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91.
Deletion or replacement of the second EGF-like domain of protein S results in loss of APC cofactor activity 总被引:2,自引:2,他引:0
Human protein S (PS), a cofactor of anticoagulant-activated protein C (APC), is a modular protein containing 4 epidermal growth factor (EGF)-like domains. EGF1 appears to mediate PS interaction with APC, but the roles of EGFs 2, 3, and 4 are less clear. We synthesized PS variants lacking single EGF domains (EGF2, 3, or 4) and assessed their APC cofactor activity in a factor Va inactivation assay. The variant lacking EGF2 (variant 134) showed the most dramatic loss of activity (approximately 10% of recombinant wild-type PS activity). Replacement of EGF2 by an additional EGF3 (variant 1334) resulted in a comparable loss of activity, suggesting that the loss of a specific rather than "spacer" function of EGF2 was responsible. We confirmed that the variant 134 had a functional gamma-carboxyglutamic acid (Gla) domain and that EGF1 was correctly folded. This is the first clear evidence that EGF2 is required for the expression of PS activity. 相似文献
92.
Aspergillus endocarditis in chronic granulomatous disease 总被引:2,自引:0,他引:2
We report the first case, to our knowledge, of Aspergillus endocarditis in chronic granulomatous disease in a patient who also had an atrial septal defect. A diagnosis was made on culture of the organism from the mass despite extensive prior investigation. The presence of distinctive skin lesions as a diagnostic clue of fungaemia is highlighted. Possible advances in diagnosis by detection of fungal cell wall components and in prophylaxis by use of itraconazole are referred to. We conclude that fungal endocarditis should be considered in this condition, especially in the presence of a structural heart defect. 相似文献
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Michael A. Simmonds 《European journal of pharmacology》1982,80(4):347-358
Compounds reported to be GABA antagonists have been studied quantitatively on dorsal funiculus fibres and terminals in the rat cuneate nucleus in vitro. The potencies of the antagonists against the GABA analogue muscimol were determined as pA2 values. Distinction was made between three different sites of antagonist action within the GABA receptor and ionophore complex. Competitive antagonists, presumed to act at the GABA receptor, and their pA2 values were bicuculline (5.98), bicuculline methochloride (5.88), strychnine (5.29) and tubocurarine (4.95). Antagonists which were not competitive and acted predominantly at the ‘picrotoxin site’ on the ionophore were picrotoxin (6.19), picrotoxinin (6.03), isopropylbicyclophosphate (5.82) and leptazol (2.89). A third type of antagonism was shown by frusemide. Attention is drawn to the picrotoxin site and its likely importance in the regulation of GABA-mediated inhibition by drugs. 相似文献
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Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT 总被引:1,自引:0,他引:1
Lipton MJ; Farmer DW; Killebrew EJ; Bouchard A; Dean PB; Ringertz HG; Higgins CB 《Radiology》1985,157(3):735-740
A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics. 相似文献
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Hyperuricemia and gout have long been known to run in families. As well as an apparently multifactorial genetic component to classic gout itself, 2 rather unusual sex-linked single-gene disorders of purine biosynthesis or recycling have been defined: deficiency of the enzyme hypoxanthine-guaninephosphoribosyl transferase (HPRT), and overactivity of PPriboseP synthase. Both result in overproduction of urate, hyperuricemia, and secondary overexcretion that may lead to acute or chronic renal damage. Familial juvenile hyperuricemic nephropathy (FJHN) and autosomal-dominant medullary cystic kidney disease (ADMCKD) are more common but less well-defined hyperuricemic conditions resulting from a decrease in the fractional excretion of filtered urate, with normal urate production. Although having features in common, ADMCKD is distinguished in particular by the presence of medullary cysts. One major group of both disorders is associated with mutations in the gene for uromodulin, but this accounts for only about one third of cases, and genetic heterogeneity is present. Whether the genes involved in these latter disorders contribute to the polygenic hyperuricemia and urate underexcretion of classic gout remains unexplored. 相似文献