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排序方式: 共有4811条查询结果,搜索用时 10 毫秒
41.
Grant R. Sutherland Elizabeth Baker Antonio Fratini John M. Opitz James F. Reynolds 《American journal of medical genetics. Part A》1985,22(2):433-443
Folate sensitive fragile sites on human chromosomes have been found to be inducible in cultured lymphocytes by high levels of thymidine but not by high levels of BrdU. The biochemical interpretation of events leading to fragile site expression has been revised since it is now clear that low levels of either thymidylate or deoxycytidine triphosphate will result in this phenomenon. A model for the DNA at a fragile site, composed of alternating repeating polypurine/polypyrimidine sequences is proposed. 相似文献
42.
Robyn M. Sutherland Stephen Brassell Qiang Liu Yvonne Paterson 《European journal of immunology》1995,25(7):1810-1814
Heme is a non-protein autoantigen which is ubiquitous in vivo, primarily complexed in various hemoproteins or bound to specialized carrier molecules. Nevertheless, heme is able to stimulate a high frequency of CD4+, class II-restricted T cells, freshly explanted from unprimed mice, to proliferate in vitro. In this study, we show that heme incorporated into various species of mammalian cytochrome c (cyt c), including murine cyt c, represents a facultative cryptic determinant, able to be recalled only at high doses of native cyt c. By contrast, avian cyt c is of comparable antigenicity to free heme. Artificially denatured carboxymethylated (CM) mammalian cyt c exhibited greatly increased antigenicity, comparable to that of heme and avian cyt c, indicating that the crypticity of heme in native mammalian cyt c is due to the resistance of the native conformation of this molecule to antigen processing within murine antigen-presenting cells. Thus, tolerance to the heme group of at least some hemoproteins, may be maintained by the crypticity of the heme, rather than by deletion of hemereactive T cells. Given the high frequency of heme-reactive T cells in unprimed mice, these findings suggest that heme may become an important modulator during an inflammatory response. 相似文献
43.
doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH) 总被引:12,自引:0,他引:12
des Portes V; Francis F; Pinard JM; Desguerre I; Moutard ML; Snoeck I; Meiners LC; Capron F; Cusmai R; Ricci S; Motte J; Echenne B; Ponsot G; Dulac O; Chelly J; Beldjord C 《Human molecular genetics》1998,7(7):1063-1070
Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical
dysgenesis disorder associated with a defect in neuronal migration.
Clinical manifestations are epilepsy and mental retardation. This disorder,
which mainly affects females, can be inherited in a single pedigree with
lissencephaly, a more severe disease which affects the male individuals.
This clinical entity has been described as X- SCLH/LIS syndrome. Recently
we have demonstrated that the doublecortin gene, which is localized on the
X chromosome, is implicated in this disorder. We have now performed a
systematic mutation analysis of doublecortin in 11 unrelated females with
SCLH (one familial and 10 sporadic cases) and have identified mutations in
10/11 cases. The sequence differences include nonsense, splice site and
missense mutations and these were found throughout the gene. These results
provide strong evidence that loss of function of doublecortin is the major
cause of SCLH. The absence of phenotype-genotype correlations suggests that
X-inactivation patterns of neuronal precursor cells are likely to
contribute to the variable clinical severity of this disorder in females.
相似文献
44.
GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies 总被引:11,自引:0,他引:11
Dibbens LM Feng HJ Richards MC Harkin LA Hodgson BL Scott D Jenkins M Petrou S Sutherland GR Scheffer IE Berkovic SF Macdonald RL Mulley JC 《Human molecular genetics》2004,13(13):1315-1319
A major challenge in understanding complex idiopathic generalized epilepsies has been the characterization of their underlying molecular genetic basis. Here, we report that genetic variation within the GABRD gene, which encodes the GABAA receptor delta subunit, affects GABA current amplitude consistent with a model of polygenic susceptibility to epilepsy in humans. We have found a GABRD Glu177Ala variant which is heterozygously associated with generalized epilepsy with febrile seizures plus. We also report an Arg220His allele in GABRD which is present in the general population. Compared with wild-type receptors, alpha1beta2Sdelta GABAA receptors containing delta Glu177Ala or Arg220His have decreased GABAA receptor current amplitudes. As GABAA receptors mediate neuronal inhibition, the reduced receptor current associated with both variants is likely to be associated with increased neuronal excitability. Since delta subunit-containing receptors localize to extra- or peri-synaptic membranes and are thought to be involved in tonic inhibition, our results suggest that alteration of this process may contribute to the common generalized epilepsies. 相似文献
45.
Stein TP; Oram-Smith JC; Leskiw MJ; Wallace HW; Long LC; Leonard JM 《The American journal of physiology》1976,230(5):1321-1325
46.
Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases 总被引:4,自引:5,他引:4
Preimplantation genetic diagnosis was performed in 61 day 3 embryos
obtained by in-vitro fertilization from seven patient carriers of
haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia
pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa,
and FG syndrome, which is characterized by mental retardation and
hypotonia. After multiplex polymerase chain reaction, 16 embryos were
diagnosed as being unaffected, and these were transferred to the uterus on
the following day (day 4). Of these embryos, six (37.5%) implanted,
resulting in the delivery of a singleton and a twin pregnancy, a late
second trimester miscarriage (twins at week 20) and a first trimester
miscarriage at week 8. All the diagnoses were confirmed by amniocentesis.
We report for the first time a late day 4 transfer of biopsied human
embryos undergoing preimplantation genetic diagnosis. This transfer
schedule allows an extra day to perform genetic analyses on single
blastomeres and to monitor any adverse effect of the biopsy procedure.
相似文献
47.
Marjolijn Bornebroek Joost Haan Marion LC Maat-Schieman Sjoerd G Van Duinen Raymund AC Roos 《Brain pathology (Zurich, Switzerland)》1996,6(2):111-114
Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
48.
The question of whether prolonged stimulation of the lateral hypothalamic area (LH) simply diminishes in rewarding effect or becomes aversive was tested in 32 rats using a taste preference technique. The animals were allowed to drink novel, coffee-flavoured water for 10 min, and then received 60 trains of LH stimulation with differing durations, at an intensity proven to be rewarding at 0.5 sec duration. In a test 24 hours later, those animals that had been stimulated with 1 or 5 sec trains showed a shift in preference from tap water to coffee water, but those stimulated with 10 sec trains did not. The results show that prolonged stimulation not only loses its positive reinforcement effect but becomes negative. 相似文献
49.
E N Ellis S M Mauer D E Sutherland M W Steffes 《Laboratory investigation; a journal of technical methods and pathology》1989,60(2):231-236
Knowledge of quantitative glomerular structure in normal man is limited. At the time of renal transplantation, 28 living-related normal kidney donors had renal biopsies performed. Tissue was processed for light and electron microscopy using standard techniques. Standard stereologic techniques were used to determine mean glomerular volume, capillary length density, fractional volumes of mesangium and capillary lumen, surface densities of the peripheral capillary, mesangial-epithelium interface, and the lumenal-mesangial interface. Volume of total mesangium/glomerulus, capillary lumenal volume/glomerulus, peripheral capillary filtration surface/glomerulus, capillary mesangial-epithelial surface/glomerulus, capillary lumenal-mesangial surface/glomerulus, capillary length/glomerulus, and average capillary diameter were calculated. There were no significant differences between males and females in any structural parameter. There were no significant correlations between age or body surface area and any structural parameter. In comparison with these normal values, previously reported diabetic patients with clinical nephropathy demonstrate markedly expanded mesangial volume/glomerulus and a diminished filtration surface/glomerulus. The availability of these normal values will allow comparison with functional data in normal humans and greater understanding of human glomerular disease. 相似文献
50.
A L Clayton U Beckford C Roberts S Sutherland A Druce J Best S Chantler 《Journal of medical virology》1985,17(3):275-282
A rapid simultaneous enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies was investigated for herpes simplex virus (HSV) detection. All HSV isolated (n = 127) were detected, whereas no response was obtained with HSV negative preparations. Equivalent results were obtained from 275 of 277 clinical specimens in the monoclonal ELISA and in an ELISA using polyclonal antibodies, confirming that appropriately selected monoclonal antibodies may be as efficacious as polyclonal antibodies in antibody-based assays. In clinical specimens, the rate of HSV detection (sensitivity) relative to tissue culture isolation was low for both assays, and the major factor responsible for this was the low concentration of virus present in some specimens. The sensitivity of ELISA obtained in routine use varied with different panels of unselected specimens and was related to the speed of development of the cytopathic effect. These results emphasise the need for caution in assigning a definitive sensitivity level to ELISA tests evaluated on different panels of specimens. 相似文献