Synaptonemal complex analysis in spermatocytes and oocytes of rainbow trout,Oncorhynchus mykiss (Pisces,Salmonidae): the process of autosome and sex chromosome synapsis

The surface-spreading synaptonemal complex (SC) technique was employed to analyze spermatocytes and oocytes of rainbow trout in order to visualize the process of autosome and sex chromosome synapsis in this species. The structure of lateral elements (LEs) of the SC and the chromosome synapsis process at the stages of leptotene, zygotene and pachytene are described. Comparative analysis of SCs of spermatocytes and oocytes showed a difference in the synaptic process, i.e. in spermatocytes all LEs were synapsed before the appearance of centromeric regions in the biarmed elements, while in the oocytes some fully synapsed LEs, including the centromeric region of the biarmed elements, were found together with fully or partially unsynapsed LEs. In males the sex chromosome synapsis starts only after all autosomes have synapsed. Irregular synapses involving three or four LEs were found in 3.4% of the cells analyzed in mid or late zygotene. Multivalents were found in males and females. Some aspects of initial meiotic development and their implications in rainbow trout cytogenetics, genetics and evolution are discussed.     

Visceral leishmaniasis in the acquired immunodeficiency syndrome: Report of two cases

Core biopsies of the bone marrow are indispensable in the evaluation of fever of unknown etiology in human immunodeficiency virus-positive patients. We report two patients in whom visceral leishmaniasis was diagnosed based on the typical morphology, staining characteristics, and ultrastructure of the organisms.     

Linkage relationships between a major gene for catechol-o-methyltransferase activity and 25 polymorphic marker systems

Segregation analysis has provided evidence suggesting the existence of a major gene for catechol-o-methyltransferase (COMT) activity in man. Five large families (4 Caucasian, 1 black), with a total of 1,189 individuals, were ascertained as part of a genetic study of blood pressure. Erythrocyte COMT activity and status at 25 polymorphic genetic marker loci were determined on more than 518 individuals in these pedigrees. Genetic linkage analysis of COMT with each of the 25 marker loci was performed in two ways: (1) using parameter estimates from segregation analysis of untransformed COMT activity, and (2) using parameter estimates from segregation analysis of the power transformation of the COMT activity that maximized the likelihood of the genetic hypothesis in each family. Tight and close linkage were excluded at 21 and 15 loci, respectively. A lod score of 1.27 at θ = 0.1 was found between the loci for COMT activity and phosphogluconate dehydrogenase (PGD). Transformation of the data had little effect on the outcome of the linkage analysis.     

家猪心脏三尖瓣复合体的形态学观测

目的　观测家猪心脏三尖瓣复合体 ,为家猪心脏研究和心脏移植积累资料。方法　甲醛固定的家猪心脏 35例 ,大体解剖并观测三尖瓣复合体。结果　家猪心脏三尖瓣复合体由瓣环、瓣膜、腱索和乳头肌构成 ,瓣环周长为 70 75± 8 4 5mm ,前瓣、后瓣、隔侧瓣、前隔连合、前后连合、后隔连合的高度分别为 14 5 8±2 6 4、14 16± 2 5 0、12 84± 2 37、6 2 9± 1 97、6 86± 1 0 1、6 5 1± 1 36mm。前隔连合、前后连合、后隔连合的宽度分别为 6 4 0± 1 5 4、6 78± 1 2 3、6 4 3± 1 4 6 ;前乳头肌起始 ,腱索附着于前瓣、后瓣和前后连合的条数分别为 3 0 0± 0 97、3 0 9± 1 0 9、2 4 4± 1 16 ;后乳肌起始 ,腱索附着于后瓣、隔侧瓣和后隔连合的条数分别为 2 6 0± 0 6 9、3 0 9± 1 6 3、1 14± 0 4 3。隔侧乳头肌起始 ,附着于前瓣、隔侧瓣、前隔连合的腱索条数分别为1 71± 0 6 7、2 37± 1 2 6、0 94± 0 4 2。结论　家猪心脏三尖瓣复合体中各结构与人类相似 ,但大小有一定差异。     

The rational design of TAP inhibitors using peptide substrate modifications and peptidomimetics

The major histocompatibility complex (MHC)-encoded transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum. This step precedes the binding of peptides to MHC class I molecules and is essential for cell surface expression of the MHC class I/peptide complex. TAP has a broad sequence specificity and a preference for peptides of around 9 amino acids. To synthesize inhibitors for TAP, we studied various alterations of the peptide substrate. The results indicate that TAP is stereospecific and that peptide bonds engineered into isosteric structures can improve translocation of the peptide. Furthermore, TAP is able to translocate peptides with large side chains that correspond to a peptide of ～ 21 amino acids in extended conformation. Peptides with longer side chains compete for the peptide binding site of TAP but fail to be translocated. Therefore, they represent the first rationally designed inhibitors of TAP.     

Reelin-immunoreactivity in the hippocampal formation of 9-month-old wildtype mouse: effects of APP/PS1 genotype and ovariectomy

Reelin, an extracellular matrix protein has an important role in the migration, correct positioning and maturation of neurons during development. Though it is generally down-regulated in the postnatal period, expression of this large glycoprotein continues in the adult brain in some cell populations. In the present study, we examined the distribution of reelin-immunoreactivity (-ir) in the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated human APP and PS1 genes, which are linked to the familial form of Alzheimer's disease (AD). The APP/PS1 mice were additionally burdened with a second risk factor for AD, namely depletion of circulating gonadal hormones by ovariectomy (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal formation. In addition, layer II projection neurons in the lateral entorhinal subfields are reelin-ir. Interestingly, ovariectomy decreases the number of reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone induces only a non-significant reduction. Unexpectedly, additional stress, e.g., depletion of gonadal hormones, does not aggravate the slight reduction in the reelin cell number in the APP/PS1 mice. We propose that the changes in normal reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and gonadal hormones are involved and which are perturbed in neurodegenerative conditions, namely AD.     

A pattern search method for putative anchor residues in T cell epitopes

The binding affinity between an antigenic peptide and its particular major histocompatibility complex (MHC) molecule seems to be largely determined by only a few residues. These residues have been called “anchors” because of their property of fitting into “pockets” inside the groove of the MHC molecule. To predict natural antigenic epitopes within a longer sequence, it therefore appears to be important to know the motif or pattern describing the anchors, i.e. the anchors amino acid residue preference and the distance between anchor residues. A large set of MHC class I-restricted peptides has been described. Peptide sequences vary in length and lack an obvious common sequence motif. For a list of peptides belonging to one type of MHC class I molecule, we describe a method to find the most prominent sequence motif with at least two anchor residues. Briefly, antigenic sequences are aligned, and two anchor positions are searched for, where all anchor residues share a high similarity. The alignments are scored according to the similarity of their anchor residues. We show that the motifs predicted for the MHC alleles A2.1, B27, K^b, K^d, D^b are in substantial agreement with experimental data. We derive binding motifs for the MHC class I alleles HLA-A1, All, B8, B14, H-2L^d and for the MHC class II alleles I-A^b and I-A^s. In some cases, higher scores were obtained by allowing a slight variation in the number of residues between anchors. Therefore, we support the view that the length of epitopes belonging to a particular class I MHC is not uniform. This method can be used to predict the natural short epitope inside longer antigenic peptides and to predict the epitopes anchor residues. Anchor motifs can be used to search for antigenic regions in sequences of infectious viruses, bacteria and parasites.     

人脐静脉内皮细胞清除补体攻膜复合物的机制

目的：探讨内皮细胞清除补体攻膜复合物（MAC）的途径及其清除动力学，方法：原代培养的人脐静脉内皮细胞以RH414荧光标记质膜双层，0℃组装亚溶剂量的MAC，37℃复苏后，LSCM实时监MAC沉积诱导的质膜囊泡化形成和胞吞，胞吐情况,流式细胞仪定量检测内皮细胞表面MAC抗原的清除情况，结果：MAC沉积后，内皮细胞有的质膜囊泡化形成，囊泡以胞吞和胞吐2种方式离开细胞，并以前者占优，37度条件下，内皮细胞清除表面MAC的半衰期约为5min。结论：内皮细胞可通过胞吞和胞吐2种机制清除细胞表面沉积的MAC，并以胞吞方式为主。     

Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside

Genetic defects of the dystrophin-glycoprotein complex (DGC) cause hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have previously described a mechanism involved in enterovirus-induced dilated cardiomyopathy: The enteroviral protease 2A directly cleaves dystrophin in the hinge 3 region, leading to functional dystrophin impairment. During infection of mice with coxsackievirus B3, the DGC in the heart is disrupted and the sarcolemmal integrity is lost in virus-infected cardiomyocytes. Additionally, dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy in vivo, suggesting a pathogenetic role of the dystrophin cleavage in enterovirus-induced cardiomyopathy. Here, we extend these experimental findings to a patient with dilated cardiomyopathy due to a coxsackievirus B2 myocarditis. Endomyocardial biopsy specimens showed an inflammatory infiltrate and myocytolysis. Immunostaining for the enteroviral capsid antigen VP1 revealed virus-infected cardiomyocytes. Focal areas of cardiomyocytes displayed a loss of the sarcolemmal staining pattern for dystrophin and -sarcoglycan identical to previous findings in virus-infected mouse hearts. In vitro, coxsackievirus B2 protease 2A cleaved human dystrophin. These findings demonstrate that in human coxsackievirus B myocarditis a focal disruption of the DGC can principally occur and may contribute to the pathogenesis of human enterovirus-induced dilated cardiomyopathy.