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161.
Koenitzer JR Isbell TS Patel HD Benavides GA Dickinson DA Patel RP Darley-Usmar VM Lancaster JR Doeller JE Kraus DW 《American journal of physiology. Heart and circulatory physiology》2007,292(4):H1953-H1960
Hydrogen sulfide (H(2)S) has recently been shown to have a signaling role in vascular cells. Similar to nitric oxide (NO), H(2)S is enzymatically produced by amino acid metabolism and can cause posttranslational modification of proteins, particularly at thiol residues. Molecular targets for H(2)S include ATP-sensitive K(+) channels, and H(2)S may interact with NO and heme proteins such as cyclooxygenase. It is well known that the reactions of NO in the vasculature are O(2) dependent, but this has not been addressed in most studies designed to elucidate the role of H(2)S in vascular function. This is important, since H(2)S reactions can be dramatically altered by the high concentrations of O(2) used in cell culture and organ bath experiments. To test the hypothesis that the effects of H(2)S on the vasculature are O(2) dependent, we have measured real-time levels of H(2)S and O(2) in respirometry and vessel tension experiments, as well as the associated vascular responses. A novel polarographic H(2)S sensor developed in our laboratory was used to measure H(2)S levels. Here we report that, in rat aorta, H(2)S concentrations that mediate rapid contraction at high O(2) levels cause rapid relaxation at lower physiological O(2) levels. At high O(2), the vasoconstrictive effect of H(2)S suggests that it may not be H(2)S per se but, rather, a putative vasoactive oxidation product that mediates constriction. These data are interpreted in terms of the potential for H(2)S to modulate vascular tone in vivo. 相似文献
162.
Novel blocker of NFAT activation inhibits IL-6 production in human myometrial arteries and reduces vascular smooth muscle cell proliferation 总被引:1,自引:0,他引:1
163.
Large-conductance calcium-activated potassium channel activity is absent in human and mouse neutrophils and is not required for innate immunity 总被引:2,自引:0,他引:2
Essin K Salanova B Kettritz R Sausbier M Luft FC Kraus D Bohn E Autenrieth IB Peschel A Ruth P Gollasch M 《American journal of physiology. Cell physiology》2007,293(1):C45-C54
Large-conductance Ca2+-activated K+ (BK) channels are reported to be essential for NADPH oxidase-dependent microbial killing and innate immunity in leukocytes. Using human peripheral blood and mouse bone marrow neutrophils, pharmacological targeting, and BK channel gene-deficient (BK/) mice, we stimulated NADPH oxidase activity with 12-O-tetradecanoylphorbol-13-acetate (PMA) and performed patch-clamp recordings on isolated neutrophils. Although PMA stimulated NADPH oxidase activity as assessed by O2 and H2O2 production, our patch-clamp experiments failed to show PMA-activated BK channel currents in neutrophils. In our studies, PMA induced slowly activating currents, which were insensitive to the BK channel inhibitor iberiotoxin. Instead, the currents were blocked by Zn2+, which indicates activation of proton channel currents. BK channels are gated by elevated intracellular Ca2+ and membrane depolarization. We did not observe BK channel currents, even during extreme depolarization to +140 mV and after elevation of intracellular Ca2+ by N-formyl-L-methionyl-L-leucyl-phenylalanine. As a control, we examined BK channel currents in cerebral and tibial artery smooth muscle cells, which showed characteristic BK channel current pharmacology. Iberiotoxin did not block killing of Staphylococcus aureus or Candida albicans. Moreover, we addressed the role of BK channels in a systemic S. aureus and Yersinia enterocolitica mouse infection model. After 3 and 5 days of infection, we found no differences in the number of bacteria in spleen and kidney between BK/ and BK+/+ mice. In conclusion, our experiments failed to identify functional BK channels in neutrophils. We therefore conclude that BK channels are not essential for innate immunity. killing assay; reactive oxygen species; BK-deficient mice; mice infection 相似文献
164.
Pseudoporphyria (PP) is characterized by skin fragility, blistering and scarring in sun-exposed skin areas without abnormalities
in porphyrin metabolism. The phenylpropionic acid derivative group of nonsteroidal anti-inflammatory drugs, especially naproxen,
is known to cause PP. Naproxen is currently one of the most prescribed drugs in the therapy of juvenile idiopathic arthritis
(JIA). The prevalence of PP was determined in a 9-year retrospective study of children with JIA and associated diseases. In
addition, we prospectively studied the incidence of PP in 196 patients (127 girls and 69 boys) with JIA and associated diseases
treated with naproxen from July 2001 to March 2002. We compared these data with those from a matched control group with JIA
and associated diseases not treated with naproxen in order to identify risk factors for development of PP. The incidence of
PP in the group of children taking naproxen was 11.4%. PP was particularly frequent in children with the early-onset pauciarticular
subtype of JIA (mean age 4.5 years). PP was associated with signs of disease activity, such as reduced haemoglobin (<11.75
g/dl), and increased leucocyte counts (>10,400/μl) and erythocyte sedimentation rate (>26 mm/hour). Comedications, especially
chloroquine intake, appeared to be additional risk factors. The mean duration of naproxen therapy before the onset of PP was
18.1 months, and most children with PP developed their lesions within the first 2 years of naproxen treatment. JIA disease
activity seems to be a confounding factor for PP. In particular, patients with early-onset pauciarticular JIA patients who
have significant inflammation appear to be prone to developing PP upon treatment with naproxen. 相似文献
165.
166.
Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration
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Schmidt WM Kraus C Höger H Hochmeister S Oberndorfer F Branka M Bingemann S Lassmann H Müller M Macedo-Souza LI Vainzof M Zatz M Reis A Bittner RE 《EMBO reports》2007,8(7):691-697
Here, we show that the murine neurodegenerative disease mdf (autosomal recessive mouse mutant 'muscle deficient') is caused by a loss-of-function mutation in Scyl1, disrupting the expression of N-terminal kinase-like protein, an evolutionarily conserved putative component of the nucleocytoplasmic transport machinery. Scyl1 is prominently expressed in neurons, and enriched at central nervous system synapses and neuromuscular junctions. We show that the pathology of mdf comprises cerebellar atrophy, Purkinje cell loss and optic nerve atrophy, and therefore defines a new animal model for neurodegenerative diseases with cerebellar involvement in humans. 相似文献
167.
Belle MD Pattison EF Cheunsuang O Stewart A Kramer I Sigrist M Arber S Morris R 《Genesis (New York, N.Y. : 2000)》2007,45(11):679-688
In this study, transgenic mice in which membrane-linked enhanced green fluorescent protein (mGFP) is expressed from the Thy1.2 promoter were used. In these mice, a subpopulation of small to medium sized DRG neurons double stained for IB4 but not for CGRP. Most of the peripheral terminals traversed the dermis and ramify within the epidermis and form superficial terminals. Within the spinal cord, these afferents terminated exclusively within the substantia gelatinosa (SG). A second fibre type in the skin also expressed mGFP, and formed club-shaped endings towards the bases of hairs. Injury to the sciatic nerve resulted in mGFP loss from the SG ipsilateral to the nerve injury, but also in the corresponding region contralaterally. Together, these findings reveal the specificity of connectivity of a defined subpopulation of DRG sensory neurons innervating the epidermis and this will facilitate analysis of their physiological functions. 相似文献
168.
169.
170.
Raina K. Plowright Peggy Eby Peter J. Hudson Ina L. Smith David Westcott Wayne L. Bryden Deborah Middleton Peter A. Reid Rosemary A. McFarlane Gerardo Martin Gary M. Tabor Lee F. Skerratt Dale L. Anderson Gary Crameri David Quammen David Jordan Paul Freeman Lin-Fa Wang Jonathan H. Epstein Glenn A. Marsh Nina Y. Kung Hamish McCallum 《Proceedings. Biological sciences / The Royal Society》2015,282(1798)
Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility. 相似文献