Chromosomes 8 and 10 workshop

The chromosomes 8 and 10 workshop took place at the Sixth World Congress on Psychiatric Genetics from October 6^th–10^th, 1998 in Bonn, Germany. Aim of the workshop was to discuss and summarize reports on potential susceptibility genes for psychiatric disorders. Linkage-findings on chromosome 8 concentrate on 8p22-p21 and include mainly schizophrenic disorders. Two areas on chromosome 10 were reported to contain potential susceptibility genes for schizophrenic as well as for affective disorders. The strongest findings were reported for 10p14-p11, while other groups communicated also linkage data for the telomeric part of the long arm to the workshop. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88: 239–243, 1999. © 1999 Wiley-Liss, Inc.     

Chromogenic in situ hybridization for Her‐2/neu‐oncogene in breast cancer: comparison of a new dual‐colour chromogenic in situ hybridization with immunohistochemistry and fluorescence in situ hybridization

Aims: Her‐2/neu testing is used as a marker for Herceptin^® therapy. The aim was to investigate new dual‐colour chromogenic in situ hybridization (CISH), in a large number of breast carcinomas (n = 205) with DNA‐specific dual‐colour probes (ZytoVision, Bremerhaven, Germany) and to compare the results with immunohistochemistry (n = 205) and fluorescence in situ hybridization (FISH) (n = 129). Methods and results: Paraffin‐embedded tissue of 205 patients was used. After immunohistochemistry with a focus on immunohistochemically uncertain cases, Her‐2/neu amplification using dual‐colour CISH (ZytoVision^®) was analysed. Validation by FISH was performed. The results were: immunohistochemistry, 27.8% with strong expression, 53.7% with uncertain overexpression and 18.5% with no expression; FISH, 25.6% amplified and 74.4% negative; CISH, 35.6% amplified, 62.9% negative and 1.5% not evaluable. Comparison of immunohistochemistry with CISH: CISH negative in 100% with immunohistochemistry 0/1+, amplified in 82.5% with immunohistochemistry 3+; 5.9% contradictory results: 4.4% immunohistochemistry 3+ and negative by CISH, 1.5% negative in immunohistochemistry but amplified by CISH; FISH (129 cases), 8.5% contradictory results to immunohistochemistry, 6.2% immunohistochemistry 3+ and negative by FISH, 2.3% negative by immunohistochemistry and amplified by FISH; comparison of CISH and FISH, 94.6% same results, 3.9% different ones, 1.6% CISH not analysable. Conclusions: CISH, using dual‐colour probes (ZytoVision^®) is as good as FISH for Her‐2/neu analysis. The few discrepant results are likely to be caused by polysomy or tumour heterogeneity.     

Gonadotropin hyperstimulation influences the35S-methionine metabolism of mouse preimplantation embryos

The effects of gonadotropin stimulation on mouse embryo uptake and incorporation of ³⁵ S-methionine were studied. We found that the uptake of ³⁵ S-methionine was reduced in embryos of stimulated females in both the two-cell and the blastocyst developmental stage. The incorporation of ³⁵ S-methionine into protein was not statistically significantly different between the embryos of stimulated and those of unstimulated females. Qualitatively, protein synthesis was equal in both groups as determined with one-dimensional SDS-PAGE. The results are discussed and we conclude that mouse embryo viability in vivo is decreased by ovarian stimulation.     

The effects of hydroxyethyl starches on intracellular calcium in platelets

Hydroxyethyl starch (HES) solutions impair platelet function. To determine whether this effect is achieved through interference of HES with intracellular activation processes, in which calcium is the key second messenger, we evaluated the agonist-induced increase of the cytoplasmic calcium concentration in the presence of HES of different molecular weights. Aliquots of citrated whole blood of 12 volunteers were incubated in vitr. with saline, HES 450 (molecular weight in kilodalton), HES 130, and HES 70, resulting in 20% hemodilution. An undiluted sample served as control. The samples were stained with Fluo-3 as the calcium-sensitive fluorescent probe with subsequent flow cytometric analysis. After determination of a baseline, platelets were activated with thrombin receptor activator peptide 6. Platelet activation with thrombin receptor activator peptide 6 resulted in a fast increase in fluorescence (approximately eightfold), representing intracellular calcium mobilization. None of the tested HES solutions exerted a statistically significant effect on the cytoplasmic calcium concentration compared with samples that were incubated with saline or that remained undiluted. These results indicate that the known inhibiting effect of HES on platelets is not achieved through interference with intracellular activation processes. IMPLICATIONS: Hydroxyethyl starch does not exert its known inhibitory effect on platelet function by interfering with intracellular activation processes.     

Treatment of persistent tachycardia with dexmedetomidine during off-pump cardiac surgery

IMPLICATIONS: After unsuccessful treatment of intraoperative tachycardia with esmolol during off-pump revascularization, heart rate was successfully reduced with a bolus and infusion of dexmedetomidine.     

Presenting the female condom to men: a dyadic analysis of effect of the woman's approach

Although male partner resistance to female condom use has been reported, little is understood about circumstances under which partners will agree to female condom use. This study documents the experiences of couples who have worked together to achieve female condom use. As part of a prospective female condom efficacy study, female participants (age 18-34) received a behavioral intervention and an assortment of take-home items. Selected women and their partners were recruited for a qualitative interview focusing on their experience with the female condom. Interviews were transcribed, double-coded, and verified using a standard retrieval coding system. Twenty-six pairs of linked interviews were analyzed dyadically: 9 couples who used the female condom "consistently," 12 "experimenters," and 5 "non-users." Women who successfully promoted the female condom to their partners used multiple presentation strategies. Initial male partner reaction did not predict continued use beyond the first trial. In conclusion, employment of multiple strategies facilitates successful introduction of the female condom into a sexual partnership.     

Downregulation of human polo-like kinase activity by antisense oligonucleotides induces growth inhibition in cancer cells

A central role for polo-like kinases (PLK) in regulating several stages of mitotic progression has been born out in several species. Overexpression of PLK1 is observed in the majority of hitherto analysed human tumors. PLK1 overexpression is a negative prognostic factor in patients suffering from non-small cell lung cancer, head and neck tumors, esophageal carcinomas and melanomas. In order to define the role of PLK1 for mitotic progression of human cells and for neoplastic cell growth, phosphorothioate antisense oligonucleotides (ASOs) were tested to selectively downregulate PLK1 expression in MDA-MB-435 (breast cancer), HeLa S3 (cervical carcinoma) and A549 (non-small cell lung cancer) cells. ASOs were identified which suppress PLK1 mRNA and protein in a dose-dependent and sequence-specific manner. This approach also led to reduced PLK1 serine/threonine kinase activity. Downregulation of cellular PLK1 levels in cancer cells altered cell cycle progression moderately with an elevated percentage (20-30%) of cells in G(2)/M. Furthermore, cells with reduced PLK1 protein gained a rounded phenotype with multiple centrosomes. Moreover, ASO treatment resulted in potent antiproliferative effects in cell culture. Considerable antitumor activity was observed in vivo against A549 cells. This study suggests that antisense inhibitors targeted against PLK1 at well tolerated doses may be considered as a cancer therapeutic agent.