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排序方式: 共有92条查询结果,搜索用时 187 毫秒
1.
A M Dunning R Houlston J Frosteg?rd J Revill J Nilsson A Hamsten P Talmud S Humphries 《Biochimica et biophysica acta》1991,1096(3):231-237
We have searched for sequence differences in the region of the apolipoprotein B (apo B) gene encoding amino acids 3130-3630 in eight individuals with reduced affinity of low density lipoprotein (LDL) for the normal LDL-receptor. All individuals were hypercholesterolaemic and were selected either on the basis of reduced fractional catabolic rate (FCR) of autologous LDL or substantially reduced binding of their LDL to normal LDL-receptors determined by an in vitro cell growth assay using the U937 macrophage-like cell line. Segments of the apo B gene were amplified by the polymerase chain reaction. Using a combination of cloning and sequencing the amplified fragment, together with chemical cleavage mismatch analysis, no sequence differences were identified in this region of the gene. We therefore conclude that variation outside the region of the apo B gene that codes for amino acids 3130-3630 must be responsible for the reduced LDL clearance in these patients. 相似文献
2.
High level of divergence of male-reproductive-tract proteins, between Drosophila melanogaster and its sibling species, D. simulans 总被引:1,自引:0,他引:1
We compared male-reproductive-tract polypeptides of Drosophila melanogaster
and D. simulans by using two-dimensional gel electrophoresis. Approximately
64% of male-reproductive-tract polypeptides were identical between two
randomly chosen isofemale lines from these two species, compared with 83%
identity for third-instar imaginal wing-disc polypeptides. Qualitatively
similar differences were found between reproductive tracts and imaginal
discs when D. sechellia was compared with D. melanogaster and with D.
simulans. When genic polymorphism was taken into account, approximately 10%
of male- reproductive-tract polypeptides were apparently fixed for
different alleles between D. melanogaster and D. simulans; this proportion
is the same as that found for soluble enzymes by one-dimensional gel
electrophoresis. Strikingly, approximately 20% of male-reproductive- tract
polypeptides of either D. melanogaster or D. simulans had no detectable
homologue in the other species. We propose that proteins of the Drosophila
male reproductive tract may have diverged more extensively between species
than have other types of proteins and that much of this divergence may
involve large changes in levels of polypeptide expression.
相似文献
3.
G F Watts W Ahmed J Quiney R Houlston P Jackson C Iles B Lewis 《BMJ (Clinical research ed.)》1988,296(6617):235-237
The plasma lipid and lipoprotein responses to two modified isoenergetic diets including meat were studied in 15 free living men with hyperlipidaemia (mean plasma cholesterol and triglyceride concentrations 8·1 and 3·4 mmol/l). A reference diet (diet A, 42% energy from fat, ratio of polyunsaturated to saturated fatty acids (P:S ratio) 0·2) was compared with a fat reduced diet (diet B, 35% energy from fat, P:S ratio 0·5) and with a further fat modified diet supplemented with fibre (diet C, 27% energy from fat, P:S ratio 1·0). Daily intake of meat and meat products (180 g/day) was the same in each dietary period; that in diet A had a fat content typical of the average British diet, whereas that in diets B and C was based on very lean meat and meat products. During consumption of diet B the plasma cholesterol concentration fell by 8·6% and low density lipoprotein cholesterol by 11%. During consumption of diet C plasma cholesterol fell by 18·5% and low density lipoprotein cholesterol by 23·8%. Triglyceride and high density lipoprotein cholesterol concentrations and body weight did not change appreciably during the study.A modified diet including a moderate amount of lean meat and meat products is compatible with a reduced lipoprotein mediated risk of atherosclerotic heart disease. 相似文献
4.
RS Fisher 《The Journal of general physiology》1977,69(5):571-604
When the outer surface of short-circuited frog skin was penetrated with microelectrodes, stable negative potentials that averaged near -100 mV were recorded consistently, confirming the results of Nagel (W. Nagel. 1975. Abstracts of the 5th International Biophysics Congress, Copenhagen. P-147.). The appearance of these stable potentials, V(O), concurrent with the observations that (a) a high resistance outer barrier R(O) accounting for approximately 75 percent or more of the transcellular resistance of control skins had been penetrated and that (b) 10(-5) M amiloride and reduced [Na] outside caused the values of V(O) to increase towards means value near -130 mV while the values of percent R(O) increased to more than 90 percent. It was of relationships were the same as the values of E(1) observed in studies of the current-voltage relationships were the same as the values of E’(1) defined as the values of voltage at the inner barrier when the V(O) of the outer barrier was reduced to zero by voltage clamping of the skins. Accordingly, these data are interpreted to mean that the values of E(1), approximately 130 mV, represent the E(Na) of the sodium pump at the inner barrier. 2,4-DNP was observed to decrease the values of transepithelial voltage less than E(1) the V(O) was negative. These data can be interpreted with a simple electrical equivalent circuit of the active sodium transport pathway of the frog skin that includes the idea that the outer membrane behaves as an electrical rectifier for ion transport. 相似文献
5.
Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes 总被引:9,自引:0,他引:9 下载免费PDF全文
Zhou XP Woodford-Richens K Lehtonen R Kurose K Aldred M Hampel H Launonen V Virta S Pilarski R Salovaara R Bodmer WF Conrad BA Dunlop M Hodgson SV Iwama T Järvinen H Kellokumpu I Kim JC Leggett B Markie D Mecklin JP Neale K Phillips R Piris J Rozen P Houlston RS Aaltonen LA Tomlinson IP Eng C 《American journal of human genetics》2001,69(4):704-711
Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype. 相似文献
6.
Genomewide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays 总被引:5,自引:0,他引:5 下载免费PDF全文
Sellick GS Longman C Tolmie J Newbury-Ecob R Geenhalgh L Hughes S Whiteford M Garrett C Houlston RS 《Nucleic acids research》2004,32(20):e164
Genomewide linkage searches aimed at identifying disease susceptibility loci are generally conducted using 300–400 microsatellite markers. Genotyping bi-allelic single nucleotide polymorphisms (SNPs) provides an alternative strategy. The availability of dense SNP maps coupled with recent technological developments in highly paralleled SNP genotyping makes it practical to now consider the use of these markers for whole-genome genetic linkage analyses. Here, we report the findings from three successful genomewide linkage analyses of families segregating autosomal recessively inherited neonatal diabetes, craniosynostosis and dominantly inherited renal dysplasia using the Affymetrix 10K SNP array. A single locus was identified for each disease state, two of which are novel. The performance of the SNP array, both in terms of efficiency and precision, indicates that such platforms will become the dominant technology for performing genomewide linkage searches. 相似文献
7.
Paula H Suss Luiz Guilherme A Capriglione Fabiane Barchiki Lye Miyague Danielle Jackowski Letícia Fracaro Andressa V Schittini Alexandra C Senegaglia Carmen LK Rebelatto Márcia Olandoski Alejandro Correa Paulo RS Brofman 《Experimental biology and medicine (Maywood, N.J.)》2015,240(7):969-978
The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of cardiovascular disease, which produces high rates of morbidity and mortality. A therapeutic option that has emerged in the last decade is cell therapy. The aim of this study was to compare the effect of transplanting human umbilical cord-derived stromal cells (UCSCs), human umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat model. IC was induced by left coronary artery ligation, and baseline echocardiography was performed seven days later. Animals with a left ventricular ejection fraction (LVEF) of ≤40% were selected for the study. On the ninth day after IC was induced, the animals were randomized into the following experimental groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after treatment, an echocardiographic analysis was performed, followed by euthanasia. The animals in all of the cell therapy groups, regardless of the cell type transplanted, had less collagen deposition in their heart tissue and demonstrated a significant improvement in myocardial function after IC. Furthermore, there was a trend of increasing numbers of blood vessels in the infarcted area. The median value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for cellular cardiomyoplasty and can be an effective therapy for improving cardiac function following IC. 相似文献
8.
Marc Y. R. Henrion Mark P. Purdue Ghislaine Scelo Peter Broderick Matthew Frampton Alastair Ritchie Angela Meade Peng Li James McKay Mattias Johansson Mark Lathrop James Larkin Nathaniel Rothman Zhaoming Wang Wong-Ho Chow Victoria L. Stevens W. Ryan Diver Demetrius Albanes Jarmo Virtamo Paul Brennan Timothy Eisen Stephen Chanock Richard S. Houlston 《PloS one》2015,10(3)
So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (P
combined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; P
combined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation. 相似文献
9.
10.
Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The
repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently
diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted
to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes
and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder
may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of
extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical
aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate
with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major
histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune
B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize
the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies
in normal individuals. 相似文献