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111.
Chronic granulomatous disease (CGD) results from defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, central to which is the membrane-bound cytochrome b-245. The cytochrome is composed of two protein subunits, the larger (gp91-phox) being deficient in X-linked CGD. In this study, we have analyzed expression of the cytochrome subunits in B-cell lines from two autosomal CGD patients for whom the disease is caused by deficiency of p22-phox, the smaller subunit. We report the presence of a 65-kD precursor of gp91- phox in the membrane fraction of both p22-phox-deficient cell lines, corresponding to the core protein with N-linked carbohydrate side chains in the high mannose form. Expression of p22-phox in these cells resulted in functional correction of NADPH oxidase. In addition, gp91- phox in the reconstituted cells was processed to its terminally glycosylated form. These data suggest that the association of the 65-kD gp91-phox precursor with p22-phox is a prerequisite for processing of the carbohydrate side chains to the complex form in the Golgi. The detection of this precursor will enable characterization of mutations disrupting the subunit interaction (either naturally occurring or derived by in vitro mutagenesis) and so aid in structure-function analysis of cytochrome b-245. Reconstitution of p22-phox-deficient cells shows the potential of gene therapy for this autosomal form of CGD. 相似文献
112.
Price CM; Rassool F; Shivji MK; Gow J; Tew CJ; Haworth C; Goldman JM; Wiedemann LM 《Blood》1988,72(5):1829-1832
The Philadelphia (Ph) translocation t(9;22)(q34;q11) occurs frequently in chronic myeloid leukemia (CML) but is less common in acute lymphoblastic leukemia (ALL) and rare in acute myeloid leukemia (AML). In most cases of CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is translocated to the breakpoint cluster region (bcr) of the BCR gene at 22q11 to form a chimeric gene encoding a novel 210-kd protein (P210 BCR-ABL) with enhanced tyrosine kinase activity. In other patients with Ph+ ALL and Ph+ AML, the breakpoint probably occurs in the first intron of the BCR gene; this results in a smaller chimeric gene which encodes a P190 BCR-ABL. We studied a patient with AML (FAB M6) arising de novo who had a "masked" Ph chromosome in association with extensive karyotypic changes. The leukemic cells initially showed rearrangement of the bcr, presence of a hybrid mRNA, and expression of the P210 BCR-ABL. These changes were absent in remission. These results support the concept that the BCR-ABL chimeric gene plays a crucial role in leukemogenesis but suggest that factors other than the position of the breakpoint in the BCR gene determine the lineage of the target cell for malignant transformation. 相似文献
113.
Background: Off-pump Coronary Artery Bypass (OPCAB) has become the standard surgical treatment of Coronary Artery Disease in most centres in India. It is clear from the current evidence that, in certain patients, OPCAB offers advantages over conventional Coronary Artery Bypass Grafting (CABG). Experience of this procedure in the Armed Forces is highlighted. 相似文献
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MK Song MJ Rosenthal AM Song K Uyemura H Yang ME Ament DT Yamaguchi EM Cornford 《British journal of pharmacology》2009,158(2):442-450
Background and purpose:
We have previously shown that treatment with zinc plus cyclo-(His-Pro) (CHP) significantly stimulated synthesis of the insulin degrading enzyme and lowered plasma insulin and blood glucose levels, alongside improving oral glucose tolerance in genetically type 2 diabetic Goto-Kakizaki (G-K) rats and in aged obese Sprague-Dawley (S-D) rats. Thus, we postulated that zinc plus CHP (ZC) treatment might also improve body weight control in these rats. We therefore determined the effects of ZC treatment on body weights in both genetically diabetic, mature G-K rats and non-diabetic, obese S-D rats.Experimental approach:
G-K rats aged 1.5–10 months and non-diabetic overweight or obese S-D rats aged 6–18 months were treated with 0–6 mg CHP plus 0–10 mg zinc·L−1 drinking water for 2–4 weeks, and changes in weight, serum leptin and adiponectin levels, food and water intakes were measured.Key results:
The optimal dose of CHP (in combination with zinc) to reduce weight and plasma leptin levels and to increase plasma adiponectin levels was close to 0.1 mg·kg−1·day−1, in either mature G-K rats and aged overweight or obese S-D rats. Food and water intake significantly decreased in ZC treated rats in both aged S-D rats and mature G-K rats, but not in young S-D and G-K rats.Conclusions and implications:
ZC treatment improved weight control and may be a possible treatment for overweight and obesity. 相似文献116.
117.
MK 《Best Practice Onkologie》2012,7(1):14
„ Jede Blutung unbekannter Ursache kann eine erworbene H?mophilie sein“, erkl?rte Dr. Andreas Tiede, Hannover. 相似文献
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Calprotectin is an abundant neutrophil cytosolic protein released during neutrophil activation or death. The use of plasma calprotectin concentration as a marker of pulmonary inflammation was tested in 31 children with cystic fibrosis, none of whom was acutely unwell or pyrexic. Twenty three were receiving antibiotics, 21 had positive sputum cultures, but none of the traditional tests clearly diagnosed ongoing infection. Plasma calprotectin was significantly higher in the cystic fibrosis group than in matched controls. Sixteen children with cystic fibrosis had values above the control range (320-1570 micrograms/l). Their chest radiograph Northern score, an index of accumulated pulmonary involvement, and their plasma copper, an index of acute phase response, both correlated with plasma calprotectin. Plasma gamma-glutamyltransferase also correlated weakly with plasma calprotectin: thus, hepatic pathology may be a confounding variable. However, the data still suggested that plasma calprotectin is a better index of inflammation than the traditional indices in general use. 相似文献