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341.
Shin JM Vagin O Munson K Kidd M Modlin IM Sachs G 《Cellular and molecular life sciences : CMLS》2008,65(2):264-281
Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration;
therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor
were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell
hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are
the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities.
Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of
a novel class of agents, the acid pump antagonists.
Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007 相似文献
342.
Hochrainer K Kroismayr R Baranyi U Binder BR Lipp J 《Cellular and molecular life sciences : CMLS》2008,65(13):2105-2117
Small HERC proteins are defined by the presence of one RCC1-like domain and a HECT domain. Having evolved out of one common ancestor, the four members of the family exhibit a high degree of homology in genomic organization and amino acid sequence, thus it seems possible that they might accomplish similar functions. Here we show that small HERC proteins interact with each other and localize to the same cellular structures, which we identify as late endosomes and lysosomes. We demonstrate interaction of HERC3 with the ubiquitin-like proteins hPLIC-1 and hPLIC-2 and we establish interaction of HERC5 with the metastasis suppressor Nm23B. While hPLIC proteins are not ubiquitinated by HERC3, HERC5 plays an important role in ubiquitination of Nm23B. In summary, although small HERC proteins are highly homologous showing the same subcellular distribution, they undergo different molecular interactions. 相似文献
343.
344.
Galanin – 25 years with a multitalented neuropeptide 总被引:1,自引:0,他引:1
Galanin, a neuropeptide widely expressed in the central and peripheral nervous systems and in the endocrine system, has been shown to regulate numerous physiological and pathological processes through interactions with three G-protein-coupled receptors, GalR1 through GalR3. Over the past decade, some of the receptor subtype-specific effects have been elucidated through pharmacological studies using subtype selective ligands, as well as through molecular approaches involving knockout animals. In the present review, we summarize the current data which constitute the basis of targeting GalR1, GalR2 and GalR3 for the treatment of various human diseases and pathological conditions, including seizure, Alzheimer's disease, mood disorders, anxiety, alcohol intake in addiction, metabolic diseases, pain and solid tumors. 相似文献
345.
Richards JB Yuan X Geller F Waterworth D Bataille V Glass D Song K Waeber G Vollenweider P Aben KK Kiemeney LA Walters B Soranzo N Thorsteinsdottir U Kong A Rafnar T Deloukas P Sulem P Stefansson H Stefansson K Spector TD Mooser V 《Nature genetics》2008,40(11):1282-1284
We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)). 相似文献
346.
347.
Scott RH Douglas J Baskcomb L Huxter N Barker K Hanks S Craft A Gerrard M Kohler JA Levitt GA Picton S Pizer B Ronghe MD Williams D;Factors Associated with Childhood Tumours 《Nature genetics》2008,40(11):1329-1334
Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor. 相似文献
348.
The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism
Dieterich C Clifton SW Schuster LN Chinwalla A Delehaunty K Dinkelacker I Fulton L Fulton R Godfrey J Minx P Mitreva M Roeseler W Tian H Witte H Yang SP Wilson RK Sommer RJ 《Nature genetics》2008,40(10):1193-1198
Here we present a draft genome sequence of the nematode Pristionchus pacificus, a species that is associated with beetles and is used as a model system in evolutionary biology. With 169 Mb and 23,500 predicted protein-coding genes, the P. pacificus genome is larger than those of Caenorhabditis elegans and the human parasite Brugia malayi. Compared to C. elegans, the P. pacificus genome has more genes encoding cytochrome P450 enzymes, glucosyltransferases, sulfotransferases and ABC transporters, many of which were experimentally validated. The P. pacificus genome contains genes encoding cellulase and diapausin, and cellulase activity is found in P. pacificus secretions, indicating that cellulases can be found in nematodes beyond plant parasites. The relatively higher number of detoxification and degradation enzymes in P. pacificus is consistent with its necromenic lifestyle and might represent a preadaptation for parasitism. Thus, comparative genomics analysis of three ecologically distinct nematodes offers a unique opportunity to investigate the association between genome structure and lifestyle. 相似文献
349.
Kao WH Klag MJ Meoni LA Reich D Berthier-Schaad Y Li M Coresh J Patterson N Tandon A Powe NR Fink NE Sadler JH Weir MR Abboud HE Adler SG Divers J Iyengar SK Freedman BI Kimmel PL Knowler WC Kohn OF Kramp K Leehey DJ Nicholas SB Pahl MV Schelling JR Sedor JR Thornley-Brown D Winkler CA Smith MW Parekh RS;Family Investigation of Nephropathy Diabetes Research Group 《Nature genetics》2008,40(10):1185-1192
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. 相似文献
350.
Stacey SN Gudbjartsson DF Sulem P Bergthorsson JT Kumar R Thorleifsson G Sigurdsson A Jakobsdottir M Sigurgeirsson B Benediktsdottir KR Thorisdottir K Ragnarsson R Scherer D Rudnai P Gurzau E Koppova K Höiom V Botella-Estrada R Soriano V Juberías P Grasa M Carapeto FJ Tabuenca P Gilaberte Y Gudmundsson J Thorlacius S Helgason A Thorlacius T Jonasdottir A Blondal T Gudjonsson SA Jonsson GF Saemundsdottir J Kristjansson K Bjornsdottir G Sveinsdottir SG Mouy M Geller F Nagore E Mayordomo JI 《Nature genetics》2008,40(11):1313-1318
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers. 相似文献