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151.
Summary Membrane-permeant weak acids and bases, when applied to the bath, modulate the resting membrane potential and the glucose-induced electrical activity of pancreatic B cells, as well as their insulin secretion. These substances alter the activity of a metabolite-regulated. ATP-sensitive K+ channel which underlies the B-cell resting potential. We now present several lines of evidence indicating that the channel may be directly gated by pH
i
. (1) The time course of K+(ATP) channel activity during exposure to and washout of NH4Cl under a variety of experimental conditions, including alteration of the electrochemical gradient for NH4Cl entry and inhibition of the Na
o
+
H
i
+
exchanger, resembles the time course of pH
i
measured in other cell types that have been similarly treated. (2) Increasing pH
o
over the range 6.25–7.9 increases K+(ATP) channel activity in cell-attached patches where the cell surface exposed to the bath has been permeabilized to H+ by the application of the K+/H+ exchanger nigericin. (3) Increasing pH
i
over a similar range produces similar effects on K+(ATP) channels in inside-out excised patches exposed to small concentrations of ATP
i
. The physiological role of pH
i
in the metabolic gating of this channel remains to be explored. 相似文献
152.
HIV-1 GP120-mediated immune suppression and lymphocyte destruction in the absence of viral infection 总被引:26,自引:0,他引:26
K J Weinhold H K Lyerly S D Stanley A A Austin T J Matthews D P Bolognesi 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(9):3091-3097
The magnitude of immunologic defects observed in HIV-1-infected individuals before the development of overt AIDS is disproportionately high in comparison to the levels of infectious virus in these patients--suggesting that factors other than direct virus-induced cytopathology may be involved. With this in mind, we investigated the immunologic consequences of the interaction between purified HIV-1 gp120 and the CD4 molecules expressed by uncommitted as well as Ag-specific lymphocytes. HIV-1 gp120 exhibited a dose-dependent immunosuppressive effect on: 1) Ag-driven proliferation of cloned CD4+ lymphocytes, 2) OKT3-driven proliferation of cloned CD4+ lymphocytes, and 3) cytolytic activity of CD4+, EBV-specific CTL. Thus, HIV-1 gp120 can, in a manner similar to OKT4A antibodies, suppress T cell activation and the expression of cytolytic activities through its interaction with CD4. Additionally, activated CD4+ lymphoblasts can be rendered susceptible to immune cytolysis by virtue of their binding of purified gp120. This "targeting" of activated lymphoblasts can occur with levels of gp120 far below that which is needed to saturate all OKT4A-defined CD4 epitopes. Adsorbed gp120 could be demonstrated on the surface of these cells for up to 12 h, a sufficient time for interaction with host cytolytic elements. The data from these in vitro modeling experiments highlight one of many potential mechanisms of HIV-1 induced immunosuppression and lymphocyte destruction that can occur in the absence of infectious virus and that is based on the unique interaction between HIV-1 gp120 and its cellular receptor, CD4. 相似文献
153.
Sequence variability of simian immunodeficiency virus in a persistently infected rhesus monkey 总被引:2,自引:0,他引:2
A juvenile rhesus monkey that was inoculated intravenously with molecularly cloned SIVmac239 became persistently infected. A modified polymerase chain reaction (PCR) procedure was used to specifically amplify full-length envelope (env) gene sequences from DNA extracted from peripheral blood mononuclear cells (PBMC), lymph node tissue, and cells infected with recovered virus at 69 and 93 weeks post-infection. Extensive sequence variability accumulated in vivo in spite of infection with molecularly cloned virus. In the central portion of env. sequence variability was largely confined to three discrete regions. 相似文献
154.
Effect of Isozyme-Selective Inhibitors of Phosphodiesterase on Histamine-Stimulated Cyclic AMP Accumulation in Guinea-Pig Hippocampus 总被引:2,自引:0,他引:2
Addition of histamine (0.1 mM) to guinea-pig hippocampal slices causes a 20- to 30-fold increase in the accumulation of cyclic AMP compared with basal levels. This accumulation represents a balance between cyclic AMP production by adenylate cyclase and cyclic AMP breakdown mediated by phosphodiesterase (PDE). However, brain tissues are known to contain several different PDE isozymes. To determine which are involved in this response to histamine, the effect of isozyme-specific PDE inhibitors on cyclic AMP accumulation was examined in the hippocampus. MB 22948 (0.1 mM), an inhibitor of PDEs I and II, had no significant effect on the response to either 1 microM or 0.1 mM histamine. SKF 94120 (0.1 mM), a PDE III inhibitor, was also without effect in the presence of 1 microM histamine, although with 0.1 mM histamine, it caused a weak (1.25-fold compared with control), but statistically significant, enhancement of cyclic AMP accumulation. However, both rolipram (0.1 mM), a PDE IV inhibitor, and 3-isobutyl-1-methylxanthine (0.1 or 1 mM), an inhibitor of all forms of PDE, significantly increased cyclic AMP accumulation (2.8- to 6.5-fold compared with controls), and the relative size of this effect decreased with increasing histamine concentration. It is concluded that PDE IV is the main PDE isozyme involved in cyclic AMP turnover in guinea-pig hippocampal slices responding to histamine. 相似文献
155.
John R. Atack Conrad May Jeffrey A. Kaye Stanley I. Rapoport 《Neurochemistry international》1990,16(4):533-538
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in 13 sequential 2 ml aliquots of cerebrospinal fluid (CSF) obtained by lumbar puncture from 7 young and 7 elderly healthy normal subjects. The slopes of the rostrocaudal gradients of AChE and BChE were calculated and compared to those of total protein concentration and the major dopaminergic metabolite homovanillic acid (HVA), for which a pronounced rostrocaudal gradient (with highest concentrations of HVA in more rostral CSF) is consistent with HVA originating primarily from the brain. AChE activity was higher in more caudal fractions of young, but not elderly subjects and there was a significant difference between the mean AChE gradient slopes in the young and old groups. These results suggest that the spinal cord makes an important contribution to AChE activity in lumbar CSF. Furthermore, the absence of a negative AChE gradient in elderly subjects may be the result of a greater rate of entry of cerebral AChE into CSF, possibly as a consequence of an increased ventricular surface area and shorter diffusion distances in atrophic elderly brains. In contrast to AChE, BChE activity and total protein concentrations were higher in more caudal CSF fractions of not only young but also old subjects. In addition, there was a significant correlation between the gradient slopes of BChE activity and total protein concentrations, suggesting that the majority of BChE activity in lumbar CSF derives from the same source as the majority of total protein, namely plasma. The diffuse (i.e. brain and spinal cord) origin of AChE in lumbar CSF would explain the relatively modest changes in lumbar CSF AChE activity in diseases involving certain central cholinergic systems, most notably Alzheimer's disease. 相似文献
156.
A new recombinant DNA strategy for the molecular cloning of rare membrane proteins. 总被引:4,自引:0,他引:4 下载免费PDF全文
B Brake P Braghetta G Banting G Bressan J P Luzio K K Stanley 《The Biochemical journal》1990,267(3):631-637
We have constructed a cDNA library in the plasmid expression vector pUEX enriched in sequences encoding membrane proteins. The procedure involved positive selection of sequences common to two different rat tissues (thus excluding tissue-specific mRNA) followed by positive selection between this material and RNA extracted from membrane bound polysomes (thus excluding cytoplasmic proteins). The resultant library prepared from rat kidney cDNA hybridized with rat liver poly(A)+ RNA, contained 30,000 clones and was shown to be enriched in cDNAs encoding membrane proteins. Seventeen clones selected because they encode large fusion proteins were shown to be single copy in the library, and not present in nucleotide data banks. Thus the strategy is particularly suitable for cloning low abundance cDNAs encoding membrane proteins. 相似文献
157.
Lipid Composition in Scrapie-Infected Mouse Brain: Prion Infection Increases the Levels of Dolichyl Phosphate and Ubiquinone 总被引:1,自引:0,他引:1
Zhizhong Guan Magnus Söderberg Pavel Sindelar Stanley B. Prusiner †Krister Kristensson Gustav Dallner 《Journal of neurochemistry》1996,66(1):277-285
Abstract: The neutral and phospholipid composition of mouse brain infected with scrapie prions was investigated. During the later stages of this disease, the level of dolichol decreased by 30% whereas the level of dolichyl phosphate increased by 30%. In terminally ill mice, there was also a 2.5-fold increase in both total ubiquinone and its reduced form. Furthermore, α-tocopherol was elevated at this stage by 50%. In contrast, no changes were observed in phospholipid amount, in phospholipid composition, and in phosphatidylethanolamine plasmalogen content during the entire disease process. The fatty acid and aldehyde composition of individual phospholipids remained unaltered as well. No modifications could be detected in cholesterol content. Thus, the majority of membrane lipids in scrapie-infected mouse brain are modified in neither quantity nor structure, but specific changes occur to a few polyisoprenoid lipids. This specificity indicates that, although prions accumulate in lysosomes, the infection process is not associated with a general membrane destruction caused by lysosomal enzyme leakage. 相似文献
158.
Michael P. Robertson Matthew Levy Stanley L. Miller 《Journal of molecular evolution》1996,43(6):543-550
The reaction of guanidine hydrochloride with cyanoacetaldehyde gives high yields (40–85%) of 2,4-diaminopyrimidine under the concentrated conditions of a drying lagoon model of prebiotic synthesis, in contrast to the low yields previously obtained under more dilute conditions. The prebiotic source of cyanoacetaldehyde, cyanoacetylene, is produced from electric discharges under reducing conditions. The effect of pH and concentration of guanidine hydrochloride on the rate of synthesis and yield of diaminopyrimidine were investigated, as well as the hydrolysis of diaminopyrimidine to cytosine, isocytosine, and uracil. Thiourea also reacts with cyanoacetaldehyde to give 2-thiocytosine, but the pyrimidine yields are much lower than with guanidine hydrochloride or urea. Thiocytosine hydrolyzes to thiouracil and cytosine and then to uracil. This synthesis would have been a significant prebiotic source of 2-thiopyrimidines and 5-substituted derivatives of thiouracil, many of which occur in tRNA. The applicability of these results to the drying lagoon model of prebiotic synthesis was tested by dry-down experiments where dilute solutions of cyanoacetaldehyde, guanidine hydrochloride, and 0.5m NaCl were evaporated over varying periods of time. The yields of diaminopyrimidine varied from 1 to 7%. These results show that drying lagoons and beaches may have been major sites of prebiotic syntheses. 相似文献
159.
Crustacean zooplankton species richness and associations in reservoirs and ponds of Aguascalientes State, Mexico 总被引:2,自引:2,他引:0
We report the species of crustacean zooplankton found in 19 resevoirs and ponds that were sampled at on at least two occasions in Aguascalientes State, Mexico, at a latitude of about 21°30 North Latitude. We collected a total of 33 cladoceran taxa, 15 calanoid and cyclopoid copepods, an Ergasilus copepod, 2 anostracans, one notostracan species and an amphipod. All these taxa had previously been reported in Mexico. As in more temperate areas, there was a significant correlation between the species richness and lake size. The species-area relationship for Aguascalientes was indistinguishable from that of more northerly lakes. The two most common associations of zooplankton species were (1) those small species that occurred with fish: Daphnia parvula, Diaphanosoma birgei, Leptodiaptomus siciloides, Mastigodiaptomus albuquerquensis, and Thermocyclops inversus, and (2) the large Daphnia schodleri that occurred with the predator Notonecta, in the absence of fish. With minor variations, these two associations also occur throughout temperate North America. 相似文献
160.
Douglas A. Burns 《Biogeochemistry》1996,32(3):339-362
Calcite treatment of chronically acidic lakes has improved fish habitat, but the effects on downstream water quality have not previously been examined. In this study, the spatial and temporal effects of watershed CaCO3 treatment on the chemistry of a lake outlet stream in the Adirondack Mountains of New York were examined. Before CaCO3 treatment, the stream was chronically acidic. During spring snowmelt before treatment, pH and acid-neutralizing capacity (ANC) in the outlet stream declined, and NO
3
–
and inorganic monomeric aluminum (AlIM) concentrations increased sharply. During that summer, SO
4
–
and NO
3
–
concentrations decreased downstream, and dissolved organic carbon (DOC) concentrations and ANC increased, in association with the seasonal increase in decomposition of organic matter and the attendant SO
4
–
-reduction process. A charge-balance ANC calculation closely matched measured downstream changes in ANC in the summer and indicated that SO
4
–
reduction was the major process contributing to summer increases in ANC. Increases in Ca2+ concentration and ANC began immediately after CaCO3 application, and within 3 months, exceeded their pretreatment values by more than 130 eq/L. Within 2 months after treatment, downstream decreases in Ca2+ concentration, ANC, and pH, were noted. Stream mass balances between the lake and the sampling site 1.5 km downstream revealed that the transport of all chemical constituents was dominated by conservative mixing with tributaries and ground water; however, non-conservative processes resulted in significant Ca2+ losses during the 13-month period after CaCO3 treatment. Comparison of substrate samples from the buffered outlet stream with those from its untreated tributaries showed that the percentage of cation-exchange sites occupied by Ca2+ as well as non-exchangeable Ca, were higher in the outlet-stream substrate than in tributary-stream substrate. Mass-balance data for Ca2+ H+, AlIM, and DOC revealed net downstream losses of these constituents and indicated that a reasonable set of hypothesized reactions involving AlIM, HCO
3
–
, Ca2+, SO
4
–
NO
3
–
, and DOC could have caused the measured changes in stream acid/base chemistry. In the summer, the sharp decrease in ANC continued despite significant downstream decreases in SO4
2– concentrations. After CaCO3 treatment, reduction of SO
4
–
was only a minor contributor to ANC changes relative to those caused by Ca2+ dilution from acidic tributaries and acidic ground water, and Ca2+ interactions with stream substrate. 相似文献