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排序方式: 共有361条查询结果,搜索用时 6 毫秒
1.
2.
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
3.
The prediction from Sokolov's (1960) theory that, following OR habituation, size of OR return is proportional to the amount of difference between the new stimulus and the habituating stimulus was tested using an auditory stimulus varying in frequency and intensity. Five Ss were allocated to each of 16 conditions, three conditions involving changes in frequency, three involving changes in intensity, nine involving changes in both frequency and intensity, with one control condition involving a repetition of the habituating stimulus. Following habituation of the GSR component of the OR to a criterion of response failure for three successive trials, magnitude of GSR under the 16 conditions was measured. Contrary to Sokolov's theory, only increase in intensity had a significantly different effect on OR return. More importantly, it was found that Ss habituating rapidly to the initial stimulus were less likely to show OR return to stimulus change. It was concluded that individual differences in habituation rate may be more important than stimulus difference effects in selective habituation. 相似文献
4.
C W Gowen E E Lawson J Gingras-Leatherman J T Gatzy R C Boucher M R Knowles 《The Journal of pediatrics》1986,108(4):517-521
Patients with cystic fibrosis (CF) have an increased nasal transepithelial potential difference (PD) which reflects increased sodium absorption across epithelium relatively impermeable to chloride. To evaluate nasal epithelial function in neonates with CF, the PD was recorded and the voltage response to superfusion of 10(-5M) amiloride, an inhibitor of sodium transport, measured between a Ringer perfused bridge on the nasal mucosa and a reference electrode in the subcutaneous space. We studied three neonates with CF with meconium ileus and compared the results with those in 24 term healthy neonates, including one obligate heterozygote for CF, and 27 control neonates with disease. All three CF neonates had raised sweat chloride values (mean 100 mEq/L) at 2 months. The CF neonates had higher PDs (-64.0 +/- 8.4 mV) than those in normal (-24.4 +/- 2.0 mV) or control (-25.8 +/- 2.0 mV) neonates. Superfusion with amiloride induced a 72% reduction in PD in the CF neonates as compared with healthy (37.5 +/- 1.0%) and diseased (36.0 +/- 1.3%) neonates. The PD and amiloride response in CF neonates are similar to those in CF infants (2.24 months), older CF children (greater than 6 years), and CF adults (-64.9 +/- 9.3 mV; 77.7 +/- 1.8%, n = 51). These results suggest that (1) nasal epithelial dysfunction is present in patients with CF shortly after birth, and (2) the nasal PD may be a diagnostic adjunct to the sweat test in the early diagnosis of CF. 相似文献
5.
Maxine Gowen Brian R. Macdonald R. Graham G. Russell 《Arthritis \u0026amp; Rheumatology》1988,31(12):1500-1507
Using cultured human osteoblast-like cells, we studied the effects of tumor necrosis factor (TNF) and recombinant human γ-interferon (γ-IFN) on osteoblast growth and function, and demonstrated that TNF stimulated bone cell proliferation and prostaglandin production while inhibiting 1,25-(OH)2D3—stimulated alkaline phosphatase activity and osteocalcin release. In contrast, γ-IFN inhibited proliferation and stimulated alkaline phosphatase activity of the cells, while inhibiting 1,25-(OH)2D3—stimulated osteocalcin production and having variable effects on the release of prostaglandins, depending on the presence of other factors. Our results suggest that TNF and γ-IFN can act directly on bone-forming cells to affect both their proliferation and their differentiated function, and that changes in the ability of cells to produce these factors in disease states may contribute to alterations in the integrity of connective tissue matrices. 相似文献
6.
SG Lindquist M Duno M Batbayli A Puschmann H Braendgaard S Mardosiene K Svenstrup LH Pinborg K Vestergaard LE Hjermind J Stokholm BB Andersen P Johannsen JE Nielsen 《Clinical genetics》2013,83(3):279-283
Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene. 相似文献
7.
In this paper a frequency plane analysis of both normal and diseased ECG signals is performed specifically for disease identification. Image processing techniques are used to develop an automated data acquisition package of 12 lead ECG signals from paper records. A regeneration domain is also developed to check the captured pattern with the original wave shape. A QRS complex detector with an accuracy level ~98.4% in up to 30% signal to noise level is developed. Discrete Fourier transform (DFT) is performed to obtain the frequency spectrum of every ECG signal. Some interesting amplitude and phase response properties of chest lead V2, V3, V4, V6 and limb lead I, II, III, AVL, AVF are seen. Both amplitude and phase properties are different for normal and diseased subjects and can serve an important role in disease identification. A statistical analysis of amplitude property is carried out to show that this property is significantly different for normal and diseased subjects. 相似文献
8.
Report of the first example of pure anti-Lua associated with hemolytic disease of the newborn. Of special interest is the fact that this serum demonstrated a marked prozone reaction in saline, papain and indirect Coombs titrations, and is the first anti-Lua serum to react well by the indirect Coombs technic. 相似文献
9.
Using cultured human osteoblast-like cells, we studied the effects of tumor necrosis factor (TNF) and recombinant human gamma-interferon (gamma-IFN) on osteoblast growth and function, and demonstrated that TNF stimulated bone cell proliferation and prostaglandin production while inhibiting 1,25-(OH)2D3-stimulated alkaline phosphatase activity and osteocalcin release. In contrast, gamma-IFN inhibited proliferation and stimulated alkaline phosphatase activity of the cells, while inhibiting 1,25-(OH)2D3-stimulated osteocalcin production and having variable effects on the release of prostaglandins, depending on the presence of other factors. Our results suggest that TNF and gamma-IFN can act directly on bone-forming cells to affect both their proliferation and their differentiated function, and that changes in the ability of cells to produce these factors in disease states may contribute to alterations in the integrity of connective tissue matrices. 相似文献
10.
Hoe NP Ireland RM DeLeo FR Gowen BB Dorward DW Voyich JM Liu M Burns EH Culnan DM Bretscher A Musser JM 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(11):7646-7651
Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease. Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain. Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells. Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli. Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin. Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin. In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes. The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing. Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment. This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics. 相似文献