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排序方式: 共有617条查询结果,搜索用时 78 毫秒
1.
2.
ASK1 associates with troponin T and induces troponin T phosphorylation and contractile dysfunction in cardiomyocytes 总被引:5,自引:0,他引:5
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![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
He X Liu Y Sharma V Dirksen RT Waugh R Sheu SS Min W 《The American journal of pathology》2003,163(1):243-251
There is increasing support for the idea that excessive production of proinflammatory mediators such as tumor necrosis factor (TNF) and reactive oxygen species (ROS) contribute to the pathogenesis of cardiac dysfunction. However, the mechanisms by which cytokine/ROS production mediates cardiac dysfunction have not been established. Given that apoptosis signal-regulating kinase 1 (ASK1) is highly expressed in cardiac muscle and that ASK1 is an important mediator in the signaling pathways induced by tumor necrosis factor, interleukin-1, and ROS, we used the yeast two-hybrid system with ASK1 as bait to identify ASK1 substrates from a human heart cDNA library. The cDNA encoding the cardiac troponin T (cTnT) was isolated. ASK1 specifically interacted with cTnT, but not cTnI, in vitro and in vivo via the C-terminal ASK1 domain. ASK1 specifically phosphorylated cTnT in vitro and in vivo. Mutations in cTnT (T194/S198) at an ASK1-phosphorylation consensus sequence significantly reduced phosphorylation by ASK1. ROS-induced ASK1 activation, cTnT phosphorylation, and contractile dysfunction in cardiomyocytes showed similar kinetics. Moreover, overexpression of constitutively active ASK1 induces cTnT phosphorylation and inhibits shortening and calcium transient in adult cardiomyocytes. We conclude that ASK1 plays an important role in regulation of cardiac contractile function by phosphorylating cTnT and may participate in cytokine/ROS-induced pathogenesis of cardiomyopathy and heart failure. 相似文献
3.
Cytomegalovirus (CMV) antigenemia assay is more sensitive than shell vial cultures for rapid detection of CMV in polymorphonuclear blood leukocytes.
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![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A Erice M A Holm P C Gill S Henry C L Dirksen D L Dunn R P Hillam H H Balfour Jr 《Journal of clinical microbiology》1992,30(11):2822-2825
We compared the cytomegalovirus (CMV) antigenemia assay with shell vial cultures of polymorphonuclear leukocyte (PMNL)-enriched blood fractions for rapid diagnosis of CMV viremia. PMNL fractions of 280 blood specimens from 171 patients (170 solid-organ transplant recipients and 1 patient undergoing pretransplant evaluation) were inoculated in shell vial and conventional CMV cultures. A commercially available kit (CMV-vue kit; INCSTAR Corp.) was used for the CMV antigenemia assay, in which PMNL preparations were stained with monoclonal antibodies directed against the CMV protein pp65. Mixed-leukocyte blood fractions from the same blood specimens were inoculated in parallel shell vial and conventional cultures. CMV viremia (defined by the isolation of CMV in conventional cultures) was detected in 32 (13%) of 245 PMNL fractions included in the final analysis. Twenty-eight (87.5%) were also positive in the CMV antigenemia assay, whereas 22 (69%) were positive in shell vial cultures. Ten (4%) additional PMNL fractions positive only in the CMV antigenemia assay were from eight patients with active CMV infections (six patients), who had previous or subsequent episodes of CMV viremia (seven patients), or in whom CMV was isolated in cultures of simultaneously obtained mixed-leukocyte fractions (three patients). Overall, the CMV antigenemia assay was significantly more sensitive than shell vial cultures for detection of CMV in the PMNL fraction of blood leukocytes (P < 0.01, McNemar's test), and we recommend it as the method of choice for rapid diagnosis of CMV viremia. 相似文献
4.
SSCP analysis of paraffin wax embedded tissues in a family with an atypical form of Fabry disease
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![点击此处可从《Journal of clinical pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kirsten Marie Madsen Lis Hasholt Johannes Berger Sven Asger S?rensen 《Journal of clinical pathology》1996,49(5):M310-M312
To investigate the distribution of a single base pair mutation within a family with one known case of Fabry disease, DNA from paraffin wax embedded necropsy material was studied using single-strand conformation polymorphism (SSCP) analysis. The proband, who presented with an atypical form of Fabry disease, had a G to A transition in exon 6 of the α-galactosidase A gene. This patient had mainly cardiac symptoms and late onset disease. Further cases of coronary disorders occurred in this family, including the proband's brother who died at 42 years of age of a cardiac disorder. Formalin fixed, paraffin wax embedded material from the brother and two more distant relatives was available for analysis. SSCP analysis showed that the proband's brother also carried the G to A transition. Thus, the atypical form of Fabry disease and unrelated cardiac diseases with similar clinical symptoms occurred within a single family. The variant form is rare but may account for a few of the numerous cases of cardiac disease in men and should be considered when clusters of cases of cardiac disease occur within a single family. 相似文献
5.
Fifteen hemizygotes and 30 heterozygotes have been diagnosed since our investigations of Fabry's disease were started 10 years ago. They belong mainly to three Danish families. Genetic counseling and prenatal diagnoses have been performed, and in vitro studies of cultured fibroblasts and endothelial cells have been made with special reference to enzyme therapy. 相似文献
6.
Nørremølle A Hasholt L Petersen CB Eiberg H Hasselbalch SG Gideon P Nielsen JE Sørensen SA 《American journal of medical genetics. Part A》2004,(2):154-159
We report on a pair of monozygotic twins belonging to a family segregating Huntington disease (HD). In routine DNA analysis of blood cells, they displayed three alleles of the CAG repeat sequence in the HD gene. Two different cell lines, carrying the normal allele together with either an expanded allele with 47 CAGs or an intermediate allele with 37 CAGs, were detected in blood and buccal epithelium from both twins. To our knowledge, this is the first case described of HD gene CAG repeat length mosaicism in blood cells. Haplotype analysis established that the 37 CAG allele most likely arose by contraction of the maternal 47 CAG allele. The contraction must have taken place postzygotically, possibly at a very early stage of development, and probably before separation of the twins. One of the twins has presented symptoms of HD for 4 years; his skin fibroblasts and hair roots carried only the cell line with the 47 CAG repeat allele. The other twin, who is without symptoms at present, displayed mosaicism in skin fibroblasts and hair roots. If the proportion of the two cell lines in the brain of each twin resembles that of their hair roots (another tissue originating from the ectoderm), the mosaicism in the unaffected twin would mean that only a part of his brain cells carried the expanded allele, which could explain why he, in contrast to his brother, has no symptoms at this time. 相似文献
7.
The objective was to evaluate a postal questionnaire screening procedure for selection of subjects with positive reactions to skin prick tests with common allergens. The project consisted of a screening, with subsequent skin prick test of two selected groups. The setting was the Glostrup Population Studies institute in Copenhagen, Denmark. Participants in the screening included 8000 subjects, aged 15–69 years. The subjects were randomly selected from the population of western Copenhagen County, Denmark. From the 6998 respondents (87.5%), 793 subjects were randomly selected (Random Group), and 788 subjects were chosen on the basis of their answers to the questionnaire (Symptom Group). Both groups were invited to take skin prick tests. Attendance rates were 75.5% (Random Group) and 80.6% (Symptom Group).
The main outcome measures were responses (yes or no) to the specific questions and the subjects' skin reaction (positive or negative). The association between symptoms and skin reactivity, adjusted for the effects of sex and age, was summarized by odds ratios. Symptoms on exposure to allergens were highly associated with positive skin reactivity. In the Symptom Group the percentage of subjects with at least one positive skin reaction was 57.7%, which was twice as much (28.4%) as in the Random Group. The results show that it was possible to select a group with high skin reactivity on the basis of the symptoms reported in the screening. Questions about exposure to allergens were the most appropriate for selection of this group. 相似文献
The main outcome measures were responses (yes or no) to the specific questions and the subjects' skin reaction (positive or negative). The association between symptoms and skin reactivity, adjusted for the effects of sex and age, was summarized by odds ratios. Symptoms on exposure to allergens were highly associated with positive skin reactivity. In the Symptom Group the percentage of subjects with at least one positive skin reaction was 57.7%, which was twice as much (28.4%) as in the Random Group. The results show that it was possible to select a group with high skin reactivity on the basis of the symptoms reported in the screening. Questions about exposure to allergens were the most appropriate for selection of this group. 相似文献
8.
Kimura T Nakamori M Lueck JD Pouliquin P Aoike F Fujimura H Dirksen RT Takahashi MP Dulhunty AF Sakoda S 《Human molecular genetics》2005,14(15):2189-2200
Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSA(LR) mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle. 相似文献
9.
The distribution of bronchial responsiveness to histamine and exercise in 527 children and adolescents 总被引:2,自引:1,他引:2
V Backer A Dirksen N Bach-Mortensen K K Hansen E M Laursen D Wendelboe 《The Journal of allergy and clinical immunology》1991,88(1):68-76
The aim of the study was to describe the bronchial responsiveness to inhaled histamine and exercise in a randomly selected group of 527 children and adolescents from Copenhagen, aged between 7 to 16 years. The distribution of the bronchial responsiveness was described as (1) the provoking concentration that causes a 20% reduction in FEV1 (2) the dose-response slope (DRS), that is, the linear slope of the dose-response curve, and (3) reduction in FEV1 after 6 minutes of exercise on a treadmill. The distribution of the concentration that causes a 20% reduction in FEV1 in the responsive range was not significantly different from a unimodal distribution, although the findings were skewed toward the less responsive end of the range (p greater than 0.05). The subjects with asthma represented a subgroup within the responsive distribution tail rather than a separate distribution peak. In asymptomatic individuals, the values of DRS were distributed symmetrically on a logarithmic scale. The deviation from normal was such that the standard deviation only slightly underestimated the "normal" range. The distribution of the bronchial response to exercise was found to be significantly different from a normal distribution. However, a significant relationship was found between the bronchial response to inhaled histamine and exercise (p less than 0.0001). We conclude that there is a log-normal distribution of the bronchial response to inhaled histamine in a random sample of children and adolescents. 相似文献
10.