Inositol lipid metabolism in human T lymphocytes activated via the T3 complex.

Cloned human T lymphocytes and a mitogenic monoclonal antibody (UCHT1) that binds to the T3 antigen complex were used to study the role of inositol lipid hydrolysis in T-cell activation. Binding of the T3 molecular complex with anti-T3 antibody induced the generation of inositol trisphosphate after a lag of 1 min. While this is commensurate with the rise in cytosolic Ca2+ in these cells, examination of the inositol lipid revealed that phosphorylation of phosphatidylinositol 4-phosphate to phosphatidylinositol 4,5-bisphosphate occurred before the generation of inositol trisphosphate. Thus, activation of an inositol lipid kinase appears to be one of the primary signals in cellular activation in human T lymphocytes.     

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei

Trypanosoma brucei evades the immune system by switching between Variant Surface Glycoprotein (VSG) genes. The active VSG gene is transcribed in one of approximately 20 telomeric expression sites (ESs). It has been postulated that ES polymorphism plays a role in host adaptation. To gain more insight into ES architecture, we have determined the complete sequence of Bacterial Artificial Chromosomes (BACs) containing DNA from three ESs and their flanking regions. There was variation in the order and number of ES-associated genes (ESAGs). ESAGs 6 and 7, encoding transferrin receptor subunits, are the only ESAGs with functional copies in every ES that has been sequenced until now. A BAC clone containing the VO2 ES sequences comprised approximately half of a 330 kb 'intermediate' chromosome. The extensive similarity between this intermediate chromosome and the left telomere of T. brucei 927 chromosome I, suggests that this previously uncharacterised intermediate size class of chromosomes could have arisen from breakage of megabase chromosomes. Unexpected conservation of sequences, including pseudogenes, indicates that the multiple ESs could have arisen through a relatively recent amplification of a single ES.     

传染性肺结核患者家庭中儿童结核感染发病及预防的研究

目的　分析传染性肺结核患者家庭中的儿童结核感染和发病情况 ,探讨预防儿童发病的有效方案。方法　对与传染性肺结核患者密切接触的儿童进行X线胸透和做结核菌素试验 ;对结核菌素强阳性者给予预防性治疗。结果　与传染性肺结核患者密切接触的儿童感染率为 88 2 %。规则预防治疗组、不规则预防治疗组和不接受预防治疗组的患病率分别为 :8 3%、4 7 6 %、5 8 8%。结论　与传染性肺结核患者密切接触的儿童属于高危人群 ,给予预防性治疗可减少发病。     

延边地区肺结核病人归口转诊模式的探讨

目的　分析延边地区建立肺结核归口转诊模式对肺结核病人的转诊到位率的影响,探讨提高转诊到位率的方法。方法 对全州8个县(市)医院、中医医院、中心卫生院、大型厂矿企事业单位职工医院的执法检查考核资料进行评价。结果 1.建立归口转诊模式前期转诊率为48.3%,转诊到位率为29.0%,后期转诊率为89.0%,转诊到位率为72.4%,有明显提高;2.前期年平均涂阳病人新登记率为13.36/10万,后期为17.86/10万,实施归口转诊模式前期与实施后期的指标有显著性差异(P<0.01)。结论 延边地区实施的肺结核病人归口转诊模式,对提高肺结核病的转诊到位率十分有效,应不断完善并深入推广。     

Analysis of immune system gene expression in small rheumatoid arthritis biopsies using a combination of subtractive hybridization and high-density cDNA arrays

Subtractive hybridization of cDNAs generated from synovial RNA which had been isolated from patients with rheumatoid arthritis (RA) or normal controls was used in conjunction with high-density array hybridization to identify genes of immunological interest. The method was designed to detect gene expression in small needle biopsy specimens by means of a prior amplification of nanogram amounts of total RNA to full-length cDNA using PCR. The latter was cut with Rsa I, ligated with adapters, hybridized with unmodified driver cDNA, and subjected to suppression subtraction PCR. Differentially expressed products were cloned into E. coli and picked into 384 well plates. Inserts were obtained by PCR across the multiple cloning site, and the products arrayed at high density on nylon filters. The subtracted cDNAs were also labelled by random priming for use as probes for library screening. The libraries chosen were the subtracted one described above and a set of 45,000 ESTs from the I.M. A.G.E consortium. Clones showing positive hybridization were identified by sequence analysis and homology searching. The results showed that the subtracted hybridization approach could identify many gene fragments expressed at different levels, the most abundant being immunoglobulins and HLA-DR. The expression profile was characteristic of macrophage, B cell and plasma cell infiltration with evidence of interferon induction. In addition, a significant number of sequences without matches in the nucleotide databases were obtained, this demonstrates the utility of the method in finding novel gene fragments for further characterisation as potential members of the immune system. Although RA was studied here, the technology is applicable to any disease process even in cases where amounts of tissue may be limited.     

复治肺结核病人的成因分析

目的　探讨复治肺结核病人形成原因。方法　使用调查表的方法 ,对前来诊治的复治涂阳肺结核病人的首次诊疗 ,管理情况进行问卷调查。结果　综合医院仍然为大多数患者的首次诊疗单位 ,因此部分肺结核患者未能得到正确的诊断、治疗和化疗管理。导致 67.2 %病人“中断”或“间断”治疗 ;另外结核病健康教育宣传做得不够 ,60 .3 %的患者诊断前未接受过防痨宣教 ,3 4.5 %的患者接受初次化疗时仍未得到宣教。这些均在导致复治病人的产生中起了重要作用。结论　加大DOTS覆盖面 ,加强归口管理力度 ,做好防治结核病教育工作是防止复治肺结核病人产生的重要环节。