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991.
Caveolin-3 in muscular dystrophy 总被引:2,自引:0,他引:2
McNally EM; de Sa Moreira E; Duggan DJ; Bonnemann CG; Lisanti MP; Lidov HGW; Vainzof M; Passos-Bueno MR; Hoffman EP; Zatz M; Kunkel LM 《Human molecular genetics》1998,7(5):871-877
The dystrophin-glycoprotein complex (DGC) serves as a link between
cytoplasmic actin, the membrane and the extracellular matrix of striated
muscle. Genetic defects in genes encoding a subset of DGC proteins result
in muscular dystrophy and a secondary decrease in other DGC proteins.
Caveolae are dynamic structures that have been implicated in a number of
functions including endocytosis, potocytosis and signal transduction.
Caveolin (VIP-21) is thought to play a structural role in the formation of
non-clathrin-coated vesicles in a number of different cell types.
Caveolin-3, or M-caveolin, was identified as a muscle- specific form of the
caveolin family. We show that caveolin-3 co- purifies with dystrophin, and
that a fraction of caveolin-3 is a dystrophin-associated protein. We
isolated the gene for human caveolin- 3 and mapped it to chromosome 3p25.
We determined the genomic organization of human caveolin-3 and devised a
screening strategy to look for mutations in caveolin-3 in patients with
muscular dystrophy. Of 82 patients screened, two nucleotide changes were
found that resulted in amino acid substitutions (G55S and C71W); these
changes were not seen in a control population. The amino acid changes map
to a functionally important domain in caveolin-3, suggesting that these are
not benign polymorphisms and instead are disease-causing mutations.
相似文献
992.
Sociodemographic risk factors for sudden infant death syndrome: associations with other risk factors
AK Daltveit LM Irgens N Øyen R Skjærven T Markestad B Alm G Wennergren G Norvenius K Helweg-Larsen 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(3):284-290
The aim of this study was to investigate associations between sudden infant death syndrome (SIDS) and social factors in the Nordic countries. A case-control study was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. Parents of 244 SIDS infants and 869 control infants matched on gender, age at death and place of birth filled in questionnaires. The dataset was analysed by conditional logistic regression. In univariate analysis, the following sociodemographic factors were associated with an increased risk of SIDS: low maternal age [odds ratio (OR) 7.8; 2.8-21.5], high birth order (OR 4.4; 2.5-7.5), single motherhood (OR 2.9; 1.7-5.0), low maternal education (OR 4.5; 2.8-7.1), low paternal education (OR 3.0; 1.9-4.7), maternal unemployment (OR 2.4; 1.8-3.4) and paternal unemployment (OR 4.0; 2.7-5.9). In a multivariate analysis where maternal smoking was also included, only paternal unemployment, young maternal age and high birth order remained significantly associated with SIDS. Housing conditions were not associated with SIDS. However, the risk of SIDS was high if the family had lived in their present home for only a few years (OR 2.3; 1.3-4.1). Sociodemographic differences remain a major concern in SIDS in a low-incidence situation and even in an affluent population with adequate health services. 相似文献
993.
Williams RJ; Henderson LM; Naidoo Y; Cassim B; Elson CJ; Bhoola KD 《Rheumatology (Oxford, England)》1997,36(4):420-425
Polymorphonuclear leucocytes (PMNs) from the synovial fluid of patients
with rheumatoid arthritis (RA) showed reduced tissue kallikrein and kinin
immunoreactivity in comparison with blood PMNs from healthy individuals as
judged visually using confocal microscopy. Similarly, synovial fluid PMNs
exhibited reduced tissue kallikrein immunoreactivity as compared with blood
PMNs from the same RA patients. Blood PMNs stimulated to degranulate in
vitro also displayed less immunostaining for tissue kallikrein and kinin
than non-stimulated PMNs. By contrast, no difference in kininogen
immunostaining was detected between RA synovial fluid PMNs and blood PMNs
from healthy people. It is considered that the results support the
hypothesis that tissue kallikrein, released from the granules of RA
synovial fluid PMNs, cleaves the kinin moiety from multifunctional
kininogen protein on the surface of the PMNs.
相似文献
994.
995.
HPLC柱切换法血浆直接进样测定氟康唑 总被引:2,自引:0,他引:2
建立了用HPLC柱切换测定血浆中氟康唑的方法。血样用0.2mol·L-1醋酸溶液简单稀释后注入填充LiChromprepRP2(25~40μm)的预柱上,用蒸馏水冲洗出血浆中蛋白和其它极性成分。切换后,浓缩在预柱上的氟康唑被流动相甲醇-0.2mol·L-1醋酸按(pH2.7)(50:50)反冲到分析柱ShimpackCLC-ODS上进行分析。预柱用净化液进行清除和再生。本法有很好的精密度与回收率,检测限为0.12μg·mL-1血浆,日间和日内测定相对标准偏差均小于6%。此分析法已成功地用于测定自愿受试者的氟康唑药代动力学及生物利用度。 相似文献
996.
Ruiz-Munoz LM; Vidal-Vanaclocha F; Lampreabe I 《Nephrology, dialysis, transplantation》1997,12(3):456-464
BACKGROUND: Oxidative stress is considered to play a role in the
pathogenesis of diabetic nephropathy. Angiotensin-converting enzyme (ACE)
inhibitors are hypotensive drugs with a well-known effect in preventing the
progression of chronic renal failure. Their mechanism of action is not
clearly established. METHODS: The effect of enalaprilat on hydrogen
peroxide (H2O2) production by cultured murine mesangial cells exposed to
5.5 (basal condition), 30 and 50 mM glucose concentrations was examined
over 8 h. A fluorimetric method quantifying, in arbitrary units, the
intracellular dichlorofluorescein (DCFH) oxidation to the highly
fluorescent compound 2'7'dichlorofluorescein (DCF) from the non-fluorescent
probe dichlorofluorescein-diacetate (DCFH-DA) was employed (a method not
previously reported for cultured mesangial cells). Experiments were
repeated three times in quadruplicate wells. RESULTS: H2O2 production by
mesangial cells exposed to 50 mM glucose was significantly increased after
1 h, compared to cells exposed to 5.5 and 30 mM glucose. This observation
was not reproduced with 50 mM mannitol. Addition of 100 ng/ml enalaprilat
to cells with 50 mM glucose significantly inhibited H2O2 production during
the 8 h of the assay. This response was similar to that obtained with 100
ng/ml catalase. Increasing enalaprilat concentrations (10, 50 and 100
ng/ml) also significantly decreased the constitutive H2O2 generation in the
presence of 5.5 mM glucose. Angiotensin II and saralasin, both at 1 microM,
did not modify H2O2 production by cells exposed to 5.5 mM glucose. In
contrast, 1 microM staurosporine, a protein kinase C (PKC) antagonist,
significantly decreased H2O2 generation in the presence of 50 mM glucose.
CONCLUSION: Enalaprilat has an antioxidant effect in cultured mesangial
cells. This action is not linked to ACE inhibition, but may be related to
an inhibition of the PKC system.
相似文献
997.
Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa 总被引:4,自引:0,他引:4
Spermatozoa are produced in the testis and undergo post-gonadalmodifications in the epididymis to acquire fertilizing ability.In epididymal plasms, high-molecular-weight proteins and suchsmall molecules as free-L carnitine convert the gametes into'competent' and functional cells. This review summarizes theknowledge pertaining to L-carnitine and the significance offree L-carnitine uptake into the mature spermatozoa of mammals.We provide an overview of the function of free L-carnitine andcarnitine esters in the metabolism of eukaryotic cells and reviewthe role of the specific carnitine acyltransferases in mitochondrialtransport of fatty acids and in modulating the acyl-coenzymeA (CoA) pools in cellular organelles. In mammals, includingman, free L-carnitine is taken from blood plasma and concentratedin the epididymal lumen. This epididymal secretion is beneficialfor spermatozoa and is not merely an excretory waste. The uptakeof free L-carnitine into the spermatozoa and its metabolic outcomeare discussed first in in-vivo and then in in-vitro situations.Free L-carnitine goes through the sperm plasma membrane by passivediffusion. Free L-carnitine is acetylated in mature spermatozoaonly. The excess acetyl-CoA from the mitochondria is probablystored as acetyl-L-carnitine and modulates the reserves of freeCoA essential to the function of the tricarboxylic acid cycle.These properties of L-carnitine of buffering CoA in the mitochondrialmatrix are known in somatic cells but are accentuated in thisstudy of the male germinal cells. In the future, a precise measurementof the in-vivo and in-vitro concentrations of free CoA and acetyl-CoAin the cellular compartments of immature and mature spermatozoamight complete these data. The relationship between the endogenouspools of free and acetylated L-carnitine and the percentageof progressive sperm motility indicates a more important metabolicfunction related to flagellar movement. In conclusion, the potentialto initiate sperm motility, which takes place in the epididymis,is probably independent of the carnitine system, while the energyproperties of acetyl-L-carnitine can only be relevant in situationsof 'energy crisis'. The uptake of 'cytoplasmic' free L-carnitinein mature spermatozoa must be a protective form of mitochondrialmetabolism useful to the survival of this isolated cell. 相似文献
998.
999.
一种筛选抗过敏药与止痒药的动物模型 总被引:19,自引:0,他引:19
探讨以4-氨基吡啶(4-AP)诱发小鼠舔体反应作为筛选抗过敏药与止痒药动物模型的可能性。4-AP1mgkg-1颈背部sc能诱发小鼠舔体反应。抗过敏药与止痒药苯海拉明、多塞平、强的松、地塞米松、肤轻松、皮炎平、色甘酸钠、酮替芬等均能明显抑制此种反应。硝苯地平与米诺地尔也有效。西米替丁与雷尼替丁无效。吗啡与地西泮能拮抗4-AP的这一作用,镇静剂量的巴比妥类与阿司匹林则无拮抗作用。研究表明,以4-AP诱发小鼠舔体反应的方法简便易行,指标明确,可作为筛选抗过敏药与止痒药的一种动物模型。 相似文献
1000.
A study of liver biopsies and liver disease among hemophiliacs 总被引:5,自引:2,他引:3
Aledort LM; Levine PH; Hilgartner M; Blatt P; Spero JA; Goldberg JD; Bianchi L; Desmet V; Scheuer P; Popper H 《Blood》1985,66(2):367-372
Hepatic histologic materials (biopsy or autopsy) and associated clinical data from 155 hemophiliacs were collected by an ad hoc hemophilia study group and analyzed retrospectively in an effort to determine the spectrum of liver disease in this population and to examine the relationship between the severity of liver disease and treatment history. Clinical information on the frequency of complications from 126 biopsies in 115 hemophilic patients provided a unique opportunity to assess the safety of liver biopsy in such patients. The incidence of cirrhosis (15%) and chronic active hepatitis (7%) was lower than previously reported. The frequency of severe liver disease (chronic active hepatitis or cirrhosis) in patients receiving large pooled concentrates was no greater than in patients treated principally with cryoprecipitate or plasma. The risks of liver biopsy in this setting are relatively high: clinically significant hemorrhage followed 12.5% of the procedures. 相似文献