The role of prostaglandins in the immunosuppressive effects of supernatants from adherent cells of murine decidual tissue

Supernatants from short-term cultures of murine decidual tissue (DS) were assessed for their regulatory effects on T cell lymphoproliferation and cytotoxic T lymphocyte (CTL) activity. DS non-specifically suppressed antigen- and mitogen-induced lymphoproliferation, spontaneous thymocyte proliferation, the mixed lymphocyte reaction (MLR) and CTL generation, but had no effect on CTL lytic activity. The immunosuppressive activity was lost after dialysis (14 kDa cut off). Supernatants from indomethacin-treated decidual tissue cultures (indomethacin-DS) lacked suppressive activity in the MLR, mitogen and thymocyte proliferation assays. Indomethacin-DS also showed markedly reduced or no suppressive effects on CTL generation. These findings suggest that prostaglandin production by the decidual component of the placenta could play a role in materno-fetal cellular interactions by regulating T cell lymphoproliferative responses and CTL generation.     

Macular halos associated with Niemann-Pick type B disease

Macular halos describe a striking clinical finding of bilaterally elevated, doughnut-shaped, white rings around th fovea. This paper presents the third well-documented report of the association of macular halos with Niemann-Pick type B disease, demonstrated by color photographs and subtle fluorescein angiographic findings. The systemic association with Niemann-Pick type B disease was confirmed by bone marrow biopsy and enzyme assay. Of 13 family members examined, only the proposita had macular halos; 10 were found to be carriers by sphingomyelinase assay. Recognition of this pathognomonic eye finding warrants more widespread awareness as a presenting sign of Niemann-Pick type B disease.     

Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers

In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated.     

Working with communities, governments and academic institutions to make pregnancy safer

The major medical causes of maternal death and the effective interventions to prevent maternal death due to these causes are known. Yet, every year, an estimated 529,000 women die during and following pregnancy and childbirth. Most of these deaths occur in developing countries where other non-medical determinants of maternal health influence the accessibility to these interventions. Improvements in maternal health can be achieved through a health systems approach. Care should be provided as a continuum throughout the life cycle and across health facilities through the health system. Communities, professional organizations and academic institutions should work actively with the government to: provide a package of service, based on population health needs, that is close to home; ensure availability of essential medicines and commodities; address financial barriers to receiving care; strengthen the health workforce; and gather and use information to improve maternal health.     

Ultrasound-directed transvaginal myolysis: preclinical studies

The ultimate goal is to develop a safe vaginal ultrasound-directed myolysis needle to treat uterine myomas. The specific preclinical study objective was to determine the optimal power to coagulate myomas in hysterectomy specimens with a prototype needle in a prospective preclinical study with an echogenic insulated needle electrode. In phase I of the study, myolysis was performed with ultrasound guidance at various powers and times. In phase II, a 20-W coagulating current was applied at defined distances from the serosa and surface temperatures measured. Myolysis with 10 to 20 W applied 5 to 10 seconds was optimal, because tissue popping occurred at 30 W or more when the needle was 5 mm or less from the serosa. The serosal temperature was never elevated above physiological ranges at any distance at this setting. Ultrasound-directed transvaginal myolysis may provide another option for women with uterine myomas if it is proven safe and effective in future clinical studies. On the basis of the observations in these preclinical studies, myolysis with 20 W for 10 seconds should be a safe parameter for clinical research, because there is no increased serosal temperature at these settings.     

Circulating platelet‐derived extracellular vesicles correlate with night‐time blood pressure and vascular organ damage and may represent an integrative biomarker of vascular health

Elevated office blood pressure (BP) has previously been associated with increased levels of circulating extracellular vesicles (EVs). The present study aimed to assess the relationship between levels of platelet derived EVs, ambulatory BP parameters, and pulse wave velocity as a marker of macrovascular organ damage. A total of 96 participants were included in the study. Platelet‐derived extracellular vesicles (pEVs) were evaluated by flow cytometry (CD41+/Annexin v+). BP evaluation included unobserved automated office BP and ambulatory BP monitoring. Carotid‐femoral pulse wave velocity (PWV) was measured as a marker of macrovascular damage. pEVs correlated with nocturnal systolic BP (r = 0.31; p = .003) and nocturnal dipping (r = ‐0.29; p = .01) in univariable analysis. Multivariable regression models confirmed robustness of the association of EVs and nocturnal blood pressure (p = .02). In contrast, systolic office, 24h‐ and daytime‐BP did not show significant associations with pEVs. No correlations were found with diastolic BP. Circulating pEVs correlated with pulse wave velocity (r = 0.25; p = .02). When comparing different hypertensive phenotypes, higher levels of EVs and PWV were evident in patients with sustained hypertension compared to patients with white coat HTN and healthy persons. Circulating platelet derived EVs were associated with nocturnal BP, dipping, and PWV. Given that average nocturnal BP is the strongest predictor of CV events, platelet derived EVs may serve as an integrative marker of vascular health, a proposition that requires testing in prospective clinical trials.     

Hot air electric hand driers compared with paper towels for potential spread of airborne bacteria

Hot air hand driers are increasingly used in both public areas and hospitals, but there is little literature on their bacteriology. Four units were examined by comparing the bacterial aerosols released from hands during use by sets of twelve subjects with those released by paper towels. Tests on two units also included hand imprints on agar plates for detection of residual bacteria. No significant difference between aerosols liberated by towels and driers were observed for two units, while the other two generated significantly fewer aerosols than towels. Impression plates revealed similar numbers of bacteria on the hands after drying by either method. Hot air hand driers appear safe from a bacteriological viewpoint.     

Secondary biogenic amine deficiencies: genetic etiology,therapeutic interventions,and clinical effects

neurogenetics - Monoamine neurotransmitter disorders present predominantly with neurologic features, including dystonic or dyskinetic cerebral palsy and movement disorders. Genetic conditions that...     

The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System

Bacteria possess the ability to evolve varied and ingenious strategies to outwit the host immune system, instigating an evolutionary arms race. Proteases are amongst the many weapons employed by bacteria, which specifically cleave and neutralize key signalling molecules required for a coordinated immune response. In this article, we focus on a family of S8 subtilisin-like serine proteases expressed as cell-envelope proteases (CEPs) by group A and group B streptococci. Two of these proteases known as Streptococcus pyogenes CEP (SpyCEP) and C5a peptidase cleave the chemokine CXCL8 and the complement fragment C5a, respectively. Both CXCL8 and C5a are potent neutrophil-recruiting chemokines, and by neutralizing their activity, streptococci evade a key defence mechanism of innate immunity. We review the mechanisms by which CXCL8 and C5a recruit neutrophils and the characterization of SpyCEP and C5a peptidase, including both in vitro and in vivo studies. Recently described structural insights into the function of this CEP family are also discussed. We conclude by examining the progress of prototypic vaccines incorporating SpyCEP and C5a peptidase in their preparation. Since streptococci-producing SpyCEP and C5a peptidase are responsible for a considerable global disease burden, targeting these proteases by vaccination strategies or by small-molecule antagonists should provide protection from and promote the resolution of streptococcal infections.