Tissue-specific extinguisher loci in the murine genome: A screening study based on a rat/mouse microcell hybrid panel

Extinction of tissue-specific traits in intertypic somatic cell hybrids is a well-known phenomenon. In the past few years, microcell hybrids have been used in attempts to dissect this phenotype genetically, and tissue-specific extinguisher loci have been mapped to two different mouse chromosomes. When transferred from fibroblasts into hepatoma cells by microcell fusion, these loci down-regulate expression of specific liver genes intrans. However, other liver genes that are extinguished in genotypically complete hybrids seem not to be extinguished in monochromosomal hybrids. To assess the generality of monochromosomal extinction phenotypes, we assembled a collection of rat hepatoma/mouse fibroblast microcell hybrids that represent most of the mouse chromosome complement, and we screened them for expression of a large number of liver-specific genes. Phosphoenolpyruvate carboxykinase gene expression was down-regulated in hybrids containing mouse chromosome 7 or mouse chromosome 11, but other extinction phenotypes were not readily apparent. These results indicate that extinction of many liver genes may be a polygenic trait.     

Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.     

Acute coronary syndromes

The first 150 words of the full text of this article appear below. Key points Coronary artery disease accounts for >30% ofdeaths in Western society. The diagnosis of myocardial infarctionshould be qualified by size, causation and time from occurrence. Mortalityis reduced by immediate or ‘primary’ percutaneouscoronary intervention or thrombolysis within the first 24 hof onset of ST-segment elevation myocardial infarction. Strategiesto reduce platelet activation (glycoprotein IIb/IIIa receptorantagonists, or clopidogrel) are now recommended in the treatmentof high-risk non-ST-segment myocardial infarction/unstable angina. Elevatedserum troponins may be the result of non-ischaemic myocardialdamage, especially in critical illness.