Monoclonal antibody against an Ir gene product?

Genetic, biochemical, and functional studies have been performed using a monoclonal antibody, Y-17, directed at a conformational or combinatorial determinant formed by certain Ae:E alpha complexes. This determinant appears to be a marker present on a subset of B cells as well as on non-T and non-B spleen cells. Besides Ae and E alpha chains, Y-17 precipitates a third chain that is indistinguishable from the A alpha chain in two-dimensional gels. This results suggests additional combinatorial complexity in the generation of I-region encoded antigens. Y-17 can inhibit the response of T cells to Ae:E alpha determinants in mixed lymphocyte cultures. Furthermore, Y-17 blocks antigen-specific T cell proliferative responses to GLPhe and pigeon cytochrome c which have been shown to require the Ae:E alpha complex as a restriction element for antigen presentation. These results provide strong evidence for the molecular identity of Ia antigens, Ir-gene products and Lad antigens.     

Novel antibacterial class

We report the discovery and characterization of a novel ribosome inhibitor (NRI) class that exhibits selective and broad-spectrum antibacterial activity. Compounds in this class inhibit growth of many gram-positive and gram-negative bacteria, including the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis, and are nontoxic to human cell lines. The first NRI was discovered in a high-throughput screen designed to identify inhibitors of cell-free translation in extracts from S. pneumoniae. The chemical structure of the NRI class is related to antibacterial quinolones, but, interestingly, the differences in structure are sufficient to completely alter the biochemical and intracellular mechanisms of action. Expression array studies and analysis of NRI-resistant mutants confirm this difference in intracellular mechanism and provide evidence that the NRIs inhibit bacterial protein synthesis by inhibiting ribosomes. Furthermore, compounds in the NRI series appear to inhibit bacterial ribosomes by a new mechanism, because NRI-resistant strains are not cross-resistant to other ribosome inhibitors, such as macrolides, chloramphenicol, tetracycline, aminoglycosides, or oxazolidinones. The NRIs are a promising new antibacterial class with activity against all major drug-resistant respiratory pathogens.     

Vibrio vulnificus typing based on simple sequence repeats: insights into the biotype 3 group

Vibrio vulnificus is an opportunistic, highly invasive human pathogen with worldwide distribution. V. vulnificus strains are commonly divided into three biochemical groups (biotypes), most members of which are pathogenic. Simple sequence repeats (SSR) provide a source of high-level genomic polymorphism used in bacterial typing. Here, we describe the use of variations in mutable SSR loci for accurate and rapid genotyping of V. vulnificus. An in silico screen of the genomes of two V. vulnificus strains revealed thousands of SSR tracts. Twelve SSR with core motifs longer than 5 bp in a panel of 32 characterized and 56 other V. vulnificus isolates, including both clinical and environmental isolates from all three biotypes, were tested for polymorphism. All tested SSR were polymorphic, and diversity indices ranged from 0.17 to 0.90, allowing a high degree of discrimination among isolates (27 of 32 characterized isolates). Genetic analysis of the SSR data resulted in the clear distinction of isolates that belong to the highly virulent biotype 3 group. Despite the clonal nature of this new group, SSR analysis demonstrated high-level discriminatory power within the biotype 3 group, as opposed to other molecular methods that failed to differentiate these isolates. Thus, SSR are suitable for rapid typing and classification of V. vulnificus strains by high-throughput capillary electrophoresis methods. SSR (>/=5 bp) by their nature enable the identification of variations occurring on a small scale and, therefore, may provide new insights into the newly emerged biotype 3 group of V. vulnificus and may be used as an efficient tool in epidemiological studies.     

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes.     

胎盘免疫调节因子对子宫内膜异位症大鼠免疫功能的影响

目的:观察胎盘免疫调节因子对大鼠子宫内膜异位症动物模型的治疗效果和对大鼠免疫功能的影响。方法:实验于2005-10/2006-12在广西医科大学医学科学实验中心及广西肿瘤防治研究所实验病理室完成。①实验材料:健康6个月龄雌性SD大鼠60只,体质量为200～250g;健康产妇胎盘在经广西医科大学第一附属医院伦理委员会同意和产妇知情同意后获得。②实验干预及分组:利用自体子宫组织移植的方法,建立雌性子宫内膜异位症大鼠模型40只,随机分为胎盘免疫调节因子小剂量组、中剂量组、高剂量组和模型对照组,分别肌注胎盘免疫调节因子剂量为0.375,0.75,1.5mg/kg和等体积生理盐水,1次/d,连续8周。③用两脚规测量移植物的体积(V=长×宽×高/mm3),采用ATP生物荧光法测定大鼠脾细胞增殖能力;采用中性红法测定腹腔巨噬细胞的吞噬功能。采用ELISA法检测治疗后各组大鼠血清中白细胞介素2水平。结果:建模成功40只,均进入结果分析。①各组移植物外观及体积:用药后8周,各胎盘免疫调节因子组移植物体积不同程度缩小(P<0.05),呈扁平状,粘连受到明显的抑制。②各组大鼠脾细胞增殖试验、腹腔巨噬细胞吞噬功能及血清白细胞介素2水平的变化:胎盘免疫调节因子中,高剂量用药组脾细胞增殖能力较模型对照组升高(P<0.05);各剂量胎盘免疫调节因子组腹腔巨噬细胞吞噬功能、白细胞介素2水平均较模型对照组升高(P<0.05)。结论:胎盘免疫调节因子治疗大鼠子宫内膜异位症显示了较好的疗效,可显著缩小子宫异位内膜的体积,提高大鼠的免疫功能。     

A mouse model of transmural myocardial necrosis due to coxsackievirus B4: observations over 12 months

The course of coxsackievirus B4 necrotizing myocarditis was studied over a 12-month period in 712 ICR Swiss mice inoculated at less than 48 h of age. Affected animals were sacrificed at intervals until 1 year. Microscopically, focal myocardial necrosis, which was often transmural in extent with mixed inflammatory exudate, and subsequent fibrous replacement were induced in 75% of the examined animals. The left ventricle (63 of 69 subjects, 91.3%), interventricular septum (39 of 69 subjects, 56.5%) and right ventricle (26 of 69 subjects, 37.7%) were most frequently involved. Thinning of the ventricular wall and grossly apparent localized ventricular bulges (aneurysms) were seen in 22 subjects (the left ventricle 16 times, the right ventricle 5 times, and the interventricular septum 5 times). Coronary arteries were normal in all instances.     

Feasibility spectrum for Doppler flowmetry of splanchnic vessels. In normal and cirrhotic populations

The calculation of absolute blood flow by Doppler flowmetry requires adequate visualization of a vessel in both transverse and longitudinal planes and an insonating angle less than 60 degrees. The percentage of the splanchnic vessels in a given population in which these criteria could be fulfilled (ie, the feasibility spectrum) is not known. To identify this spectrum in our patient sample, 100 consecutive nonselected patients (58 female, 42 male) and 34 cirrhotics (31 male, three female) were prospectively studied. In addition, from the group of 42 nonselected patients, 31 males with no evidence of liver disease were matched for age, weight, and height with the 31 male cirrhotics. The echo-Doppler feasibility (EDF; success percentage) was determined for the hepatic, superior mesenteric, and splenic arteries and portal, superior mesenteric, and splenic veins. In the nonselected sample, the EDF varied from 86% for the portal vein to 60% for the superior mesenteric artery. In cirrhotics, the EDF ranged from 88% for portal vein to 29% in splenic artery. The total EDF for the nonselected sample (68%) was significantly higher than the EDF for cirrhotics (54%; P less than .001). Physical factors (weight, age, height, and sex) affected the EDF in the nonselected patient sample but not in cirrhotics. We conclude that analysis of EDF of splanchnic vessels in these groups clearly demonstrates that the composition of the patient sample has an important bearing on the feasibility spectrum of Doppler study. Female subjects who are thin, young, and short and lighter male patients are better candidates for abdominal Doppler flowmetry.