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101.
Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis 总被引:2,自引:0,他引:2
DC Hooper S Spitsin RB Kean JM Champion GM Dickson I Chaudhry H Koprowski 《Canadian Metallurgical Quarterly》1998,95(2):675-680
Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO) produced by lipopolysaccharide-stimulated cells of a mouse monocyte line. In this study, we used uric acid to treat experimental allergic encephalomyelitis (EAE) in the PLSJL strain of mice, which develop a chronic form of the disease with remissions and exacerbations. Uric acid administration was found to have strong therapeutic effects in a dose-dependent fashion. A regimen of four daily doses of 500 mg/kg uric acid was required to promote long-term survival regardless of whether treatment was initiated before or after the clinical symptoms of EAE had appeared. The requirement for multiple doses is likely to be caused by the rapid clearance of uric acid in mice which, unlike humans, metabolize uric acid a step further to allantoin. Uric acid treatment also was found to diminish clinical signs of a disease resembling EAE in interferon-gamma receptor knockout mice. A possible association between multiple sclerosis (MS), the disease on which EAE is modeled, and uric acid is supported by the finding that patients with MS have significantly lower levels of serum uric acid than controls. In addition, statistical evaluation of more than 20 million patient records for the incidence of MS and gout (hyperuricemic) revealed that the two diseases are almost mutually exclusive, raising the possibility that hyperuricemia may protect against MS. 相似文献
102.
JM Gimble GM Pighetti MR Lerner X Wu SA Lightfoot DJ Brackett K Darcy AB Hollingsworth 《Canadian Metallurgical Quarterly》1998,253(3):813-817
PURPOSE: To evaluate the usefulness of Doppler ultrasonography (US) in the diagnosis of hyperfiltration in patients with insulin-dependent diabetes mellitus (IDDM). MATERIALS AND METHODS: Eighty-one consecutive patients with IDDM were studied. All patients were normotensive and had normal creatinine and blood urea nitrogen levels. The glomerular filtration rate (GFR) was evaluated by means of plasma clearance of chromium-51 ethylenediaminetetraacetic acid, urinary albumin excretion, US evaluation of renal volume, and Doppler evaluation of resistance index (RI) in the renal interlobar arteries. The patients were divided according to GFR into the following groups: those with hyperfiltering kidneys (group 1, n = 40) and those with normofiltering kidneys (group 2, n = 41). RESULTS: The median renal volume was 351 mL (95% CI = 337 mL, 379 mL) in group 1 and 318 mL (95% CI = 300 mL, 335 mL) in group 2 (P = .005). The number of patients with microalbuminuria was significantly lower in group 1 than in group 2 (P = .02). The median RI was significantly lower in group 1 (0.55; 95% CI = 0.53, 0.57) than in group 2 (0.57; 95% CI = 0.56, 0.59) (P = .04). An RI of less than 0.5, a renal volume greater than 410 mL/m2, and the absence of microalbuminuria were independent predictors of hyperfiltration. An RI of less than 0.5 and a renal volume greater than 410 mL/m2 showed high specificity (98% and 95%, respectively) and poor sensitivity (25% and 23%, respectively) in the diagnosis of hyperfiltration in IDDM patients. CONCLUSION: Both RI and renal volume showed correlation with GFR, but neither parameter is sufficiently sensitive in screening for hyperfiltration in IDDM patients. 相似文献
103.
We have developed a flexible physiological monitoring and analysis system for physiological studies in which data are obtained over extended periods. Our system uses low-cost personal computer hardware to concentrate data from existing multiple monitoring devices. All monitored parameters are displayed on a single screen and recorded in a single file. The system automates the process of physiological record keeping by providing continuous displays of vital signs. In addition, audible and visual alarms are produced when vital signs are outside of acceptable ranges, prompting the experimenter to take corrective actions. The central element of the system is a program running in a dedicated manner on an IBM PC-compatible computer. The program is written in the C language and makes use of a graphics library to display traces and analysis results in real time on any standard display for the PC. This program assigns the analog channels of an A/D board to particular physiological parameters by initially reading a configuration file, which also describes the alarm conditions and analysis routine for each parameter. All hardware specific code is isolated into well-defined modules. The program is both highly flexible with regard to different sets of parameters and highly portable for different experimental and computer environments. 相似文献
104.
Tailored written invitations for second round breast cancer screening: a randomised controlled trial 总被引:1,自引:0,他引:1
P Meldrum D Turnbull HM Dobson C Colquhoun WH Gilmour GM McIlwaine 《Canadian Metallurgical Quarterly》1994,1(4):245-248
OBJECTIVES: Firstly, to determine if attendance for second round mammography screening in those sent a tailored letter (that is, making reference to their screening history) is increased compared with those sent a standard letter; secondly, to investigate the acceptability of tailored letters. SETTING: North West Glasgow Breast Screening Centre. METHODS: A randomised controlled trial. RESULTS: Overall attendance was unrelated to whether the women were sent a tailored or standard letter; 60% of those sent the standard letter attended (922/1531) compared with 62% of those sent the tailored letter (956/1552) (chi 2 = 0.61, P = 0.4) (difference 2%; 95% confidence interval -2% to 5%). There were no significant differences in percentage attendance within each of the study subgroups: women who attended previously and received an all clear result, women who attended previously and received a false positive result, women who were invited previously and failed to attend, and women who were previously too young to be invited for screening. However, there was a statistically significant difference in percentage attendance between these four groups, independent of letter type (chi 2 = 510, P < 0.00001). Although women found the letters acceptable and understandable, they did not seem to pay close attention to the content. CONCLUSIONS: Tailoring invitation letters does not have a significant effect on uptake rates for breast screening and does not justify the additional workload required. 相似文献
105.
Prevention of T cell anergy by signaling through the gamma c chain of the IL-2 receptor 总被引:1,自引:0,他引:1
VA Boussiotis DL Barber T Nakarai GJ Freeman JG Gribben GM Bernstein AD D'Andrea J Ritz LM Nadler 《Canadian Metallurgical Quarterly》1994,266(5187):1039-1042
When stimulated through their antigen receptor without requisite costimulation, T cells enter a state of antigen-specific unresponsiveness termed anergy. In this study, signaling through the common gamma chain of the interleukin-2 (IL-2), IL-4, and IL-7 receptors in the presence of antigen was found to be sufficient to prevent the induction of anergy. After culture with IL-2, IL-4, or IL-7, Jak3 kinase was tyrosine-phosphorylated, which correlated with the prevention of anergy. Therefore, a signal through the common gamma chain may regulate the decision of T cells to either clonally expand or enter a state of anergy. 相似文献
106.
107.
SA Jones S Horiuchi D Novick N Yamamoto GM Fuller 《Canadian Metallurgical Quarterly》1998,28(11):3514-3522
The soluble IL-6 receptor (sIL-6R) is generated through either proteolytic shedding of the cognate receptor (PC-sIL-6R), or released as the product of differential mRNA splicing (DS-sIL-6R). Using monocytic THP-1 cells, we demonstrate that both mechanisms are independently regulated, and that each process contributes to sIL-6R production. Shedding of the IL-6R was activated by the Ca2+ ionophore, ionomycin, and inhibited by the TNF-alpha protease inhibitor (TAPI). In contrast, basal sIL-6R release was unaffected by Ca2+ depletion and largely insensitive to TAPI. Moreover, although IL-6R shedding was inactivated by serum starvation, non-stimulated production remained intact. Basal sIL-6R production via differential mRNA splicing was shown through the inhibitory action of brefeldin A and an enzyme-linked immunosorbent assay specific for DS-sIL-6R. Release of this isoform was unaffected by ionomycin or TAPI, indicating that Ca2+ mobilization activates PC-sIL-6R generation, but not DS-sIL-6R. The divergent control of these sIL-6R isoforms indicates that they may independently influence the inflammatory response. 相似文献
108.
Chard (Beta vulgaris L. var. cicla) is one of the plants used as hypoglycaemic agent by diabetics in Turkey and it has been reported to reduce blood glucose. The purpose of this study was to investigate the effect of feeding chard on diabetes induced impairments in rat skins. Uncontrolled induced diabetes caused significant increases in nonenzymatic glycosylation of skin proteins, lipid peroxidation and blood glucose. Administration of chard extract inhibited these effects except the increase in lipid peroxidation. SDS-polyacrylamide gel electrophoresis revealed no significant differences in any protein bands between any of the groups. The data indicate that the use of chard may be effective in preventing or at least retarding the development of some diabetic complications. 相似文献
109.
CTLs from patients with Chediak-Higashi syndrome (CHS) are unable to destroy target cells recognized via the TCR. To determine the mechanism responsible for the loss of cytotoxicity, CD8+ CTL clones have been derived from a patient with CHS. Individual CTL clones show poor killing that can be increased in longer assays. However, in the presence of cycloheximide, the small amount of killing observed is abolished, indicating killing arises from newly synthesized proteins, rather than from proteins stored in granules. In this study, we show that the CHS CTL clones express normal levels of the lytic proteins granzyme A, granzyme B, and perforin, which are processed properly during biosynthesis and targeted correctly to giant lytic granules. Despite the difference in size, CHS and normal lytic granules are similar, in that both contain the lysosomal enzyme cathepsin D and the lytic protein granzyme A, and lack the mannose-6-phosphate receptor (MPR). However, unlike normal CTL clones, the CHS CTL clones are unable to secrete their giant granules in which the lytic proteins are stored. After cross-linking the TCR, CHS CTL clones fail to secrete granzyme A, as assayed by both enzyme release and confocal microscopy. We suggest that the defect in CHS lies in a protein that is involved in membrane fusion and is essential for the secretion of lysosomal compartments in certain hemopoietic cells. 相似文献
110.
The first isolated case of agenesis of the mastoid antrum, previously only described in association with the congenital syndromes trisomy 13 and mandibulofacial dysostosis, is reported. The loss of this important surgical landmark may result in disorientation and iatrogenic trauma. The surgeon must be aware of its existence, and where it is suspected the middle fossa dura should be exposed and followed posteriorly until the lateral sinus is encountered. 相似文献