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51.
52.
L. J. Dowie J. E. Smith A. J. MacGilchrist R. Fraser J. W. Honour J. L. Reid C. J. Kenyon 《European journal of clinical pharmacology》1988,35(6):625-629
Summary The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole.Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected.These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 hydroxysteroid dehydrogenase, 17 hydroxylase or 11 hydroxylation; 21 hydroxylase activity may be marginally attenuated. 相似文献
53.
G. I. Sandle G. Fraser S. Long G. Warhurst 《Pflügers Archiv : European journal of physiology》1990,417(3):259-263
Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl– conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl–149 mmol/ 1 in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (–0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl– conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a –21 mV shift of their reversal potential when bath Cl– was decreased from 149 mmol/l to 53 mmol/l (calculated Cl–:cation permeability ratio 171), and (iii) were highly sensitive to the Cl– channel blocker diphenylamine-2-carboxylic acid (DPC, 10–3 mol/l). This cAMP-activated Cl– channel bears many similarities to other Cl– channels within intestinal epithalia, and may represent the apical Cl– channel operating in HCl-secreting gastric parietal cells. 相似文献
54.
Budowle B Johnson MD Fraser CM Leighton TJ Murch RS Chakraborty R 《Critical reviews in microbiology》2005,31(4):233-254
Because of the availability of pathogenic microorganisms and the relatively low cost of preparing and disseminating bioweapons, there is a continuing threat of biocrime and bioterrorism. Thus, enhanced capabilities are needed that enable the full and robust forensic exploitation and interpretation of microbial evidence from acts of bioterrorism or biocrimes. To respond to the need, greater resources and efforts are being applied to the burgeoning field of microbial forensics. Microbial forensics focuses on the characterization, analysis and interpretation of evidence for attributional purposes from a bioterrorism act, biocrime, hoax or inadvertent agent release. To enhance attribution capabilities, a major component of microbial forensics is the analysis of nucleic acids to associate or eliminate putative samples. The degree that attribution can be addressed depends on the context of the case, the available knowledge of the genetics, phylogeny, and ecology of the target microorganism, and technologies applied. The types of genetic markers and features that can impact statistical inferences of microbial forensic evidence include: single nucleotide polymorphisms, repetitive sequences, insertions and deletions, mobile elements, pathogenicity islands, virulence and resistance genes, house keeping genes, structural genes, whole genome sequences, asexual and sexual reproduction, horizontal gene transfer, conjugation, transduction, lysogeny, gene conversion, recombination, gene duplication, rearrangements, and mutational hotspots. Nucleic acid based typing technologies include: PCR, real-time PCR, MLST, MLVA, whole genome sequencing, and microarrays. 相似文献
55.
56.
Competitive control of the self-renewing T cell repertoire 总被引:1,自引:0,他引:1
We develop a mathematical model for the self-renewing part of the T cell
repertoire. Assuming that self-renewing T cells have to be stimulated by
immunogenic MHC-peptide complexes presented on the surfaces of
antigen-presenting cells, we derive a model of T cell growth in which
competition for MHC-peptide complexes limits T cell clone sizes and
regulates the total number of self-renewing T cells in the animal. We show
that for a sufficient diversity and/or degree of cross-reactivity, the
total T cell number hardly depends upon the diversity of the T cell
repertoire or the diversity of the set of presented peptides. Conversely,
for repertoires of lower diversity and/or cross-reactivity, steady-state
total T cell numbers may be limited by the diversity of the T cells. This
provides a possible explanation for the limited repertoire expansion in
some, but not all, mouse T cell re-constitution experiments. We suggest
that the competitive interactions described by our model underlie the
normal T cells numbers observed in transgenic mice, germ-free mice and
various knockout mice.
相似文献
57.
Functional stability of dorsolateral prefrontal neurons 总被引:2,自引:0,他引:2
Stable multiday recordings from the dorsolateral prefrontal cortex of 2 monkeys performing 2 Go/NoGo visual-discrimination tasks (one requiring well-learned responses, the other requiring learning) demonstrate that the majority of prefrontal neurons were "functionally stable". Recordings were made using a series of removable microdrives, each implanted for 3-6 mo, housing independently mobile electrodes. Action potential waveforms of 94 neurons were stable over 2-9 days; 66/94 (70%) of these cells responded each day, 22/94 (23%) never responded significantly, and 6/94 (6%) responded one day but not the next. Of 66 responsive neurons, 55 were selective for either Go or NoGo trials, individual stimuli, or eye movements. This selectivity was functionally stable (i.e., maintained) for 46/55 neurons across all recording days. Functional stability was also noted in terms of response strength (baseline firing rates compared with poststimulation firing rates) and event-related response timing. Two neurons with consistent responses in familiar testing conditions responded flexibly when the monkeys learned to make correct responses to novel stimuli. We conclude that the majority of prefrontal neurons were functionally stable during the performance of well-learned tasks. Such stability may be a general property of prefrontal neurons, given that neurons with 4 different types of task selectivity were found to be functionally stable. Conceptually similar studies based on long-term recordings in other cortical regions reached similar conclusions, suggesting that neurons throughout the brain are functionally stable. 相似文献
58.
Localization of a gene for otosclerosis to chromosome 15q25-q26 总被引:5,自引:0,他引:5
Tomek MS; Brown MR; Mani SR; Ramesh A; Srisailapathy CR; Coucke P; Zbar RI; Bell AM; McGuirt WT; Fukushima K; Willems PJ; Van Camp G; Smith RJ 《Human molecular genetics》1998,7(2):285-290
Among white adults otosclerosis is the single most common cause of hearing
impairment. Although the genetics of this disease are controversial, the
majority of studies indicate autosomal dominant inheritance with reduced
penetrance. We studied a large multi- generational family in which
otosclerosis has been inherited in an autosomal dominant pattern. Five of16
affected persons have surgically confirmed otosclerosis; the remaining nine
have a conductive hearing loss but have not undergone corrective surgery.
To locate the disease- causing gene we completed genetic linkage analysis
using short tandem repeat polymorphisms (STRPs) distributed over the entire
genome. Multipoint linkage analysis showed that only one genomic region, on
chromosome 15q, generated a lod score >2.0. Additional STRPs were typed
in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and
D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis
gene.
相似文献
59.
Ogawa M Fraser S Fujimoto T Endoh M Nishikawa S Nishikawa SI 《International reviews of immunology》2001,20(1):21-44
It has been widely accepted that hematopoietic and endothelial cell lineages diverge from a common progenitor referred to as the hemangioblast. Recently, analyses of the potential of progenitor cells purified from mouse embryos as well as embryonic stem cells differentiating in vitro resolved intermediate stages between mesodermal cells and committed precursors for hematopoietic and endothelial cell lineages. There are two distinct hematopoietic cell lineages which have different origins, i.e., primitive hematopoietic lineage derived from mesoderm or hemangioblasts and definitive hematopoietic lineage derived from endothelial cells. The endothelium is suggested to provide a milieu in which the definitive hematopoietic lineage acquires multiple potentials. 相似文献
60.
Use of modified resistogram to type Candida albicans isolated from cases of vaginitis and from faeces in the same geographical area. 总被引:1,自引:0,他引:1 下载免费PDF全文
Ninety strains of Candida albicans were isolated from vaginal swabs taken by general practitioners from cases of vaginal candidosis. One hundred and nine strains were also isolated from 300 specimens of faeces received from outpatients living in the same geographical area. These strains were typed using a modification of the resistotyping method. We were unable to find any significant differences between the two populations of strains. This suggests that no particular resistotype has an increased ability to cause vaginitis. 相似文献