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Artery-Clogging Process Linked to High-Fat Diet

It is well-known that a diet rich in saturated fats can lead to atherosclerosis. Scientists have blamed such a diet for increasing blood plasma levels of "bad" cholesterol, which is deposited in arteries via a number of pathways.

But many now believe that high fat diets are harmful not only because of the role they play in this type of cholesterol deposition. Toru Seo, Ph.D., assistant professor of pediatrics, and master's degree student Chuchun Chang found that a previously underappreciated mechanism of "bad" cholesterol deposition, called selective uptake, becomes increasingly active when animals are fed a high fat diet. Atherosclerosis itself seems to stimulate selective uptake, kicking off a vicious cycle that promotes cholesterol deposition, which in turn promotes atherosclerosis. Their findings were published in the August Journal of Clinical Investigation. Dr. Seo is now working on therapies that can reduce selective uptake and interrupt the cycle.

Dr. Seo, a member of the Institute of Human Nutrition, will be among those attending the institute's annual retreat and 50th Anniversary Scientific Symposium on Nov. 18 and 19. For information about the event call 212-305-4808 or visit http://cumc.columbia.ed/dept/ihn.

This research was supported by the NIH and American Heart Association.

Radiation Scores Direct, Indirect Hits

The arrows point to fragments of damaged chromosomes that have broken off from a bystander cell's nucleus.

Even cells that are not hit by low dose radiation show signs of radiation damage. The arrows point to fragments of damaged chromosomes that have broken off from a bystander cell's nucleus.

A low dose of radiation not only harms the cells it hits, but also damages cells that are 50 to 75 cells away, according to new findings published in the Sept. 14 Proceedings of the National Academy of Sciences by David Brenner, Ph.D. professor of radiation oncology and other researchers in the Center for Radiological Research.

The experiment is the first clear demonstration that the "radiation bystander effect" occurs in normal, three-dimensional human tissue; it had been previously documented in two-dimensional cell cultures.

The findings suggest that the risk of cancer from low doses of radiation (i.e., X-rays, CT scans, or radon) may be greater than currently believed. No epidemiological data exist to calculate the risk of low dose radiation; instead, risk has been extrapolated with questionable assumptions from the cancer rates of atomic bomb survivors who received higher doses of radiation.

The center's researchers believe the bystander effect is caused by signals sent from the irradiated cells to bystander cells. In a second upcoming article in the Proceedings of the National Academy of Sciences, Tom K. Hei, Ph.D., professor of environmental health sciences and radiation oncology, and his co-investigators have extended the bystander observation to define the precise mechanism involved.

Both of these studies are supported by a newly awarded five-year, $8.5 million NIH grant to Dr. Hei to determine the mechanisms of the radiation-induced bystander effect. "The unequivocal demonstration of the bystander effect represents a paradigm shift in radiation biology since generations of students had been taught that heritable effects required the direct deposition of radiant energy in DNA. It is now apparent that the target for heritable damage is not only larger than the DNA, but larger than the cell itself," says Dr. Hei. The other co-investigators are Drs. Sally Amundson, Charles Geard, Hari Bhat, Howard Lieberman, David Brenner and Hongning Zhou.

"These studies should give us a better handle on understanding the cancer risks from low dose radiation," Dr. Hei says.

This work was supported by US Department of Energy and NIH.

1918 Flu Pandemic Yields Insight

In 1918, the "Spanish flu" swept around the world, killing more people than had died during any other single event in history.

Mailman researchers have now found evidence that in New York City the flu epidemic was heralded by a smaller wave of flu deaths the preceding spring. The research appeared in the Aug. 2 issue of the Proceedings of the National Academy of Sciences.

"It is thought that 'herald waves' probably happen before other pandemics, too, and if we look carefully, we may be able to spot one before a future pandemic and have some indication of what's to come, although there are no guarantees when it comes to influenza pandemics," says the study's senior author, Stephen Morse, Ph.D., associate professor of epidemiology.

Dr. Morse and his student, Donald Olson'05 (now with the New York City Department of Health), detected the first wave of Spanish flu in New York City by analyzing historical mortality records.

Unlike regular flu seasons, influenza epidemics kill more healthy adults between ages 15 and 45 while sparing the young and very old. Their analysis revealed a similar pattern in a small peak of deaths several months before the start of the epidemic.

The research was funded by Centers for Disease Control and Prevention and the Arts and Letters and Achelis Foundations.

Use of Acupuncture Explored in HIV/AIDS

Joyce K. Anastasi, Ph.D., R.N., Helen Pettit Professor of Clinical Nursing, is studying the efficacy of acupuncture in treating HIV patients who suffer from chronic nausea, a common side effect that may be caused by HIV-related infections or reactions to the drug cocktails used to treat them. Dr. Anastasi is also studying the traditional Chinese medicine approach called acupuncture/moxibustion to reduce the pain associated with distal symmetric peripheral neuropathy, a type of nerve damage in the arms and legs.

"There are few effective noninvasive interventions to help patients with HIV," says Dr. Anastasi, director of the School of Nursing's Center for AIDS Research and the Integrative Therapies in Primary Care Subspecialty Program, who has concentrated on this research area for more than a decade. Dr. Anastasi will collaborate with Douglas Dieterich, M.D., professor of medicine and gastroenterology at the Mount Sinai School of Medicine. "We hope to continue to find out which interventions show promise and to perfect our methodology to perfect our treatment approach."

The study is funded by a four-year, $2.6 million grant from the National Institute of Nursing Research (NINR), a branch of the NIH. In addition, the NIH awarded Dr. Anastasi a $649,000 grant to test the use of acupuncture/moxibustion.

Landmark NIMH Study Helps Define Treatment Choices for Schizophrenia

A large study funded by NIH's National Institute of Mental Health provides, for the first time, detailed information comparing the effectiveness and side effects of five medications – both new and older – that are used to treat people with schizophrenia. Jeffrey Lieberman, M.D., chairman of Columbia's Department of Psychiatry and director of the New York State Psychiatric Institute, was the PI on the study.

Overall, the medications were comparably effective but were associated with high rates of discontinuation due to intolerable side effects or failure to adequately control symptoms. One new drug, olanzapine, was slightly better than the other drugs but also was associated with significant weight-gain and metabolic changes. Surprisingly, the older, less expensive medication used in the study generally performed as well as the newer ones.

In the $42.6 million CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial, which included 1,400 people, researchers directly compared an older medication (perphenazine), available since the 1950s, to four newer medications (olanzapine, quetiapine, risperidone, and ziprasidone), introduced in the 1990s. The purpose of the study was to learn whether there are differences among the newer medications and whether they hold significant advantages over the older medications; these newer drugs, known as atypical antipsychotics, cost roughly 10 times as much as the older ones.

"There is considerable variation in the therapeutic and side effects of antipsychotic medications. Doctors and patients must carefully evaluate the tradeoffs between efficacy and side effects in choosing an appropriate medication. What works for one person may not work for another," says Dr. Lieberman.

CATIE is part of an overall NIMH effort to conduct "practical" clinical trials in real world settings that address public health issues important to those persons affected by major mental illnesses.