No abstract

Pneumonia is a major cause of morbidity and mortality in elderly people, especially in those with chronic medical conditions such as chronic heart and lung diseases. We prospectively examined the effect of influenza and pneumococcal vaccinations on the rate of hospitalization for and complications of pneumonia, all respiratory tract conditions and mortality in elderly bedridden patients and found that both febrile days and pneumonia cases decreased. Thus, these results show that it is valuable to vaccinate for influenza elderly people even if they are confined to bed. Furthermore, the tuberculin skin test is an easy method to check the cell-mediated immunity in the elderly people. In the tuberculin skin test, all Japanese over 65 years old should have positive status. A negative result indicates depressed cell-mediated immunity. We undertook a trial to vaccinate tuberculin negative elderly people with BCG vaccine and found that the risk of pneumonia is decreased to a similar degree to that in subjects with positive tuberculin test results. We conclude that vaccination might be an effective strategy for the prevention of pneumonia in elderly people with limited activities of daily living.

Abstract. In neutrophils, binding and phagocytosis facilitate subsequent intracellular killing of microorganisms. Activity of Na+/H ÷ exchangers (NHEs) participates in these events, especially in regulation of intracellular pH (pHi) by compensating for the H ÷ load generated by the respiratory burst. Despite the importance of these functions, comparatively little is known regarding the nature and regulation of NHE(s) in neutrophils. The purpose of this study was to identify which NHE(s) are expressed in neutrophils and to elucidate the mechanisms regulating their activity during phagocytosis. Exposure of cells to the phagocytic stimulus opsonized zymosan (OpZ) induced a transient cytosolic acidification followed by a prolonged alkalinization. The latter was inhibited in Na+-free medium and by amiloride analogues and therefore was due to activation of Na+/H + exchange. Reverse transcriptase PCR and cDNA sequencing demonstrated that mRNA for the NHE-1 but not for NHE-2, 3, or 4 isoforms of the exchanger was expressed. Immunoblotting of purified plasma membranes with isoform-specific antibodies confirmed the presence of NHE-1 protein in neutrophils. Since phagocytosis involves Fc~/(Fc~R) and complement receptors such as CR3 (a 132 integrin) which are linked to pathways involving alterations in intracellular [Ca2+]i and tyrosine phosphorylation, we studied these pathways in relation to activation of NHE-1. Cross-linking of surface bound antibodies (mAb) directed against Fc~/Rs (Fc-,/RII > Fc-yRIII) but not 132 integrins induced an amiloride-sensitive cytosolic alkalinization. However, anti-132 integrin mAb diminished OpZ-induced alkalinization suggesting that NHE-1 activation involved cooperation between integrins and Fc~Rs. The tyrosine kinase inhibitors genistein and herbimycin blocked cytosolic alkalinization after OpZ or FcvR cross-linking suggesting that tyrosine phosphorylation was involved in NHE-1 activation. An increase in [Ca2+]i was not required for NHE-1 activation because neither removal of extracellular Ca 2÷ nor buffering of changes in [Ca2+]i inhibited alkalinization after OpZ or Fc~R cross-linking. In summary, Fc~/Rs and 132 integrins cooperate in activation of NHE-1 in neutrophils during phagocytosis by a signaling pathway involving tyrosine phosphorylation. NEUTROPmLS react to invading microorganisms and mediators present within an inflammatory milieu with a variety of rapid and coordinated responses which include movement of cells out of the vascular space along a gradient of chemotactic molecules followed by phagocytosis and killing of the microorganisms. This bactericidal function is effected by complex processes involving secretion of proteolytic enzymes and reactive oxygen intermediates (produced by the NADPH oxidase) into the phagolysosome (for review see Sha'afi and Molski, 1988). During these processes, dynamic alterations occur in leu-

No abstract

The recent rapid increase in the prevalence of emerging tobacco- and nicotine-containing products, such as e-cigarettes, is being driven in part by their reduced-risk potential compared to tobacco smoking. In this study, we examined emission levels for selected cigarette smoke constituents, so-called "Hoffmann analytes", and in vitro toxicity of aerosol from a novel tobacco vapor product (NTV). The NTV thermally vaporizes a nicotine-free carrier liquid to form an aerosol which then passes through tobacco, where it absorbs tobacco-derived flavors and nicotine. The NTV results were compared with those for 3R4F cigarette smoke. Chemical analysis of the NTV aerosol demonstrated that Hoffmann analyte levels were substantially lower than in 3R4F smoke and that the most were below quantifiable levels. Results from in vitro bacterial reverse mutation, micronucleus and neutral red uptake assays showed that, in contrast with 3R4F smoke, the NTV aerosol failed to demonstrate any measurable genotoxicity or cytotoxicity. The temperature of tobacco during NTV use was measured at approximately 30 °C, which may explain the lower Hoffmann analyte emission and in vitro toxicity levels. These results suggest that the aerosol from the NTV has a very different toxicological profile when compared with combustible cigarette smoke.