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81.
Impaired mitochondrial beta-oxidation in a patient with an abnormality of the respiratory chain. Studies in skeletal muscle mitochondria. 总被引:1,自引:0,他引:1 下载免费PDF全文
N J Watmough L A Bindoff M A Birch-Machin S Jackson K Bartlett C I Ragan J Poulton R M Gardiner H S Sherratt D M Turnbull 《The Journal of clinical investigation》1990,85(1):177-184
Defects of complex I of the mitochondrial respiratory chain are important causes of neurological disease. We report studies that demonstrate a severe deficiency of complex I activity with less severe abnormalities of complexes III and IV (less than 5, 63, and 30% of control values, respectively) in a skeletal muscle mitochondrial fraction from a 22-yr-old female with weakness, lactic acidemia, and the deposition of intramuscular neutral lipid. The observation that lipid accumulates in this and other patients with complex I deficiency suggests impaired mitochondrial fatty acid oxidation. To investigate this mechanism we have shown impaired flux through beta-oxidation [( U-14C]hexadecanoate oxidation was 66% of control rate) and accumulation of specific acyl-CoA ester intermediates. The changes in fatty acid metabolism in complex I deficiency are secondary to the reduced state within the mitochondrial matrix with low NAD+/NADH ratios. 相似文献
82.
83.
Moderate and severe reactions in blood donors 总被引:2,自引:0,他引:2
During the period April 1985 to March 1986, 217 blood donors were found to have moderate (syncopal) to severe (convulsive) reactions. This population was compared to 5630 randomly selected donors who did not have reactions. An examination of demographic, physical, and societal/emotional factors was conducted to determine if any were predictive of reactions in donors. The results of the research supported the hypothesis that first-time donors have a higher frequency of reactions (1.7%) than do repeat donors (0.19%). A review of the above predictive factors documented that, with regard to demographic factors, 1) the number of prior donations was inversely proportional to the risk of reaction; 2) the gender of the donor was not predictive; and 3) youth was a predictor of reactions. An analysis of the physical factors revealed that donors who reacted were of lower weight (mean, 153.7 lb) than those who did not (mean, 166.4 lb) and that systolic blood pressure was slightly lower in the group with reactions. Although the difference was significant (3 torr), it was not thought to be significant clinically. In a comparison of a group with systolic blood pressure ranging from 80 to 100 torr and a group with systolic blood pressure ranging from 120 to 140 torr, the first group had a 70-percent higher risk of reaction. Finally, with regard to the last category of societal or emotional factors, the research demonstrates 1) that the ingestion of caffeinated beverages was associated with a reduced risk of reactions; 2) that the food intake of donors who reacred was significantly different from that of those who had no reaction, but this difference was not thought to be clinically significant; and 3) that the duration between registration and the onset of phlebotomy was directly predictive of reaction status. The research indicates that first-time donor status and several specific demographic, physical, and societal or emotional factors are predictors of donor reactions. 相似文献
84.
J Williams DCH FRCP KA Richards MSc UK Study Group 《International journal of clinical practice》1997,51(3):147-153
A total of 323 children aged 4-11 years who were receiving, or had symptoms indicating a clinical requirement for, inhaled corticosteroid at a daily dose of 400 μg budesonide (BUD) or beclomethasone dipropionate (BDP), or 200 μg fluticasone propionate (FP), were randomised into this multicentre, open-label, parallel group study. Patients received either FP 100 μg b.d. administered via the Accuhaler/Diskus inhaler (n=159) or BUD 200 μg b.d. administered via a Turbohaler inhaler (n=164) for four weeks and recorded daily their morning and evening peak expiratory flow (PEF), asthma symptoms and use of relief medication. Device handling was assessed by a questionnaire, with responses recorded on three- or five-point ordinal scales. The primary efficacy parameter was mean percent predicted morning PEF. The device handling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use, ease of telling how many doses were left, ease of knowing whether a dose had been inhaled and overall liking of the device. More patients in the Accuhaler/Diskus group (85%) than in the Turbohaler group (58%) said they would be happy to receive the same device again, while 8% and 25% respectively said they would not be happy to be given it again. In addition, the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group, indicating that FP 200 μg daily via Accuhaler/Diskus inhaler is at least as clinically effective as BUD 400 μg daily via the Turbohaler inhaler. 相似文献
85.
86.
Ragan BG Nelson AJ Bell GW Iwamoto GA 《Medicine and science in sports and exercise》2007,39(11):1942-1948
PURPOSE: Analgesic balms (AB) are widely used in sports medicine. We previously have examined effects of various counterirritant-based AB on pressor responses evoked by muscular contraction (MC), mediated by group III and IV muscle afferents known to produce exercise and nociceptive responses. Our purpose was to examine trolamine salicylate-based analgesic balm (TS) effects. METHODS: Ten healthy, adult male and female cats were used. Decerebration under halothane allowed elimination of anesthesia. Electrical stimulation of L7 and S1 ventral roots evoked static MC (30 s). After control runs, commercial TS (10% concentration) was applied to the skin over the contracting muscles of one hind limb (N = 5). MC was evoked every 10 min, alternating between sides. Ipsilateral (T = 0, T + 20, T + 40, T + 60 min) and contralateral (T - 10, T + 10, T + 30, T + 50 min) responses were analyzed. Five additional cats received AB minus TS. RESULTS: There were significant attenuations in both peak mean arterial pressure (MAP), in the last 12 s and the last 6 s of the 30 s of MC for both contra- and ipsilateral limbs occurring at T + 50 and T + 60 min after TS application, respectively. No significant changes in heart rate (HR) responses were seen for either the ipsi- or contralateral stimulation. There were no changes in MAP or HR in control cats. CONCLUSIONS: These results indicate that TS affects the end of the 30 s of MC, which is thought to be mainly chemically mediated through group IV afferents. TS represents the salicylate class of AB and has no counterirritant properties. TS works as an inhibitor of cyclooxygenase (prostaglandin formation) and is, at least in part, blood borne. 相似文献
87.
Background
The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden.Methods
Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented.Objectives
To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria.Results
Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin''s lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant.Conclusion
Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians.Running title: Epstein-Barr virus, Hodgkin''s lymphoma in Nigerians 相似文献88.
We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation. 相似文献
89.
R Rodríguez-Rodríguez P Yarova P Winter KA Dora 《British journal of pharmacology》2009,158(6):1609-1620
Background and purpose:
Extracellular nucleotides play a crucial role in the regulation of vascular tone and blood flow. Stimulation of endothelial cell P2Y1 receptors evokes concentration-dependent full dilatation of resistance arteries. However, this GPCR can desensitize upon prolonged exposure to the agonist. Our aim was to determine the extent and nature of P2Y1 desensitization in isolated and pressurized rat small mesenteric arteries.Experimental approach:
The non-hydrolyzable selective P2Y1 agonist ADPβS (3 µM) was perfused through the lumen of arteries pressurized to 70 mmHg. Changes in arterial diameter and endothelial cell [Ca2+]i were obtained in the presence and absence of inhibitors of protein kinase C (PKC).Key results:
ADPβS evoked rapid dilatation to the maximum arterial diameter but faded over time to a much-reduced plateau closer to 35% dilatation. This appeared to be due to desensitization of the P2Y1 receptor, as subsequent endothelium-dependent dilatation to acetylcholine (1 µM) remained unaffected. Luminal treatment with the PKC inhibitors BIS-I (1 µM) or BIS-VIII (1 µM) tended to augment concentration-dependent dilatation to ADPβS (0.1–3 µM) and prevented desensitization. Another PKC inhibitor, Gö 6976 (1 µM), was less effective in preventing desensitization. Measurements of endothelial cell [Ca2+]i in pressurized arteries confirmed the P2Y1 receptor but not M3 muscarinic receptor desensitization.Conclusions and implications:
These data demonstrate for the first time the involvement of PKC in the desensitization of endothelial P2Y1 receptors in pressurized rat mesenteric arteries, which may have important implications in the control of blood flow by circulating nucleotides. 相似文献90.