The cross-clade neutralizing activity of a human monoclonal antibody is determined by the GPGR V3 motif of HIV type 1

Both polyclonal and monoclonal human antibodies (Abs) to the V3 domain of HIV-1 gp120 display cross-clade neutralizing activity against primary isolates and T cell-adapted virus strains. The most broadly neutralizing of the human anti-V3 monoclonal Abs (mAbs), 447-52D, recognizes 14 amino acids, including the GPxR core epitope at the tip of the V3 loop. Monoclonal Ab 447-52D neutralized 92% of 38 primary isolates carrying the GPGR V3 motif regardless of whether the viruses belonged to clades A, B, F, or H; in contrast, none of 19 viruses with the GPGQ and other non-GPGR/Q sequences at the tip of the V3 loop was sensitive to mAb 447-52D. These data are consistent with the crystallographic resolution of a complex of the Fab fragment of mAb 447-52D with a V3 peptide that shows that the binding specificity of the mAb is due to recognition of the GPGR motif at the tip of the loop. The critical role of the Arg residue in this motif was determined using viruses pseudotyped with the envelope of primary isolate CA1 containing the GPGR motif or with a mutated envelope with a Gln (Q) replacing the Arg (R) at the tip of the loop. While the wild-type pseudovirus was neutralized by mAb 447-52D, the pseudovirus carrying the point mutation was resistant to neutralization. These data illuminate the structural basis for both the breadth and specificity of a broadly neutralizing human mAb and contribute to our understanding of the epitopes recognized by Abs that protect against infection with HIV-1.     

Role of euroSCORE II in predicting long-term outcome after percutaneous catheter intervention for coronary triple vessel disease or left main stenosis

Objectives

The SYNTAX score (Ssc) assessing the complexity of coronary anatomy predicts survival after percutaneous coronary intervention (PCI). We tested the hypothesis that the newly developed euroSCORE II (eSC2) can improve the prediction of outcome after complex PCI by the Ssc.

Methods and results

Our study comprised 1262 consecutive patients with triple vessel disease or left main stenosis, who were contacted 3 years after elective PCI with drug-eluting stents. We calculated eSC2, Ssc, logistic euroSCORE, and ACEF score. Prediction of 3-year all-cause mortality by these scores was assessed by Cox proportional hazard models. Models were compared by the Hosmer–Lemeshow test for calibration (HL), the C-statistics (AUC) for discrimination and by net reclassification indices (NRI). eSC2 and Ssc were significant predictors of 3-year mortality (unadjusted hazard ratios [95%-confidence limits], 1.050 [1.033–1.067], 1.180 [1.146–1.215], respectively, P < 0.001). The predictive value of eSC2 was improved by logarithmic transformation. Adding eSC2 to the model with Ssc improved calibration (HL 7.4 vs. 11.1) and discrimination (increase in AUC [95%-confidence limits] 0.12 [0.07 to 0.17]) and yielded a significant NRI of 0.38 (95%-confidence limits 0.28 to 0.47). The absolute difference in 3-year mortality between strata of Ssc (≤ 22, > 22–32, > 32) was smaller with eSC2 < 1% (1.4%, 3.4%, 9.7%, respectively), than with eSC2 > 1.6% (11.2%, 20.2%, 30.6%, respectively). The predictive ability of eSC2 was similar to that of the other clinical scores.

Conclusions

eSC2 predicts 3-year mortality after complex PCI and modifies the impact of angiographic complexity on outcome.     

Fast and Precise Non-Contact Measurement of Cylindrical Surfaces with Air Gauges

In this paper, the results of an investigation on the application of air gauges in the measurement of out-of-roundness parameters are presented. The principle of the measuring system is explained, in particular the novel design of the floating gauge head. An algorithm for fully automated measurement and data processing is described. The results from a series of initial measurements provided the data for further simulations, which revealed possible sources of errors. The simulations helped to evaluate the influence of some of the parameters on the final measurement results. After various accuracy tests, the method accuracy (MA) parameter was calculated in relation to the dedicated reference form tester. The result MA = 9.29% was judged to be highly satisfactory considering the short measurement time and non-contact method.     

Obesity is not an obstacle for successful autogenous arteriovenous fistula creation in haemodialysis.

BACKGROUND: Obesity, which is often associated with diabetes, is increasingly encountered in the haemodialysed population, and this may produce difficulty in autogenous arteriovenous fistula creation. Prosthetic angioaccess or catheters, when used in place of autogenous fistulas, increase thrombotic and infectious complications in these already challenged patients. METHODS: This prospective study was undertaken to assess the feasibility of autogenous arteriovenous fistula creation in 71 obese patients (BMI 34.6 +/- 7.8). We performed a two-stage procedure, in which radio-cephalic fistula formation was followed by subcutaneous transposition of the venous component for safe and easy puncture. RESULTS: Fistulas suitable for puncture, having blood flows of 799 +/- 285 ml/min, and sufficient to perform adequate haemodialysis (Kt/V 1.24) were achieved in 85% of the patients. Primary patency rates were 65% and 59% at 6 and 12 months, respectively, and secondary patency rates were 83% both at 6 and 12 months. CONCLUSIONS: Obesity does not prevent successful autogenous arteriovenous fistula formation, and may protect forearm venous vessels from the iatrogenic damage that occurs before the onset of haemodialysis therapy.     

Granuloma histiocyticum prostatae et testis

Zusammenfassung Beschrieben werden 2 Fälle von granulomatösen Veränderungen in Prostata und Hoden, die der Malakoplakie sehr ähneln. Mikroskopisch sind sie durch Infiltrate aus eosinophüen Histiocyten und verschiedenen entzündlichen Zellelementen gekennzeichnet.Es wird vorgeschlagen, die Bezeichnung Malakoplakie nur für plattenförmige Veränderungen im Harntrakt anzuwenden. Extravesicale tumorähnliche oder infiltrierende Granulome sollten als Granuloma histiocyticum bezeichnet werden.

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Granuloma histiocyticum prostatae et testis:

Summary Two cases are described of granulomatous changes in prostates and testes which resemble closely malakoplakia. Microscopically, these changes are characterized by infiltrates of eosinophilic histiocytes and various inflammatory cells.It is suggested that the term malakoplakia be used only for the plaque-like changes in the urinary tract. Extravesical tumor-like or infiltrating granulomata should be called granuloma histiocyticum.