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1.
Floriano P Silva-Junior Herbert L M Guedes Laura C Garvey Aniesse S Aguiar Saulo C Bourguignon Enrico Di Cera Salvatore Giovanni-De-Simone 《Toxicon》2007,50(1):18-31
BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da by electron spray mass spectrometry. The enzyme was shown to be highly glycosylated with 42% of N-linked carbohydrates composed of Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6-aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective. The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin-like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1muM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like protein C, protease-activated receptor-1 or inhibitors such as hirudin and antithrombin. A non-denaturing procedure using PNGase F and neuraminidase followed by hydrophobic interaction chromatography was employed to obtain active BJ-48 forms with variable carbohydrate content. Compared to the native enzyme, total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in their specific activities upon heating at 55/65 degrees C or treatment with SBTI. These results point out a role for BJ-48 glycosylation in thermostability and controlling the access of some canonical protein inhibitors to the active site. 相似文献
2.
LY Chow MRCPsych D Chung MRCPsych V Leung MB BS TF Leung MB ChB CM Leung MRCPsych 《International journal of clinical practice》1997,51(5):330-331
Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis. 相似文献
3.
The prevalence of antibodies to 13 antigens of Legionellaceae were compared in three populations: 583 blood donors, 140 tuberculosis patients and 66 patients with acute non Legionellosis pneumonia. Antibody levels were determined by indirect immunofluorescence (IFA) using formalized antigens prepared from bacteria developed in embryonated hen yolk sac. The very weak prevalence of anti L. pneumophila antibodies in a healthy population [almost nil for serogroups 2, 3, 4 and 5; 1.5% for serogroup 6, maximum of 2.5% for serogroup 1 (titres of 16)] confirms the positive and presumptive criteria that have been recommended by Centers for Disease Control (CDC). But as regards the other Legionellae studied, these criteria cannot be applied owing to the prevalences that are higher in healthy populations (until 14.5% with levels of 16-32 and 1% with levels of 64-128 for L. bozemanii) and clearly amplified in tuberculosis patients and in acute pneumonia. Although the significance of these antibodies remains to be discussed, with formalized antigens, it seems reasonable as regards these species to assign a threshold of 256 for the presumptive and positive criteria following seroconversion. 相似文献
4.
Changes in regional cerebral blood flow during brain maturation in children and adolescents. 总被引:25,自引:0,他引:25
C Chiron C Raynaud B Mazière M Zilbovicius L Laflamme M C Masure O Dulac M Bourguignon A Syrota 《Journal of nuclear medicine》1992,33(5):696-703
Regional cerebral blood flow (rCBF) was studied by SPECT using 133Xe in 42 children, aged 2 days to 19 years, considered as neurologically normal. rCBF was measured on cortical regions and on the cerebellum and thalamus. Curves for reference values and standard deviation were defined for each region. At birth, cortical rCBFs were lower than those for adults; after birth they increased until 5 or 6 yr of age to values 50%-85% higher than those for adults and thereafter decreased, reaching adult levels between 15 and 19 yr. Neonatal values of rCBF on cerebellum and thalamus were slightly higher than adult level, but not significantly; after age 1, they followed the common pattern for cortical curves. When rCBFs were expressed in percent global CBF, they were lower at birth than adult levels in the cortex, then increased and reached a plateau corresponding to the adult value before the second year of age. The time needed to reach normal adult values differed for each cortical region. The shortest time was found on the primary cortex and the longest on the associative cortex. Cognitive development of the child seems to be related to changes in blood flow of the corresponding brain regions. 相似文献
5.
以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用1HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IVb2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。 相似文献
6.
7.
Alain Verloes Paul Jamblin Lucien Koulischer Jean-Pierre Bourguignon 《Clinical genetics》1996,49(1):2-5
We report two patients, born of consanguineous parents, affected by a disorder resulting in mild growth retardation. Hallmarks are amelogenesis imperfecta (absence of the enamel cap) associated with brachyolmia-like anomalies: platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping and herniation of the nuclei, and broad femoral necks. Inheritance appears to be autosomal recessive. 相似文献
8.
Previous work has shown that sustained increased and decreased cell
proliferation, induced by dietary zinc deficiency and caloric restriction
respectively, influence the course of N- nitrosomethylbenzylamine
(NMBA)-induced esophageal carcinogenesis in rats. The present study
considered whether the increased cell proliferation and esophageal tumor
incidence induced by zinc deficiency are reversed upon zinc replenishment.
Weanling rats were maintained initially on a deficient diet containing 4
p.p.m. zinc. After 5 weeks, carcinogen-treated animals were given six
intragastric doses of NMBA (2 mg/kg twice weekly). Controls were untreated.
After the second NMBA dose, the rats were divided into three dietary
groups. One group was continued on the deficient diet, while the other two
groups were switched to diets containing either 75 or 200 p.p.m. zinc, with
half of the members in each group fed ad libitum and half pair-fed with
deficient rats. NMBA-untreated controls were similarly replenished. At
various time points, esophageal cell proliferation was assessed in five
animals from each group by immunohistochemical detection of cells in S
phase, with in vivo 5-bromo-2'deoxyuridine labeling. At 11 weeks after the
first dose, esophageal tumor incidence was greatly reduced, from 100% in
the deficient group to 26 and 14% respectively in the replenished groups
fed ad libitum 75 and 200 p.p.m. zinc and to 14 and 11% respectively in the
replenished groups pair-fed 75 and 200 p.p.m. zinc. In addition, the number
of tumors per esophagus was reduced from 9.93 +/- 4.25 in deficient rats,
to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished animals. Following
zinc replenishment, esophageal cell proliferation, as measured by labeling
index (LI), the number of labeled cells and the total number of cells, was
markedly decreased in NMBA-untreated and -treated esophagi as compared with
those in corresponding deficient esophagi. Thus, the esophageal cell
proliferation induced by zinc deficiency is reversed by zinc replenishment
and replenished animals have a markedly lower incidence of esophageal
tumors.
相似文献
9.
10.
Dáfne Cardoso Bourguignon da Silva Gláucia Toribio Finoti Seixas Orlei Ribeiro de Araujo Rodrigo Genaro Arduini Fabianne Altruda de Moraes Costa Carlesse Antonio Sergio Petrilli 《The Brazilian journal of infectious diseases》2012,16(4):361-365
BackgroundUsual treatment regimens with vancomycin often fail to provide adequate serum levels in patients with severe infections.MethodsRetrospective analysis of vancomycin trough serum measurements. The following parameters were calculated by Bayesian analysis: vancomycin clearance, distribution volume, and peak estimated concentrations. The area under the concentration curve (AUC) (total daily dose/24 h clearance of vancomycin) was used to determine the effectiveness of treatment through the ratio of AUC/minimum inhibitory concentration (MIC) above 400, using MIC = 1 μg/mL, based on isolates of Staphylococci in cultures.ResultsSixty-one vancomycin trough measurements were analyzed in 31 patients. AUC/MIC > 400 was obtained in 34 out of 61 dosages (55.7%), but the mean vancomycin dose required to achieve these levels was 81 mg/kg/day. In cases where the usual doses were administered (40–60 mg/kg/day), AUC/MIC > 400 was obtained in nine out of 18 dosages (50%), in 13 patients. Trough serum concentrations above 15 mg/L presented a positive predictive value of 100% and a negative predictive value of 71% for AUC/MIC > 400.ConclusionHigher than usual vancomycin doses may be required to treat staphylococcal infections in children with oncologic/hematologic diseases. Since the best known predictor of efficacy is the AUC/MIC ratio, serum trough concentrations must be analyzed in conjunction with MICs of prevalent Staphylococci and pharmacokinetic tools such as Bayesian analysis. 相似文献