Genotype at a major locus with large effects on apolipoprotein B levels predicts familial combined hyperlipidemia

A sample enriched for familial combined hyperlipidemia (FCHL) was examined for evidence of an association between genotype at an apolipoprotein B (apoB) elevating locus defined by complex segregation analysis and FCHL. Complex segregation analysis detected a locus with a large effect on plasma apoB levels and was used to compute the most probable genotype of family members. None of the 35 normolipidemic adults carried a copy of the allele associated with elevated apoB levels, yet 58% of the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 28 (7%) normal children had 1 copy of this allele and none had 2 copies, while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copies. Further, 4l of 48 (85%) individuals classified as having hyperapobetalipoproteinemia did not carry a copy of this “elevated apoB” allele. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot be explained solely by the presence of elevated apoB levels in FCHL, suggesting that the locus controlling apoB levels may play an etiologic role in FCHL. © 1993 Wiley-Liss, Inc.     

Weight gain in first-episode psychosis.

OBJECTIVE: To examine the extent of weight gain in the first year of treatment in an early psychosis program. METHOD: Subjects were 114 individuals who had experienced a first episode of psychosis and had completed 1 year in a comprehensive first-episode program. Weight and body mass index were calculated on entry to the program and at 6 and 12 months. Most of the subjects were all being prescribed second-generation antipsychotics. RESULTS: Significant increases in mean weight were observed in these young individuals over the course of the first year of treatment. CONCLUSIONS: If we are to work toward optimum treatment for first-episode subjects then potential weight gain needs to be addressed at the beginning of treatment and monitored during treatment.     

Potentiation of benzoate toxicity by glyoxylate. Inhibition of pyruvate carboxylase and the urea cycle

It has been proposed that administration of non-nitrogenous precursors to glycine is necessary to realize the full potential of benzoate metabolism as a pathway for disposal of waste nitrogen during ammonia intoxication (Coude et al., Clin Chim Acta 136: 211-217, 1984). However, when glyoxylate, a keto acid precursor to glycine, was administered with benzoate 1 hr prior to a challenge of ammonia, protection against ammonia toxicity was less successful than with benzoate alone. At the cellular and subcellular levels, glyoxylate and benzoate each inhibited the urea cycle in isolated hepatocytes and pyruvate carboxylase in isolated mitochondria. The action of each drug was associated with depletion of aspartate content in isolated hepatocytes and reduction of pyruvate-dependent incorporation of CO2 into aspartate in assays with isolated mitochondria. Depression of aspartate regeneration by inhibition of pyruvate carboxylase is a likely mechanism for impairment of urea cycle activity by both drugs. In whole animals, inhibition of pyruvate carboxylase may contribute to benzoate toxicity and the adverse influence of glyoxylate on benzoate therapy.     

Isolation and characterization of marine luminous bacteria from shallow coastal waters of Taiwan.

BACKGROUND AND PURPOSE: Marine luminous bacteria were isolated and identified from samples in shallow coastal waters of Taiwan during the relatively warm seasons. METHODS: Identification of the luminous isolates was performed based on differences of phenotypic and genotypic characteristics together with data from phylogenetic analysis. RESULTS: Twenty seven strains of marine luminous bacteria were isolated. They were divided into five types based on differences of phenotypic characteristics. However, they could be clustered into only two genotypes according to the analysis of restriction patterns of polymerase chain reaction-amplified 16S rRNA genes digested with various restriction enzymes. The characterization data together with the 16S rRNA gene-based phylogenetic analysis revealed that the isolates included in phenotype I (seven isolates) could be Photobacterium leiognathi, and those included in phenotypes II-V (twenty isolates) might be classified as Vibrio harveyi. However, phylogeny based on gyrB sequences indicated that phenotypes II-V could be classified into two species, V. harveyi and Vibrio campbellii. CONCLUSION: Culturable luminous bacteria in the shallow coastal waters of Taiwan during the sampling period are dominated by V. harveyi/campbellii and P. leiognathi, and the former species appeared to be more prevalent and numerous than the latter species in general.     

Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.     

Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue.

(11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. METHODS: Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. RESULTS: NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma. CONCLUSION: In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.