Plasma neurotensin release and gastric emptying in the dumping syndrome

Seventy-three patients were studied after ingesting a liquid glucose meal, tagged with ¹¹³Indium. Nineteen of these patients were awaiting surgery for their duodenal ulcer, while 54 were studied postoperatively, 25 of whom experienced troublesome postprandial (dumping) symptoms in their daily lives. The radioactive marker emptied significantly faster in the symptomatic patients than in the symptomfree, pre and post-operative groups (initial emptying rate 3.45 ± 0.23, compared with 1.16 ± 0.19 and 1.27 ± 0.15% fall in counts/min respectively; p < 0.01). Initial (20 min) rises in the plasma concentrations of neurotensin-like immunoreactivity measured during the test correlated significantly with the rate of gastric emptying in all patients, being greatest in patients with dumping symptoms. Physiological concentrations of neurotensin have been shown to delay gastric emptying. The excessive rise in plasma neurotensin-like immunoreactivity in patients with dumping symptoms, presumably occuring as a result of the rapid passage of nutrients to the neurotensin-rich ileum, may possibly have a compensatory role in slowing further emptying from the stomach.     

The Inheritance of Enzyme Variants for Tyrosine Aminotransferase, Nadp-Dependent Malate Dehydrogenase, Nadp-Dependent Isocitrate Dehydrogenase, and Tetrazolium Oxidase in TETRAHYMENA PYRIFORMIS, Syngen 1

The isozymic patterns of tyrosine aminotransferase, NADP malate dehydrogenase, NADP isocitrate dehydrogenase, and tetrazolium oxidase were examined by starch-gel electrophoresis in Tetrahymena pyriformis, syngen 1. The genetics of the alleles controlling these enzymes was studied through a breeding program. Each enzyme locus was shown to assort vegetatively, as do other loci in this organism. A detailed analysis of the assortment process for the tyrosine aminotransferase locus indicated that the rate of stabilization of heterozygotes into pure types was essentially identical to previously-reported rates for other loci.     

Strengths and limitations of molecular sequence comparisons for inferring the phylogeny of the major groups of fishes

Although the phylogenetic relationships of the major groups of fishes have been extensively studied with morphological characters, not all have been convincingly resolved. Analyses of molecular sequences from these groups may provide additional insights into problematical relationships, but are only just beginning to appear. We compare our own results from analyses of 18s ribosomal RNA sequences with those of other studies using globins, parvalbumins, insulin, 28s ribosomal RNA, and portions of two mitochondria1 genes (12S ribosomal RNA and cytochrome b ). Our evaluation of these studies reveals some of the difficulties encountered in reconstructing ancient divergences within the fishes, including unequal rates of evolution (among regions of a molecule as well as among lineages), gene duplication, extinction of lineages, and a possible rapid radiation of gnathostome higher taxa. The importance of evaluating the robustness of particular phylogenetic hypotheses is stressed. Some molecules appear to be inappropriate for investigating higher level divergences within the fishes; others are more promising, but must be examined in more taxa to allow an adequate evaluation of their utility. Convincing support for particular hypotheses of relationship will ultimately require congruence of trees generated from independent molecular data sets.     

Lactobacilli as effectors of host functions: no influence on the activities of enzymes in enterocytes of mice.

Preparations of lactobacilli are often used as dietary supplements to improve the growth and efficiency in utilizing food of animals of commercial value. We tested in an experimental model whether the effects of lactobacilli on growth of and food utilization by animals may be due to alteration of the activities of absorptive enzymes in the small bowel. Germfree mice housed in isolators under tightly controlled conditions were monoassociated with one of four strains of indigenous Lactobacillus spp. From 1 to 5 weeks later, the activity of alkaline phosphatase was assayed in homogenates of segments of the upper small intestines of the associated animals and of matched germfree controls. The specific activity of the enzyme was the same in the mice in the two groups. In other experiments, epithelial cells were isolated from the upper small intestines of mice associated with eight Lactobacillus strains (octa-associated) and from those of matched germfree mice and assayed for alkaline phosphatase, phosphodiesterase, and thymidine kinase activities. The epithelial cells were harvested sequentially from the tips of the villi toward the crypts of Lieberkühn of the intestines. In all preparations, mice of both types yielded an equivalent mass (wet weight) of cells. The protein content of the cells reflected the mass. The activities of the microvillous membrane enzymes alkaline phosphatase and phosphodiesterase and the cytosol enzyme thymidine kinase were the same whether or not the animals contained the bacteria. Therefore, any effects on animal growth and food utilization observed when lactobacilli are used as dietary supplements may not be due to a direct alteration by the bacteria of the absorptive enzymes of the host animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer

Background  

Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer.     

Characterization of a novel mutation in the cardiac ryanodine receptor that results in catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects. It is primarily caused by mutations in the cardiac ryanodine receptor (RyR2). The mechanism by which these mutations cause arrhythmia remains controversial, with discrepant findings related to the role of the RyR2 binding protein FKBP12.6. The purpose of this study was to characterize a novel RyR2 mutation identified in a kindred with clinically diagnosed CPVT.Single-strand conformational polymorphism analysis and direct DNA sequencing were used to screen the RyR2 gene for mutations. Site-directed mutagenesis was employed to introduce the mutation into the mouse RyR2 cDNA. The impact of the mutation on the interaction between RyR2 and a 12.6 kDa FK506 binding protein (FKBP12.6) was determined by immunoprecipitation and immunoblotting and its effect on RyR2 function was characterized by single cell Ca²⁺ imaging and [³H]ryanodine binding.A novel CPVT mutation, E189D, was identified. The E189D mutation does not alter the affinity of the channel for FKBP12.6, but it increases the propensity for store-overload-induced Ca²⁺ release (SOICR). Furthermore, the E189D mutation enhances the basal channel activity of RyR2 and its sensitivity to activation by caffeine.The E189D RyR2 mutation is causative for CPVT and functionally increases the propensity for SOICR without altering the affinity for FKBP12.6. These observations strengthen the notion that enhanced SOICR, but not altered FKBP12.6 binding, is a common mechanism by which RyR2 mutations cause arrhythmias.Key words: arrhythmia, calcium, death sudden, genetics, ion channels