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排序方式: 共有1114条查询结果,搜索用时 178 毫秒
11.
Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis 总被引:7,自引:2,他引:7
Li DY; Toland AE; Boak BB; Atkinson DL; Ensing GJ; Morris CA; Keating MT 《Human molecular genetics》1997,6(7):1021-1028
Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular
disease that affects the aorta, carotid, coronary and pulmonary arteries.
Previous molecular genetic data have led to the hypothesis that SVAS
results from mutations in the elastin gene, ELN. In these studies, the
disease phenotype was linked to gross DNA rearrangements (35 and 85 kb
deletions and a translocation) in three SVAS families. However, gross
rearrangements of ELN have not been identified in most cases of autosomal
dominant SVAS. To define the spectrum of ELN mutations responsible for this
disorder, we refined the genomic structure of human ELN and used this
information in mutational analyses. ELN point mutations co-segregate with
the disease in four familial cases and are associated with SVAS in three
sporadic cases. Two of the mutations are nonsense, one is a single base
pair deletion and four are splice site mutations. In one sporadic case, the
mutation arose de novo. These data demonstrate that point mutations of ELN
cause autosomal dominant SVAS.
相似文献
12.
Dongari-Bagtzoglou AI; Warren WD; Berton MT; Ebersole JL 《International immunology》1997,9(9):1233-1241
CD40, a member of the tumor necrosis factor-alpha receptor family, is
constitutively expressed by cells of hematopoietic and non- hematopoietic
origin, including fibroblasts. Signaling through this receptor molecule
regulates inflammatory cytokine secretion by many cell types. Based on the
recently described cytokine secretory heterogeneity of fibroblast cell
subsets, we hypothesized that secretion of inflammatory cytokines by
gingival fibroblast cultures may be dictated by the existence of
differential proportions of cytokine- secreting subpopulations which
express high levels of CD40. After examining a large number of gingival
fibroblast (GF) cultures we find that the frequency of IL-6- and
IL-8-secreting cells mirrors the frequency of cells expressing high levels
of CD40 in these cultures. In addition, we demonstrate a direct functional
relationship between CD40 expression and IL-6 or IL-8 secretion by showing
that ligation of this molecule on GF, and CD40+ fibroblast subsets in
particular, up- regulates secretion of these cytokines in vitro.
相似文献
13.
Kim YH; de Kretser DM; Temple-Smith PD; Hearn MT; McFarlane JR 《Molecular human reproduction》1997,3(4):307-313
Using mechanical and chemical dissection methods, fibrous sheath was
isolated both from normal ejaculated human spermatozoa and from rabbit
cauda epididymal spermatozoa. The same techniques did not produce a pure
preparation of fibrous sheath from ejaculated rabbit spermatozoa,
suggesting that further cross-linking and stabilization of sperm structures
occurs in response to components of the seminal plasma. The isolation
procedures were monitored by phase contrast microscopy and the purity of
the fibrous sheath was verified by electron microscopy. Sodium dodecyl
sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human
fibrous sheath revealed at least 14 protein bands of which the most
intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5
kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which
the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid
composition of the purified fibrous sheath from human and rabbit
spermatozoa was similar, being high in aspartic acid and/or asparagine and
glutamic acid and/or glutamine, serine, alanine, leucine, lysine and
glycine, but low in histidine, tyrosine and isoleucine. This composition is
similar to that reported for the rat and suggests that mammalian sperm tail
fibrous sheaths are composed of similar types of proteins, although there
are apparent differences in protein components between species.
相似文献
14.
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry 总被引:8,自引:1,他引:8
Nistico L; Buzzetti R; Pritchard LE; Van der Auwera B; Giovannini C; Bosi E; Larrad MT; Rios MS; Chow CC; Cockram CS; Jacobs K; Mijovic C; Bain SC; Barnett AH; Vandewalle CL; Schuit F; Gorus FK; Tosi R; Pozzilli P; Todd JA 《Human molecular genetics》1996,5(7):1075-1080
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus
is determined by a combination of environmental and genetic factors, which
include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin
gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2
cannot explain the clustering of type 1 diabetes in families, and a role
for other genes is inferred. In the present report we describe linkage and
association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte
associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong
candidate gene for T cell- mediated autoimmune disease because it encodes a
T cell receptor that mediates T cell apoptosis and is a vital negative
regulator of T cell activation. In addition, we provide supporting evidence
that CTLA-4 is associated with susceptibility to Graves' disease, another
organ- specific autoimmune disease.
相似文献
15.
Induction of a differentiated ciliated cell phenotype in primary cultures of Fallopian tube epithelium 总被引:5,自引:1,他引:5
Human Fallopian tubal epithelial cells in culture lose morphological
features associated with the epithelium in situ and the extent to which
they retain their in-vivo phenotype or function is unknown. In order to
address this question, immunocytochemical markers were identified which
distinguish secretory (HMFG2+, LhS28-) from ciliated (HMFG2-, LhS28+)
epithelial cells in tissue sections of Fallopian tube. These markers were
used to analyse the phenotype of tubal cells in vitro. Primary cultures of
human tubal epithelial cells were seeded onto glass and grown to confluence
before addition of oestradiol-17beta. In the absence of hormone, tubal
epithelial cells expressed cytokeratins and nuclear receptors for oestrogen
and progesterone and adopted a homogeneous (HMFG2+, LhS28-) secretory cell
phenotype. Following the addition of oestradiol-17beta, a proportion of
cells became positive for LhS28. The induction of a ciliated epithelial
cell phenotype was confirmed by scanning electron microscopy, where on
permeable collagen membranes, approximately one-third of tubal epithelial
cells became ciliated in the presence of oestradiol-17beta. We suggest that
in vitro, tubal epithelial cells adopt an immature secretory-like phenotype
and that oestrogen can induce differentiation to a ciliated epithelial cell
phenotype.
相似文献
16.
17.
Thierry J Perrier-Gros-Claude JD Clavier B Dumas M Aubert G Barbe G Bland S Boucaud-Maitre Y Boyer M Carricajo A Chomarat M Clergeau P Delubac F Fevre D Fuhrmann C Gravagnat B Lelievre H Letouzey MN Mandjee A Martelet P Meley R Reverdy ME Ros A Roure C Tixier A 《Pathologie-biologie》1999,47(10):1060-1064
Throughout 1996, 22 hospital-based laboratories in the Rh?ne-Alpes region of France collected pneumococcal strains and used a standardized protocol to record the following data; patient age and sex; type of specimen; and determination of susceptibility to at least the following antibiotics: oxacillin 1 microgram and 5 micrograms, erythromycin (Ery), tetracycline (Tet), chloramphenicol (Chl), rifampin (Rmp), and loracarbef. For penicillin-nonsusceptible strains (PNSSs), which were identified based on results with oxacillin, MICs for penicillin G, amoxicillin (Amx), and cefotaxime (Ctx) were determined using the E Test, at the study site and agar dilution at the coordinating center. Of the 1153 strains, 65.5% were from adults and 31.8% from children; patient age was unknown in 2.7% of cases. PNSPs (MIC > 0.06 mg/l) contributed 32.9% of strains (I: 23.3%; R: 9.6%) and were more common in children (41.1%) than in adults (28.1%). The frequency of PNSSs varied across specimen types: 27.9% in blood cultures (305 strains), 15.6% in cerebrospinal fluid (32), 38.7% in protected bronchopulmonary specimens (31), 31.5% in unprotected bronchopulmonary specimens (434), 50.8% in acute otitis media (118), and 34.4% in other specimens (221). Among PNSSs, nonsusceptibility (I + R) to other antibiotics was variable: Ery, 62.1%; Tet, 41.5%; Chl, 40.4%; Rmp, 1.1%. Corresponding figures for the overall strain population were Ery, 33.3%; Tet, 22.7%; Chl, 22.8%; Rmp, 0.9%. In addition, 56.5% of PNSSs exhibited multiple drug resistance. Resistance to amoxicillin (MIC > 2 mg/l) was demonstrated for only 5 strains. No strains were resistant to loracarbef or cefotaxime. Serotypes of the 379 PNSSs were as follows: 23F, 26.6%; 14 (25.6%); 9V (18.2%), 6 (8.7%), 15 (5%), 19 (4.5%). 相似文献
18.
J B Su F Barbe B Crozatier D J Campbell L Hittinger 《Journal of cardiovascular pharmacology》1999,34(5):700-710
To determine the short-term effects of angiotensin-converting enzyme (ACE) inhibition on hemodynamics and circulating levels of norepinephrine, angiotensin, and bradykinin, responses to enalaprilat and perindoprilat were examined at doses of 0.03, 0.3, and 1 mg/kg in permanently instrumented conscious dogs with pacing-induced heart failure (right ventricular pacing, 240-250 beats/min, 3 weeks). All doses of the two inhibitors produced similar decrease in mean aortic pressure and increase in cardiac output. Neither inhibitor affected plasma norepinephrine level. Both compounds induced a similar 60-80% decrease in blood angiotensin II level, a similar two- to eightfold increase in blood angiotensin I level, and a 80-95% decrease in the angiotensin II/angiotensin I ratio. There were also a fourfold to 10-fold increase in blood bradykinin-(1-9) level, a twofold increase in blood bradykinin-(1-7) level, and a 70-85% decrease in bradykinin-(1-7)/bradykinin-(1-9) ratio. In addition, the changes in total peripheral resistance induced by the two ACE inhibitors were weakly but significantly correlated with the changes in blood angiotensin II or blood bradykinin-(1-9). Thus whatever the specificity of enalaprilat and perindoprilat, both inhibitors produced similar acute hemodynamic effects in dogs with heart failure, which was associated with marked decrease in circulating angiotensin II level and increase in bradykinin-(1-9) level. This study, which measures for the first time in heart failure the blood bradykinin level after ACE inhibitors, indicates, in concert with angiotensin II reduction, a role for increased bradykinin-(1-9) level in mediating short-term hemodynamic effects of ACE inhibition in this model of heart failure. 相似文献
19.
K Suzuki T Ezoe J Tohyama J Matsuda MT Vanier K Suzuki 《Acta paediatrica (Oslo, Norway : 1992)》2003,92(S443):54-62
Spontaneously occurring genetic lysosomal storage diseases are as rare in other mammalian species as in man. However, the advent of gene targeting technology has revolutionized the state of animal models of genetic diseases. Nearly all lysosomal storage diseases known in man have been duplicated in the mouse. The technology now allows, not only complete inactivation of endogenous genes, but also the introduction of essentially any type of mutation. These animal models can overcome many of the limitations inherent in studies of human patients - rarity of the disease, extremely complex genetic background and logistical and ethical constraints in the design and execution of experiments with human subjects. For example, genetic manipulations of germ cells or cross-breeding experiments between two mutants are readily feasible with animal models. Two major areas of the utility of animal models are the clarification of the pathophysiology/pathogenetic mechanism of disease and the exploration of therapeutic approaches. Examples of experiments using animal models of lysosomal storage disease are presented, primarily from studies undertaken in our own laboratory.
Conclusion : Animal models have proved invaluable in extending our knowledge of the lysosomal storage diseases and exploring potential therapies. 相似文献
Conclusion : Animal models have proved invaluable in extending our knowledge of the lysosomal storage diseases and exploring potential therapies. 相似文献
20.
Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic brain injury in the rat 总被引:15,自引:0,他引:15
Strauss KI Barbe MF Marshall RM Raghupathi R Mehta S Narayan RK 《Journal of neurotrauma》2000,17(8):695-711
Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome. 相似文献