排序方式: 共有33条查询结果,搜索用时 31 毫秒
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Summary After injection of microspheres into both renal arteries of rats, an irreversible shock syndrome develops, resulting in death within 4–12 h. Ligation of both renal pedicles after injection of microspheres prevents the shock. It is presumed that kininogenases released from the kidneys participate in the pathogenesis of the shock syndrome.These studies were supported in part by the Deutsche Forschungsgemeinschaft within the SFB 90, Cardiovasculäres System. 相似文献
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During the maturation of red blood cells from rats after stress erythropoiesis, adenyl cyclase activity and beta-adrenoceptor density (pmoles/mg protein) decrease at distinctly different rates suggesting a different turnover of these membrane units. 相似文献
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Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm 总被引:2,自引:0,他引:2
ME Lindsay D Schepers NA Bolar JJ Doyle E Gallo J Fert-Bober MJ Kempers EK Fishman Y Chen L Myers D Bjeda G Oswald AF Elias HP Levy BM Anderlid MH Yang EM Bongers J Timmermans AC Braverman N Canham GR Mortier HG Brunner PH Byers J Van Eyk L Van Laer HC Dietz BL Loeys 《Nature genetics》2012,44(8):922-927
Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies. 相似文献
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Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome 总被引:24,自引:0,他引:24
Neptune ER Frischmeyer PA Arking DE Myers L Bunton TE Gayraud B Ramirez F Sakai LY Dietz HC 《Nature genetics》2003,33(3):407-411
Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in fibrillin-1 (encoded by FBN1 in humans and Fbn1 in mice), a matrix component of extracellular microfibrils. A distinct subgroup of individuals with Marfan syndrome have distal airspace enlargement, historically described as emphysema, which frequently results in spontaneous lung rupture (pneumothorax; refs. 1-3). To investigate the pathogenesis of genetically imposed emphysema, we analyzed the lung phenotype of mice deficient in fibrillin-1, an accepted model of Marfan syndrome. Lung abnormalities are evident in the immediate postnatal period and manifest as a developmental impairment of distal alveolar septation. Aged mice deficient in fibrillin-1 develop destructive emphysema consistent with the view that early developmental perturbations can predispose to late-onset, seemingly acquired phenotypes. We show that mice deficient in fibrillin-1 have marked dysregulation of transforming growth factor-beta (TGF-beta) activation and signaling, resulting in apoptosis in the developing lung. Perinatal antagonism of TGF-beta attenuates apoptosis and rescues alveolar septation in vivo. These data indicate that matrix sequestration of cytokines is crucial to their regulated activation and signaling and that perturbation of this function can contribute to the pathogenesis of disease. 相似文献
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Hematocrit (HCT) measurements were made in intact and splenectomized conscious dogs to determine if observed decreases in HCT were produced by plasma volume expansion or splenic sequestration of erythrocytes. We found that in conscious dogs HCT is a poor indicator of changes in plasma volume. 相似文献
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The degree of stimulation of adenylcyclase activity, in membranes from immature red blood cells from rats, brought about by isoprenaline, guanylyl-imidodiphosphate and sodium fluoride is strongly dependent on the basal activity of the enzyme. The inversal relationship between basal activity and the maximal degree of stimulation by (--) isoprenaline, shows an apparent seasonal dependence. 相似文献
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A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2 总被引:18,自引:0,他引:18
Loeys BL Chen J Neptune ER Judge DP Podowski M Holm T Meyers J Leitch CC Katsanis N Sharifi N Xu FL Myers LA Spevak PJ Cameron DE De Backer J Hellemans J Chen Y Davis EC Webb CL Kress W Coucke P Rifkin DB De Paepe AM Dietz HC 《Nature genetics》2005,37(3):275-281
We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor beta receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFbeta signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFbeta signaling. These data definitively implicate perturbation of TGFbeta signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events. 相似文献
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Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy 总被引:20,自引:0,他引:20
Gerull B Heuser A Wichter T Paul M Basson CT McDermott DA Lerman BB Markowitz SM Ellinor PT MacRae CA Peters S Grossmann KS Drenckhahn J Michely B Sasse-Klaassen S Birchmeier W Dietz R Breithardt G Schulze-Bahr E Thierfelder L 《Nature genetics》2004,36(11):1162-1164
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations. 相似文献
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