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We studied the molecular basis of protein C deficiency in a family with a history of thromboembolic disease. An approximately 50% reduction in anticoagulant activity despite normal levels of protein C amidolytic activity and antigen was detected in plasma from the proband. All the exons and intron/exon junctions of the protein C gene were studied using a strategy that combined polymerase chain reaction amplification with DNA sequencing of the amplified fragments. We identified a C-to-A change at nucleotide number 1387 of the protein C gene in the proband and his mother, and this mutant was designated protein C Osaka 10. The C-to-A change resulted in the substitution of Ser for Arg at position -1, which is the processing protease cleavage site. The mutant protein C was partially purified from plasma of the patient's mother using barium adsorption followed by ion-exchange column chromatography. It eluted at the same sodium chloride concentration as normal protein C, and thus gamma-carboxylation of the mutant protein appeared to be normal. The apparent molecular weight of this mutant protein C was the same as that of the normal protein on immunoblotting. Amino-terminal sequence analysis showed that the light chain of the mutant protein C had an additional Ser at position-1. Thus, the loss of anticoagulant activity of protein C Osaka 10 can be explained by alteration of the conformation of the Gla domain by the additional Ser in the mutant molecule. 相似文献
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A novel bisditerpenoid alkaloid named pukeensine was isolated from Aconitum pukeense W. T. Wang (Ranunculaceae). Its proposed structure was suggested by spectral evidence. This bisditerpenoid alkaloid skeleton has not been found previously. 相似文献
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We hypothesized that maternal serum levels of the isoenzyme creatine kinase (CK)-BB, which is highly expressed in the placenta, may be elevated during the early second trimester in gestations destined to deliver prematurely or of a small-for-gestational-age infant (birthweight below 10th percentile). To test this hypothesis, we compared maternal serum CK-BB levels and percentage of CK-BB over total CK, in 69 normal pregnancies (delivering at term of appropriate-for-gestational-age infants) with those of 25 cases complicated by preterm delivery at < or = 34 weeks (n = 14), of a small-for-gestational-age infant (n = 8), or both (n = 3). No differences were present in maternal serum CK BB levels between normal and complicated pregnancies. Moreover, no correlation was found between gestational age at delivery and CK BB levels (r = 0.03; p = 0.7). 相似文献
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YZ Ling JS Li K Kato Y Liu X Wang GT Klus K Marat IP Nnane AM Brodie 《Canadian Metallurgical Quarterly》1998,6(10):1683-1693
Some epimeric 20-hydroxy, 20-oxime, 16 alpha, 17 alpha-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase (P450(17) alpha) and 5 alpha-reductase (5 alpha-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereo-selectivity for 20 beta-ol [20 alpha/20 beta-OH (4 alpha/4 beta) = 1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20 alpha-ol (4 alpha b). The 20 alpha- and 20 beta-hydroxy-4,16-pregnadien-3-one (9 alpha) and (9 beta) were synthesized from the alcohols 4 alpha b and 4 beta b. Several 20-oxime pregnadienes and 16 alpha, 17 alpha-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17 alpha,20-aziridine (13b) and 20(R)-17 beta,20-aziridine (14a). Several compounds inhibited the human P450(17) alpha with greater potency than ketoconzole. The 5 alpha-R enzyme assay showed that while (9 alpha) did not have any activity, (9 beta) and (3b) were potent 5 alpha-reductase (IC50 = 21 and 31 nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5 alpha-R (IC50 = 63 and 115 nM, compared to 33 nM for finasteride) and P450(17) alpha (IC50 = 43 and 25 nM, compared to 78 nM for ketoconazole). 相似文献
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The effect of Paeonia lactiflora (PL) on platelet cytosolic free calcium and erythrocyte membrane Ca(2+)-Mg(2+)-ATPase activity in hyperlipid rabbits were observed. Results showed the level of platelet cytosolic free calcium in the PL group (276.25 +/- 27.00 nmol/L) was significantly lower than that in the cholesterol group (390.88 +/- 70.00 nmol/L), P < 0.01, the basal and calmodulin-stimulated activities of erythocyte membrane Ca(2+)-Mg(2+)-ATP ase in PL group (0.79 +/- 0.05 mumol.pi-1.mg-1.h-1 and 1.34 +/- 0.10 mumol.pi-1.mg-1.h-1) were higher than that in the cholesterol group (0.65 +/- 0.09 mumol.pi-1.mg-1.h-1 and 1.04 +/- 0.13 mumol.pi-1.mg-1.h-1). 相似文献
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Multiple closely related, yet distinct, isoforms exist for each of the cardiac contractile proteins. The isoform composition of the heart changes in response to developmental and physiologic cues. This paper reviews the molecular basis for cardiac contractile protein isoform diversity and the functional consequences of isoform shifts. 相似文献