Prevalences of herpesviruses DNA sequences in salivary gland biopsies from primary and secondary Sj?gren's syndrome using degenerated consensus PCR primers.

BACKGROUND: Sj?gren's syndrome (SS) is an autoimmune exocrinopathy associated with multiple autoantibodies, lymphocyte infiltration of various organs, and functional deficiency of T cells. Several viruses have been implicated by PCR based studies, but their contribution to the pathophysiology of SS is still controversial. OBJECTIVES: In an attempt to explore the presence of human herpesviruses DNA sequences in salivary glands biopsies from patients suffering of SS, a recently developed strategy based on PCR with consensus degenerated primers that allowed to detect known and eventually unknown herpesviruses was used. STUDY DESIGN: Salivary glands biopsies from 55 patients suffering of primary and SS syndrome were explored by herpesviruses consensus PCR primers and all the PCR products were sequenced. RESULTS: Nine out of 55 salivary glands were positive by PCR and sequence analyses allowed to identify Epstein-Barr virus (EBV) in 6 cases and herpes simplex virus (HSV)-1 in 3 cases. We did not detect any sequences that could be related to a new herpesvirus. CONCLUSION: In view of the good sensitivity of the technique used, our study is not consistent with SS being associated with an unknown herpesvirus. However, our results suggest that EBV and HSV-1 could be implicated in a subset of SS cases and this possibility needs to be explored, to assess the potential benefit of antiviral drugs in some cases.     

Intraluminal Radiation for Esophageal Cancer: A Howard University Technique

The objective of radiotherapeutic management in esophageal cancer is to accomplish maximum tumor sterilization with minimal normal tissue damage. This sincere effort is most often countered by the differential in tumor dose response vs normal tissue tolerance. Intraluminal isotope radiation, with its inherent advantage of rapid dose falloff, spares the lungs, the spinal cord, and other vital structures, yet yields adequately high doses to esophageal tumor. Though in existence since the turn of the century, the method of intracavitary radium bougie application dropped out of favor due to technical difficulties imposed by the size of the radium source and radiation exposure to the personnel involved. The authors describe a simple “iridium 192 afterloading intraluminal technique” that eliminates technical problems and reduces radiation exposure considerably.     

Treatment of idiopathic inflammatory myositis associated interstitial lung disease: A systematic review and meta-analysis

Objective

Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD.

Linkage of the horizontally acquired ypm and pil genes in Yersinia pseudotuberculosis

The superantigen-encoding ypm gene and the pil gene cluster governing type IV pilus biogenesis have been laterally acquired by Yersinia pseudotuberculosis. PCR assays on 270 unrelated strains from various environmental and animal sources revealed a significant association of ypm and pil in isolates.     

Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies

Apart from its role in elevating red blood cell number, erythropoietin (Epo) exerts protective functions in brain, retina and heart upon ischaemic injury. However, the physiological non-erythroid functions of Epo remain unclear. Here we use a transgenic mouse line (Tg21) constitutively overexpressing human Epo in brain to investigate Epo's impact on ventilation upon hypoxic exposure. Tg21 mice showed improved ventilatory response to severe acute hypoxia and moreover improved ventilatory acclimatization to chronic hypoxic exposure. Furthermore, following bilateral transection of carotid sinus nerves that uncouples the brain from the carotid body, Tg21 mice adapted their ventilation to acute severe hypoxia while chemodenervated wild-type (WT) animals developed a life-threatening apnoea. These results imply that Epo in brain modulates ventilation. Additional analysis revealed that the Epo receptor (EpoR) is expressed in the main brainstem respiratory centres and suggested that Epo stimulates breathing control by alteration of catecholaminergic metabolism in brainstem. The modulation of hypoxic pattern of ventilation after i.v. injection of recombinant human Epo in WT mice and the dense EpoR immunosignal observed in carotid bodies showed that these chemoreceptors are sensitive to plasma levels of Epo. In summary, our results suggest that Epo controls ventilation at the central (brainstem) and peripheral (carotid body) levels. These novel findings are relevant to understanding better respiratory disorders including those occurring at high altitude.     

Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse; involvement of SNARE complexes

The mechanism by which T cell antigen receptors (TCR) accumulate at the immunological synapse has not been fully elucidated. Since TCRs are continuously internalized and recycled back to the cell surface, we investigated the role of polarized recycling in TCR targeting to the immunological synapse. We show here that the recycling endosomal compartment of T cells encountering activatory antigen-presenting cells (APCs) polarizes towards the T cell-APC contact site. Moreover, TCRs in transit through recycling endosomes are targeted to the immunological synapse. Inhibition of T cell polarity, constitutive TCR endocytosis, or recycling reduces TCR accumulation at the immunological synapse. Conversely, increasing the amount of TCRs in recycling endosomes before synapse formation enhanced their accumulation. Finally, we show that exocytic t-SNAREs from T cells cluster at the APC contact site and that tetanus toxin inhibits TCR accumulation at the immunological synapse, indicating that vesicle fusion mediated by SNARE complexes is involved in TCR targeting to the immunological synapse.     

Predictive factors of virologic success in HIV-1-infected children treated with lopinavir/ritonavir

Predictive factors of the virologic success of the use of lopinavir/ritonavir (LPV/r) in HIV-infected children are unknown, especially in children who have been pretreated with protease inhibitors (PIs). This longitudinal, single-center, observational study included 69 children (21 PI-naive and 48 PI-experienced) who had received LPV/r for at least 3 months. The mean (+/- SD) age was 10.3 +/- 4.8 years, and the mean baseline of CD4 percentage and HIV-1 RNA was 14.9% +/- 9.8% and 4.8 +/- 1.05 log10 copies/mL, respectively. The mean duration of follow-up was 16.5 +/- 8.3 months. At 6, 12, and 18 months, 52%, 57%, and 49% of all children, respectively, had a viral load less than 50 copies/mL. The risk of virologic failure, defined as 2 consecutive viral loads greater than 1000 copies/mL, was significantly higher when the children were previously treated with PIs and when the baseline LPV mutation score exceeded 3 mutations. In the pretreated children, the ratio of the plasma LPV maximal concentration to the baseline LPV score mutation was also associated with failure, independently of resistance score. Finally, in children failing an LPV-containing regimen, accumulation of additional PI-associated resistance mutations was evidenced in viral isolates from children with prior PI treatment, even with viral replication levels less than 10,000 copies/mL. In pretreated children, LPV plasma levels should be optimized in an attempt to achieve sufficient drug concentrations to overcome the resistance level.