A New Role for Mitochondria

The mitochondrion has been dubbed the workhorse of the cell, respon-sible for creating the energy required for the activities of life—breathing, eating, and reproducing. Recent research also has shown the mitochondrion plays a role in helping cells die, also a natural part of life. Now, P&S investigators have found a completely novel role for this subcellular organelle: The mitochondrion seems to help protect the body against a foreign invader.

Led by Dr. Jahar Bhattacharya, professor of clinical physiological medicine at St. Luke’s-Roosevelt Hospital Center, a team of investigators has found for the first time that the mitochondrion releases chemicals in a key initiation step of the body’s immune response. The researchers showed that mitochondria inside cells that line the blood vessels near the site of an infection release hydrogen peroxide. Hydrogen peroxide then acts inside the cell to push a substance, called P-selectin, to the cell surface, making the cell sticky and attractive to immune cells called leukocytes floating in the blood. After binding to these blood vessel cells, the leukocytes are able to find their way to the site of local infection. The research was published in the December 2002 issue of the Journal of Immunology.

Patients at Risk for Suicide Not Adequately Treated

Some patients with major depression who are being released from inpatient facilities are not being adequately treated with antidepressants, putting them at increased risk of suicidal behavior, according to findings from researchers at P&S and the New York State Psychiatric Institute.

Led by Dr. Maria Oquendo, associate clinical professor of psychiatry, the researchers studied whether antidepressant treatment led to fewer suicide attempts in 136 patients two years after their release from two East Coast hospitals. The researchers found that patients who became depressed again after discharge were seven times more likely to attempt suicide. Further, they found that not enough patients received antidepressants to determine whether the drugs could prevent suicide. Eighteen patients received no antidepressants, while the average dose for the others was less than that recommended by accepted guidelines. The study findings were published in the October 2002 issue of the American Journal of Psychiatry.

Researchers Stop Progression of Multiple Sclerosis in Mice

Researchers at P&S have succeeded in blocking most symptoms of multiple sclerosis in a mouse model of the disease. Multiple sclerosis is an autoimmune disease that attacks the central nervous system. Treatments slow—but cannot stop—spinal cord damage, which prevents nerve conduction to and from the brain.

The researchers, led by Dr. Shi Du Yan, associate professor of clinical pathology, found that most symptoms could be prevented by blocking a receptor on immune cells primed to attack the spinal cord in the mouse model. The research was reported in the March 2003 Nature Medicine.

Deciphering a Different Kind of Code

You may have great genes, but if the genes are tightly wrapped up in the proteins that organize DNA into chromosomes, those genes can’t be accessed and turned on. Now a regulatory code that controls if an enveloped gene will be active or silent has been deciphered for the first time by P&S researchers.

Cells can get access to genes by pushing the chromosomal proteins, called histones, away from the gene’s DNA. But first the cell must decipher a code, which consists of a chemical modification of the histones. Understanding the histone code could lead to therapies that shut down or turn on genes in diseases, such as cancer, that have aberrant patterns of gene expression.

Dr. Dimitris Thanos, associate professor of biochemistry and molecular biophysics, and his postdoctoral researcher, Dr. Theodora Agalioti, cracked the histone code that controls the human beta-interferon gene. The research was published in the Nov. 1, 2002, issue of Cell.

Rare Disorders May Provide Clues to More Common Ones

Charcot-Marie-Tooth disorder may not be as familiar to most people as Alzheimer’s or Parkinson’s diseases, but all three diseases are characterized by dysfunction or death of particular neurons in the brain or the peripheral nervous system. New research by Columbia researchers on some mutations associated with CMT may lead to a better understanding of how cells lose function in CMT and other neurodegenerative diseases, according to Dr. Ronald Liem, professor of pathology and of anatomy and cell biology, Dr. Liem’s Ph.D. student, Dr. Raul Perez-Olle, and Dr. Conrad Leung, assistant professor of clinical pathology. The three researchers found that the mutations caused abnormal bundling and aggregation of neuronal proteins, similar to protein aggregates found in other neurodegenerative diseases like Alzheimer’s, Parkinson’s or Lou Gehrig’s diseases. The research was published in the December 2002 issue of the Journal of Cell Science.

The aggregates may lead to the degeneration of peripheral nerves that is characteristic of CMT. If so, understanding CMT could provide insights into cell degeneration in other diseases characterized by aggregates.

Colonoscopy vs. Sigmoidoscopy

Columbia research reviewed eight years of data to compare colonoscopy with sigmoidoscopy. The benefits and risks of the two procedures have been debated partly because of the greater risk of perforation of the large bowel with colonoscopy.

Sigmoidoscopy was believed to have a much lower incidence of perforation than colonoscopy, but few studies had compared perforation rates for the two procedures directly. To compare the perforation risk in people age 65 and older, Mailman School of Public Health graduate student Nicolle M. Gatto and Dr. Alfred I. Neugut, professor of medicine at P&S and professor of epidemiology at Mailman, and colleagues used a national database of people who had at least one colonoscopy or sigmoid-oscopy between 1991 and 1998.

The researchers found the perforation rate in colonoscopies to be approximately twice the rate for sigmoidoscopies. Of 39,286 colonoscopies in the analysis, 77 perforations were recorded (1.96 perforations per 1,000 colonoscopies) compared with 31 perforations in 35,298 sigmoidoscopies (0.88 perforations per 1,000 sigmoidoscopies). The findings appeared in the Feb. 5, 2003, issue of the Journal of the National Cancer Institute. But the difference in risk between the two procedures has been narrowing because the perforation risk from colonoscopy has decreased over the years, possibly because of improvements in technology and in the training of people performing the procedures.

New Clues about Essential Tremor

Shaky hands and voice sometimes resemble the tremor associated with Parkinson’s disease but stem from an even more common movement disorder—essential tremor. Though it’s up to 20 times more common than Parkinson’s, essential tremor is more mysterious. No cellular defect has been linked to the disease, which affects up to 6 percent of the population, and its environmental and genetic roots remain obscure.

New research from Dr. Elan D. Louis, assistant professor of neurology, and colleagues may lead to answers on both fronts. Using a new brain imaging technique called magnetic resonance spectroscopic imaging, they identified a brain region in tremor patients where cells may be dying. They also found that an environmental toxin called harmane, found in common plant-derived foods, may trigger the disease. The research was published in the Nov. 15, 2002, issue of Neuroscience Letters and the Dec. 24, 2002, issue of Neurology.

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