Investigation of activating and inhibitory killer cell immunoglobulin-like receptors and their putative ligands in type 1 diabetes (T1D)

Genetic and environmental factors play important roles in predisposing an individual to the development of type 1 diabetes (T1D). Several studies have investigated the role of killer cell immunoglobulin-like receptors (KIRs) and their HLA-class I ligands in susceptibility to T1D development, but only some of these studies have demonstrated an association. KIRs and their corresponding HLA class I ligands were investigated in Saudi patients with T1D compared with healthy controls. No significant differences in KIR gene distribution were observed between T1D patients and healthy controls. However, the homozygous C1/C1 ligand was considered a risk factor in predisposing individuals to T1D, whereas C2/C2 and HLA-Bw4 were considered protective factors against T1D. KIR2DL2/2DS2-C1C1 and KIR2DL3-C1C1 were significantly associated with T1D, and KIR2DS1-C2C2 and KIR2DL1-C2C2 were significantly less frequent in T1D patients. Stratification of KIR-HLA class I ligands in terms of the absence/presence of specific genotypes has different indications for susceptibility to T1D.     

活化型肝星状细胞中miRNA-193下调α-平滑肌肌动蛋白的表达

目的:研究活化型肝星状细胞(HSC)中miRNA-193(miR 193)下调肝纤维化相关基因的表达。方法:将大鼠miR-193的前体序列(pre-miR-193)克隆到真核表达载体pcDNA3.1(+)中,经酶切和DNA测序鉴定,获得质粒pcDNA3.1-miR-193;通过脂质体转染法将质粒转染到大鼠的活化型肝星状细胞(HSC-T6)中,采用荧光素酶报告基因分析法和免疫印迹检测肝纤维相关基因的表达。结果:构建的真核表达载体pcDNA3.1-miR-193经酶切鉴定及DNA测序显示,目的片段的大小与预期结果一致;荧光素酶报告基因分析法和免疫印迹检测显示,重组质粒转染到活化型H-SC-T6中后,肝纤维化相关基因的α-平滑肌肌动蛋白(α-SMA)的表达呈明显下降趋势,而胶原蛋白Ⅰα1和Ⅰα2的下调作用不明显。结论:miR-193能抑制活化型肝星状细胞中肝纤维化相关基囚α-SMA的表达。     

HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais

Little is known of the role of classical HLA-A and -B class I alleles in determining resistance, susceptibility, or the severity of acute viral infections. Appropriate paradigms for immunogenetic studies of acute viral infections are dengue fever (DF) and dengue hemorrhagic fever (DHF). Both primary and secondary infections with dengue virus (DEN) serotypes 1, 2, 3 or 4, can result in either clinically less severe DF or the more severe DHF. In secondary exposures, a memory response is induced in immunologically primed individuals, which can both clear the infecting dengue virus and contribute to its pathology. In a case-control study of 263 ethnic Thai patients infected with either DEN-1, -2, -3 or -4, we detected HLA class I associations with secondary infections, but not in immunologically naive patients with primary infections. HLA-A*0203 was associated with the less severe DF, regardless of the secondary infecting virus serotype. By contrast, HLA-A*0207 was associated with susceptibility to the more severe DHF in patients with secondary DEN-1 and DEN-2 infections only. Conversely, HLA-B*51 was associated with the development of DHF in patients with secondary infections, and HLA-B*52 was associated with DF in patients with secondary DEN-1 and DEN-2 infections. Moreover, HLA-B44, B62, B76 and B77 also appeared to be protective against developing clinical disease after secondary dengue virus infection. These results confirm that classical HLA class I alleles are associated with the clinical outcome of exposure to dengue virus, in previously exposed and immunologically primed individuals.     

Lymphocytes expressing alpha1beta1 integrin (very late antigen-1) in peripheral blood of patients with arthritis are a subset of CD45RO(+) T-cells primed for rapid adhesion to collagen IV

We report that very late antigen-1 (VLA-1(+)) CD3(+)CD45RO(+) T-cells are selectively segregated from VLA-1(-) peripheral blood (PB) mononuclear cells (MC), in which CD3(+) T-cells are evenly CD45RO(+) and CD45RO(-), when PBMC are stained with a monoclonal antibody (mAb) to VLA-1 and passaged on immunomagnetic columns. In contrast, both VLA-1(+) and VLA-1(-) MC isolated from synovial fluid (SF) are mainly CD45RO(+)CD3(+) T-cells. VLA-1(+) MC formed 13 +/- 5.3% of MC eluting from columns loaded with PBMC of patients with seropositive rheumatoid arthritis (n = 6) and 2.3 +/- 1.6% of patients (n = 4) with other arthritides (P < 0.022). Importantly, only the VLA-1(+) MC from PB and SF adhered to collagen IV upon triggering with phorbol 12-myristate 13-acetate. Moreover, adhesion and migration on collagen IV were preferentially maintained in lines cultured from VLA-1(+) T-cells, and both were inhibited by mAb to the VLA-1 alpha1 I domain. These results suggest that VLA-1(+) CD45RO(+) T-cells in patients with arthritis could play a role in both systemic and local inflammation by rapidly adhering to collagen IV.     

小儿肾病综合征血管紧张素I转换酶基因多态性研究

目的：探讨ACE基因第16内含子插入／缺失多态性与肾病综合征、血清ACE活性的关系。方法：采用聚合酶链式反应（PCR）检测82例肾病综合征患儿和38例正常儿童ACE基因并同时用酶偶联法测血清ACE活性。结果：①82例肾病综合征患儿中ACE基因Ⅱ型，ID型和DD型频率分别为47．6％（39／82），24．4％（20／82）和28％（23／82）。对照组分别为47．3％（18／38），23．7％（9／38）和29％（11／38），肾病综合征患儿和正常儿童之间ACE基因I／D多态性频率差异无显著性意义（P＞0．05）。②38例正常儿童和82例肾病综合征患儿血清ACE活性比较差异无显著性意义（P＞0．05），ACE各基因型中血清ACE活性差异有显著性意义（P＜0．01），DD型＞ID型＞Ⅱ型。结论：①小儿肾病综合征ACE基因Ⅱ型，ID型和DD型频率分布和正常儿童差异无显著性意义（P＞0．05）。②ACE基因多态性与血清ACE活性密切相关。     

Eating disorders and comorbidity

Summary This review summarizes the current literature on the comorbidity of psychiatric disorders with anorexia nervosa, bulimia nervosa and binge eating disorder. The elevated prevalence of depres-sion, anxiety disorders, obsessive-compulsive disorders, substance abuse, childhood sexual abuse, and personality disorders will be reviewed. In addition, the relationship of eating disorders to body dysmorphic disorder, the menstrual cycle, pregnancy, and diabetes will be discussed.     

Ganglioside expression in tissues of mice lacking beta2-microglobulin

This study presents a comparative analysis of gangliosides from lymphoid (spleen and thymus) and other (brain, liver, lungs and muscle) tissues of C57BL/6 mice lacking the gene for beta2-microglobulin (beta2M), a constitutive component of the MHC class I molecule. Ganglioside fractions in the tissues of mice homozygous (beta2M-/-) and heterozygous (beta2M-/+) for the gene deletion were determined by high performance thin-layer chromatography (HPTLC), followed by immunostaining with specific polyclonal antibodies. Ubiquitous gangliosides GM3(Neu5Ac) and GM3(Neu5Gc) were the dominant gangliosides in the lungs of the control beta2M-/+ mice, whereas the homozygous knockout mice had substantially decreased expression of these structures. The lungs of the beta2M-/- mice also had reduced expression of T-lymphocyte-specific GM1b-type gangliosides (GM1b and GalNAc-GM1b). beta2M-deficient mice also had more GM1a and GD1a gangliosides in the liver, and several neolacto-series gangliosides were increased in the brain and lungs. This study provides in vivo evidence that the beta2M molecule can influence the acquisition of a distinct ganglioside assembly in different mouse organs, implicating its non-immunological functions.     

IFNgamma and TNFalpha account for a pro-clonogenic activity secreted by activated murine peritoneal macrophages

In the present study, we found that murine peritoneal macrophages elicited by BCG or Listeria monocytogenes release into the media an activity capable of stimulating the lung colonization as well as the expression of MHC class I antigens in B16 melanoma cells. A similar activity has previously been found in media conditioned by Corynebacterium parvum-elicited macrophages. Analysis by gel filtration chromatography of media conditioned by Corynebacterium parvum-, BCG- or Listeria monocytogenes-elicited macrophages revealed that the material responsible for the pro-clonogenic activity concentrated in chromatographic fractions corresponding to molecular weights (25 to 52 kDa) which are characteristic of certain cytokines. Thus, we challenged the various macrophage-conditioned media with polyclonal antibodies against IFNγand TNFα, and found that the macrophage pro-clonogenic activity was completely abolished in the presence of anti-IFNγantibodies, but only partially inhibited by anti-TNFαantibodies. This finding suggests a cooperative participation of the two cytokines to the pro-clonogenic activity of the media conditioned by Corynebacterium parvum-, BCG- or Listeria monocytogenes-elicited macrophages. This revised version was published online in July 2006 with corrections to the Cover Date.     

The interface between tapasin and MHC class I: identification of amino acid residues in both proteins that influence their interaction

Prior to the binding of antigenic peptide, a complex of chaperone proteins associates with the Major Histocompatibility Complex (MHC) class I heavy chain/β₂m heterodimer. Although each dornain of the MHC class I heavy chain contains amino acid resid uses that influence chaperone binding, there are several pieces of evidence that point to an interaction between the MHC clas 1α2/α3 domains and tapasin. In egard to the site on tapasin involved in the tapasin/MHC interface, we have found that a particular region of tapasin (containing amino acid residues 334–342) is necessary for the binding of tapasin to the MHC class I heavy chain. Our results also indicate that amino acids in this region of tapasin also affect the proportion of MHC class I open forms expressed at the cell surface and MHC class I egress from the endoplasmic reticulurn. Based on these results and those obtained by other laboratories, a model for MHC class I/tapasin interaction is proposed.