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Two forms of membrane-bound β-glucosidase in the spleen of normal individuals were distinguished by their thermostability properties. The heat-labile form A predominates; it catalyzes the hydrolysis of the natural substrate, glucosylceramide, and is activated by the detergent, sodium taurocholate. The minor heat-stable form B is inactive against glucosylceramide and is inhibited by taurocholate. The activity of form A increases from childhood to adult life, as does the activity of the soluble β-glucosidase and of glucosylceramide β-glucosidase. In the spleen of nine patients with different types of Gaucher's disease the residual membrane-bound β-glucosidase was predominantly heat-stable and inhibited by taurocholate. There was no clear correlation between the properties of the residual enzyme in the different types of the disorder and their respective clinical severity. The results are discussed in relation to the biochemical pathogenesis and the enzymatic diagnosis of Gaucher's disease. 相似文献
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STEVENSON A.; YAQOOB M.; MASON H.; PAI P.; BELL G.M. 《QJM : monthly journal of the Association of Physicians》1995,88(1):23-28
To investigate possible mechanisms of hydrocarbon or solvent-inducedrenal damage, we studied three groups of healthy men employedin a UK manufacturing plant. Group 1 (n = 111) were occupationallyexposed to hydrocarbon-based paints, Group 2 (n = 100) wereoccupationally exposed to petroleum-based mineral oils, andGroup 3 (n = 92) had low background occupational exposure tohydrocarbons. Occupational atmospheric exposure levels for toluene,xylene, butanol and oil mist around the time of this study werewithin UK permissible limits. Group 4 (controls) were maleswith no known occupational hydrocarbon or solvent exposure (n= 108). Circulating laminin antibodies and the auto-antibodyimplicated in Goodpasture's syndrome (anti-GBM) were measured,as were serum laminin, a basement membrane turnover marker,and soluble E-selectin, an endothelial activation marker. Group1 had a significantly greater proportion of subjects with highlevels of both anti-laminin antibodies and soluble E-selectin;Group 2 had significantly more subjects with raised anti-GBMantibodies, laminin and soluble E-selectin. Mean levels of solubleE-selectin were increased in Groups 1 and 2. In a small butsignificant proportion of these workers exposed to hydrocarbons/mixedsolvents there are alterations both to basement membranes, resultingin autoantibody production, and to overlying vascular endothelialcells. 相似文献
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Renal impairment with chronic hydrocarbon exposure 总被引:6,自引:2,他引:4
YAQOOB M.; BELL G.M.; STEVENSON A.; MASON H.; PERCY D.F. 《QJM : monthly journal of the Association of Physicians》1993,86(3):165-174
Occupational hydrocarbon exposure is believed by some investigatorsto play an important role in the development of several non-neoplasticrenal diseases. In view of the continuing debate in this areaof nephrology we adopted a cross-sectional approach by investigatingthe prevalence of clinical or sub-clinical renal dysfunctionin subjects chronically exposed to hydrocarbons at their worksite. Three groups of healthy men working in different and separateareas of a major car manufacturing plant in the North-west ofEngland participated in the study. Group 1 comprised 112 paintsprayers with exposure to paint-based hydrocarbons, group 2comprised 101 volunteers working in the transmission area ofthe plant with exposure to petroleum-based mineral oils, andgroup 3 comprised 92 automated press operators with minimalbackground exposure to lubricants who acted as internal controls.Early markers of renal dysfunction such as serum creatinine,urinary total protein, albumin, transferrin, retinol bindingprotein, N-acetyl-glucosaminidase, 相似文献
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YAQOOB M.; MCCLELLAND P.; PATRICK A.W.; STEVENSON A.; MASON H.; WHITE M.C.; BELL G.M. 《QJM : monthly journal of the Association of Physicians》1994,87(10):601-607
Two groups of patients with insulin-dependent diabetes mellitusof >10 years duration and either persistent normoalbuminuria(group 1, n = 49; albumin excretion <30mg/day) or microalbuminuria(group 2, n = 33; albumin excretion 30300 mg/day) wereinvestigated for evidence of free oxygen radical activity (erythrocyticsuperoxide dismutase and glutathione peroxidase) and oxidantinjury (serum malondialdehyde). Glomerular proteinuria (albu-minuria,transferrinuria), tubular proteinuria (ret-inol-binding protein)and tubular enzymuria (N-acetyl-glucosaminidase and leucineaminopeptidase) were also measured. Healthy controls (n = 38)were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration ofdiabetes and recent glycaemic control. Serum cholesterol andcreatinine were similar in all three groups. Free-radical activityand oxidant injury were significantly higher in groups 1 and2 than in controls (p< 0.001). Glomerular proteinuria, tubularproteinuria and enzymuria were significantly higher in group2 than in group 1 and controls (p<0.01). Group 1 had significantlyhigher transferrinuria, tubular enzymuria and tubular proteinuriathan controls. However, groups 1 and 2 were similar in degreeof free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damageaccompany and may even precede microalbuminuria. The presenceof these abnormalities in the absence of glomerular proteinuriafavours the hypothesis that alterations first occur in the peritubularmicrocirculation, which by causing oxidant injury and tubulardamage, may initiate diabetic nephropathy. 相似文献
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5-amino salicylic acid absorption and metabolism in ulcerative colitis patients receiving maintenance sulphasalazine, olsalazine or mesalazine 总被引:2,自引:2,他引:0
G. L. STRETCH B. J. CAMPBELL A. D. DWARAKANATH M. YAQOOB A. STEVENSON A. I. MORRIS & J. M. RHODES 《Alimentary pharmacology & therapeutics》1996,10(6):941-947
Background: All 5-aminosalicylic acid (5-ASA) preparations are potentially nephrotoxic, but there has been concern that newer delivery systems may increase this risk, either because of altered absorption or altered metabolism. Previous studies of 5-ASA absorption and excretion have usually either been performed in healthy controls or have only examined short-term therapy. 5-ASA and N-acetyl-5-ASA have therefore been measured in blood samples, and N-acetyl-5-ASA in urine samples, from patients with ulcerative colitis on long-term maintenance with different 5-ASA preparations and compared with sensitive markers of renal damage. Methods: Patients receiving mesalazine (Asacol) (n=13), sulphasalazine (n=12) or olsalazine (Dipentum) (n=8), all at doses within the recommended range were studied. Six-hour and trough serum concentrations of 5-ASA and N-acetyl-5-ASA and 24-h urinary excretion of N-acetyl-5-ASA were measured by high-performance liquid chromatography. Results: Absorption of 5-ASA, assessed as 24-h excretion of N-acetyl-5-ASA expressed as molar % of ingested dose, was greater in patients receiving mesalazine, 23.25±10.65% (mean±s.d.; n=13), than those receiving sulphasalazine (11.16±10.52%, n=12; P=0.003) or olsalazine (9.70±3.89%, n=8; P<0.002). The ratio of 5-ASA:N-acetyl-5-ASA in the serum 6 h after dose was also greater with mesalazine (1.02±0.44, mean±s.d.) than sulphasalazine (0.54±0.44, P<0.02) or olsalazine (0.38±0.44, P<0.005). Urinary markers of tubular damage were increased in four of 33 patients, but showed no correlation with concentration of 5-ASA or N-acetyl-5-ASA in serum and N-acetyl-5-ASA in urine, nor with lifetime dose or average daily dose of 5-ASA. Conclusions: In patients with ulcerative colitis receiving maintenance 5-ASA therapy there was greater absorption and less acetylation of 5-ASA from mesalazine (Asacol) compared with sulphasalazine or olsalazine, but no evidence from this study that this resulted in increased nephrotoxicity. 相似文献
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YAQOOB MUHAMMAD; GOLDSMITH HENRY JOHN; AHMAD RASHEED 《QJM : monthly journal of the Association of Physicians》1990,74(1):105-109
Bovine tuberculosis is now rare in the western world. We reporta case of bovine genitourinary tuberculosis causing obstructiverenal failure. This combination does not appear to have beenpreviously reported. 相似文献
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