Characterization of a monoclonal anti-Bw4 antibody (Tü109): Evidence for similar epitopes on the Bw4 and Bw6 antigens

The production and serologic, as well as immunochemical properties of a cytotoxic murine IgG monoclonal antibody (Tü109) that precipitates HLA-class I molecules, are described. In the microcytotoxicity assay Tü109 supernatant was demonstrated on a panel of 424 HLA-ABC, -DR, -DQ, -MT typed normal Caucasian blood donors to define an epitope on HLA-B locus molecules in great association with the supertypic specificity Bw4. Reactivity of supernatant showed MHC linked inheritance of the Tü109 determinant and discriminated the HLA-Bw4/Bw6 associated HLA-B locus split antigens. Weak or lack of binding on lymphocytes from some HLA-Bw4 heterozygous individuals, particularly typing for HLA-Bw44, appeared to be due to qualitative and/or quantitative variations of HLA-B locus molecules on the cell surface. With Tü109 ascites fluid, however, extra-reactivity on all HLA-Bw6⁺ cells was demonstrated. Preferential binding of supernatant to HLA-Bw4, but reactivity of ascites fluid with HLA-Bw6⁺ molecules in addition, was furthermore confirmed by IEF analysis of antigens immunoprecipitated with Tü109 from cell lysates. Thus the antibody may help to analyze the evolutionary relationship of the diallelic specificities Bw4 and Bw6.     

The use of a double-marker shuttle vector to study DNA double-strand break repair in wild-type and radiation-sensitive mutants of the yeast Saccharomyces cerevisiae

An episomal DNA vector (YpJA18), encoding two selectable recombinant yeast genes (TRP1, URA3), was constructed to assess the fidelity of DNA repair in haploid repair-competent (RAD) wild-type yeast and several radiation-sensitive mutants. Either a DNA double-strand break (DSB) or a double-strand gap of 169 bp (DSG) was introduced by restriction enzymes in-vitro within the coding sequence of the URA3 gene of this vector. To eliminate transfer artefacts, selection was first applied for the undamaged TRP1 gene followed by counter selection for URA3 gene activity, which indicated correct repair of the DSB and DSG. Correct repair of the damaged URA3 gene was found to be about 90% in RAD cells (normalized for the expression of undamaged URA3 in TRP ⁺ transformants). Plasmids isolated from the transformants (URA ⁺ TRP ⁺) carry both unique sites (ApaI and NcoI) within the URA3 gene indicating the precise restitution of the 169-bp gap. An excision-repair-defective rad4-4 mutant repaired these lesions as correctly as RAD cells, whereas the mutants rad50-1, rad51-1 and rad54-1, proven to be defective in DSB repair and mitotic recombination, showed less than 5% correct repair of such lesions. In contrast, a representative of the RAD6 epistasis group of genes, the rev2-1 mutant which is sensitive towards UV and ionizing radiation, had a significantly reduced ability (about 20%) for the correct repair of both DSBs and DSGs.     

Characterization of a reovirus isolate from a rattle snake,Crotalus viridis,with neurological dysfunction

Summary A virus isolate from the brain of a rattle snake with central nervous system (CNS) symptoms was identified as a reovirus. The isolate did not agglutinate pig erythrocytes and was not neutralized by antisera against avian reovirus S1133 and mammalian reovirus type 3. The cytopathic effect in Vero cells was characterized by formation of syncytial giant cells. Electrophoretic analysis of the genome revealed 10 segments of dsRNA. The isolate displayed characteristics distinct from avian and mammalian reoviruses.     

Myoepitheliale Tumoren der Kopfspeicheldrüsen

This tutorial focuses on myoepithelial tumors of salivary glands, an entity with heterogeneous cytomorphology and inconsistent immunophenotype. Moreover, the clinical course cannot be predicted reliably from cytomorphological and immunophenotypic analysis. This heterogeneity causes problems in routine diagnostic, so that diagnosis ultimately rests on conventional histology. In a representative series of myoepitheliomas and malignant myoepitheliomas, antibodies against cytokeratins 5/6, S 100 protein and vimentin produced the most consistent reactivity profile. Staining for cytokeratins 5/6 is a useful addition to the established immunohistologic marker panel in the work-up of myoepitheliomas, because of its reliable expression in most cases and because it may underline the epithelial nature of the lesion. Comparative genomic hybridisation (CGH) profiles of myoepitheliomas and myoepithelial carcinomas showed no chromosomal aberration in less than 50% of myoepithelial carcinomas, so that CGH is of limited help in a given case. In a case that was represented in three separately localized manifestations of the disease that differed in their CGH profiles, gross genetic aberrations suggest to be acquired during tumor progression and should raise the suspicion of malignancy. Thus, diagnosis of myoepithelial tumors of salivary glands has to rest on morphological grounds with support of a restricted panel of immunohistologic markers.     

Significant association of strictures and internal fistula formation in Crohn’s disease

Intestinal inflammation in Crohn’s disease (CD) may be complicated by the occurrence of strictures and fistulae. The pathogenesis of fistula formation is unknown. We therefore wanted to determine whether mechanical factors might contribute to the development of fistulae. Furthermore, we tried to define the path of internal fistulae through the muscular layer. For this purpose, surgical resection specimens from 42 consecutive patients with CD were prospectively studied. In gross examination the whole bowel was cut into circumferential cross sections 0.3 cm thick. Abnormal areas were histologically examined. Strictures were found in 38 patients (90.5%), and fistulae were observed in 27 (64.3%) patients. In 11 (40.7%) specimens fistulae were found within a stricture, in 15 (55.6%) at the proximal end, and in 1 (3.7%) no stricture was found. In 7 (25.9%) cases with fistulae, herniated mucosa was found within the muscularis propria or the subserosa. In 7 (25.9%) cases a blood vessel was identified near a fistula traversing the muscularis propria. From these findings we conclude that that mechanical factors may contribute to fistula formation. This is further supported by the fact that fistulae appear to traverse the muscular layer along piercing vessels. Received: 21 January 2000 / Accepted: 7 March 2000     

A meta-analytic review of HIV behavioral interventions for reducing sexual risk behavior of men who have sex with men

This meta-analysis examines the efficacy of international HIV prevention interventions designed to reduce sexual risk behavior of men who have sex with men (MSM). We performed a comprehensive search of published and unpublished English-language reports of HIV prevention interventions that focus on MSM and evaluated changes in risky sexual behavior or biologic outcomes related to sexual risk. Data from 33 studies described in 65 reports were available as of July 2003. Studies with insufficient data to calculate effect sizes were excluded from the meta-analysis. Interventions were associated with a significant decrease in unprotected anal intercourse (odds ratio [OR] = 0.77, 95% confidence interval [CI]: 0.65-0.92) and number of sexual partners (OR = 0.85, 95% CI: 0.61-0.94) and with a significant increase in condom use during anal intercourse (OR = 1.61, 95% CI: 1.16-2.22). Interventions successful in reducing risky sexual behavior were based on theoretic models, included interpersonal skills training, incorporated several delivery methods, and were delivered over multiple sessions spanning a minimum of 3 weeks. Behavioral interventions provide an efficacious means of HIV prevention for MSM. To the extent that proven HIV prevention interventions for MSM can be successfully replicated in community settings and adapted and tailored to different situations, the effectiveness of current HIV prevention efforts can be increased.     

Morbid obesity. Second gastric operations for poor weight loss

This is a report of a clinical investigation of weight gain occurring after initial good weight loss following an operation performed to treat morbid obesity. The reasons for weight gain or poor weight loss after the first operation, the indications for a second operation, and the effectiveness and complications of four different "second" operations were examined. Thirty-five patients who were weight loss failures, a subgroup of 556 patients upon whom one of five bariatric operations had been performed, provided the clinical material for this investigation. The findings indicate that technical and nontechnical patient factors are responsible for the failure of the initial bariatric operation. The most effective second operation to treat weight loss failures was gastric bypass with Roux-en-Y gastrojejunostomy (GBRY). More difficult to perform than when done as the first bariatric operation, GBRY when done as a second operation is associated with a higher complication rate.