Showing papers by "Guy's and St Thomas' NHS Foundation Trust published in 1994"
TL;DR: The findings suggest that selective impairment of the responsiveness of the forearm vasculature to muscarinic agonists is not universal in patients with essential hypertension.
Abstract: Background Previous studies suggest that vascular endothelial function may be impaired in essential hypertension. Although muscarinic agonists dilate blood vessels by releasing an endothelium-derived relaxing factor closely related to nitric oxide, nitroprusside dilates vessels by a mechanism that is independent of the endothelium. The finding of an impaired response to muscarinic agonists but a normal response to nitroprusside in patients with hypertension has suggested that endothelial function is abnormal in hypertension. Methods We reassessed this issue by measuring forearm blood flow by plethysmography during the infusion of vasodilators into the brachial arteries of 95 subjects: 37 normotensive controls (mean [±SE] arterial blood pressure, 92 ±1 mm Hg) and 58 patients with essential hypertension (mean arterial blood pressure, 121 ±1 mm Hg). Results In an initial study, vascular responses to the vasodilators carbachol and nitroprusside were similar in normotensive controls (n = 19) and hypertensive p...
296 citations
Journal Article•
TL;DR: This study demonstrates that direct DNA diagnosis establishes the genotype at the FRAXA-FMR-1 locus, and validate the use of direct DNA testing for fragile X diagnosis as well as for carrier identification and support and complete the established relationships among the DNA results and the cytogenetic, physical, and psychological aspects of the disease.
Abstract: We report the results of a 14-center collaborative study of genotype-phenotype correlations in 318 fragile X families; these families comprised 2,253 individuals, 1,344 of whom carried a fragile X mutation and 693 of whom had a typical full fragile X mutation This study demonstrates that direct DNA diagnosis establishes the genotype at the FRAXA-FMR-1 locus There was a significantly higher prevalence of “mosaic” cases among males who carry a full mutation (12%) than among females who carry a full mutation (6%); the mosaic males had a larger expansion than did the mosaic females Mental status of premutated individuals did not differ from that of those with a normal genotype Both the abnormal methylation of the FMR-1–EagI site and the size of the expansion were highly correlated with cytogenetics, facial dysmorphism, macroorchidism, and mental retardation (MR) Among female carriers of a full mutation, those with MR had significantly larger expansion than did those without MR Among 164 independent couples, 3 unrelated husbands carried a premutation that suggests that the prevalence of fragile X premutations in the general population is ~09% of the X chromosomes Our data validate the use of direct DNA testing for fragile X diagnosis as well as for carrier identification and support and complete the established relationships among the DNA results and the cytogenetic, physical, and psychological aspects of the disease
285 citations
Journal Article•
TL;DR: Findings provide the first objective evidence for the central role of UV radiation in the development of AFX and also represent the first in vivo demonstration of solar UV-induced mutations in a human mesenchymal neoplasm.
Abstract: Atypical fibroxanthoma (AFX) is an uncommon neoplasm of the superficial soft tissue occurring in actinically damaged skin of elderly patients. Sun-exposed skin also represents the main site of squamous and basal cell carcinomas and malignant melanoma, and a key role for ultraviolet (UV) radiation in their pathogenesis has long been suspected. UV-related mutations of the p53 gene have been identified in human skin cancers. To verify whether the pathogenesis of AFX is related to the effect of sunlight, p53 protein and gene status have been investigated in a series of 10 cases of AFX. Seven of 10 showed p53 immunoreactivity in most of the neoplastic cells. Molecular analysis of the p53 gene revealed an abnormal single strand conformation polymorphism pattern in all the p53 positive cases. Polymerase chain reaction direct sequencing revealed that all the mutations involved cytosine bases. Four cases showed C to T transitions (including two CC-TT double base substitutions) and two cases showed C to G transversion. All but one mutation took place at dipyrimidine sites. These findings provide the first objective evidence for the central role of UV radiation in the development of AFX and also represent the first in vivo demonstration of solar UV-induced mutations in a human mesenchymal neoplasm.
138 citations
TL;DR: Single strand conformational polymorphism analysis failed to show any germline p53 mutations as a cause of the syndrome in this three generation family with Cowden syndrome and Lhermitte-Duclos disease.
Abstract: Cowden syndrome is an autosomal dominant condition of multiple hamartomas. Patients with this phakomatosis have an increased risk of breast cancer and thyroid tumours. Lhermitte-Duclos disease is usually a sporadic condition of cerebellar ganglion cell hypertrophy, ataxia, mental retardation, and self-limited seizure disorder. We describe a three generation family with Cowden syndrome and Lhermitte-Duclos disease. Karyotyping performed on the peripheral lymphocytes of the proband and her affected mother showed a 46,XX complement. Single strand conformational polymorphism analysis failed to show any germline p53 mutations as a cause of the syndrome in this family.
111 citations
TL;DR: A three-dimensional model for the BTK kinase domain, based on the core structure of cAMP-dependent protein kinase, was used to interpret the structural basis for disease in eight independent point mutations in patients with XLA.
Abstract: X-linked agammaglobulinemia (XLA) is a hereditary defect of B-cell differentiation in man caused by deficiency of Bruton tyrosine kinase (BTK) A three-dimensional model for the BTK kinase domain, based on the core structure of cAMP-dependent protein kinase, was used to interpret the structural basis for disease in eight independent point mutations in patients with XLA As Arg-525 of BTK has been thought to functionally substitute for a critical lysine residue in protein-serine kinases, the mutation Arg-525-->Gln was studied and found to abrogate the tyrosine kinase activity of BTK All of the eight mutations (Lys-430-->Glu, Arg-520-->Glu, Arg-525-->Gln, Arg-562-->Pro, Ala-582-->Val, Glu-589-->Gly, Gly-594-->Glu, and Gly-613-->Asp) were located on one face of the BTK kinase domain, indicating structural clustering of functionally important residues
78 citations
Journal Article•
5 citations
TL;DR: An add-on module is described for generating a beep to indicate the blood oxygen saturation which has been specifically designed to operate in the MR environment.
Abstract: Many commercially available pulse oximeters have a variable pitch blood oxygen saturation indicator, which emits a 'beep' between 175 Hz and 675 Hz with each heart beat. The frequency of this beep is dependent on the blood oxygenation measured by the oximeter, higher frequencies corresponding to higher blood saturation percentages. This is a useful feature for an anaesthetist, rapidly communicating potentially life-threatening situations in an easily detectable manner. Most available oximeters with an audio output feature are vulnerable to the effects of magnetic resonance scanning. In this article an add-on module is described for generating a beep to indicate the blood oxygen saturation which has been specifically designed to operate in the MR environment.
5 citations