Analytical electron microscopic study of mitochondrial inclusions in canine myocardial infarcts.

An analytical electron microscopic study, utilizing scanning transmission electron microscopy and energy-dispersive x-ray spectroscopy, was made of two types of mitochondrial inclusions identified in canine myocardial infarcts. The data were obtained from thin sections of tissues that were fixed in aldehyde, osmicated and embedded in epoxy resin. Calcium peaks of variable intensity were detected in inclusions which contained very electron-dense spicular material and which were localized to muscle cells at the peripheries of the infarcts. These findings indicate that the spicular inclusions represent early stages in the process of mitochondrial calcification in myocardial infarcts. In contrast, calcium or other trace elements were not detected in moderately electron-dense amorphous inclusions which were present in mitochondria of muscle cells throughout the infarcts. With the tissue preparative techniques employed, the possibility cannot be excluded that the amorphous inclusions contained calcium, either in small amounts or in a readily diffusable state, in vivo. The data, however, are in accord with the previously advanced hypothesis that the amorphous inclusions represent precipitates of denatured mitochondrial protein formed during the evolution of irreversible cellular injury. This study provides further evidence that analytical electron microscopy can yield important information regarding the nature of various inclusions occurring in normal and diseased tissues.     

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs

The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans.     

Short communication: PCR‐based detection of the polymorphism at codon 136 in the ovine prion protein gene

Abstract

In many breeds of sheep, a polymorphism at codon 136 of the prion protein gene has been shown to be strongly associated with the risk of developing scrapie. A single‐step procedure for detecting this allelic variation is described here. When performed on a series of animals, the test was in complete agreement with their genotypes as had been previously determined by sequencing. The test is potentially easier and quicker to perform than any of the variety of methods that are currently used for this purpose.     

(1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: a novel class of potent MSK-1-inhibitors

A novel series of imidazo[4,5-c]pyridines bearing a 1,2,5-oxadiazol-3-ylamine functionality has been developed. These are potent inhibitors of mitogen and stress-activated protein kinase-1.     

No association between HIV and intimate partner violence among women in 10 developing countries

Background

Intimate Partner Violence (IPV) has been reported to be a determinant of women''s risk for HIV. We examined the relationship between women''s self-reported experiences of IPV in their most recent relationship and their laboratory-confirmed HIV serostatus in ten low- to middle-income countries.

Methodology/Principal Findings

Data for the study came from the most recent Demographic and Health Surveys conducted in Dominican Republic, Haiti, India, Kenya, Liberia, Malawi, Mali, Rwanda, Zambia and Zimbabwe. Each survey population was a cross-sectional sample of women aged 15–49 years. Information on IPV was obtained by a face-to-face interview with the mother with an 81.1% response rate; information on HIV serostatus was obtained from blood samples with an 85.3% response rate. Demographic and socioeconomic variables were considered as potentially confounding covariates. Logistic regression models accounting for multi-stage survey design were estimated individually for each country and as a pooled total with country fixed effects (n = 60,114). Country-specific adjusted odds ratios (OR) for physical or sexual IPV compared to neither ranged from 0.45 [95% confidence interval (CI): 0.23–0.90] in Haiti to 1.35 [95% CI: 0.95–1.90] in India; the pooled association was 1.03 [95% CI: 0.94–1.13]. Country-specific adjusted ORs for physical and sexual IPV compared to no sexual IPV ranged from 0.41 [95% CI: 0.12–1.36] in Haiti to 1.41 [95% CI: 0.26–7.77] in Mali; the pooled association was 1.05 [95% CI: 0.90–1.22].

Conclusions

IPV and HIV were not found to be consistently associated amongst ever-married women in national population samples in these lower income countries, suggesting that IPV is not consistently associated with HIV prevalence worldwide. More research is needed to understand the circumstances in which IPV and HIV are and are not associated with one another.     

Activation tagging: a means of isolating genes implicated as playing a role in plant growth and development

Activation T-DNA tagging has been used to generate a variety of tobacco cell lines selected by their ability to grow either in the absence of auxin or cytokinin in the culture media, or under selective levels of an inhibitor of polyamine biosynthesis. The majority of the cell lines studied in detail contain single T-DNA inserts genetically co-segregating with the selected phenotype. While most of the plants regenerated from the mutant cell lines appear phenotypically normal, several display phenotypes which could be inferred to result from disturbances in the content, or the metabolism, of auxins and cytokinins, or polyamines. The tagging vector is designed to allow the isolation of tagged plant genes by plasmid rescue. Confirmation that the genomic sequence responsible for the selected phenotype has indeed isolated is provided by PEG-mediated protoplast DNA uptake of rescued plasmids followed by selection for protoplast growth under the original selective conditions. Several plasmids have been rescued from the mutant lines which confer on transfected protoplasts the ability to grow either in the absence of auxin or cytokinin in the culture media, or under selective levels of an inhibitor of polyamine biosynthesis. This review describes the background to activation tagging and our progress in characterizing the genes that have been tagged in the mutant lines we have generated.     

Galanin in the porcine pancreas.

Galanin, a 29 amino acid neuropeptide, was recently isolated from pig intestine. We studied the localization, nature and effect of galanin in pig pancreas. Galanin immunoreactive nerve fibers were regularly found in the pancreas. A peptide chromatographically similar to synthetic galanin was identified in pancreas extracts. The effect of galanin on the endocrine and exocrine secretion was studied in isolated pancreases, perfused with a synthetic medium containing 3.5, 5 or 8 mmol/l glucose and synthetic galanin (10(-10)-10(-8) mol/l). There was no effect on the basal exocrine secretion. The output of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) was measured in the effluent. There was no effect on PP secretion. At a perfusate glucose concentration of 5 mmol/l, galanin at 10(-9) mol/l increased insulin secretion by 55 +/- 14% (mean +/- S.E.M., n = 5) of basal secretion, and at 10(-8) mol/l by 58 +/- 27% (n = 6). At 8 mmol/l glucose, insulin secretion increased by 25 +/- 10% (n = 6) and 62 +/- 17% (n = 8). At 5 mmol/l glucose glucagon secretion was increased by 15 +/- 3% (n = 5) by galanin at 10(-9) mol/l and by 29 +/- 11% (n = 5) by galanin at 10(-8) mol/l, and at 8 mmol/l glucose by 66 +/- 27% and 41 +/- 25%. Somatostatin secretion was inhibited to 72 +/- 2% (n = 5) of basal secretion by galanin at 10(-9) mol/l and to 65 +/- 7% (n = 7) at galanin at 10(-8) mol/l, both at 5 mmol/l glucose. At 8 mmol/l the figures were 83 +/- 6% and 70 +/- 10%. Insulin secretion in response to square wave increases in glucose concentration from 3.5 to 11 mmol/l (n = 5) increased 2-fold during simultaneous perfusion with galanin (10(-8) mol/l).