OCTOBER 1998 MEDTIPS
Much of the research described below is done in the new John D. VanNuys Medical Sciences Building at the Indiana University School of Medicine. It will be dedicated October 23, 1998.
A better understanding of the pathways that govern how cell growth and death occurs in the lining of human blood vessels may lead to drug or gene therapies for a variety of diseases such as hypertension and asthma. Vascular smooth muscles surround blood vessels and control blood pressure. Damage to these muscle cells may stimulate them to grow in an uncontrolled fashion blocking blood flow or constricting an asthmatic's airways. According to a cellular physiologist at the Indiana University School of Medicine, Patricia Gallagher, Ph.D., increased knowledge of the system of checks and balances that prevents unwanted smooth muscle growth will bring us closer to new control of these life-threatening diseases.
Identifying the various genes underlying alcohol seeking behaviors and alcoholism is a major aspect of the work of Indiana University School of Medicine molecular biologist Howard Edenberg, Ph.D. Using high tech methodologies such as the DNA amplifying process Polymerase Chain Reaction (PCR) for genotyping, he is studying microsatellite polymorphisms (simple-sequence repeats) to identify regions of the human genome that contain genes that affect the risk for alcoholism. "No one gene will make you an alcoholic, but genes do influence how vulnerable a person is. Once we can identify these genes, we will better understand the disease of alcoholism, and be better able to design treatments," says Edenberg. His work also has relevance to other multi-gene disorders including heart disease, cancers, hypertension, and diabetes.
Blood cell development is a risky business. Stem cells, the mothers of all red blood cells, must proliferate enough to ensure their own survival, but differentiate enough to supply enough of the many kinds of blood cells needed for the body's survival. But too much differentiation and the body does not have enough red blood cells. Both situations are fatal. Robert Hromas, MD, of the Indiana University School of Medicine, is identifying the proteins that control this process, especially those linked to myeloid leukemia. He has discovered six new proteins that slow or stop the growth of blood cells developing in the marrow. Two of these proteins, called Exodus -1 and Exodus - 2 also slow the growth of chronic myelogenous leukemia. "It is possible that the Exodus family of proteins can be used in the future as a treatment for chronic myelogenous leukemia," Dr. Hromas said.
Patients with kidney infection or disease are at greater risk for permanent impairment when treated for kidney stones with shock wave lithotripsy, according to Andrew Evan, Ph.D., a professor of anatomy at the Indiana University School of Medicine. Lithotripsy is used to break up kidney stones and upper ureteral stones. The treatment applies external pressure to break the stones into tiny fragments, but the shock waves now have been shown to impair blood flow to kidneys that are not healthy at the time of treatment. Many lithotripsy patients, particularly those over the age of 60, have kidney disease or infection when treated with this popular shock wave therapy.
A viral protein that prevents human white blood cells and other inflammatory cells from reaching the site of an infection has been identified by Kenneth H. Fife, M.D., Ph.D. and colleagues at the IU School of Medicine. This novel viral mechanism could result in a new method for treating auto-immune conditions such as asthma and rheumatoid arthritis by blocking inflammation. These are the first viral chemokine-like proteins shown to counteract the cell attracting activity of human chemokines.
There are many types of warts according to Dr. Darron Brown of the Indiana University School of Medicine. Warts on the hands and feet are caused by "cutaneous type" human papillomaviruses (HPV). There are approximately 45 known varieties of this type of HPV. Some of these lesions may become malignant in certain people, such as kidney transplant recipients, but most do not. Genital HPVs, of which there are approximately 35 identified types, cause a range of diseases including genital warts, cervical dysplasia, and cervical cancer.
Nearly 1 million cases of genital warts and 15,000 cases of cervical cancer are diagnosed each year in the United States. Both conditions are caused by the human papillomavirus. A previously uncharacterized genital HPV type has been isolated, cloned, and sequenced by Darron R. Brown, M.D. in his laboratory at the Indiana University School of Medicine. The recently identified type, known as HPV 83, was isolated from genital lesions removed from immunosuppressed patients. HPV 83 appears to cause changes in experimental infection suggestive of malignancy, and has been found in cancer of the cervix. The work was published in the September 15 issue of Virology. "Effective vaccines against HPV will require inclusion of many HP types, because antibodies against one type may not inactivate other types," said Brown. Therefore, identification and cloning of additional HPV types could facilitate this process. His laboratory is continuing work to characterize additional HPVs and to develop vaccines.
Why do some human papillomaviruses (HPV) cause benign warts while others cause life-threatening cancers? An Indiana University School of Medicine molecular biologist, Ann Roman, Ph.D., is trying to solve this mystery. To exist, the viruses must invade cells that have the potential to multiple and make what are normally quiet, inactive cells change into multiplying cells. How does this occur and what happens next? "We are studying viral proteins which function to subvert the checkpoints that an uninfected cell has so that it only grows when it is appropriate to do so," says Roman, "and the cellular proteins which attempt to keep the virus under control."
CONTACT: Cindy Fox Aisen
317-843-2276 or 317-274-7722
E-mail: caisen@iupui.edu
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