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April 27, 1995

RESEARCH NOTES

Treatment at WPIC available for depressed teens

Researchers at Pitt's Western Psychiatric Institute and Clinic (WPIC) are offering, through a research study, free treatment for teenagers with clinical depression. As many as 1 million teens in this country suffer from clinical depression. Without the proper treatment, the depression can sometimes lead to suicide.

For this reason, WPIC researchers are studying a group of adolescents, ages 12-18, who have been diagnosed with depression. People suffering from clinical depression exhibit a variety of symptoms including: changes in appetite, weight, or sleep pattern; irritability or anger; fatigue; poor concentration; loss of interest in favorite activities; feelings of guilt or worthlessness; and sometimes thoughts of suicide.

For more information or to inquire about eligibility for the free treatment study, call Catherine Kalas at (412) 624-1232.

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Cancer society awards grant

The American Cancer Society has awarded Ronald H. Goldfarb, an associate professor of pathology and neurosurgery, $213,000 to study proteases (degradative enzymes) that may help activated natural killer (A-NK) cells fight metastatic, or widespread, cancer in patients.

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Substances that defend body against HIV discovered here

Researchers at the University of Pittsburgh Medical Center (UPMC) have discovered that a group of immune cells which first encounter HIV produce a host of previously undetected substances, some of which intensify the body's early immune defense against HIV. Charles Rinaldo, a professor of pathology at UPMC, is the lead investigator on the study. The research, funded by the National Institutes of Health as part of the Multicenter AIDS Cohort Study, was presented at the American Society for Microbiology's Second National Conference on Human Retroviruses and Related Infections. At the same conference, Pitt researchers reported that the immune systems of people who are infected with HIV for nine years or more and who fail to develop full-blown AIDS have unique properties that may confer disease resistence. These findings could be important to the development of therapies that prevent the onset of AIDS in HIV-infected people.

The study, funded by the National Institutes of Health as part of the Multicenter AIDS Cohort Study, was conducted in collaboration with Therion Biologics in Cambridge, Mass., which is developing vaccines for cancer and AIDS.

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A research team at Pitt has created a new class of potential drugs that selectively inhibit Ras, Patients with heart pump can be discharged

Patients with end-stage heart disease who are implanted with the Novacor wearable heart pump at Pitt's medical center now can be discharged to their homes while awaiting a heart transplant. As part of a multi-center trial, the FDA has approved the discharge of patients to within 30 miles of the medical center.

The battery-powered Nova-cor is a left ventricular assist system (LVAS) which is temporarily implanted in patients to maintain the pumping action of the heart. Electronic components are worn on a belt or carried in a shoulder bag.

The action will not only improve the quality of life for patients, but also has the potential to reduce health care costs.

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NIH awards grant

Pitt's Brain Trauma Research Center has been awarded a $5.3 million, five-year grant from the National Institutes of Health (NIH) for the study of severe traumatic brain injury.

According to Donald Marion, assistant professor of neurological surgery and director of the center, this is the only such center sponsored by the NIH in this region and one of eight nationwide.

Under the NIH grant the center will investigate the cellular and biochemical mechanism responsible for death and disability following a head injury.

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Researchers from the University of Pittsburgh Medical Center (UPMC) reported their findings at the annual meeting of the American Association for Cancer Research in Toronto.

*Dexamethasone improves the ability of vitamin D (calcitriol) to inhibit cancer growth in animals, according to researchers at the Pittsburgh Cancer Institute (PCI), UPMC. Vitamin D is known to slow the growth of cancer cells, but it can cause high, life- threatening blood levels of calcium or hypercalcemia, according to Candace Johnson, principal investigator for the study and co-director of the PCI's Experimental Therapeutics Program.

The research team found that dexamethasone given in combination with vitamin D curbed growth of established squamous cell tumors in mice and inhibited the initiation of tumors in mice that were seeded with these cancer cells. In addition, dexamethasone reduced the hypercalcemia associated with vitamin D.

*In the first report of its kind, researchers have found differences between the lining of blood vessels that feed tumors and the lining of normal blood vessels.

The research may ultimately reveal properties of the lining, or extracellular matrix (ECM), that can be manipulated to prevent tumors from spreading through it and into the bloodstream, according to Ruth Modzelewski, lead investigator on the study at PCI.

*Highly malignant brain tumor cells inserted with the gene for interleukin-4 (IL-4) were inhibited from growing once transplanted inside rat brains, according to research led by Michael Bozik, from the Brain Tumor Center at the Pittsburgh Cancer Institute.

In their work, PCI researchers found evidence that tumors were infiltrated with natural killer cells, which have an innate cancer-killing ability. Transplanted brain tumor cells that did not contain the IL-4 gene failed to attract effective immune cells and grew uncontrollably.

Further studies are underway at PCI to develop a brain tumor vaccine using IL-4 gene transfer technology.

*Cultured cells lacking genes for metallothioneins are much more sensitive to certain chemotherapy drugs, according to research conducted at the UPMC.

Metallothioneins (MT) are small metal-binding proteins that are overexpressed in some cancer cells and that are thought to normally protect the cells against injuries from exposures to heavy metals, mutagens, nitric oxide, anticancer agents and free radicals The work suggests that certain chemotherapy drugs fail because the increased expression of metallothioneins by cancer cells essentially quenches the anti-cancer activity of those drugs.

According to a study published in "Annals of Internal Medicine", the amount of human immunodeficiency virus (HIV) RNA, or viral load, in the plasma of infected patients is the most powerful indicator of how quickly they will progress to AIDS.

The study, conducted at Pitt, shows that a detection of HIV RNA by branched DNA signal amplification (bDNA) more accurately predicts HIV disease outcome than other commonly used markers. John W. Mellors, associate professor of medicine and director of the Pitt Treatment Evaluation Unit is lead investigator on the study.

Currently, plans are underway to submit the bDNA assay for review by regulatory agencies worldwide. Research for this study was funded in part by the National Institutes of Health.

According to a study presented by surgeons from Pitt's Medical Center, the use of thoracoscopic lung reduction surgery in patients with severe emphysema offers significant improvement in pulmonary function.

Emphysema is the progressive enlargement of the lungs' peripheral air sacs and affects 2 million people in the U.S. The procedure for the first time, offers patients with advanced pulmonary disease an alternative to lung transplantation. Robert Keenan, associate professor of surgery, is the principal investigator in the study.

Variations in structural proteins found in the nucleus of prostate cells may indicate whether a cell will become cancerous, according to Robert Getzenberg, assistant professor of pathology, surgery, medicine and pharmacology at the Pittsburgh Cancer Institute.

An estimated 244,000 new cases of prostate cancer will be diagnosed in 1995, making this disease the most commonly diagnosed cancer and the second leading cause of cancer death in men.

Getzenberg and his colleagues identified proteins that were present only in the normal prostate and were missing in both prostate cancer and benign prostatic hyperplasia (BPH), a common, non-cancerous enlargement of the prostate; proteins found only in the prostate cancer cells and missing in the normal prostate and BPH; and proteins that appeared in both normal and BPH samples, but were absent from prostate cancers.

The researchers have now isolated and studied several nuclear matrix proteins that differ in prostate cancers that tend to spread, versus prostate cancers that did not spread.


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