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排序方式: 共有59条查询结果,搜索用时 15 毫秒
1.
Mapping the Von Hippel -- Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis 总被引:3,自引:0,他引:3
Richards Frances M.; Phipps Maude E.; Latlf Farida; Yao Masahlro; Crossey Paul A.; Foster Kelth; Llnehan W. Marston; Affara Nabeel A.; Lerman Michael I.; Zbar Berton; Ferguson-Smith Malcolm A.; Maher Eamonn R. 《Human molecular genetics》1993,2(7):879-882
Von HlppelLindau (VHL) disease is a dominantly Inheritedfamillal cancer syndrome In which affected individuals havea greatly increased predisposition to the development of haemangloblastomasof the central nervous system and retina, renal cell carcinomaand phaeochromocytoma. The VHL gene has been mapped to chromosome3p25 -p26 by genetic linkage studies and we have previouslydemonstrated that the VHL gene is tightly linked to the D3S601locus (Zmax = 18.86 at 相似文献
2.
3.
Montagnese S Schiff S De Rui M Crossey MM Amodio P Taylor-Robinson SD 《Journal of viral hepatitis》2012,19(5):307-315
Neuropsychological assessment has three main applications in clinical hepatology: (i) to detect, grade and monitor liver failure-related cognitive alterations in end-stage liver disease (hepatic encephalopathy), (ii) to substantiate complaints of attention or concentration difficulties in patients with non-cirrhotic chronic hepatitis C viral infection, and (iii) to screen patients who are being considered for liver transplantation for early signs of dementia. However, there is limited agreement on how cognitive assessment should be conducted in these patients, and how results should be interpreted and used to implement clinical decisions. In this review, we summarize the available literature on neuropsychological dysfunction in patients with cirrhosis and with chronic hepatitis C viral infection and provide some guidance on how to utilize neuropsychological assessment in practice. 相似文献
4.
K. Foster P. A. Crossey P. Cairns J. W. Hetherington F. M. Richards M. H. Jones E. Bentley N. A. Affara M. A. Ferguson-Smith E. R. Maher 《British journal of cancer》1994,69(2):230-234
To investigate the role of tumour-suppressor genes on the short arm of chromosome 3 in the mechanism of tumorigenesis in non-familial renal cell carcinoma, we analysed 55 paired blood-tumour DNA samples for allele loss on chromosome 3p and in the region of known or putative tumour-suppressor genes on chromosomes 5, 11, 17 and 22. Sixty-four per cent (35/55) of informative tumours showed loss of heterozygosity (LOH) of at least one locus on the short arm of chromosome 3, compared with only 13% at the p53 tumour-suppressor gene and 6% at 17q21. LOH at chromosome 5q21 and 22q was uncommon (2-3%). Detailed analysis of the regions of LOH on chromosome 3p suggested that, in addition to the VHL gene in chromosome 3p25-p26, mutations in one or more tumour-suppressor genes in chromosome 3p13-p24 may be involved in the pathogenesis of sporadic renal cell carcinoma (RCC). We also confirmed previous suggestions that chromosome 3p allele loss is not a feature of papillary RCC (P < 0.05). 相似文献
5.
Glew RH Cole DM Mehla GS El-Nafaty AU Crossey MJ Tzamaloukas A VanderJagt DJ 《Clinica chimica acta; international journal of clinical chemistry》2005,353(1-2):95-101
BACKGROUND: The incidence of preeclampsia is high in northern Nigeria, as it is in many other developing countries, and preeclampsia is associated with significant maternal and fetal morbidity and mortality. We inquired if proteinuria or hypertension alone could account for the altered concentrations of urinary lysosomal hydrolases that have been reported in preeclamptic women and pregnant women without preeclampsia. METHODS: The activities of urinary beta-hexosaminidase and beta-galactosidase were determined fluorometrically in pregnant women assigned to one of four groups: Group I: 41 preeclamptic women; Group II: 31 hypertensive aproteinuric women; Group III: 44 normotensive proteinuric women; and Group IV: 52 healthy pregnant women (controls). RESULTS: The urinary beta-hexosaminidase concentrations were decreased in the preeclamptic women (P<0.005) and proteinuric women (P<0.001) when compared to the healthy pregnant controls. There was no significant difference in beta-hexosaminidase concentrations between the hypertensive women and the healthy pregnant controls. The urinary beta-galactosidase concentrations for preeclamptic, hypertensive, and proteinuric women did not differ significantly versus healthy pregnant controls. CONCLUSIONS: The reduced urinary excretion of beta-hexosaminidase in preeclamptic women is associated with proteinuria, but not hypertension. Measuring urinary concentrations of lysosomal hydrolases alone or in conjunction with urinary protein concentrations is not likely to be useful in predicting or monitoring the clinical course of preeclampsia; however, it might prove important in gaining a more complete understanding of the pathogenesis of renal tubular epithelial cell injury and proteinuria that occurs in preeclampsia. 相似文献
6.
Wheatcroft SB Shah AM Li JM Duncan E Noronha BT Crossey PA Kearney MT 《Diabetes》2004,53(10):2645-2652
Type 2 diabetes is preceded by years of insulin resistance and is characterized by reduced bioavailability of the antiatherosclerotic signaling molecule nitric oxide (NO) and premature atherosclerosis. The relationship between resistance to the glucoregulatory actions of insulin and its effects on the vasculature (in particular NO-dependent responses) is poorly characterized. We studied this relationship in mice heterozygous for knockout of the insulin receptor (IRKO), which have a mild perturbation of insulin signaling. Male heterozygous IRKO mice aged 8-12 weeks were compared with age- and sex-matched littermates. IRKO mice had fasting blood glucose, insulin, free fatty acid, and triglyceride levels similar to those of wild-type mice. Intraperitoneal glucose and insulin tolerance tests were also similar in the two groups. Insulin levels in response to a glucose load were approximately twofold higher in IRKO compared with wild-type mice (1.08 +/- 0.11 vs. 0.62 +/- 0.13 ng/ml; P = 0.004). Despite this mild metabolic phenotype, IRKO mice had increased systolic blood pressure (124 +/- 4 vs. 110 +/- 3 mmHg; P = 0.01). Basal NO bioactivity, assessed from the increase in tension of phenylephrine preconstricted aortic rings in response to the NO synthase inhibitor N(G)-monomethyl-l-arginine, was reduced in IRKO (61 +/- 14 vs. 152 +/- 30%; P = 0.005). Insulin-mediated NO release in aorta, assessed as the reduction in phenylephrine constrictor response after insulin preincubation, was lost in IRKO mice (5 +/- 8% change vs. 66 +/- 9% reduction in wild-type; P = 0.03). Insulin-stimulated aortic endothelial NO synthase phosphorylation was also significantly blunted in IRKO mice (P < 0.05). These data demonstrate that insulin-stimulated NO responses in the vasculature are exquisitely sensitive to changes in insulin-signaling pathways in contrast to the glucoregulatory actions of insulin. These findings underscore the importance of early intervention in insulin-resistant states, where glucose homeostasis may be normal but substantial abnormalities of the vascular effects of insulin may already be present. 相似文献
7.
Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice 总被引:12,自引:0,他引:12
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IGF binding protein-1 (IGFBP-1) is a secretory product of decidualized endometrium and a major constituent of amniotic fluid. It is thought to modulate the actions of the IGFs on trophoblast cells and is therefore potentially important in regulating placental development and fetal growth. To investigate this hypothesis, we have studied the effects of decidual IGFBP-1 excess on fetoplacental growth in transgenic mice overexpressing human IGFBP-1. Endogenous fetal IGFBP-1 overexpression is associated with a transient impairment of fetal growth in midgestation. Maternal decidual IGFBP-1 excess is also associated with impaired fetal growth in midgestation independent of fetal genotype, indicating placental insufficiency. Our data also demonstrate that amniotic fluid IGFBP-1 is derived almost exclusively from maternal sources. Decidual IGFBP-1 overexpression has a marked effect on placental development. Placental morphology is abnormal in transgenic females due to altered trophoblast invasion and differentiation. These changes result in an increase in placental mass throughout pregnancy. This study provides the first compelling in vivo evidence that IGFBP-1 plays a role in placentation and suggests that IGFBP-1 has a pathological role in preeclampsia, a disorder characterized by shallow uterine invasion and altered placental development. 相似文献
8.
Genetic linkage between Von Hippel--Lindau disease and three microsatellite polymorphisms refines the localisation of the VHL locus 总被引:5,自引:0,他引:5
Crossey P.A.; Maher E.R.; Jones M.H.; Richards F.M.; Latif F.; Phipps M.E.; Lush M.; Foster K.; Tory K.; Green J.S.; Oostra B.; Yates J.R.W.; Linehan W.M.; Affara N.A.; Lerman M.; Zbar B.; Nakamura Y.; Ferguson-Smith M.A. 《Human molecular genetics》1993,2(3):279-282
Von HippelLindau (VHL) disease is a dominantly inheritedfamilial cancer syndrome characterised by the development ofretinal and central nervous system haemangioblastomas, renalcell carcinoma and phaeochromocytoma. The gene for VHL diseasehas been mapped to chromosome 3p25p26 and presymtomaticdiagnosis using linked DNA markers is available. We have previouslymapped the VHL disease gene to a 4 cM interval between D3S1250and D3S18. To increase access to presymptomatic diagnosis andto accelerate progress towards isolating the VHL disease genewe attempted to identify microsatellite DNA markers linked tothe disease gene by genetic linkage analysis in 29 families.We found significant linkage between the VHL disease gene anddinucleotide (CA) repeat polymorphisms at D3S1038 (Zmax = 22.24at 相似文献
9.
Detailed mapping of germline deletions of the von Hippel--Lindau disease tumour suppressor gene 总被引:1,自引:0,他引:1
Richards Frances M.; Crossey Paul A.; Phlpps Maude E.; Foster Keith; Latif Farida; Evans Gareth; Sampson Julian; Lerman Michael I.; Zbar Berton; Affara Nabeel A.; Ferguson-Smith Malcolm A.; Maher Eamonn R. 《Human molecular genetics》1994,3(4):595-598
Von Hlppel-Llndau disease is a domlnantly Inherited familialcancer syndrome characterised by the development of retinalangiomatosis, cerebellar and spinal hemangloblastoma, renalcell carcinoma, phaeochromocytoma and pancreatic tumours. AcDNA (g7) which detects frequent genomic rearrangements in VHLdisease patients on Southern analysis, and contains the partialcoding sequence of the VHL gene has been isolated recently.To characterise the nature of the genomic rearrangements inVHL disease we initially screened 116 patients with VHL diseaseand identified 22 patients (19%) with abnormal fragments InEcoR1 digested DNA probed with g7. We then established thatthe coding sequence contained within g7 is represented in 3exons, and designed exon specific probes to investigate the22 patients with genomic rearrangements. All 22 patients weredemonstrated to have germline deletions, but the deletions wereheterogeneous with 7 patients having deletions confined to the5' exon 1, and 8 with non-overlapping deletions of exon 3. In7 unrelated patients, including 2 new mutations, the germilnedeletions were similar in size and position. There was no relationshipbetween the clinical phenotype and the deletion of individualexons. Although phaeochromocytoma was less frequent in kindredswith germllne deletions than those without detectable deletions,the difference was not statistically significant (1/19 versus16/72 respectively, x2 = 1.84 p<0.1). 相似文献
10.
Joshua Tognarelli Nimzing G. Ladep Mary M. E. Crossey Edith Okeke Mary Duguru Edmund Banwat Simon D. Taylor-Robinson 《Nigerian medical journal》2015,56(4):231-235
Hepatocellular carcinoma (HCC) exhibits a huge disease burden on West Africa, with a large proportion of all HCC cases worldwide occurring in the sub-region. The high HCC prevalence is due to the endemicity of a number of risk factors, most notably hepatitis B, C and HIV. West African HCC also displays a poor prognosis. Generally speaking, this is owing to more aggressive tumours, late patient presentation and inadequate management. Exposure to chronic viral hepatitis, more carcinogenic West African strains of hepatitis B virus and carcinogens such as aflatoxin B1 all encourage tumour growth. Lack of patient confidence in the healthcare system contributes to poor health-seeking behaviors and management of the disease can be lacking, due in part to poor health infrastructure, resources available and lack of access to expensive treatment. There is also much we do not know about West African HCC, especially the effect rising obesity and alcohol use may have on this disease in the future. Suggestions for improvement are discussed, including surveillance of high-risk groups. Although there is much to be done before West African HCC is thought to be a curable disease, many steps have been taken to move in the right direction. 相似文献