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Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus. 总被引:10,自引:0,他引:10 下载免费PDF全文
M Stoffel P Froguel J Takeda H Zouali N Vionnet S Nishi I T Weber R W Harrison S J Pilkis S Lesage et al. 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(16):7698-7702
DNA polymorphisms in the glucokinase gene have recently been shown to be tightly linked to early-onset non-insulin-dependent diabetes mellitus in approximately 80% of French families with this form of diabetes. We previously identified a nonsense mutation in exon 7 in one of these families and showed that it was the likely cause of glucose intolerance in this dominantly inherited disorder. Here we report the isolation and partial sequence of the human glucokinase gene and the identification of two missense mutations in exon 7, Thr-228----Met and Gly-261----Arg, that cosegregate with early-onset non-insulin-dependent diabetes mellitus. To assess the molecular mechanism by which mutations at these two sites may affect glucokinase activity, the crystal structure of the related yeast hexokinase B was used as a simple model for human beta-cell glucokinase. Computer-assisted modeling suggests that mutation of Thr-228 affects affinity for ATP and mutation of Gly-261 may alter glucose binding. The identification of mutations in glucokinase, a protein that plays an important role in hepatic and beta-cell glucose metabolism, indicates that early-onset non-insulin-dependent diabetes mellitus may be primarily a disorder of carbohydrate metabolism. 相似文献
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Chest computed tomography (CT), including high-resolution CT with thin (1.5-mm) sections was used to evaluate proved (pathologically or clinically) lymphangitic spread (LS) of tumor in 12 patients. These appearances were compared with thin-section scans obtained in 11 healthy subjects. Thin-section CT demonstrated findings consistent with thickening of the normal lung interstitium. In all patients, thin sections showed an increase in the number of peripheral lines (1-2 cm in length) that were diffuse in generalized disease and localized in focal disease. Normal peripheral arcades were not increased in number, but the limbs forming the arcades were thickened in all patients. A diffuse increase in linear and curvilinear structures (reticular pattern) was seen toward the center of the lung. Polygonal structures 1-2 cm in diameter were seen in seven patients with LS but not in healthy subjects. Fissures were thickened in nine patients. Selected 1.5-mm-thick CT sections are recommended through abnormal areas (seen at CT or on chest radiographs) or if these are normal at three levels (midapex, hilus, and 3 cm above the diaphragm) when scanning patients with tumors known to cause LS. 相似文献
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The present report describes the treatment of a long standing exhibitionism case by covert sensitization and private exposure in front of his wife within an A-BC-B-BC-C single case experimental design. The therapeutic phase of the treatment lasted 10 weeks. Results show that the combination of covert sensitization and private exposure seems to be an interesting technique for married exhibitionists and their wives. Covert sensitization was used to eliminate deviant fantasies and private exposure seemed to have rendered exhibitionism socially acceptable. The various measures of subjective responses indicated that there were no exhibitionist activities during baseline and treatment nor during the year's follow-up, and the patient has been asymptomatic for more than 2 years, as confirmed by a recent follow-up visit. Controlled studies with larger groups of patients are now needed to prove the efficacy of this active, nonaversive and economical treatment for exhibitionists and their wives. 相似文献
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Evaluation of occupational exposure to mixed dusts and polycyclic aromatic hydrocarbons in silicon carbide plants 总被引:2,自引:0,他引:2
Workers in the silicon carbide industry have experienced occupational health diseases, particularly lung disorders such as silicosis. The silicon carbide production process mainly employs petroleum coke, sawdust, pure crystalline silica and graphite. Since crystalline silica is present in the occupational environment, the airborne dust content of various polymorphs of silica, especially quartz, cristobalite and tridymite, was determined by X-ray diffraction analysis. The analytical method was modified to eliminate graphite, since it overlaps with the main diffraction plane of quartz. Exploratory field surveys were conducted to identify the minerals present in that occupational environment and to evaluate the validity of the analytical method. The surveys provided information on the mineralogical nature of the dust, its respirable content and the concentration of silica polymorphs. Polycyclic aromatic hydrocarbons also were measured, and the effect of their adsorption on graphite was evaluated. 相似文献
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MG Bøe R Salvesen & Å Mygland 《Cephalalgia : an international journal of headache》2009,29(8):855-863
Several studies have shown the benefit of withdrawal therapy when medication overuse headache (MOH) is suspected. Our aim was to compare the effect of withdrawal therapy in patients followed by a neurologist (group A, n = 42) and a primary care physician (PCP) (group B, n = 38). Patients were randomized to A or B, and follow-up was at 3, 6 and 12 months. Calculated mean headache (MH at 6 months + MH at 12 months)/2 (primary end-point) was similar; A 1.04 (0.87, 1.21) and B 1.02 (0.82, 1.21) ( P = 0.87). The number of patients with 50% improvement of headache days was also similar; 14/42 in group A vs. 12/34 in B ( P = 0.86) at 3 months, 15/42 vs. 11/33 ( P = 0.83) at 6 months and 15/42 vs. 14/38 ( P = 0.92) at 12 months. Days without headache during the last 9 months of follow-up were 123 (96, 150) in group A and 137 (112, 161) in B ( P = 0.62). After 3 months one-third were classified as MOH. Patients with MOH improved similarly in group A and B, and so did patients without MOH. Within 1 year 7/42 in A and 9/38 in B had recurrent medication overuse ( P = 0.43). In summary, there were no significant differences in follow-up results between the two groups. 相似文献
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Ebba Lohmann MD Marie‐Laure Welter MD Valérie Fraix MD Paul Krack MD Suzanne Lesage MD Sophie Laine BS Marie‐Laure Tanguy MD PhD Jean‐Luc Houeto MD Valérie Mesnage MD Pierre Pollak MD Alexandra Durr MD PhD Yves Agid MD PhD Alexis Brice MD French Parkinson's Disease Genetics study group 《Movement disorders》2008,23(5):740-743
Patients with parkin mutations are known to have slower PD progression and a better response to levodopa at lower doses than patients with idiopathic Parkinson's disease. To determine the effects of deep brain stimulation (DBS) on such patients, we have compared the follow‐up after surgery of 7 patients with one parkin mutation, 7 patients with two parkin mutations, and 39 patients without parkin mutations. Twelve to 24 months after neurosurgery, the daily doses of levodopa equivalent were significantly lower in patients with two parkin mutations, indicating that these patients benefit from DBS, and they might have more durable results. © 2008 Movement Disorder Society 相似文献
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