Too Much Or Too Little Sleep Increases Diabetes Risk

Men who sleep too much or too little are at an increased risk of developing Type 2 diabetes, according to a study by the New England Research Institutes in collaboration with Yale School of Medicine researchers.

The data published in the March issue of Diabetes Care were obtained from 1,709 men, 40 to 70 years old. The men were enrolled in the Massachusetts Male Aging Study and were followed for 15 years with home visits, a health questionnaire and blood samples.

Six to eight hours of sleep was found to be most healthy. In contrast, men who reported they slept between five and six hours per night were twice as likely to develop diabetes and men who slept more than eight hours per night were three times as likely to develop diabetes, according to the lead author, H. Klar Yaggi, M.D., professor in Yale's Department of Internal Medicine, pulmonary section. Previous data from the Nurses Health Study have shown similar results in women.

"These elevated risks remained after adjustment for age, hypertension, smoking status, self-rated health status and education," Yaggi said.

He said researchers are just beginning to recognize the hormonal and metabolic implications of too little sleep. Among the documented effects, Yaggi said, are striking alterations in metabolic and endocrine function including decreased carbohydrate tolerance, insulin resistance, and lower levels of the hormone leptin leading to obesity. The mechanisms by which long sleep duration increase diabetes risk requires further investigation.

"There is a lot of interest in determining whether sleep disturbances such as a reduced amount of sleep or disorders like sleep apnea may actually worsen the metabolic syndrome," said Yaggi. Metabolic syndrome is a cluster of risk factors including high blood pressure, obesity, high cholesterol and insulin resistance which increase the risk for heart disease and stroke.

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Co-authors include Andre Araujo and John McKinlay. The research was supported in part by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Disorders, the Yale Mentored Clinical Research Scholars Program from the National Center for Research Resources, and a career development award from the Veterans Affairs Health Services and Research and Development Service.

Diabetes Care 29: 657-661 (March 2006)

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Diagnostic blood test inventor dies

LONDON, March 27 (UPI) — British immunologist Robin Coombs, inventor of a widely used blood test named for him, has died at the age of 85.

Coombs invented the test that's used to diagnose anemia and to test for the presence of antigens in Rh disease, which affects about 4,000 babies a year because the mother's blood is incompatible with that of her fetus.

The British Society for Immunology, a group he helped found, reported Coombs died Jan. 25, but his death was not widely reported in the British press until this month, The New York Times said Monday.

Robert Royston Amos Coombs was born in London and grew up in South Africa and spent most of his academic career at Cambridge University, retiring during the late 1980's.

He is survived by his wife, Anne; a son, Robert; a daughter, Rosalind; and four grandchildren.

Copyright 2006 by United Press International. All Rights Reserved.

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Cell Barrier Shows Why Bird Flu Not So Easily Spread Among Humans

Although more than 100 people have been infected with the H5N1 avian influenza virus, mostly from close contact with infected poultry, the fact that the virus does not spread easily from its pioneering human hosts to other humans has been a biomedical puzzle.

Now, a study of cells in the human respiratory tract reveals a simple anatomical difference in the cells of the system that makes it difficult for the virus to jump from human to human.

The finding, reported March 22 in the journal Nature, is important because it demonstrates a requisite characteristic for the virus to equip itself to easily infect humans, the key development required for the virus to assume pandemic proportions.

The new report, by a research group led by University of Wisconsin-Madison virologist Yoshihiro Kawaoka, describes experiments using tissue from humans that showed that only cells deep within the respiratory system have the surface molecule or receptor that is the key that permits the avian flu virus to enter a cell.

Flu viruses, like many other types of viruses, require access to the cells of their hosts to effectively reproduce. If they cannot enter a cell, they are unable to make infectious particles that infect other cells – or other hosts.
"Our findings provide a rational explanation for why H5N1 viruses rarely infect and spread from human to human, although they can replicate efficiently in the lungs," the authors of the study write in the Nature report.

By looking at human tissues, Kawaoka's group noted that the cells in the upper portions of the respiratory system lacked the surface receptors that enable avian H5N1 virus to dock with the cell. Receptors are molecules on the surface of cells that act like a lock. A virus with a complementary binding molecule – the key – can use the surface receptor to gain access to the cell. Once inside, it can multiply and infect other cells.

"Deep in the respiratory system, (cell) receptors for avian viruses, including avian H5N1 viruses, are present," explains Kawaoka, who also holds an appointment at the University of Tokyo. "But these receptors are rare in the upper portion of the respiratory system. For the viruses to be transmitted efficiently, they have to multiply in the upper portion of the respiratory system so that they can be transmitted by coughing and sneezing."

The upshot of the new finding, says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine, is that existing strains of bird flu must undergo key genetic changes to become the type of flu pathogen most feared by biomedical scientists.

"No one knows whether the virus will evolve into a pandemic strain, but flu viruses constantly change," Kawaoka says. "Certainly, multiple mutations need to be accumulated for the H5N1 virus to become a pandemic strain."

The finding suggests that scientists and public health agencies worldwide may have more time to prepare for an eventual pandemic of avian influenza. Periodically, animal forms of influenza such as bird flu evolve to become highly contagious human pathogens.

Most scientists agree a pandemic of avian influenza will occur at some time. The worst-case scenario would be a form of influenza similar to the strain of 1918 that killed between 30 million and 50 million people globally.

The new work may also help scientists keep track of evolving strains of influenza and provide earlier warning of potential pandemics. For the H5N1 strain of flu virus to evolve to a pathogen easily transmissible from one human to another, changes need to occur in the virus' hemagglutinin surface protein – a molecule embedded in the virus membrane – to recognize human receptors, Kawaoka says.

"Mutations in the hemagglutinin for avian H5N1 viruses to recognize human receptors are needed for the virus to become a pandemic strain," Kawaoka explains.

Viruses isolated from humans infected with avian flu can thus be monitored in a way to provide more advance warning of a potential pandemic.

"Identification of H5N1 viruses with the ability to recognize human receptors would bring us one step closer to a pandemic strain," says Kawaoka. "Recognition of human receptors can serve as molecular markers for the pandemic potential of the isolates."

The new study was conducted in collaboration with Kyoko Shinya and Shinya Yamada of the University of Tokyo; Masahito Ebina of the Institute of Development, Aging and Cancer; Masao Ono of Tohoku University; and Noriyuki Kasai of the Institute for Animal Experimentation in Japan.

Source: University Of Wisconsin-Madison

  

Study Shows That Cells Have A Natural

Scientists here have discovered a previously unknown mechanism that cells use to fight off the human immunodeficiency virus (HIV), the cause of AIDS.

The findings indicate that two proteins that normally help repair cellular DNA can also destroy the DNA made by HIV after it enters a human cell. This HIV DNA is essential for the virus to survive and reproduce.

The study was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and published in the Proceedings of the National Academy of Sciences.

The findings could lead to a possible new strategy for treating HIV infection and AIDS, one that might complement current therapies and would probably be less susceptible to viral drug resistance – an increasingly urgent dilemma for patients and doctors.

Currently, doctors treat people with AIDS using combinations of drugs that target the virus itself. These drugs do not eliminate HIV from the body, but they do block its ability to reproduce and spread, and they restore most people with AIDS to good health.

In time, however, HIV can develop mutations that render those drugs ineffective.

“Our findings identify a new potential drug target, one that involves a natural host defense,” says principal investigator Richard Fishel, professor of molecular virology, immunology and molecular genetics and a researcher with the OSUCCC – James. “HIV treatments that target cellular components should be far less likely to develop resistance.”

Fishel's laboratory colleague and first author Kristine Yoder discovered the role of the cellular repair proteins while trying to answer a different question.

Before HIV infects a cell, it carries its genetic material in the form of RNA, or ribonucleic acid. Once inside a cell, the virus makes a copy of its genes in the form of DNA. This DNA copy – known as cDNA – then travels to the cell nucleus. There, it becomes inserted, or integrated, into the cell's DNA. There it is known as a provirus, and it will generate new HIV in an infected patient and eventually cause AIDS.

The process of integration, which is absolutely required for a productive infection, begins with the help of an enzyme, integrase, which is supplied by HIV. But the job is finished by DNA repair enzymes provided by the host cell.

Yoder originally wanted to identify which repair enzymes were involved.

During these experiments, Yoder learned that cells with high levels of two proteins called XPB and XPD had lower levels of HIV provirus in their chromosomes. Both proteins help the cell repair damaged DNA.

Yoder, Fishel and their collaborators then introduced mutations into the genes for the two proteins, which crippled the proteins' ability to repair DNA. When cells with these mutations were then infected with HIV, they showed higher levels of provirus in their chromosomes.

“When we weakened a DNA repair pathway, we got more integration of the provirus,” Yoder says. “This was a total surprise.”

Next, the researchers wanted to learn whether the normal cells used in the study had lower proviral levels because they were making less HIV cDNA or because the HIV cDNA was being destroyed before it integrated.

To answer that question, the researchers used antiretroviral drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs prevent HIV from making the cDNA copy of its RNA genetic material. The researchers exposed newly infected cells to the drugs and then measured changes in the amount of cDNA over time.

These experiments showed that the cDNA was destroyed faster in cells with normal XPB and XPD compared to cells with mutant XPB or XPD. Cells with normal XPB protein lost half their proviral DNA after 4.6 hours, while cells with low levels of the protein lost half after about 7.7 hours. Similarly, cells with normal XPD protein lost half the proviral DNA after 3.5 hours, while cells with mutated protein lost half after five hours.

These experiments also showed that the two proteins destroyed the HIV cDNA before it is integrated into the chromosome.

“Overall, our results indicate that these two DNA repair proteins participate in the destruction of HIV cDNA in cells,” Fishel says. “This process reduces the pool of HIV cDNA that can integrate into host chromosomes, thereby protecting cells from infection.”

The researchers are now working to learn how the proteins destroy the HIV cDNA. These studies could lead to drugs that might help the proteins destroy more HIV cDNA and in shorter time.

Source: Ohio State University