Folding and function of the myelin proteins from primary sequence data.

To explain how the myelin proteins are involved in the organization and function of the myelin sheath requires knowing their molecular structures. Except for P2 basic protein of PNS myelin, however, their structures are not yet known. As an aid to predicting their molecular folding and possible functions, we have developed a FORTRAN program to analyze the primary sequence data for proteins, and have applied this to the myelin proteins in particular. In this program, propensities for the secondary structure conformations as well as physical-chemical parameters are assigned to the amino acids and the pattern of these parameters is examined by calculating their average values, autocorrelation functions and Fourier transforms. To compare two proteins, their sequences are aligned using a unitary scoring matrix, and homologies are searched by plotting a two-dimensional map of the correlation coefficients. Comparison of the corresponding myelin basic proteins (MBP) and P0 glycoproteins (P0) for rodent and shark showed that the conserved residues included most of the amino acids which were predicted to form the alpha or beta conformations, while the altered residues were mainly in the hydrophilic and turn or coil regions. In both rodent and shark the putative extracellular domain of P0 glycoprotein displayed consecutive peaks of beta propensity similar to that for the immunoglobulins, while the cytoplasmic domain showed alpha-beta-alpha folding. To trace the immunoglobulin fold along the P0 sequence, we compared the beta propensity curve of P0 with that of the immunoglobulin M603, whose three-dimensional structure has been determined. We propose that the flat beta-sheets of P0 are orientated parallel to the membrane surface to facilitate their homotypic interaction in the extracellular space. An extra beta-fold in the extracellular domain of shark P0 compared with rodent P0 was found, and this may result in a greater attraction between the apposed extracellular surfaces and may account for a smaller extracellular space as measured by x-ray diffraction. A computer search of the myelin protein sequences for functional motifs revealed sites for N-glycosylation, phosphorylation, nucleotide binding, and certain enzyme activities. We note especially that there are potential nucleotide binding sites in proteolipid protein (PLP), MBP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). This is consistent with the experimental observations that PLP acts like an ionophore or proton channel when reconstituted into planar lipid bilayers, MBP binds GTP, and CNP catalyzes in vitro the hydrolysis of 2',3'-nucleotides into corresponding 2'-nucleotides.     

Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I-associated myelopathy

We investigated the presence of anti-human T-lymphotropic virus type I (HTLV-I) IgM in sera and cerebrospinal fluid from patients with HTLV-I-associated myelopathy (HAM) by Western blot analysis. Analyses of 36 serum samples revealed that most patients (31/36; 86.1%) had anti-HTLV-I IgM, whereas only four of 23 (17.4%) HTLV-I carriers had it. In studies of cerebrospinal fluid, anti-HTLV-I IgM was detected in 24 of 36 (66.7%) HAM patients, whereas none was detected in nine HTLV-I carriers. The differences were statistically significant (p less than 0.01). These results suggest that persistent active replication of HTLV-I occurs in the central nervous system as well as in the peripheral blood of HAM patients, and may contribute to the development of HAM.     

Sources of stress in Australian adolescents: factor structure and stability over time

Adolescent stress is an emerging area of importance in considerations of the health of young people. Exposure to stress predicts a range of both physical and mental health problems in adolescents and relates, as well, to the initiation of important health risk behaviours. Yet the measurement of stress in adolescents has been as fraught with methodological difficulty as it has been for adults. This paper examines the Adolescent Stress Questionnaire (ASQ) which was developed specifically to address the domain of stressors specific to adolescent experience and looks at three cohorts of responses to this questionnaire over time (1995, 1998 and 2001). It assesses the stability of the original 7‐factor structure of the ASQ over time, and while confirmatory factor analysis indicates that stability to be acceptable, it also suggests that either adolescent stressors themselves, or the language by which they are reported, vary sufficiently over time to warrant the refinement of the instrument. Copyright © 2002 John Wiley & Sons, Ltd.     

一种有效去除脂血对血清多种生化指标测定干扰的方法

目的 :探讨一种去除脂血对血清生化项目测定干扰的方法。方法 :沉淀、离心沉淀去除血清中过量的乳糜微粒。结果 :该法简便去脂效果彻底 ,不影响测定结果。结论 :获得了一种满意的去脂方法     

抗大肠癌噬菌体人单链抗体的初步鉴定及序列分析

目的 :对抗大肠癌细胞的单克隆噬菌体单链抗体进行初步鉴定和测序分析。方法 :采用细胞ELISA ,免疫组化 ,DNA序列测定和计算机分析方法 ,对 5个单克隆噬菌体抗体 (CH2 73,CH2 0 5 ,CH2 0 9,CHA12 ,CH72 3)进行初步鉴定和序列分析。结果 :5个抗体均对人大肠癌细胞、人胚肾上皮细胞和其它某些人肿瘤细胞反应 ,也与人正常肝细胞有弱阳性反应 ,但不与鼠源性的癌细胞和正常细胞反应。细胞免疫组化进一步证实了ELISA结果的正确性。大肠癌免疫组化对大肠癌组织有特异性的结合反应 ,而不与正常大肠组织反应。测序结果为CH2 73ScFv全长 732bp ;V ,D ,J分别属于VH3 30 D1 2 6 JH3 linker V1 13 JL2 ,GenBank序号为AY0 2 8777和AY0 2 8996 ;CH2 0 5全长 36 6bp ,V ,D ,J分别VH1 4 6 D6 13 JH3,GenBank序号为AF35 936 5 ;CH2 0 9,CHA12和CH72 3的ScFv基因完全相同 ,全长 72 3bp ,其VH DH JH与CH2 73ScFv基因中的VH DH JH 完全一致 ,V ,D ,J分别属于VH3 30 D1 2 6 JH3 linker L2 Jκ2 ,GenBank序号为AF36 3774。结论 :噬菌体抗体具有结合人大肠癌组织和细胞的活性 ,为进一步开发临床应用人源抗肿瘤抗体和小分子抗体片段奠定基础     

Multiple spike-train analysis using mutual interval matrix

The principal-component approach is applied to the analysis of sequences of neuronal action potentials (spike trains). Multiple spike trains are represented as a sequence of vectors of mutual interspike intervals and are considered to be part of the trajectory of a dynamic system. The trajectory matrix is decomposed into a number of ‘basic spike patterns’ and their relative magnitudes by singular-value decomposition. The representation provides a convenient framework for analysis of dynamic relations and cooperation between neurons in an observed network. Examples of applications to simulated and cerebellar data are presented.     

中西医结合治疗难治性原发性肾病综合征20例

目的 :探讨难治性原发性肾病综合征 ( PNS)的中西医结合治疗途径。方法 :选择 PNS患者2 0例 ,逐步撤减激素至停用 ,停免疫抑制剂 ,酌情给予降压、利尿、降脂、提高血浆胶体渗透压 ,自拟“健肾汤”、辨证辨病加减 ,治疗前后分别测定 2 4 h尿蛋白定量、血浆白蛋白、胆固醇、Scr(血肌酐 )、Ccr(肌酐清除率 )。结果 :治疗 8周后 2 4 h尿蛋白、血浆胆固醇显著下降 ,血浆白蛋白显著上升 ,肾功能明显改善 ( P<0 .0 1 )。病情完全缓解 40 % ,部分缓解 45 % ,无效 1 5 % ,总有效率 85 %。结论 :中西医结合治疗 PNS取得一定疗效 ,值得临床和实验进一步研究。     

间接免疫荧光法检测特异性IgG抗体对流行性出血热诊断意义

本文报告用间接免疫荧光法检测特异性IgG抗体对流行性出血热的诊断意义。53例不同病期的出血热患者的血清,其间接荧光抗体的阳性率为49/53(占92.45％)。有77.36％的患者血清,检出IgG抗体的时间是在发病后的1～2周。血清中IgG的滴度与疾病的严重性无密切相关。另25例非EHF患者,其血清特异性IgG抗体均为阴性。可见检测特异性IgG抗体对EHF的诊断颇为有用。     

免疫调节药在肿瘤患者住院治疗中的应用分析

目的 了解肿瘤住院患者使用免疫调节药的现状，为临床合理用药提供参考。方法对2003～2005年免疫调节药应用情况运用药物使用频度（DDDs）、年均增率（AARG）等分析方法，进行统计分析。结果 免疫调节药销售金额年均增长率达106.69%。生物反应修饰剂销售金额占总金额的65.93%。生物反应修饰剂和增强免疫功能中成药用药频度相当。排序靠前的是金黄色葡萄球菌滤液注射液、参芪扶正注射液，用量上升最快的是香菇多糖注射液、胸腺素α1注射液。结论 免疫调节药是肿瘤放化疗必备用药，在肿瘤患者住院治疗中应用广泛。整体上该类药物的应用基本合理。疗效显著且作用广泛的药物成为临床首选。