Notes: [Auszug] ...The 7 November election in the United States promises to be one of the most closely fought in decades. The presidency is the biggest prize, but it is also possible that one or both houses of Congress will change hands. Moreover, with two or more of the nine Supreme Court justices likely to ...

Notes: Abstract. Suppose that a group A acts via automorphisms on a nilpotent group G having coprime order. Given an A-invariant character $\chi \in {\rm Irr}(G)$ , we show that the A-primitive irreducible characters that induce $\chi $ from an A-invariant subgroup of G all have equal degree. We use this result to obtain some information about the characters of groups of p-length 1.

Notes: Abstract Purpose: The overall purpose of this study was to determine the potential efficacy of epoxide-containing piperazines as a new class of anti-cancer agents. Two representative compounds, specifically NCO-700, a 4-trimethoxyphenyl-substituted epoxide-piperazine, and TOP-008, a 4-phenylpropenyl-substituted epoxide-piperazine were tested in cytotoxic assays with human breast and prostate cancer cell lines. A second objective was to determine if these two compounds had anti-cancer activity in vivo when tested against xenograft tumors in nude mice or human tumors grown under the kidney capsule in mice. A final objective of this study was to establish if NCO-700 and TOP-008 achieved cancer cell killing through an apoptotic mechanism. Methods: The anti-proliferative activity of NCO-700 and TOP-008 were tested in a 7 day cell-survival assay utilizing a number of well characterized breast (HS-578T, T47D, MCF-7) and prostate (DU-145, PC-3, LNCaP) cancer cell lines. In vivo studies with the two compounds were performed, in nude mice bearing DU-145 xenograft tumors, and in normal mice in which DU-145 prostate cancer cells and HS-578T breast cancer cells were grown as solid tumors in the subrenal capsules of the animals. Apoptotic cell death of cancer cells was determined by a number of established techniques that detect apoptosis, including the confocal laser microscopy of treated cells and mitochondrial leakage assays utilizing the cationic dye, JC-1. Finally, the activation of the caspase cascade, enzymes that carry out apoptosis in mammalian cells, was examined in treated cells by immunoblot assays. Results: NCO-700 and TOP-008 displayed cytotoxicity to HS-578T human breast cancer cells, with ED50 values in the 3–6 μM range. Cytotoxicity to androgen receptor-negative human prostate cancer cells (PC-3 and DU-145 cells) occurred with ED50 values in the 5–20 μM range. Cytotoxicity to hormone receptor-positive breast and prostate cancer cell lines occurred at 10 to 20-fold higher concentrations of the two compounds. When human prostate (DU-145) or breast cancer (HS-578T) cells were grown as solid tumors in the subrenal capsules of mice, significant anti-tumor activity of NCO-700 was observed at 20 mg/kg and 50 mg/kg body weight respectively, for prostate and breast tumors. In nude mice bearing DU-145 prostate tumor xenografts, 50 mg/kg doses of the two compounds either stopped (TOP-008) tumor growth or slowed (NCO-700) growth. The mechanism of cytotoxicity was shown to be through apoptosis, (a) by confocal microscopy studies revealing nuclear fragmentation, (b) by mitochondrial studies revealing disruption of the mitochondrial membrane and release of the cationic dye, JC-1, into the cytoplasm and (c) by protein immunoblot assays indicating that over a 6 h period, TOP-008 induced a significant accumulation of the pro-apoptotic protein, bak, in the mitochondrial fraction of HS-578T human breast cancer cells, accompanied by activation, at 2.5 h, of caspase-3. Conclusions: These studies indicated that the epoxide-containing piperazines, as exemplified by NCO-700 and TOP-008, were effective anti-cancer agents when tested in vitro and in vivo against human breast and prostate tumors. Our studies also indicated that TOP-008 induced the initiation of the caspase cascade leading to apoptosis. Previous toxicology studies in rodents and dogs, as well as a Phase I study in humans, showed NCO-700 to be a well-tolerated, non-toxic compound. Taken together with our current findings, these results suggest that this class of compounds has the potential to be relatively safe, new chemotherapeutic agents for refractory breast and prostate cancers.

Notes: Abstract. Isolated absence of a single pulmonary valve is extremely unusual. We present a 16-year-old male with the absence of one cusp resulting in significant pulmonary regurgitation, right ventricular enlargement, and dilatation of the main pulmonary artery and its branches. Surgery consisted of creating a valve cusp from the posterior wall of the pulmonary artery at the base of the pulmonary trunk. Follow-up at 3.5 years revealed good results with only mild pulmonary stenosis and regurgitation.

Notes: Abstract The remodelling of connective tissue components is a fundamental requirement for a number of pivotal processes in cell biology. These may include myoblast migration and fusion during development and regeneration. In other systems, similar biological processes are facilitated by secretion of the matrix metalloproteinases (MMPs), especially the gelatinases. This study investigated the activity of the gelatinases MMP-2 and 9 by zymography on cell conditioned media in cultures of cells derived from explants of the human masseter muscle and in the murine myoblast cell-line C2C12. Expression of MMP-9 by western blotting and TIMP-1, the major inhibitor of MMPs, by northern blotting, during all phases of myoblast proliferation, migration, alignment and fusion, was also measured. Irrespective of the origin of the cultures, MMP-9 activity was secreted only by single cell and pre-fusion cultures whilst MMP-2 activity was secreted at all stages as well as by myotubes. The loss of MMP-9 activity was due to the loss of MMP-9 protein expression. TIMP-1 mRNA was not detectable at the single cell stage but its expression increased as cells progressed through the pre-fusion and post-fusion stages to reach a maximal in myotube containing cultures. Migration of cells derived from human masseter muscle was inhibited, using a specific anti-MMP-9 blocking monoclonal antibody (6-6B). These data are consistent with the concept that regulation of matrix turnover via MMP-9 may be involved in the events leading to myotube formation, including migration. Loss of expression of this enzyme and expression of TIMP-1 mRNA is associated with myotube containing cultures. Consequently, the ratio between MMPs and TIMPs maybe important in determining myoblast migration and differentiation.