CD8 CTL responses in vaccines: emerging patterns of HLA restriction and epitope recognition

We evaluated MHC-class I-restricted CTL responses induced by HIV-1 clade B-based vaccines in nine HIV-1 seronegative vaccine recipients with regard to their patterns of HLA restriction and epitope recognition. We found that seven of nine volunteers developed detectable CTL reactivities against novel epitopes within the HIV-1 Env and Gag proteins. Although four of nine subjects were HLA-A*0201, none of the cellular responses was restricted in the context of this allele. The type of responses observed in this sampling of vaccines appeared similar to those reported during primary infection and among long term non-progressors, with three out of nine subjects recognizing HLA-B27 or HLA-B17(57)-restricted epitopes. Although the majority of CTL responses were directed against novel epitopes, these effectors were still able to mediate cross-clade reactivities.     

Evaluation of the role of staphylococci in the pathomechanism of conjunctivitis

International Ophthalmology - Determination of the association between ica genes and phenotypic biofilm formation in staphylococcal isolates involved in conjunctivitis, their antibiotic resistance...     

The influence of resection height on proximal femoral strain patterns after Metha short stem hip arthroplasty: an experimental study on composite femora

Purpose

The number of candidates for a total hip arthroplasty (THA) is steadily increasing, while the average patient age is decreasing for primary THA. The rise in THA is mainly due to excellent clinical outcomes and the extended longevity of modern implants. Short stem arthroplasties with predominantly metaphyseal fixation such as the Metha® stem are suggested for young patients. It is hypothesised that the more physiological load transfer of these devices reduces stress shielding, which in turn may reduce the risk of aseptic loosening. However, patients with femoral deformities often require a deviation of the resection height. To this end, our aim was to evaluate how resection height influences strain patterns in order to characterise possible limits for short stem implantation.

Methods

Biomechanical testing using ten strain gauges on synthetic bone illustrated the strain patterns of three different resection heights (0, +5 and +10 mm) for the Metha stem.

Results

The greatest differences in strains were displayed at the “high” (most proximal) resection height (+10 mm) when compared to the non-implanted strain pattern. At the medial calcar, the strain was 143 % for +10 mm, 96 % for +5 mm and 94 % for 0 mm. Overall, discrepancies were less for deeper resections.

Conclusions

The deeper the resection, the more similar the strain patterns are when compared to a non-implanted synthetic bone. Changes in strain patterns are induced by variation in the varus/valgus positioning of the implant and by different offsets.     

Improvement in the healing of colonic anastomoses by vitamin B5 and C supplements. Experimental study in the rabbit

To study the effects of vitamins B5 and C on the healing process of colonic anastomoses, 3 groups of 20 rabbits were given daily either placebo (group A), or vitamin B5 (100 mg/kg: group B) or vitamin C (100 mg/kg: group C). After 8 days of supplementation, via a midline incision and under general anaesthesia, 2 colonic segments were removed, and the continuity was restored. On the 3rd post-operative day, the rabbits were killed and the anastomoses were removed. Mechanical properties of both normal colon and anastomoses were determined by using bursting pressure tests, number of burst anastomoses, fibroblast count, hydroxyproline concentration and determination by microanalysis of trace element content: Mg, P, S, Ca, Fe, Cu, Zn and Mn. Vitamin B5 (p = 0.03) and vitamin C (p less than 0.01) both decreased the number of burst anastomoses. Furthermore the required bursting pressure values were higher with vitamin C (p = 0.01) than in controls. Both vitamins restored normal Zn levels at the anastomotic site, whereas these levels decreased on the 3rd post-operative day during the normal healing process of colonic anastomosis. Moreover, vitamins B5 and C increased Fe, Cu and Mn levels, which are intimately all involved in collagen synthesis. Vitamins B5 and C enhance the colonic wound healing process in the rabbit, acting together in synergy in vivo as well as in vitro, as previously demonstrated.     

The role of the PI3K/mTOR signaling pathway in Staphylococcus epidermidis small colony variants intracellular survival

The objective of this study was to analyze how Staphylococcus epidermidis SCV and WT strains manipulate the PI3K/Akt/mTOR signaling pathway. Six S. epidermidis strains with normal phenotype (WT) and six S. epidermidis strains with SCV phenotype were isolated in parallel from six patients with the prosthetic hip joint infections.

THP-1 activated cells were incubated with or without PI3K inhibitor—wortmannin or with mTOR inhibitor—rapamycin. Next, macrophages were exposed to S. epidermidis WT and SCV strains. After 4 h incubation, bacterial survival inside macrophages as well as PI3K-mTOR activation was analyzed.

SCV strains of S. epidermidis increased the level of Akt phosphorylation, compared to uninfected macrophages and to their parental WT forms. Wild type variants of S. epidermidis phosphorylated Akt at similar or lower levels as control uninfected cells.

Next, the induction of mTOR target, phosphorylated ribosomal protein S6, was measured in bacteria-infected macrophages. The level of phosphorylation was significantly reduced when the cells were exposed to WT strains of S. epidermidis. In contrast, the SCV strains activated S6 protein mostly at a level comparable to the control cells. Rapamycin inhibited mTOR activation as the number of p-S6 positive cells decreased in the tested cases.

To conclude, the SCV strains activate the PI3K-Akt signaling pathway in opposite to WT strains. This fact however did not influence the increase in the number of live SCV bacteria as compared to the WT strains. Knowing that the PI3K-Akt pathway is involved in proinflammatory cytokines suppression, SCVs seem to use this pathway to reduce the inflammatory response during the infection.     

Effects of cyclic adenosine monophosphate and prostaglandins on Na+- and HCO3--induced dissipation of a proton gradient in isolated gastric mucosal surface cells of rabbits

One mechanism that surface cells can use to regulate intracellular pH is Na+/H+ exchange. The presence of another means to modify intracellular pH, HCO3-, was investigated, as were the effects of cyclic adenosine monophosphate and prostaglandins on an intracellular proton gradient. Isolated surface cells were preincubated in NH4+ to establish an intracellular proton gradient, which was measured using acridine orange. The addition of HCO3- causes gradient dissipation, an effect sensitive to 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid but not to extracellular chloride. The HCO3--evoked dissipation of the proton gradient is diminished by cyclic adenosine monophosphate, isobutyl-methylxanthine, and prostaglandin E2, but not by prostacyclin. The Na+-evoked dissipation of the gradient is diminished by cyclic adenosine monophosphate and isobutylmethylxanthine, but not by prostaglandin E2 or prostacyclin. Cyclic adenosine monophosphate, isobutylmethylxanthine, and the prostaglandins are without effect in the absence of Na+ or HCO3-. The data suggest that extracellular HCO3- influences an intracellular proton gradient, but the precise mechanism involved is not established in this study. The data may also explain why prostaglandins are in some instances not cytoprotective for surface cells.