Detection of three types of hepatitis C virus in blood donors: investigation of type-specific differences in serologic reactivity and rate of alanine aminotransferase abnormalities

The serologic reactivity and epidemiology associated with different hepatitis C virus (HCV) variants were investigated in a cohort of 113 anti-HCV-positive donors. In Scotland, HCV type 1 accounted for one- half of all infections; 40 percent of subjects were infected with HCV type 3, and the remainder were infected with type 2. Reactivity with the NS-4-encoded antigens in the first-generation anti-c100 assay was absent in 68 percent of donors infected with types 2 and 3, as compared with 10 percent for those infected with type 1. Even when combined with surrogate marker testing, first-generation tests would have failed to detect 12 percent of HCV-infected blood donors. The age distribution, incidence of past infection with hepatitis B virus, and reported risk factors were similar in donors infected with types 1 and 3 (mean ages were 31.9 and 29.9; 18 and 17.5% were positive for antibody to hepatitis B core antigen; and 47 and 48% had past intravenous drug abuse). However, the distributions of alanine aminotransferase levels were significantly different in those infected with type 3 (abnormally raised in 83%) and those infected with type 1 (55% abnormal alanine aminotransferase; p < 0.05) or type 2 (60%; p < 0.01) and those who were nonviremic (8%; p < 0.0001). These data suggest that HCV type 1 is the most common HCV infection in blood donors and that infection with HCV type 3 may be associated with more severe liver disease, because of more recent infection or because of a greater inherent pathogenicity of type 3 variants.     

辽西地区农村汉族青少年体型发育规律的Heath-Carter体型法分析

目的:分析辽西地区农村汉族青少年的体型发育规律和特点,为体质人类学补充必要的数据。对象:按整群分层抽样法,抽取2001-07/2003-09辽西地区锦州、盘锦、葫芦岛、义县和绥中的农村13所中小学7～19岁经学校正常体质检查证明身体健康的汉族学生为调查对象,按性别分两大组,每大组按年龄分12小组,7～18岁每岁为1个年龄组,18～19岁为1个年龄组,每小组44～82人,共分24组,搜集完整资料1280名(男666名,女614名)。采用Heath-Carter体型法,每项指标测量2次,取平均值,10项指标由专人负责,测试数据按年龄和性别在微机中建立数据库,依次计算出各年龄组的内因子、中因子和外因子,体型图上的X,Y坐标值,身高/体质量1/3,样本中平均体型点到所有体型点空间距离的均数,三维空间中两个体型点间的差异,体脂百分比和各类体型分布频数。结果:参加调查1280名,均进入结果分析。①7～17岁青少年身高、体质量随年龄的增加而增长。平均身高、体质量男生大于女生。身高/体质量1/3指数除7、8、10、12和13岁外,各年龄组男生>女生,平均值男生>女生。体脂含量除8岁外,其他年龄组女生>男生,平均值女生>男生。②男生的体型均值3.6-2.5-3.7,属外胚层-内胚层均衡体型,女生平均体型值为4.3-2.2-3.3,属于偏外胚层的内胚层体型。体型频数的变化提示辽西农村汉族男生体型分布在内胚层和外胚层的体型较多,女生分布较集中,主要在内胚层体型。③内因子男生在3.0～4.0,女生在3.5～5.2,各年龄组女生>男生;中因子男生在1.6～3.9,女生在0.8～3.4,除7、11和17岁女生>男生外,其他年龄组男生>女生或男女相等,平均值男生>女生。外因子男生在3.0～5.0,女生在3.0～4.1,7、8、10、12、13岁女生>男生,11、14、15、16、17、18岁男生>女生。因此,女生的内因子占优势,皮下脂肪更发达,体态丰满,男生中因子占优势,骨骼粗壮,肌肉发达,随着年龄的增长,男生的身体相对瘦高程度增长,身材修长。④男女各年龄组间体型比较,7,8,9,10,11,12,13,14,15,16,17,18～19岁三维空间中两个体型点间的差异值分别为0.45,0.67,1.03,0.56,0.76,0.30,0.93,2.60,1.86,1.37,1.21,1.47,8～11岁年龄组男女间体型差异有显著性(t=2.66,2.75,2.95,3.58,P<0.05)。⑤与城市青少年相比,农村青少年身高低5～6cm(男女分别为u=6.24,5.90,P<0.01),体质量低3～6kg(男女分别为u=6.93,4.60,P<0.01)。结论:辽西地区农村男生较女生骨骼粗壮,肌肉发达,女生的皮下脂肪更发达,体态丰满,随着年龄的增长,男生的身体相对瘦高,身材修长。与城市青少年相比,农村青少年仍矮瘦,与国外资料和国内少数民族相比,辽西地区农村汉族青少年骨骼肌肉欠发达,身材修长。     

DIAPHRAGMATIC PARALYSIS IN MOTOR NEURONE DISEASE: USE OF NON-INVASIVE INVESTIGATIVE AND THERAPEUTIC TECHNIQUES

SUMMARY Two cases of bilateral diaphragmatic weakness are described in which the condition was the presenting feature of motor neurone disease. Inspiratory muscle strength was assessed by a non-invasive technique involving measurements of pressures generated within the mouth. One patient with severe inspiratory muscle weakness is being treated with domiciliary nasal ventilation and has returned to a good-quality life. The other patient with less severe weakness has thus far required no ventilatory support.     

Mapping of monoclonal antibodies to human factor IX

We used recombinant DNA techniques to map a panel of six monoclonal antibodies (MoAbs) to regions of the human factor IX molecule. A-2 maps to 17 amino acids at the amino terminus of the heavy chain of IXa; 2D5, an inhibitor of clotting, is defined to 36 amino acids of the first EGF- like domain of human factor IX. A-4, A-5, C10D, and FXC008 all map to a region of the heavy chain containing amino acids 180 through 310, suggesting an immunodominant site. FXC008 has been reported to interfere with binding of factor IXa to factor VIII:Ca.     

In vitro autoradiographic and in vivo scintigraphic localization of somatostatin receptors in human lymphatic tissue

Receptors for the neuropeptide somatostatin (SS) were evaluated in vitro and in vivo in various human lymphatic tissues, ie, thymus, spleen, and lymph nodes; thymic carcinoids and thymomas were also tested. The receptors were measured in vitro using receptor autoradiography on tissue sections incubated with the SS analog 125I- [Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-SS-28. All tissues were SS-receptor positive for either radioligand, except the thymomas. In thymic tissue, the receptors were diffusely located in the medulla, presumably on epithelial cells. In the spleen, the red pulp was strongly labeled. In the lymph nodes, the germinal centers were preferentially labeled. In all tissues, the receptors were of high affinity (kd thymus, 0.84 nmol/L; kd spleen, 1.6 nmol/L; kd lymph node, 0.62 nmol/L) and specific for SS. Displacement by nanomolar concentrations of SS-14, SS-28, and octreotide was observed, as was guanosine triphosphate dependency. The in vivo visualization of somatostatin receptors was performed after injection of 111In-DTPA- octreotide and gamma-camera scintigraphy. The spleen, but not thymus or lymph nodes, were visualized. These data suggest an important role for SS in regulating immune functions through SS receptors in thymus, spleen, and lymph nodes. Furthermore, SS may regulate neuroendocrine functions in the thymus.     

Characterization of a factor IX variant with a glycine207 to glutamic acid mutation

Factor IXTaipei9 is a factor IX variant from a hemophilia B patient with reduced levels of circulating protein molecules (cross-reacting material reduced, CRM). This variant contained a glycine (Gly) to glutamic acid (Glu) substitution at the 207th codon of mature factor IX. The functional consequences of the Gly-->Glu mutation in factor IXTaipei9 (IXG207E) were characterized in this study. Plasma-derived IXG207E exhibited a mobility similar to that of normal factor IX on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its specific activity was estimated to be 3.5% that of the purified normal factor IX in a one-stage partial thromboplastin time assay (aPTT). Cleavage of factor IXG207E by factor XIa or factor VIIa-tissue factor complex appeared to be normal. When the calcium-dependent conformational change was examined by monitoring quenching of intrinsic fluorescence, both normal factor IX and IXG207E exhibited equivalent intrinsic fluorescence quenching. Activated factor IXG207E (IXaG207E) also binds antithrombin III equally as well as normal factor IXa. However, aberrant binding of the active site probe p-aminobenzamidine was observed for factor XIa-activated factor IXG207E, indicating that the active site pocket of the heavy chain of factor IXaG207E was abnormal. Moreover, the rate of activation of factor X by factor IXaG207E, as measured in a purified system using chromogenic substrates, was estimated to be 1/40 of that of normal factor IXa. A computer-modeled heavy-chain structure of factor IXa predicts a hydrophobic environment surrounding Gly-207 and this Gly forms a hydrogen bound to the active site serine-365. The molecular mechanism of the Gly-->Glu mutation in factor IXTaipei9 might result in the alteration of the microenvironment of the active site pocket which renders the active site serine-365 inaccessible to its substrate.