Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication

Individuals with the recessive condition trimethylaminuria exhibit variation in metabolic detoxication of xenobiotics by hepatic flavin- containing monooxygenases. We show here that mutations in the human flavin-containing monooxygenase isoform 3 gene ( FMO3 ) impair N - oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype. Three disease-causing mutations in nine Australian-born probands have been identified which share a particular polymorphic haplotype. Nonsense and missense mutations are associated with a severe phenotype and are also implicated in impaired metabolism of other nitrogen- and sulfur-containing substrates including biogenic amines, both clinically and when mutated proteins expressed from cDNA are studied in vitro . These findings illustrate the critical role played by human FMO3 in the metabolism of xenobiotic substrates and endogenous amines.      

Human hepatoma cells secrete single chain factor X, prothrombin, and antithrombin III

The human hepatoma cell line, Hep G2, was analyzed for the ability to synthesize and secrete several coagulation proteins. Using specific radioimmunoassays, factor X, prothrombin, and antithrombin III were present in 8-day culture supernatants at 62, 405, and 1,220 ng/mL, respectively. Factor IX was not detected, either in supernatants or in cell extracts. Intrinsically labeled factor X was secreted as a single- chain polypeptide of 66,000 daltons, as measured by sodium dodecylsulfate-polyacrylamide gels under nonreduced and reduced conditions. Immunoblots of Hep G2 supernatants and normal human plasma also indicate the presence of single-chain factor X. These findings support the hypothesis of a postsecretion proteolytic cleavage of factor X into the two-chain form. Prothrombin and antithrombin represented their plasma protein counterparts structurally, with molecular weights of 73,000 and 61,000, respectively. Secreted factor X, prothrombin, and antithrombin III were biologically active, as determined in coagulation or chromogenic assays, and all three activities were neutralized by monospecific antibodies. Vitamin K increased the quantity of prothrombin secreted by twofold, without affecting the rate of secretion over a five-day culture period, and had an apparent transient inhibitory effect on secretion of antithrombin III. Warfarin caused a three to fourfold decrease in the rate and quantity of secreted prothrombin, but did not affect intracellular concentrations. The intracellular and extracellular concentrations and rate of secretion of antithrombin III were not modulated by warfarin. These data suggest that the Hep G2 cell line may provide a useful model for assessing the regulation of biosynthesis and secretion of human coagulation proteins.     

Accuracy of CT-guided biopsies in 158 patients with thoracic spinal lesions

Objective： To determine the accuracy of CT-guided thoracic spinal biopsy, to compare the results with those previously reported, and to determine if there are any factors that influence the accuracy of CT-guided thoracic spinal biopsy. Methods： In total, 158 consecutive CT-guided percutaneous thoracic spine procedures （performed at our hospital between April 2000 and July 2010） were reviewed. The 158 lesions were categorized by location and radiographic features. Pathological and clinical follow-up were used to determine accuracy. Results： The diagnostic accuracy of CT-guided thoracic spinal biopsy was 90.5% overall. Biopsy of metastatic bone disease （98.2%） was significantly more accurate than biopsies of primary tumors （80.9%） and of hematological malignancies （47.0%） （P〈0.05 and P〈O.005, respectively）. The diagnostic accuracy of CT-guided thoracic spinal biopsy was significantly higher for the lower thoracic spine （97.6%） than for the middle （90.0%） or upper thoracic spine （80.4%） （P〈0.05 and P〈0.025, respectively）. The diagnostic accuracy was significantly higher for lytic lesions （96.4%） than for sclerotic lesions （81.3%） （P〈0.010）. The accuracy of biopsies performed using the transpedieular approach （91.0%） was not significantly different from that of biopsies performed using posterolateral approaches （91.5%） （0.25〈P〈0.5）. Conclusion： Percutaneous CT-guided thoracic spinal biopsy is a viable alternative to open surgical biopsy. The diagnostic accuracy was not affected by any of the variables except for lesion level, histology, and radiographic features.     

紫外分光光度法测定背景未知的复方制剂组分

本文利用目标转换因子分析中具有使纯组分光谱可向自身逼近的性质,提出了一种迭代目标转换因子分析算法,用于寻找未知背景光谱.通过在复方扑热息痛注射液分析中的应用,扑热息痛和安替比林的平均回收率均为100.0％,变异系数分别为1.1％和1.0％。结果表明本法为含有未知背景的多组分体系的紫外分光光度分析提供了可行的途径。     

Colored overlays for visual perceptual deficits in children with reading disability and attention deficit/hyperactivity disorder: are they differentially effective?

The Transient Channel Deficit (TCD) model of reading disability was evaluated by examining the effects of color overlays on the reading ability of four groups of children (n = 15 each) with reading disability and comorbid conditions involving math and ADHD. These 60 children were evaluated for reading accuracy and rate on measures of word decoding and reading comprehension under three color transparency conditions (blue, red, no overlay). Results indicated that color overlays did not differentially affect the reading performance of individuals with and without reading disabilities. However, blue transparencies significantly improved reading comprehension in all groups, and reduced reading rate. These findings indicate that the TCD model may need to be reexamined. An alternative hypothesis for the observed effects, involving facilitation of attention processes, was posted.