Health Meaning

Some 20 million people in the US alone suffer from liver disease, and more than 40 000 of them die every year. liver transplants could save many of these lives, but there are only enough donor livers to treat about 4,000 US patients each year. Now researchers have developed a way to grow liver cells in the laboratory by temporarily making them cancerous, then use them to reconstruct a damaged rat liver. The technique could one day help prolong the lives of patients waiting for a donor organ, or even eliminate the need for a transplant

When the liver suffers chronic damage -. Often hepatitis or too alcohol-- cells eventually stop division and member fails. So far it has been difficult to grow liver replacement cells in the laboratory. But in 1996, Philippe Leboulch of the Massachusetts Institute of Technology and Harvard Medical School have developed a technique of introducing a cancer oncogene called T antigen in cells, so "immortalizing" that they continually increase in culture. To keep the cells of cancer remain forever, he designed the oncogene so that it can be cut to the DNA of cells later by an adenovirus carrying a pair of "genetic scissors."

When Ira Fox, a surgeon liver transplantation at the University of Nebraska Medical Center in Omaha, has heard of this system, he immediately called Leboulch and proposed a collaboration to a trial in liver cells. the new team set to see if they could grow enough cells to save the life of rats that had been about 0% of their livers surgically removed. This treatment is always fatal, but when the researchers injected their hepatocytes in the spleens of the animals up 60% of the animals survived, they report in February 18 Science .

the success is "very encouraging," says hepatologist Roy Chowdhury of the Albert Einstein College of Medicine in New York . But he noted that the liver failure in humans is different; a virus or a toxin may persist, said Chowdhury, and perhaps damage the transplanted cells, too.

Rides, thinning hair, bones and weak muscles - physical degeneration of aging is well known. But it is still a mystery why the body breaks down as it gets older. Now, using a hot new technology, researchers finally found the genes that make cells show their age.

DNA microarrays, also called DNA chips, fueled the excitement in the research community because they can test the activity of many genes immediately. In essence, microarrays are embedded size nail chips with known DNA extracts. To find out what is happening inside a cell, the researchers expose the chip fluorescently labeled genetic material that is sent inside the cell. Active genes leave telltale traces as they correspond with mapped locations on the chip.

A team led by Richard Lerner and Peter Schultz of the Scripps Research Institute in La Jolla, California, used microarrays to analyze gene activity in fibroblasts, the cells that help form skin and connective tissue. They tested the cells of healthy people of different ages and also children with Hutchinson-Guilford progeria, a rare inherited disease that resembles an accelerated form of aging

The researchers found that expression of only 61 genes -. Out of a total of some 6300 tested - changed with age. Many of the same changes have also taken place in fibroblasts of patients with progeria, a finding indicating that these individuals are in fact age abnormally fast, they report to March 31 Science . Among the genes depending on the age, many are known to help cells divide, providing support to the idea that aging stops cell division.

It will take more work to confirm that these genes are differentially active in aging people, not just cell lines differently aged, says Leonard Guarente aging specialist at the Massachusetts Institute of Technology. But Guarente said, "This is an extremely interesting piece of work." It is still a way to the beauty salon, however. Lerner said: "The Fountain of Youth here ... I do not think"

A new transplant technique has enabled eight diabetic patients to completely stop their insulin injections. The study, described this morning at the meeting Transplant 00 in Chicago, is "truly a milestone in the treatment of diabetes," said Hugh Auchincloss transplant surgeon at Harvard Medical School.

Type I or childhood onset, diabetes affects hundreds of thousands of people in the United States is believed to start when the immune system kills insulin-producing cells in the pancreas. insulin plays a key role in regulating the blood glucose by promoting the conversion of sugar into glycogen. to compensate for the lost cells, diabetics must inject insulin several shots a day. Even with these injections, however, wide variations in the levels of sugar in the blood trigger side effects ranging from kidney failure and nerve damage to blindness.

for years, researchers have sought ways to transplant cells producing healthy insulin in diabetic patients. Most were only partially; patients less than one in 10 can do without insulin injections one year after the transplant, and they all have to endure the side effects of immunosuppressive drugs.

A new protocol developed by transplant surgeons James Shapiro, Jonathan Lakey, and colleagues from the University of Alberta in Edmonton, Canada, has had much better initial results. The eight team patients - one of them treated there more than a year -. Have normal blood sugar without insulin injections

The team attributes the success to several factors. First, they transplanted islet cells as soon as possible after the removal of an organ donor. Second, do not use any non-human proteins for preparing the cells prior to transplant. Finally, they used a new anti-rejection drug that blocks a protein CD25 specific immune system, instead of steroid drugs used commonly. These drugs are known to be hard on the pancreatic cells, says immunologist transplant Norma Kenyon of the University of Miami in Florida, but the cells seem to tolerate the new drug more easily.

Kenyon warns that patients who are age 29-53, must remain on immunosuppressive drugs for the rest of their lives. Auchincloss and stresses that each graft requires two donor pancreases, so that the treatment would only be available for "a small fraction" of diabetics. To help more patients, researchers will learn how to grow human islet cells in culture or to find a way to use animal islets. The protocol is "a really great step," Auchincloss said. "But is was only a step. It is actually not the cure. "

In people with schizophrenia, a brain circuit that regulates emotion is overwhelmed by a chemical messenger called dopamine. The new discovery confirms a long-standing hypothesis about schizophrenia and provides the most direct evidence to date on why schizophrenics lose touch with reality.

The devastating symptoms of schizophrenia include delusions, hallucinations and paranoia. Like all effective antipsychotic drugs block a receptor for the neurotransmitter dopamine, the researchers guessed there are more than 30 years that dopamine circuits were overactive in people with the disease. This could be caused by an excess of dopamine, a too large number of dopamine receptors, or both. Indeed, the autopsies showed schizophrenics an overabundance of one type of dopamine receptors in the striatum, a part of the brain that helps to regulate emotion. But because most people with schizophrenia were treated with antipsychotic drugs, some researchers have argued that it was a result of drug treatment rather than the disease.

To measure whether the circuitry of dopamine-sensitive were overactive in schizophrenia, Anissa Abi-Dargham of Columbia University College of Physicians and Surgeons in New York and colleagues compared 18 schizophrenia with 18 normal subjects . First they treated patients and controls for 2 days with a drug that knocks off dopamine receptors. Then they gave the patients a mimetic radiolabeled dopamine which could accumulate on dopamine receptors emptied. Using a brain imaging method called emission tomography single photon, they compared the amount of dopamine molecules like landed on the receptors in the two groups.

In people with schizophrenia, the amount of dopamine-like molecules bound to the receptors increased twice that in controls, they report in the edition July 5 of Proceedings of the national Academy of sciences . It most likely means that schizophrenics have both more dopamine available and most of the dopamine receptors. In addition, the increase occurred in the October 2 chronic patients - who had used antipsychotic drugs in the past -. And in the eight newly diagnosed patients who had never been treated with medication

The search for "can potentially help us understand how antipsychotic drugs work," says psychiatrist and neuroscientist Francine Benes from Harvard Medical School in Boston. But psychiatrist Shitij Kapur of the University of Toronto is warning that researchers still need a way to measure dopamine directly into the brains of live schizophrenic. But "assuming this is in place," dit- it, "the whole story [dopamine] will start to come together."

For more information on schizophrenia of the National Institute of Mental Health: www.nimh.nih. gov / publicat / schizoph.htm

An international team of scientists is homing on the site of a third gene that might be involved in the development of hereditary breast cancer. If the gene is found, the work will pave the way to improved genetic counseling and cancer screening and treatment for family members with breast cancer history.

The shortcomings of so-called "susceptibility genes" contribute to the development of 5% to 10% of all breast cancers, which greatly increases the risk of contracting the disease from a woman. In to date, researchers have identified two genes predisposing to breast cancer, called BRCA1 and BRCA2 , but faults in these genes probably represent no more than one third of all hereditary breast cancer.

to track other susceptibility genes, research teams from Finland, Sweden, Iceland and the United States have joined forces. They identified 37 families that are affected with high rates of breast cancer, but who are not known BRCA1 or BRCA2 mutations. using a technique called comparative genomic hybridization of tumor DNA and normal tissue of 61 women, researchers found five probable areas for breast cancer genes. To refine their search, dim teams throughout these regions using two new mathematical models. Finally, they drew on the well-established methods of genotyping and linkage analysis to identify similar DNA segments shared by patients with breast cancer in a family.

Together, these techniques have given a region on chromosome 13 as the probable site of a third susceptibility gene, the teams reported in the August 15 Proceedings of the National Academy of Sciences . While it may take months to years to identify the faulty gene, this work is "an important intermediate step in seeking the reduction," said team member Olli Kallioniemi, a geneticist cancer in National Institute of research on the human genome in Bethesda, Maryland.

other scientists welcomed the announcement carefully, however. population geneticist mark Skolnick, scientific director for Myriad Genetics Inc. of Salt Lake City, which led the team that identified BRCA1 , finds the work "potentially very important," but warns that the statistical data are not conclusive.

Mary-Claire King, a geneticist at the University of Washington, Seattle, pioneered research of genes predisposing to breast cancer, leases integrative approach of the teams. But she noted that both Skolnick and BRCA2 also lies on chromosome 13. It is possible, they note that undiscovered faults around this gene may have confused the analysis. definitive proof that the team had indeed found a new gene linked to breast cancer, they say, will not come until researchers reproduce their work in other family groups or find gene itself.

Related Sites
The NCI's information page on Breast Cancer (CancerNet)

The old saying "put a thief to catch a thief" is best known as the inspiration for Alfred Hitchcock's 1955 film To Catch a Thief . But with a twist, it's also a good description of a new technique to fight against common infections: set a microbe to catch a microbe. By orchestrating common bacteria to produce microbicides, researchers hope to find a first line of defense against infections of all kinds.

all bacteria are bad. Some live safely and on humans, including one called strain Streptococcus gordonii than that normally found in the mouth. To supplement this easy living microbe and arm themselves against pathogens, a team of researchers led by microbiologist Luciano Polonelli the University of Parma in Italy changed S. gordonii so it secretes antibodies . Imitations of antibodies the action of a "killer toxin" naturally produced by certain strains of yeast, and destroys microbes such as Candida albicans , a fungus that causes vaginal yeast infections; Pneumocystis carinii , which causes a kind of pneumonia often deadly for AIDS patients; strains and multi-resistant tuberculosis drugs.

To test whether the engineered microbe could fight against the disease, the researchers infected vaginally with rats Candida . They then introduced vaginal colonies established engineering S. gordonii in eight rats, and microbes cleared the infection in 75% of animals. None of the untreated animals recovered from infection. This makes the microbe as effective as flucanozole, an antifungal drug commonly used to treat yeast infections. And since microbes produce antibodies continuously, they also prevent Candida infections. Antifungal drugs, however, are used to fight against established infections.

In principle, the same technique could be used to develop bacteria that could repel all kinds of infections, said immunologist Larry Zeitlin Epicyte Pharmaceutical Inc. of San Diego. But obtaining regulatory approval to release genetically modified bacteria will be difficult, he said. "It is a really smart idea," Zeitlin said the new technique, "but whether it will pan out is difficult to predict."

Related Sites

Technical Information Candida albicans , the University of Minnesota

researchers are trying to assess the hazards of arsenic have encountered an obstacle: They need an arsenic isotope for their studies, and the only place in the world which makes it is exhausted. It could take until mid-01 before enough is produced to replenish the two dozen laboratories around the world who need the isotope.

The shortage comes at a particularly bad time. In May, the Environmental Protection Agency of the United States (EPA) proposed a cost reduction of levels of arsenic, a natural contaminant in drinking water. EPA also funds a burst of research into the causes of cancer how arsenic because immobilizing the elusive mechanism could reveal whether the limit should be so strict. To understand the mechanism, researchers use arsenic-73 to find genes that metabolize arsenic and explore how these metabolites enter cells and damage DNA.

But the Department of Los Alamos National Laboratory Energy in New Mexico did not produce any arsenic-73 since the beginning of 1999. They were the isotope smashing protons an accelerator in a rubidium bromide target, but the source of the protons - a tritium production program - closed. A new facility isotope production was expected to open next year, but the massive fires that swept the region this spring pushed the completion date to mid-02. Los Alamos ran out of its inventory arsenic-73 around July.

"None of us knew about it until it is too late" to make other plans, said Marc Mass, an EPA toxicologist. There are other plotters, he said, but they are expensive and too insensitive to some experiments. Los Alamos officials say they can do arsenic-73 to another accelerator, perhaps in Canada - but it can still be six months before any arsenic-73 is available, said Gene Peterson, Programme Director and Isotope Production distribution of laboratory

that's little comfort to arsenic researchers, who are at the end of their minds. Vas Aposhian toxicologist at the University of Arizona in Tucson, who bought the last arsenic-73 millicuries this summer, said he and his colleagues "will scream bloody murder" when provisioning their laboratory works a few weeks. Miroslav Styblo, a biochemist at the University of North Carolina, Chapel Hill, tried to convince his colleagues of an accelerator in his native Prague to do a lot of arsenic-73. But "so far," he said, "we do not have realistic promises."

Related Sites

Los Alamos Isotope Production and Distribution Program

EPA proposed rule arsenic from drinking water

chemotherapy may save lives, but it comes with unpleasant side effects. Drugs target rapidly dividing cells, allowing them to home to tumors, but they also kill normal cells as those of the hair follicles. Although the resulting hair loss is not life threatening, it can be extremely distress for patients. Now a team reports that they can prevent hair loss caused by chemotherapy in first rats rub the skin of animals with a newly developed drug.

The new drug targets an enzyme called cyclin-dependent kinase 2 (CDK2), which results in key stage in the cycle of cell division. Many researchers in industry and academia are looking for CDK inhibitors, mainly in the hope of developing agents to block the growth of cancer cells. But William Kaelin of the Dana-Farber Cancer Institute in Boston, who is among those who do this work, emphasizes that CDK inhibitors offer two possibilities. They can be used, he said, to find "be smarter ways to kill cancer cells or smarter ways to protect normal cells."

Focusing on the latter objective, a team led by Stephen Davis Glaxo Wellcome Research and Development in the Research Triangle Park, North Carolina, has developed a powerful CDK2 inhibitor for topical application. The researchers tested the drug in both animal models. In one, the researchers transplanted human scalp hair in mice. When they applied the CDK2 inhibitor to growing hair transplants, the researchers report in the January 5 version of Science , temporarily inhibited cell division of the hair follicle. In a second model, rubbed the drug in hair newborn rats and gave them a chemotherapeutic agent. The drug prevented hair loss in half of the animals and reduced in another 20%. It was not as effective against a combination of two chemotherapy drugs, protection of only 33% of hair loss in animals. Davis also said his team did not detect any interference with the ability of chemotherapy drugs to kill cancer cells in animal tumor models.

Oncologist David Fisher of the Dana-Farber described the work to date as a "huge advance." He hypothesizes that it may also be possible to design inhibitors to protect other tissues normal which were damaged by chemotherapy drugs the lining of the intestine. - where damage causes nausea and vomiting. - It is a possibility, if a non-resorbable version can be produced

When the Albany Medical Center in New York announced last November that it would assign a new annual award in biomedical research, something made the price stand out: a cool half million dollars. Now the center has given its top prize on Arnold Levine, president of Rockefeller University in New York and co-discoverer of a protein that goes wrong in cancer.

The award was established with a gift of $ 50 million to the Albany Medical Center in Morris Silverman, a businessman from New York who was educated near Albany. The award recognizes researchers who have made important contributions to medicine and biomedical research. It is the largest annual award in science or medicine in the US, according to a spokesman Albany door probably only a second award for the Nobel Prize, which last year was worth $ 915,000.

Levine won the award, announced on March 14, for his contribution to cancer biology. In 1979, p53, a protein that is defective in more than 50% of co-discovered human cancers. The protein normally cleans up after the cells with damaged DNA by clamping down on cell division or inducing cell suicide; otherwise, cancer cells proliferate. Levine has not only helped to recognize the role of p53 in cancer, he also played a leading role in the cloning of the first DNA p53 and identification of a key protein that binds p53 and modulate its function. It is now testing compounds that could kick a defective p53 protein back in action or crank up the amount of p53 available to limit the damage.

"Arnie has made a fundamental contribution to each step in the development of the p53 field," said Frank McCormick, director of the University of California, San Francisco Comprehensive Cancer Research Center and author of several reviews p53. He praises Levine for an open and collaborative style of research that has influenced many p53 researchers. "In such a competitive field this is a major achievement in itself," said McCormick.

Related Sites

The Albany Price Medical Center

Rockefeller University

More on p53

The children suffer lasting brain damage from poisoning lead moderate even when treated quickly with a drug that removes lead in their blood, according to a large clinical trial reported in issue 10 May the New England Journal of medicine . The results mean that the only way to avoid permanent brain damage from lead poisoning is to prevent it in the first place, experts say.

Severe lead poisoning causes brain damage, seizures and death, especially in children. Low to moderate levels of lead, which occur in 1 to 20 children under 6 in the US, cause more subtle damage. Even years after exposure, young children have reduced attention span and decreased ability to think and reason abstractly. A drug called succimer orally mops that lead in the blood can save the lives of children seriously poisoned. But no one knew if it could prevent brain damage in moderately poisoned children.

To find out, epidemiologist Walter Rogan of the National Institute of Sciences of Environmental Health in Research Triangle Park, North Carolina, colleagues enlisted medical centers four cities that regularly treat children poisoned lead. The double-blind trial, eventually included 780 2 years, 75% were African American, who had been poisoned, mostly dust from deteriorating lead paint in their urban homes. The research team removed the lead paint and cleaned houses. Then they gave the children either succimer or placebo pills for several months. The children were tested three years later, when they were 5 -. The youngest age at which cognitive deficits can be measured reliably

Although drug therapy reduced blood lead values ​​significantly compared to placebo treated children showed no differences in IQ, memory, conceptual thinking, or hyperactive behavior of untreated children. The researchers will test again the differences after the children enter primary school, but so far "there is not even a hint" of a difference, said Rogan.

The document is "very important because it shows that you can treat children up to the kazoo with a chelating agent and you get nowhere," says pediatrician John Rosen, who heads the main program to children's Hospital of Montefiore in the Bronx, new York. Together with other studies, the new results underline the need to remove or replace the lead-based paint, which was banned in 1976 in the United States, but still coats the walls of 25 million homes. "This is an entirely preventable disease and healing is decontamination," Rosen said.

Related Sites

Page the treatment of children exposed to lead host (TLC) clinical trial of lead poisoning prevention program
Childhood Centers for
general information about lead poisoning and housing policy of the national advocacy group Center for Disease Control and Prevention Lead-Safe Housing