Pharmacogenomic assessment of treatment options in gestational diabetes.

Gene expression profiles offer a multidimensional view of metabolic diseases, typically characterized by a single parameter, and can provide a basis for choosing between therapies yielding a common clinical end point. We applied such an approach in gestational diabetes mellitus (GDM). Gene expression was examined in four maternal tissues and placentas from normal patients and euglycemic GDM patients, undergoing elective Cesarean sections at term, treated either by diet or diet plus insulin. Deviations from normal were 11-fold greater for the patients treated by diet, alone, than for patients treated by diet plus insulin. Assuming the achievement of a "normal" gene expression profile, in addition to euglycemia, is a desirable outcome of treatment, insulin treatment appears to have a beneficial effect in the treatment of GDM. Subsequently, we utilized the expression data to identify serum biomarkers that provide ways to monitor the benefits of insulin treatment in GDM.

Luteinizing hormone-releasing hormone does not inhibit testosterone production in rat interstitial cells in vitro.

The effects of LHRH and a potent LHRH agonist (LHRHa) on invitro testosterone production by enzyme-dispersed rat interstitial cells were evaluated. In a series of in vitro experiments, neither basal nor human menopausal gonadotropin (hMG)-stimulated testosterone production were significantly affected by doses of LHRH or LHRHa ranging from 10(-12)--10(-5) M. In addition, adult male rats were treated chronically with once daily injections of LHRH or LHRHa (2 micrograms/rat) or the vehicle for 1--7 days and decapitated 24 h after the last injection, and their testes were removed and weighed. Testicular weights decreased significantly by day 3 and were maximally decreased by day 6. In vitro testosterone production in response to 1--5 mIU human menopausal gonadotropin was markedly impaired (greater than 50%) in cells from rats treated with LHRHa for 2 days or longer and in rats treated with LHRH longer than 3 days. These data indicate that 1) LHRH and LHRHa do not alter in vitro testosterone production by dispersed rat interstitial cells and 2) interstitial cells of rats pretreated with LHRH and LHRHa exhibited impaired in vitro testosterone production. The data do not, however, rule out a direct effect of LHRH or LHRHa on testicular systems other than those involved in steroidogenesis.

The significance of hematogenous tumor cell clumps in the metastatic process.

The relationship between the size distribution of vessels in an implanted tumor, the size distribution of tumor cell clumps collected in the venous effluent of the tumor, and the development of pulmonary metastases have been studied. The purpose is to evaluate the importance of clumps and their site of formation in the metastatic process. The results demonstrate a negative exponential character for both the size distribution of effluent tumor clumps and the tumor vessel population. Tumor trauma or massage increases total tumor cells and clumps released into the effluent. Serial amputation demonstrates that tumor cells are continuously being released on a day-by-day basis in vivo. A linear relationship exists between the proportion of vessels with diameters large enough to pass a tumor clump of a given size and the proportion of clumps of that size within the venous effluent. Injection of tumor cells in clumps of 6 to 7 cells produces a significantly greater number of metaststic foci than does a similar number of single tumor cells; larger clumps produce significantly more metastatic foci than do smaller clumps matched for the number of cells. These studies verify the significance of tumor clumps in the metastatic process. It is suggested that tumor cell clumps arise locally within the vascular bed of the tumor.