by the joint United Nations Programme on HIV / AIDS and the world health Organization. "This is grim news," Peter Piot, executive director of UNAIDS, told a press conference today. Half of all new infections were 15 to 24 years -. About 7000 per day

most affected are the countries of sub-Saharan Africa, where nearly 12 million people died of AIDS-related illnesses --83% of all AIDS deaths up 'now. This region had 4 million new infections in 1998, and the rate of infection shows no signs of reflux. "The worst is yet to come," predicts Agathe Lawson, the UNAIDS representative in Côte d'Ivoire.

While AIDS deaths have declined in North America and Western Europe, health authorities have made some inroads in limiting the spread of HIV. As every year during the last decade, the number of new infections has hovered around 75,000.

C hicago - Most AIDS researchers have long believed that HIV-1 the main form of the AIDS virus jumped from chimps to humans. But the data in support of this theory has been difficult to find. Now Beatrice Hahn of the University of Alabama at Birmingham and colleagues have reconstructed what is being hailed as the best case yet for the chimpanzee connection

Hahn genetic detective work -. She described in the speech here at the opening of the Sixth Conference on Retroviruses and Opportunistic Infections - indicates that a particular chimpanzee subspecies, found in an area that includes Gabon, Cameroon and Guinea Equatorial is the original source of the rights of HIV-1 infections. She speculates that butchering chimpanzees - a practice, she noted, is common in some West African equatorial regions - may have provided the route for transmission. A paper on the results will be published in Thursday's Nature

HIV virus as scientists had already found in only three chimpanzees :. Two of Gabon and a third of what was then Zaire. (Viruses appear to cause disease in animals.) An analysis of the genetic sequences of these viruses, called SIVcpz, revealed that both Gabon strains are closely related to HIV-1 strains found in humans, but the Zaire strain is quite different, leading some to doubt that chimpanzees were the original reservoir. Hahn has now isolated another strain SIVcpz from a tissue sample from a chimpanzee named Marilyn who died in a research colony in the United States in 1985; it was found that similarly to the Gabon strains.

Hahn and colleagues analyzed mitochondrial DNA of four chimpanzees and found that the Gabonese animals and Marilyn all belonged to a subspecies, Pan troglodytes troglodytes . The Zairian animal belonged to a different subspecies P.T. schweinfurthii . Hahn believes that SIVcpz perhaps chimpanzees for hundreds of thousands of years, and that the viral strains have evolved to be specific subspecies of chimpanzees, which are isolated from each other by rivers. Some subspecies can harbor the virus, she said, while others may be infected with a strain that is less likely to spread among humans.

Vanessa Hirsch, a primate researcher at the National Institute of Allergy and Infectious Diseases, said she is impressed by the data. "Everybody has somehow been pussy-foot around the issue of whether chimpanzees are the source," says Hirsch. "Like most isolates are studied, it becomes more credible."

an AIDS research institute long prioritized vaccines has finally found a director. After a search of 18 months, the National Institutes of Health (NIH) appoint University of Michigan, Ann Arbor, molecular biologist Gary Nabel as the first head of the high profile new center Science Now has learned. The announcement could come as early as tomorrow.

In May 1997, President Bill Clinton announced the creation of the new vaccine research center with much fanfare ( Science 23 May 1997, p. 1184). He said the center, under construction on the outskirts of Washington, NIH campus, would spearhead efforts to develop, within a decade, a vaccine to prevent people from contracting HIV. While planning for the center forged ahead, however, the NIH administrators had difficulty recruiting a director, with several candidates victim of bureaucratic conflicts. The delay has prompted criticism from some AIDS activists, who said the administration did not follow well on its plans.

Earlier this year, however, word leaked that Nabel had emerged as the leading candidate for the position. New rankled some vaccine researchers, who noted that while he is a recognized authority on the use of gene therapy to combat AIDS, there is a newcomer to vaccine research. Yet the selection Nabel is "a great choice," said the researcher AIDS Ashley Haase of the University of Minnesota, Minneapolis. Nable "may be relatively new to the [vaccine] game," he said, "but it will bring a new perspective and get a lot of support" the veterans in the field.

Even the infamous bacteria Helicobacter pylori , which can cause chronic gastritis and peptic ulcers, may have qualities redemption. The inhabitant of the ubiquitous stomach produces an antibacterial peptide that can offer protection against other enteric pathogens, according to a study in tomorrow's issue of Nature .

H. pylori plagues one in two human stomachs in the Western world, often for life, but most infections go unnoticed. The microbe is even more widespread in the developing world, leading some scientists to speculate that H. pylori can be part of our natural gastrointestinal flora - some say it might even offer some benefits his host, like many other enteric bacteria. Last year, a study suggested that H. pylori could boost immunity to other intestinal pathogens such as cholera causing Vibrio cholerae . It is also known that many bacteria produce antibiotics compounds that ward off competitors.

So molecular microbiologist Staffan Normark of the Karolinska Institute in Stockholm, Sweden, wondered if H. pylori did something similar. Preparation of H. pylori "shake" in a high-tech version of a blender, Normark and his team found that it effectively killed other bacteria, such as Escherichia coli and Bacillus megaterium . They then searched the genome of H. pylori for sequences that match those of two dozen antibacterial peptides called cecropins, first isolated from insects in the 70 They found that the first 20 amino acids of a protein called RpL1 match a sequence of the cecropin. When the researchers synthesized this peptide, they found that he killed 99.5% of E. coli culture in just 20 minutes. H. pylori , on the other hand, was resistant to cecropin.

"Unlike conventional antibiotics, these peptides kill very quickly," said Normark, "and they are also active against bacteria that do not divide," which would make them attractive cecropins for drug developers. But it remains to see if the H. pylori in your stomach protects against notorious bugs such as E. coli strain that causes food poisoning or V. cholerae .

For Martin Blaser, an infectious disease specialist at Vanderbilt University in Nashville, Tennessee, "it is very refreshing to see evidence that there are potential benefits" of H. pylori to compensate for the damage it causes. "In a world in black and white," he said, " H. pylori is gray."

A high-pressure solution can significantly improve the delivery of therapeutic DNA into cells without the need for virus carriers. The discovery, reported in tomorrow Proceedings of the National Academy of Sciences , could help improve the chances of success of cardiovascular transplants and other operations.

A type of gene therapy called antisense therapy, designed to interfere with the expression of certain unwanted genes. the base by base, scientists build a short strand of DNA that exactly matches a portion of the gene's DNA sequence. Inside a cell, the antisense sequence binds to and inactivates the gene messenger RNA that normally direct the cellular machinery to produce the corresponding protein. Cardiologists, among them surgeon Michael Mann and colleagues at Harvard Medical School in Boston, showed that the use of antisense DNA to block the genes associated with graft rejection and disease can significantly improve the success surgery in laboratory animals. The challenge was to develop a way to circumvent the immune system and cell defenses and deliver foreign DNA to good cells.

A preferred technique for delivering foreign DNA into cells is to use a modified virus as the messenger. Mann and his team have a different approach. They removed over 100 rat hearts and filled the cavities of the heart and blood vessels with a saline solution containing an antisense sequence designed to block a gene for an inflammatory protein. After bathing the heart for 30 minutes at pressures up to 2 atmospheres, they transplanted hearts again in rats. Three days later, they found that half the nuclei of cardiac cells had taken the antisense DNA. Delivery rates with other techniques, including modified viruses have rarely exceeded 30%.

When researchers have tried this high pressure perfusion technique on the veins of the human legs, 0% of cell nuclei took antisense DNA, and production of inflammatory proteins dropped. Researchers still do not why the method works, but it may simply involve more effective dissemination and, perhaps, the changes induced by the pressure in the cell and nuclear membranes.

The results impress experts gene therapy. "I think it's great," says Gary Nabel, director of the National Institutes Vaccine Research Center of Health, who worked on cardiovascular gene therapy. The technique is particularly interesting, he says, because "it can be simplified and put into practice in the operating room," where surgeons could manipulate transplanted tissue as needed. Nabel also believes that high-pressure solutions could be adapted for use in gene therapies that provide replacement genes to cells, possibly without removing the body tissues.

The National Institutes of Health (NIH), flush with cash thanks to strong congressional support for biomedicine in recent years, is to enter the synchrotron construction company. Yesterday, officials of the NIH announced plans to spend $ 18 million this year to help pay for upgrades to and synchrotrons California- based in New York, which ricochet powerful X-ray beams out materials to determine their atomic structure . NIH officials say they hope the money will help meet the growing demand for "beam time" among biologists seek to reveal the secrets of the cell at the atomic scale.

synchrotrons have long been a favored tool among physicists, chemists and materials scientists, making funding for stage size machines province Department of Energy (DOE). But the ministry strapped increasingly sought NIH to help, as the number of researchers in biology in plants proliferated around 5% in 190 to almost one third in 1997. with the genome project churning of new protein sequences by hundreds, demand should grow. "We said that we must do something about it," says Marvin Cassman, who heads NIH National Institute of General medical sciences in Bethesda, Maryland

much this something -. $ 14 million - will kick-off of a 4 year, $ 53 million upgrade of the storage ring central electron synchrotron Stanford Radiation Laboratory (SSRL) in Menlo Park, California. When completed in 02, updated the ring, which produces highly focused X-ray beams popular with users, should generate 10 to 100 times the power of X-rays in progress, allowing researchers to collect data faster and the study of crystals smaller protein than they can now. The remaining $ 4 million will support new X-ray detectors and storage ring improvements to national synchrotron light source at Brookhaven National Laboratory in Upton, New York.

"I think it's extremely important," said the director SSRL Keith Hodgson of the new leadership of NIH. "Given the difficult economic climate in DOE, I think [upgrades] would have been difficult to remove." By supporting improvements to central storage rings, said Hodgson, NIH money will benefit not only biologists, but all users of the machines.

Scientists have come a step closer to understanding the cause of childhood diabetes, a disease in which the immune system body destroys its own insulin-producing cells. A paper in the September issue of Nature Medicine suggests that the insulin itself, on the surface of cells that produce it, triggers destruction. The study may help develop strategies to prevent the disease

Previous studies had shown that T cells, immune cells that normally fight infection, are responsible for the attack. - And destroy - the so-called island b cells, insulin factories in the pancreas. The attack can rob patients of the ability to produce insulin for the rest of their lives. Many scientists are trying to identify this protein in b cells is the antigen that triggers the attack, hoping that it can be used in some way to "teach" the immune system that n is not an enemy.

Much of the research involved the CD4 or "helper" T cells, which interact with other immune cells to trigger the production of antibodies and other immune responses, contributing to the development of diabetes. But immunologists Susan Wong, Charles Janeway and colleagues from Yale University were more interested in another class of T cells, called CD8 cells or killer T. In 1996, they isolated an aggressive CD8 cells from mice with a disease very similar to human diabetes and showed that, when transplanted into other mice, it causes diabetes in less than a week. Because cells from young mice that are not sick yet, but later developed diabetes, the researchers thought that the cells could play a role in the first phase of the disease, maybe even start the immune attack on islet cells.

In the current study, the team set out to find that the CD8 cells could recognize the islet cells. First, they took the tumor cells multiply rapidly and genetically engineered to produce them en masse hundreds of pancreatic proteins. Then, they inserted a gene in their CD8 T cells that causes the cells turn blue when they cling to the particular antigen which activates them. In this way they were able to identify insulin as the antigen; they may even identify a specific sequence of nine amino acids of the hormone that T cells recognized.

Wong said it is the first time researchers have identified a trigger for the CD8 cells in autoimmune disease. "It is a beautiful study," agrees immunologist George Eisenbarth of Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver. "This new insight into the role of insulin is exciting."

In addition, Wong said, the conclusion that insulin is the likely culprit bolsters the rationale for an idea that is already being tested. For reasons not well understood, some trigger disease antigens, when taken orally, can suppress immune reactions that would otherwise be directed against them, and clinical trials are underway to see if the oral insulin can inhibit the development of diabetes in children at risk of disease. The results suggest another possibility as well, Eisenbarth said. If insulin reactive CD8 cells are the source of the disease, researchers may be able to find ways to disarm.

Drugs called statins, taken by tens of millions of people to lower their cholesterol levels, may be beneficial for bones as well. In tomorrow Science , the researchers suggest that statins trigger bone growth in rodents. If they work the same in humans, statins could be the first drug capable of stimulating growth of bones weakened by osteoporosis, a disease that often affects postmenopausal women.

Statins levels of blood cholesterol by blocking an enzyme called HMG CoA reductase -A, which helps synthesize lipids. But there were already indications that drugs could do much more than that. For example, a 1998 analysis of many studies have shown that people who take medications in large clinical trials had lower death rates from all causes, not just heart disease.

Even so, the effect on the bone was a "total surprise," says endocrinologist Greg Mundy biotechnology company OsteoScreen and the University of Texas Health Science Center in San Antonio. He and his team was screening a library of 30,000 natural compounds to find potential medicines that strengthen bone. What they wanted was something to stimulate the production of bone morphogenetic protein 2 (BMP-2), which stimulates bone growth . a single compound worked :. lovastatin, a molecule derived from a strain of the fungus Aspergillus terreus

to check the actions of the drug in animals, the team injected lovastatin in the fabric above the cap bones of young mice. After dosing the animals three times a day for 5 days, the researchers found that the bone treated increased by nearly 50% greater than in mice injected with a control solution. Another statin called simvastatin, also looked promising, this time in female rats whose ovaries were removed to mimic the hormonal changes of menopause, when many women begin to lose bone density. In rats given oral doses of statins for 35 days, the leg bones and vertebrae were nearly twice as dense as in rats that received placebo. How the drug works is still a mystery.

The observation could be "a real breakthrough" in osteoporosis, says Lawrence Riggs, an endocrinologist at the Mayo Clinic in Rochester, Minnesota, since the drugs available today can slow bone current loss, but can not completely repair the weakened bones. The researchers point out that the doses used to control cholesterol levels may be too low to strengthen bones. However, work can point to similar molecules that could better promote bone formation. - Perhaps with the bonus of lower cholesterol

W ASHINGTON , DC - A little nicotine can go a long way toward the improving the lives of people with a condition called Tourette syndrome. Small doses of nicotine may increase the effects of other drugs, allowing patients to reduce their dose, neuroscientist Paul Sanberg of the University of Florida, Tampa, reported Feb. 21 at the annual meeting of the American Association for the Advancement science, which publishes science

people with Tourette syndrome have verbal tics and muscle. NOW; they shrug, wave, grin, or uncontrollable shaking their heads, and can bark or occasionally blurt curses. Most of the estimated 100,000 American children with this syndrome take small doses of powerful antipsychotic drugs such as haloperidol in controlling these symptoms. But the drugs also slow thinking and movement, and other serious side effects such as dizziness, headaches and dehydration.

During the last decade, Sandberg and others have gathered anecdotal evidence that low doses of nicotine patches or gum to enhance the potential of tic-calming other medicines also affect seen in rats. These observations suggest that children could reduce their total consumption of drugs by adding a bit of nicotine in their diet. "We're not talking about tobacco," says Sandberg

To test this hypothesis, Sanberg and colleagues enrolled 70 children aged 8 to 17 in a double-blind trial. half of them wore skin patches releasing 7 milligrams of nicotine per day for 8 weeks, while the other half was placebo spots. All continued to take their medication. The first group included much more normally, with fewer tics and verbal outbursts, Sanberg reported. Even when the dose of haloperidol participants was lowered halfway through the study, "the level of improvement was maintained." Sandberg declined to reveal the details of the study because the data are not yet published.

The study did not suggest that children become addicted to nicotine, or no previous trial. But there were minor side effects such as stomach pain and itching caused by the patch. Sandberg and others are now trying to find nicotinelike substances without the side effects that could be taken orally.

The medical community has been eagerly awaiting the data, said Gerald Erenberg, a pediatric neurologist at the Cleveland Clinic Foundation in Ohio. But "because nicotine was watching a villain as such, we are conservative about the results," he said. Erenberg said he hopes the study will be replicated by other researchers.

- S AN F rancisco - For drug makers, discovery a new drug is not the whole battle. Getting a compound inside the cells can be equally challenging. drug soluble in water, for example, can travel in the bloodstream, but once they arrive at their destination, they are stopped by the fatty membrane surrounding cells. The researchers found a chemical tag that seems to act as a universal pass, escorting compounds inside cells.

Discover the new mat, a peptide, or a short protein fragment, was inspired in part by a surprising source: the AIDS virus. In the early 1980s, researchers discovered that a protein fragment called Tat helps HIV viral proteins enter cells. Other research teams have shown that binding Tat drug can help boost absorption. But Tat is difficult to synthesize and too expensive for widespread use, so a team led by organic chemist Paul Wender of Stanford University undertook to find a cheaper alternative, more effective.

The researchers began by analyzing Tat then systematically rearrange its amino acids. After testing many candidates, they found only one version - a chain of arginine - which was even more effective than Tat in infiltrating cells. When they tested the peptide, it carries a drug through the grafted human skin on a mouse - an impossible feat without the peptide, they reported last week at a meeting of the American Chemical Society

"This is a. significant development," said John Voorhees, a dermatologist at the University of Michigan Medical School in Ann Arbor. When doctors treat skin conditions, they give a drug in capsule and hopefully some of them will make its way from the intestine to the bloodstream and eventually inside the cells skin. A topical cream may be more effective for the treatment of conditions such as psoriasis and eczema and may carry fewer side effects, Voorhees said.

When Napoleon died in exile on the island of St. Helena in 1821, he was poisoned by arsenic, or is it succumbed to stomach cancer his doctors say? The debate, smoldering for years, received a public release this month in Paris.

Ben Weider, tycoon fitness equipment and student longtime Napoleon who heads the International Napoleonic Society based in Montreal, made the case for arsenic poisoning before a group 'french historians, scientists and politicians at a luncheon on May 5, the 179th anniversary of the death of Napoleon. He argues that Napoleon was quietly assassinated - to avoid any possibility of his return to France - by infusions of arsenic in his wine. He said several hair analyzed by the FBI in 1995 showed high arsenic levels ranging from 20 to 50 parts per million. (The average today is about 1 ppm.) Statements by those around Napoleon in his last years are full of allusions to physical problems - such as light sensitivity, hair loss, sleep problems, and neurological symptoms - compatible with arsenic poisoning, he said. In addition, he says the autopsy reports show that Napoleon died fat, which is incompatible with withering away of cancer.

The leaders of the Napoleonic Society of America, based in Clearwater, Florida, say the arsenic theory Weider is complete hogwash. President Robert Snibbe says there is no evidence that the analyzed hair was actually Napoleon, and the general lack of a main symptoms of arsenic poisoning: palms and soles of the feet leathery . Philip Corso, a plastic surgeon at the Medical School of Yale University, said there were five large autopsy reports by eight doctors, who all agree that Napoleon suffered extensive stomach cancer . According to Corso, Napoleon's father died of stomach cancer, and he himself had predicted he would die of the same disease.

To solve the question of identity, Corso gave some hair to scientists from the State University of Pennsylvania, but he says they need a lot more hair to get any useful DNA. Meanwhile, Snibbe trying to get permission to dig a nephew of Napoleon who is buried in Florida, to get a DNA reference family. All sides, of course, would settle the matter by digging big man himself from his tomb at Les Invalides.

South Korea is home to some of the most difficult bugs in the world. The country has achieved this dubious distinction in part by antibiotics readily available. Now it is finally cracking down by requiring doctors' prescriptions.

For decades, Korea has allowed pharmacists to sell drugs freely as a way to help people who were too poor to see doctors. Ironically, the practice has become a lucrative sideline for physicians, who supplemented their income by doubling pharmacists.

The long-term result of this policy, combined with the spread of resistant clones elsewhere, was a Sky-high rate of resistance to antibiotics that bacteria evolve enthusiastically in response to repeated challenges. According to a 1997 study by Song Jae Hoon, head of the infectious diseases division at Samsung Medical Center in Seoul, more than 80% of pneumococci were resistant to penicillin. The rate of resistance to antibiotics 10 others have also surpassed those of nine other Asian countries studied.

The government finally responded to the problem by requiring patients to get doctors' prescriptions for most drugs. The new law came into force on July 1, triggering an unprecedented strike six days by doctors. But some older antibiotics are still exempt from the new law - the Korean Medical Association says that the majority of government policy makers and advisers are pharmacists

Deceit by patients can be generalized in clinical trials, researchers warn. The degree of cheating in a test - a whopping 30% - is "surprisingly high" and "worrying", two teams report this month Chest , the journal of the American College of Chest Physicians. Based on this and other recent studies, the authors warn that "some kind of duplicity ... can be expected in almost all clinical trials."

The massive cheating turned after two research teams - one at Johns Hopkins University and the other at the University of California, Los Angeles (UCLA) - examined how often former smokers suffering from obstructive lung disease are unable to use the bronchodilator inhalers. Michael Simmons, a UCLA biostatistician, and four colleagues told volunteers in this trial that the use of drugs would be monitored. But they do not mention that a small device on the inhaler was recording the exact time and extent of use.

When the researchers looked at patterns of use of the inhaler later, they found that many patients just poured the inhalers before their quarterly clinic visits - indicating that they dumping of the drug in order to appear to be in compliance with the treatment regimen. Among 101 patients monitored for a year, 30 "undervalued" drug from an inhaler at least once misrepresented a doctor during an examination that they had taken the drug.

Cynthia Rand, a health psychologist at Hopkins and co-author of the study, explains that many other researchers identified the non-compliance as a problem, but this study breaks all previous records for the extent of the deception. To the surprise of researchers, patients duplicity proved to be "our finest, eager patients to please, the most enjoyable," said Rand. After reviewing dozens of factors such as race, gender, education, smoking history, the researchers were unable to find the quality that set apart cheaters. In addition, those who were dishonest about taking their medication were less likely to lie about current smoking (verified by testing saliva).

Rand said there is no way to predict who will cheat. An important lesson, she said, is that no amount of exhortation will make consistent volunteers -. Unless supported by a good method of checking

cheating patient may have "serious and potentially significant" impact on the results of clinical research, said Rand. If unsupported, cheaters are misclassified as followers scrupulous, introducing "a lot of noise" in the data. Analysis of dose-response calculations can be badly skewed in studies that do not carefully monitor cheating, she fears.

The extent of cheating in this study is a revelation, says psychiatrist Bruce Bender of the National Jewish Medical and Research Center in Denver, Colorado. The report is not good news, Bender adds, because it suggests that many clinical trials may be underestimating the potency of the drug.

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Summary Chest article

PARIS - Researchers from the Biomedical research agency giant France, INSERM, rejoice over a 16% increase in the the organization for the year 01. the research budget windfall announced by INSERM CEO Claude Griscelli last week, is the largest increase since 1983. It will give the organization 260 laboratories an extra $ $ 13 million compared to the current research budget of approximately $ 83 million. In addition, 100 new research positions will be created, bringing the total number of scientists around 4000.

The new currency represents "a significant amount," said neuroscientist Marc Peschanski, laboratory director of INSERM neuroplasticity and Therapeutics near Paris. "It will really mean something" for laboratories. Geneticist Judith Melki, director of the Molecular Neurogenetics Laboratory in the Paris suburb of Evry, added that the influx of new money will help boost the "modest" argue that the laboratory INSERM received in recent years .

Griscelli said science that such a large increase was "totally unexpected." Indeed, other public research organizations were awarded smaller amounts - the basic research agency CNRS, for example, receive a blow from 9% Research thumb. Griscelli said that one reason the government smiled so hard on INSERM may be that the agency was prepared to shape its research program based on the priorities set by the Ministry of Research, who wants to see research on life sciences to repay in new therapies and products ( science , September 8, p. 1667). As CNRS researchers have strongly resisted what many see as government interference in research directions, INSERM has largely accepted the guiding hand of government. Thus the new money will be spent in a number of priority areas, including gene therapy, vaccines, research in psychiatry, and epidemiology

Griscelli insists that the basic science continue to receive strong support at INSERM :. "I do not know want to prioritize decreasing funding for basic research."

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INSERM

The number of new HIV infections in sub-Saharan Africa may have stabilized, according to new figures released today by the Joint United Nations Programme on HIV / AIDS (UNAIDS) and the World health Organization (WHO). At the end of this year, there will be about 3.8 million new infections, down from 4 million in 1999, according to the report. But the extent of the disease is still alarming; worldwide, the number of people living with HIV or AIDS has increased to 36.1 million, more than 50% higher than the WHO predicted in 1991.

UNAIDS attributes the slight decrease Sub-Saharan Africa to prevention programs in countries such as Uganda, and the fact that infection rates are already so high that relatively few people in vulnerable groups are left to infect. The decline of the infection "is not bad news, but it is certainly not good news," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. The facts are that dark last year, 2.4 million people died of AIDS in the region, while the number of people living with the disease has risen to 25.3 million.

Meanwhile, the number of new HIV infections jumped 67% in the Eastern Europe the figures are particularly grim in Russia, where 50,000 new HIV infections were recorded in 00. - more than in all previous years ". it just exploded, "said Seth Berkley, president of the International AIDS Vaccine Initiative in New York City. The number of people with AIDS in Eastern Europe and Central Asia is now 700,000, against 920,000 in the US

The increase in HIV infections in Eastern Europe is mainly among injecting drug users -. For the time being. The problem, says Berkley, is that once HIV spreads to the rest of the population, it quickly becomes a generalized epidemic.

Related Sites

The UNAIDS / WHO report

HIV research at NIAID

The International AIDS Vaccine Initiative

Marijuana is known to set the mood for love, particularly among women. Now scientists have new perspectives on how the drug exerts its effects - at least in rats. A study published in the January 23 Proceedings of the National Academy of Sciences shows that the influences of drug active substances acts through two chemical messengers known to have a strong influence on reproductive behavior.

In rats as in people, sexual behavior requires certain hormones. If the ovaries are removed from a female rat, for example, she will not raise her rump when she is ready to mate. This behavior can be restored with injections of the sex hormones estrogen and progesterone - and also with plans of the active ingredient of marijuana, 9-tetrahydrocannabinol (THC)

To get a better handle on this Indeed, molecular biologist Shaila. Mani from Baylor College of Medicine in Houston injected rats with chemicals that block one of the three receptors in the brain cannabinoid receptor 1 (CB1), which is known to bind to THC and thought to trigger its effects psychotropic; a progesterone receptor; and a dopamine receptor, a neurotransmitter known to be involved in pleasurable activities like sex. With any of these receptors blocked, a stroke THC could not restore the sexual behavior of rats. Apparently, the THC uses somehow both dopamine and ways of progesterone, says Mani.

This is a surprise. "Nobody expected that cannabinoids may interact with dopamine and progesterone," says pharmacologist Nephi Stella of the University of Washington, Seattle. He thinks the study can generate new interest for THC effect on sexual behavior. But Mani warns that such behavior, while directly controlled by progesterone in rats, is much more complex in humans. In other words, smoking a joint can have a subtle effect on the behavior of women

-. C aroline S Eydel

Related Sites

homepage Nephi Stella

cannabinoids in the brain

Pharmacology information on Central cannabinoids

Efforts to curb exposure to tobacco smoke in the United States paid dramatically, according to a new report from the Centers for Disease Control and Prevention (CDC) Atlanta. It's just a conclusion of a report published today, which presents the first data on the exposure of the general population to 24 environmental chemicals.

The CDC's goal was to create a basic range of chemical exposure to a section of the population of the country. With this baseline in hand, researchers will be able to determine if a person has had an exceptionally high exposure to a chemical environment, a necessary first step in determining whether a chemical exposure may have caused birth defects or other health effects. In 1999, researchers from the National Health and Nutrition Examination Survey CDC (NHANES) visited 12 sites around the country, collecting blood and urine samples of 3800 people. CDC analyzed the samples traces of 27 chemicals, including toxic metals, cotinine (a marker of tobacco smoke), and metabolites of malathion and other pesticides. They also examined the phthalate metabolites - chemicals found in other household products soap, shampoo, hair spray, and -. That cause reproductive harm in laboratory animals

The researchers found good news in both cases for which data existed earlier. blood cotinine levels fell by 75% compared to 1991 NHANES. "It is really remarkable," said Richard Jackson, director of CDC's National Center for Environmental Health (NCEH). Exposure through lead also declined. For children aged 1 to 5, the blood levels fell 2 7 to 2.0 microgram per deciliter (mg / dL). (A level of 10 ug / dL is associated with adverse effects on learning and behavior of children.)

most other compounds, however, have never been measured in the general population. It is not known if baseline levels represent a health risk, said Jim Pirkle of NCEH Division of laboratory sciences. But already the measures provide clues to further investigation. two phthalates levels stand out among the others, so the CDC researchers focus on finding how they enter the body.

public health experts welcomed the report. "history has been made today," said John Balbus of George Washington University in Washington, told a news conference. "It is a small but significant." CDC plans to increase the number of chemicals, it tests 100 in 4 years, but even that is a tiny fraction of the tens of thousands in use today.

Related site

The CDC report

PARIS - When a research team has identified a new mutation in BRCA1 , a human gene linked to a higher risk of breast cancer and ovarian cancer, the announcement included a broadside against a biotechnology company that holds patents on the gene. The attack is the opening volley in a battle that control the patents for certain cancer tests in Europe, and the fight is likely to get even uglier.

Mutations in BRCA1 and a related gene, BRCA2 , are thought to be responsible for up to 10% of all breast cancers. Myriad Genetics, a biotechnology company based in Salt Lake City Utah, holds at least 17 patents worldwide on the use of these genes and has developed an automated test for mutations. But because the test does not capture faults as the newly identified mutation, it represents "a potential threat" to the French cancer patients, representatives of complaint from the Institut Curie in Paris.

The Curie laboratories and 16 others are considering the challenge of a European patent granted to Myriad last January for BRCA1 and BRCA2 applications. The reason is that a team led by Dominique Stoppa-Lyonnet Curie geneticist has found a new mutation - a deletion of three exons or coding regions, in BRCA1 . The mutation described in the number of the month of Journal of Medical Genetics , was taken with a technique developed by researchers at the Pasteur Institute in Paris, and led team argues Curie the technique should be used as an alternative or complement to the test from Myriad.

European Patent Myriad, and more, he meanwhile, can make this impossible, French researchers say. Myriad officials counter that the criticisms are off base. "If there is a technique that can detect an undetected mutation by our test, we're not stopping anyone to do this test done," says Greg Critchfield, president of Myriad Genetic Laboratories. However, if Myriad was to develop techniques to detect similar mutations in the new one, the company would have the exclusive right to use, Critchfield said. "A company has to protect its intellectual property rights"

the France Genetics and Cancer Group - a network of 17 laboratories, including the Curia, that the conduct BRCA1 and BRCA2 test using a variety of methods - discusses a legal challenge Myriad patent received in January. This procedure "opposition" must be filed no later than October.

Related Sites

information Myriad BRCA1 and BRCA2 testing
The Institut Curie