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991.
Bensen JT Hsu FC Brown WM Sutton BS Norris JM Tracy RP Jenny NS Saad MF Haffner S Bowden DW Langefeld CD 《Human heredity》2004,57(3):128-137
OBJECTIVE: Plasminogen activator inhibitor type-1 (PAI-1) plays a central role in fibrolysis and has recently been hypothesized to influence components of the insulin resistance syndrome. We consider whether the 4G/5G polymorphism influences components of insulin resistance and obesity solely through PAI-1 protein levels or also though a secondary pathway. In addition, we explore whether transforming growth factor (TGF-beta1), a key regulator of PAI-1 expression, modifies the influence of the PAI-1 4G/5G polymorphism on these traits. METHODS AND RESULTS: The Insulin Resistance and Atherosclerosis (IRAS) Family Study genotyped 287 African American (18 pedigrees) and 811 Hispanic American (45 pedigrees) individuals for the 4G/5G PAI-1 and two TGF-beta1 polymorphisms (R25P, C-509T). Individuals were recruited from three clinical centers located in San Antonio (urban Hispanic), San Luis Valley (rural Hispanic) and Los Angeles (African American). The presence of the 4G PAI-1 allele was positively associated with PAI-1 protein level (combined sample p < 0.0001). Hispanic Americans average 65% higher PAI-1 protein levels than African Americans (p < 0.0001). Consistently across ethnic groups, increased PAI-1 protein levels were associated with increased insulin resistance and overall and central obesity (p value < 0.0001, combined sample). Adjusting for PAI-1 protein levels, there was evidence of an association of PAI-1 genotype (4G) with insulin sensitivity (p < 0.002) and subcutaneous fat (p < 0.01). These associations were not influenced by TGF-beta1 genotypes. CONCLUSIONS: PAI-1 protein is a strong correlate of insulin resistance (IR) and obesity in Hispanics and African Americans. However, PAI-1 4G/5G polymorphism appears to influence insulin resistance and obesity beyond its direct influence on serum PAI-1 protein levels. 相似文献
992.
993.
Effect of H. pylori on the expression of TRAIL, FasL and their receptor subtypes in human gastric epithelial cells and their role in apoptosis 总被引:6,自引:0,他引:6
Martin JH Potthoff A Ledig S Cornberg M Jandl O Manns MP Kubicka S Flemming P Athmann C Beil W Wagner S 《Helicobacter》2004,9(5):371-386
BACKGROUND AND AIMS: In the human stomach expression of TNF-related apoptosis inducing ligand (TRAIL) and its receptors and the modulatory role of Helicobacter pylori are not well described. Therefore, we investigated the effect of H. pylori on the expression of TRAIL, FasL and their receptors (TRAIL-R1-R4, Fas) in gastric epithelial cells and examined their role in apoptosis. MATERIALS AND METHODS: mRNA and protein expression of TRAIL, FasL and their receptors were analyzed in human gastric epithelial cells using RT-PCR, Western blot, and immunohistochemistry. Gastric epithelial cells were incubated with FasL, TRAIL and/or H. pylori, and effects on expression, cell viability and epithelial apoptosis were monitored. Apoptosis was analyzed by histone ELISA, DAPI staining and immunohistochemistry. RESULTS: TRAIL, FasL and their receptor subtypes were expressed in human gastric mucosa, gastric epithelial cell primary cultures and gastric cancer cells. TRAIL, FasL and H. pylori caused a time- and concentration-dependent induction of DNA fragmentation in gastric cancer cells with synergistic effects. In addition, H. pylori caused a selective up-regulation of TRAIL, TRAIL-R1 and Fas mRNA and protein expression in gastric cancer cells. CONCLUSIONS: Next to FasL and Fas, TRAIL and all of its receptor subtypes are expressed in the human stomach and differentially modulated by H. pylori. TRAIL, FasL and H. pylori show complex interaction mediating apoptosis in human gastric epithelial cells. These findings might be important for the understanding of gastric epithelial cell kinetics in patients with H. pylori infection. 相似文献
994.
Metzger S Bauer P Tomiuk J Laccone F Didonato S Gellera C Mariotti C Lange HW Weirich-Schwaiger H Wenning GK Seppi K Melegh B Havasi V Balikó L Wieczorek S Zaremba J Hoffman-Zacharska D Sulek A Basak AN Soydan E Zidovska J Kebrdlova V Pandolfo M Ribaï P Kadasi L Kvasnicova M Weber BH Kreuz F Dose M Stuhrmann M Riess O 《Human genetics》2006,120(2):285-292
The expansion of a polymorphic CAG repeat in the HD gene encoding huntingtin has been identified as the major cause of Huntington’s disease (HD) and determines 42–73% of the variance in the age-at-onset of the disease. Polymorphisms in huntingtin interacting or associated genes are thought to modify the course of the disease. To identify genetic modifiers influencing the age at disease onset, we searched for polymorphic markers in the GRIK2, TBP, BDNF, HIP1 and ZDHHC17 genes and analysed seven of them by association studies in 980 independent European HD patients. Screening for unknown sequence variations we found besides several silent variations three polymorphisms in the ZDHHC17 gene. These and polymorphisms in the GRIK2, TBP and BDNF genes were analysed with respect to their association with the HD age-at-onset. Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at . 相似文献
995.
Goidts V Armengol L Schempp W Conroy J Nowak N Müller S Cooper DN Estivill X Enard W Szamalek JM Hameister H Kehrer-Sawatzki H 《Human genetics》2006,119(1-2):185-198
Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic
divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee,
bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC
array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were
used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific
but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla.
The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this
degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific
gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications
(SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of
the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific
inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may
have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints
emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
996.
997.
Doyen CM Montel F Gautier T Menoni H Claudet C Delacour-Larose M Angelov D Hamiche A Bednar J Faivre-Moskalenko C Bouvet P Dimitrov S 《The EMBO journal》2006,25(18):4234-4244
The histone variant H2A.Bbd appeared to be associated with active chromatin, but how it functions is unknown. We have dissected the properties of nucleosome containing H2A.Bbd. Atomic force microscopy (AFM) and electron cryo-microscopy (cryo-EM) showed that the H2A.Bbd histone octamer organizes only approximately 130 bp of DNA, suggesting that 10 bp of each end of nucleosomal DNA are released from the octamer. In agreement with this, the entry/exit angle of the nucleosomal DNA ends formed an angle close to 180 degrees and the physico-chemical analysis pointed to a lower stability of the variant particle. Reconstitution of nucleosomes with swapped-tail mutants demonstrated that the N-terminus of H2A.Bbd has no impact on the nucleosome properties. AFM, cryo-EM and chromatin remodeling experiments showed that the overall structure and stability of the particle, but not its property to interfere with the SWI/SNF induced remodeling, were determined to a considerable extent by the H2A.Bbd docking domain. These data show that the whole H2A.Bbd histone fold domain is responsible for the unusual properties of the H2A.Bbd nucleosome. 相似文献
998.
Schwaiger S Seger C Wiesbauer B Schneider P Ellmerer EP Sturm S Stuppner H 《Phytochemical analysis : PCA》2006,17(5):291-298
The analytical assessment of edelweiss (Leontopodium alpinum) herb extracts, used in traditional alpine medicine, has resulted in the development of a HPLC-PAD-MS method that allows baseline separation of almost all constituents. Peak assignment of 14 analytes was achieved by comparison of retention times, UV and mass spectra with those of reference compounds either commercially available (luteolin, apigenin and chlorogenic acid) or isolated from edelweiss plants by column chromatography. Ten of the isolated analytes were identified as the known natural products: quercetin-3-O-beta-D-glucoside, luteolin-7-O-beta-D-glucoside, luteolin-3'-O-beta-D-glucoside, luteolin-4'-O-beta-D-glucoside, apigenin-7-O-beta-D-glucoside, 6-hydroxy-luteolin-7-O-beta-D-glucoside, luteolin-7,4'-di-O-beta-D-glucoside, chrysoeriol-7-O-beta-D-glucoside, leontopodic acid and 3,5-dicaffeolyquinic acid. One analyte, 3,4,5-tri-(E)-caffeoly-D-glucaric acid proved to be a new natural product and was named leontopodic acid B. Structure elucidation was carried out by means of MS and NMR spectroscopy in all cases. The aerial plant parts of L. alpinum (capitula, inflorescence leaves, stems, stem leaves and leaves of the basal rosette) showed variable amounts of the above-mentioned constituents, although qualitative differences were not observable. 相似文献
999.
Punkt K Schering S Löffler S Minin EA Samoilova VE Hasselblatt M Paulus W Müller-Werdan U Demus U Koehler G Boecker W Buchwalow IB 《Biochemical and biophysical research communications》2006,348(1):259-264
Nitric oxide (NO) mediates fundamental physiological actions on skeletal muscle. The neuronal NO synthase isoform (NOS1) was reported to be located exclusively in the sarcolemma. Its loss from the sarcolemma was associated with development of Duchenne muscular dystrophy (DMD). However, new studies evidence that all three NOS isoforms-NOS1, NOS2, and NOS3-are co-expressed in the sarcoplasm both in normal and in DMD skeletal muscles. To address this controversy, we assayed NOS expression in DMD myofibers in situ cytophotometrically and found NOS expression in DMD myofibers up-regulated. These results support the hypothesis that NO deficiency with consequent muscle degeneration in DMD results from NO scavenging by superoxides rather than from reduced NOS expression. 相似文献
1000.