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151.
152.
The humoral immune response of neonates to T cell-independent type 2 (TI-2) Ags is markedly defective. We previously demonstrated that multivalent membrane Ig cross-linking, using dextran-conjugated anti-Ig Abs (anti-Ig-dextran), is an in vitro model for membrane Ig-dependent TI-2 induction of Ig secretion. In this work, we demonstrate that highly purified neonatal B cells are intrinsically defective in IgM secretion in response to anti-Ig-dextran and cytokines in vitro, as well as other modes of B cell activation, relative to adult B cells. However, costimulation of anti-Ig-dextran-activated neonatal B cells with either CD40-ligand, a recombinant bacterial lipoprotein, or LPS restores the IgM secretory response of neonatal B cells to adult levels. Analysis of Ig isotype secretion indicates that neonatal B cells have an enhanced capacity to secrete IgE and IgA relative to other Ig isotypes. These data suggest that neonatal B cells are competent to secrete Ig in response to TI-2 Ags if adequate costimuli are provided, and thus may have particular relevance for the design of vaccine strategies in the immunodeficient host. The data also suggest that neonatal B cells are programmed to secrete relatively enhanced amounts of IgE and IgA, which may be relevant for antimicrobial resistance at mucosal surfaces. 相似文献
153.
154.
高速连续数据记录系统中双页缓存的设计和实现 总被引:2,自引:0,他引:2
在高速连续数据记录系统中,存储设备需要速度匹配单元来实现高速连续数据记录,文章讨论了双页缓存在高速连续记录系统中的作用,并以实际开发的记录系统为例,详细介绍了双页缓存的设计和实现。 相似文献
155.
The current model for the tricarboxylic acid cycle in Dictyostelium discoideum is based on extensive experimental studies of enzyme kinetics in vitro and of metabolite fluxes measured in vivo. In the previous papers (Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22912-22918; 22919-22925; 22926-22933; 22934-22943) of this series we have carried out extensive analyses of the current model within the framework of biochemical systems theory with a view toward understanding the behavior of the integrated system. The model was found to be ill determined with respect to at least three of its features. In this paper we propose a minimal modification in the model that is consistent with previous experimental data but also includes recycling of amino acids for protein synthesis, one of the neglected features identified as important in the previous analysis. We again perform an analysis within the framework of biochemical systems theory to determine the systemic consequences of this change. The results show that the robustness of the modified model, as determined by the parameter sensitivities, is improved by 2 orders of magnitude over that of the previous model. Analysis of the dynamics shows that the turnover times for the pools of alanine, glutamate, and aspartate are reduced by 2 orders of magnitude and made more physiologically realistic. The distribution of flux is no longer rigidly fixed, and problems previously centered on the metabolism of pyruvate have been partially alleviated. Continued discrepancies lead us to question the degree to which kinetic data obtained with purified enzymes in vitro faithfully reflect the kinetic behavior of the integrated enzyme system in vivo. We must continue to re-examine the manner in which the kinetics of reactions in vivo are represented and to reassess the physical conditions that prevail in vitro and in vivo. Results in this paper direct our attention toward specific aspects of the system where these efforts should be focused. Thus, a minimal modification of the previous model has led to several improvements that make it more representative of the tricarboxylic acid cycle in D. discoideum, and the analysis in this paper leads to further predictions for improving the model. 相似文献
156.
Increasing knowledge of the pharmacological effects of melatonin has suggested various possible therapeutic applications for the hormone. Because, as a natural substance, melatonin cannot be patented, melatonin-related compounds have been synthesized by industrial groups. The scope of such compounds is also to specifically target the recently discovered melatonin receptor subtypes. The sleep-inducing properties of melatonin are disputed, but are distinct from those of benzodiazepines. The observed effects on sleep latency or sleep efficiency, which remain to be confirmed, could be accounted for by the effects of melatonin on core body temperature and on circadian rhythms. There is also an urgent need for safety data, both in animals and in humans, particularly when long-term use is envisaged. 相似文献
157.
J Arenas MR Gonzalez-Crespo Y Campos MA Martin A Cabello JJ Gomez-Reino 《Canadian Metallurgical Quarterly》1996,39(11):1869-1874
OBJECTIVE: To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies. METHODS: Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed. RESULTS: Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes. CONCLUSION: Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency. 相似文献
158.
159.
The autoantigen in adjuvant arthritis in Lewis rats is still unknown despite the knowledge that the 65 kDa mycobacterial heat-shock protein (hsp) is involved in the disease process. T cells and antibodies obtained from rats with adjuvant arthritis respond to chondrocyte membrane antigen(s). In Western blots a 65 kDa chondrocyte membrane protein (CH65) is stained by sera from arthritic rats. In addition, spleen cells from rats with adjuvant arthritis proliferate in vitro to chondrocyte membranes and CH65 as antigens. Furthermore, pretreatment of rats with CH65 or mycobacterial hsp65 but not human hsp60, induces a significant retardation of the onset of adjuvant arthritis in Lewis rats. The data suggest that CH65 is a potential autoantigen involved in the pathogenesis of adjuvant arthritis in Lewis rats. 相似文献
160.
CONTEXT: Although the long-term health benefits of good glycemic control in patients with diabetes are well documented, shorter-term quality of life (QOL) and economic savings generally have been reported to be minimal or absent. OBJECTIVE: To examine short-term outcomes of glycemic control in type 2 diabetes mellitus (DM). DESIGN: Double-blind, randomized, placebo-controlled, parallel trial. SETTING: Sixty-two sites in the United States. PARTICIPANTS: A total of 569 male and female volunteers with type 2 DM. INTERVENTION: After a 3-week, single-blind placebo-washout period, participants were randomized to diet and titration with either 5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS) (n = 377) or placebo (n = 192) for 12 weeks. MAIN OUTCOME MEASURES: Change from baseline in glucose and hemoglobin A1c (HbA1c) levels and symptom distress, QOL, and health economic indicators by questionnaires and diaries. RESULTS: After 12 weeks, mean (+/-SE) HbA1c and fasting blood glucose levels decreased with active therapy (glipizide GITS) vs placebo (7.5% 0.1% vs 9.3%+/-0.1% and 7.0+/-0.1 mmol/L [126+/-2 mg/dL] vs 9.3+/-0.2 mmol/L [168+/-4 mg/ dL], respectively; P<.001). Quality-of-life treatment differences (SD units) for symptom distress (+0.59; P<.001), general perceived health (+0.36; P= .004), cognitive functioning (+0.34; P=.005), and the overall visual analog scale (VAS) (+0.24; P=.04) were significantly more favorable for active therapy. Subscales of acuity (+0.38; P=.002), VAS emotional health (+0.35; P=.003), general health (+0.27; P=.01), sleep (+0.26; P=.04), depression (+0.25; P=.05), disorientation and detachment (+0.23; P= .05), and vitality (+0.22; P=.04) were most affected. Favorable health economic outcomes for glipizide GITS included higher retained employment (97% vs 85%; P<.001), greater productive capacity (99% vs 87%; P<.001), less absenteeism (losses = $24 vs $115 per worker per month; P<.001), fewer bed-days (losses = $1539 vs $1843 per 1000 person-days; P=.05), and fewer restricted-activity days (losses = $2660 vs $4275 per 1000 person-days; P=.01). CONCLUSIONS: Improved glycemic control of type 2 DM is associated with substantial short-term symptomatic, QOL, and health economic benefits. 相似文献