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排序方式: 共有1198条查询结果,搜索用时 38 毫秒
91.
Chen Y Rao F Wen G Gayen JR Zhang K Vaingankar SM Biswas N Mahata M Friese RS Fung MM Salem RM Nievergelt C Bhatnagar V Hook VY Ziegler MG Mahata SK Hamilton BA O'Connor DT 《Cellular and molecular neurobiology》2010,30(8):1395-1400
Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive renal disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed both common and unusual variants in both the open reading frame and such regulatory regions as the proximal promoter and 30-UTR. In chromaffin cell-transfected CHGA 30-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 30-UTR displayed statistical associations with hypertension. Genetic variation in the proximal CHGA promoter predicted glomerular filtration rate in healthy twins. However, for hypertensive renal damage, both end-stage renal disease and rate of progression of earlier disease were best predicted by variants in the 30-UTR. Finally, mechanistic studies were undertaken initiated by the clue that CHGA promoter variation predicted circulating endothelin-1. In cultured endothelial cells, CHGA triggered co-release of not only the vasoconstrictor and pro-fibrotic endothelin-1, but also the pro-coagulant von Willebrand Factor and the pro-angiogenic angiopoietin-2. These findings, coupled with stimulation of endothelin-1 release from glomerular capillary endothelial cells by CHGA, suggest a plausible mechanism whereby genetic variation at the CHGA locus eventuates in alterations in human renal function. These results document the consequences of genetic variation at the CHGA locus for cardiorenal disease and suggest mechanisms whereby such variation achieves functional effects. 相似文献
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93.
Background
SEN virus is a blood-borne, circular ssDNA virus and possessing nine genotypes (A to I). Among nine genotypes, SENV-D and SENV-H genotypes have the strong link with patients with unknown (none-A to E) hepatitis infections. Infection with blood-borne viruses is the second important cause of death in thalassemic patients. The aim of this study was to determine the frequency of SENV-D and SENV-H genotypes viremia by performing nested-PCR in 120 and 100 sera from healthy blood donors and thalassemic patients in Guilan Province, North of Iran respectively. Also, to explicate a possible role of SEN virus in liver disease and established changes in blood factors, the serum aminotransferases (ALT and AST) and some of the blood factors were measured.Results
Frequency of SENV-D, SENV (SENV-H or SENV-D) and co-infection (both SENV-D and SENV-H) viremia was significantly higher among thalassemic patients than healthy individuals. Frequency of SENV-H viremia was significantly higher than SENV-D among healthy individuals. In comparison to SENV-D negative patients, the mean of mean corpuscular hemoglobin was significantly higher in SENV-D positive and co-infection cases (P < 0.05). The means of AST and ALT were significantly higher in thalassemic patients than healthy blood donors, but there were not any significant differences in the means of the liver levels between SENV-positive and -negative individuals in healthy blood donors and thalassemic patients. High nucleotide homology observed among PCR amplicon's sequences in healthy blood donors and thalassemic patients.Conclusions
The high rate of co-infection shows that different genotypes of SENV have no negative effects on each other. The high frequency of SENV infection among thalassemic patients suggests blood transfusion as main route of transmission. High frequency of SENV infection in healthy individuals indicates that other routes rather than blood transfusion also are important. Frequency of 90.8% of SENV infection among healthy blood donors as well as high nucleotide homology of sequenced amplicons between two groups can probably suggest that healthy blood donors infected by SENV act partly as a source of SENV transmission to the thalassemic patients. In conclusion, SENV-D isolate in Guilan Province may be having a pathogenic agent for thalassemic patients. 相似文献94.
Sahashi K Masuda A Matsuura T Shinmi J Zhang Z Takeshima Y Matsuo M Sobue G Ohno K 《Nucleic acids research》2007,35(18):5995-6003
We have found that two previously reported exonic mutations in the PINK1 and PARK7 genes affect pre-mRNA splicing. To develop an algorithm to predict underestimated splicing consequences of exonic mutations at the 5′ splice site, we constructed and analyzed 31 minigenes carrying exonic splicing mutations and their derivatives. We also examined 189 249 U2-dependent 5′ splice sites of the entire human genome and found that a new variable, the SD-Score, which represents a common logarithm of the frequency of a specific 5′ splice site, efficiently predicts the splicing consequences of these minigenes. We also employed the information contents (Ri) to improve the prediction accuracy. We validated our algorithm by analyzing 32 additional minigenes as well as 179 previously reported splicing mutations. The SD-Score algorithm predicted aberrant splicings in 198 of 204 sites (sensitivity = 97.1%) and normal splicings in 36 of 38 sites (specificity = 94.7%). Simulation of all possible exonic mutations at positions −3, −2 and −1 of the 189 249 sites predicts that 37.8, 88.8 and 96.8% of these mutations would affect pre-mRNA splicing, respectively. We propose that the SD-Score algorithm is a practical tool to predict splicing consequences of mutations affecting the 5′ splice site. 相似文献
95.
A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family
Miyamoto Y Matsuda T Kitoh H Haga N Ohashi H Nishimura G Ikegawa S 《Human genetics》2007,121(5):625-629
Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of
the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity.
Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic
factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense
mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial
phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases. 相似文献
96.
While proteolytic enzymes are involved in the pathogenesis of multiple sclerosis (MS), the involvement of cathepsins has not
been characterized in detail. To better understand the role of cathepsins, cDNA microarray analysis was used to study the
brains of proteolipid protein transgenic (plp
tg
/−) mice, an animal model that closely mimics the failure of remyelination in MS. Analysis revealed upregulated expression of
cathepsins L, H and B and their inhibitor, cystatin C. By in situ hybridization, the induction of cathepsins was primarily limited to microglia/macrophages of the white matter,
with continuous expression from 2 to 8 months of age. Elevated protein level of cathepsins was confirmed at 4 months of age.
In contrast, elevated expression of cystatin C was found in astrocytes. The ratio of microglia/macrophages to astrocytes increased
throughout the course of demyelination, suggesting that the ratio of secreted cathepsins to cystatin C increased during that
period. We propose that in MS, remyelination may be impaired by increasing activity of cathepsins inadequately controlled
by cystatin C.
Special issue dedicated to Anthony Campagnoni. 相似文献
97.
98.
A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation 总被引:4,自引:0,他引:4
99.
100.
Dysregulation of the Bmi‐1/p16Ink4a pathway provokes an aging‐associated decline of submandibular gland function
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Kimi Yamakoshi Satoshi Katano Mayu Iida Hiromi Kimura Atsushi Okuma Madoka Ikemoto‐Uezumi Naoko Ohtani Eiji Hara Mitsuo Maruyama 《Aging cell》2015,14(4):616-624
Bmi‐1 prevents stem cell aging, at least partly, by blocking expression of the cyclin‐dependent kinase inhibitor p16Ink4a. Therefore, dysregulation of the Bmi‐1/p16Ink4a pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi‐1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi‐1/p16Ink4a pathway occurs during aging in vivo. Using real‐time in vivo imaging of p16Ink4a expression in Bmi‐1‐KO mice, we uncovered a novel function of the Bmi‐1/p16Ink4a pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16Ink4a expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging‐related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly. 相似文献