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21.
Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB 总被引:8,自引:1,他引:8
Levy G; Levi-Acobas F; Blanchard S; Gerber S; Larget-Piet D; Chenal V; Liu XZ; Newton V; Steel KP; Brown SD; Munnich A; Kaplan J; Petit C; Weil D 《Human molecular genetics》1997,6(1):111-116
Usher syndrome is recognized as the most frequent cause of hereditary
deaf-blindness. Usher syndrome type I (USH1), the most severe form of the
disease, is characterized by profound congenital sensorineural deafness,
constant vestibular dysfunction, and retinitis pigmentosa of prepubertal
onset. This form is genetically heterogeneous and five loci (USH1A-E) have
been mapped thusfar. However, only the gene responsible for USH1 B (which
accounts for approximately 75% of USH1 cases) has been characterized. It
encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted
2215 amino acid sequence. Primers covering the complete myosin VIIA coding
sequence as well as the 3' non coding sequence were designed, allowing
direct sequence analysis of each of the 48 coding exons and flanking splice
sites in seven patients affected by USH1. Four novel mutations were thereby
identified. The possibility should now be considered of a sequence-based
prenatal diagnosis in some of the families affected by this very severe
form of Usher syndrome.
相似文献
22.
23.
Richard Meehan Ulric Duncan Laureen Neale Gerald Taylor Harold Muchmore Nan Scott Keith Ramsey Eric Smith Paul Rock Randall Goldblum Charles Houston 《Journal of clinical immunology》1988,8(5):397-406
We investigated the effects on immune function after progressive hypobaric hypoxia simulating an ascent to 25,000 ft (7620 m) over 4 weeks. Multiple simultaneousin vitro andin vivo immunologic variables were obtained from subjects at sea level, 7500 ft (2286 m), and 25,000 ft during a decompression chamber exposure. Phytohemag-glutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells were reduced at extreme altitudes. Mononuclear-cell subset analysis by flow cytometry disclosed an increase in monocytes without changes in B cells or T-cell subsets. Plasma IgM and IgA but not IgG levels were increased at altitudes, whereas pokeweed mitogen-stimulatedin vitro IgG, IgA, and IgM secretion was unchanged. During exposure to 25,000 ft,in vitro phytohemagglutinin-stimulated interferon production and natural killer-cell cytotoxicity did not change statistically, but larger intersubject differences occurred. IgA and lysozyme levels (nasal wash) and serum antibodies to nuclear antigens were not influenced by altitude exposure. These results suggest that T-cell activation is blunted during exposure to severe hypoxemia, whereas B-cell function and mucosal immunity are not. Although the mechanism of alteredin vitro immune responsiveness after exposure to various environmental stressors has not been elucidated in humans, hypoxia may induce alterations in immune regulation as suggested byin vitro immune assays of effector-cell function.Some of this study's results were presented as an abstract at the FASEB meeting in St. Louis, Missouri, 1986. 相似文献
24.
25.
26.
Posthuma D de Geus EJ Neale MC Hulshoff Pol HE Baaré WEC Kahn RS Boomsma D 《Behavior genetics》2000,30(4):311-319
The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis. 相似文献
27.
Evolutionary silencing of the human elastase I gene (ELA1) 总被引:6,自引:0,他引:6
28.
E. Kimble T. Kowalski D. White A. Raychauduri G. Pastor H. Chertock W. Lee R. Neale A. Hamdan J. Wasley 《Inflammation research》1991,34(1-2):125-128
CGS 22745, and aralkyl hydroxamic acid, inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) synthesis in guinea pig leukocytes (IC50=0.6M). The compound did not appreciably affect cyclooxygenase (ram seminal vesicles), 12-lipoxygenase and thromboxane synthase (human platelets) or 15-lipoxygenase (human neutrophils). CGS 22745 inhibited A23187-induced formation of LTB4 in blood (IC50's of 4.3, 0.56 and 3.2 M for human, dog and rat, respectively). At 1 mg/kg i.v. in dogs, it caused 96% inhibition of A23187-stimulated LTB4 formationex vivo after 5 min. Its effective biological half-life was >160 min. In dogs at 3 and 10 mg/kg p.o., CGS 22745 inhibitedex vivo A23187-stimulated LTB4 formation at 3 hr by 48% and 97%, respectively. The inhibition persisted up to 6 hr (26% at 3 mg/kg; 49% at 10 mg/kg). CGS 22745 (3, 10 and 30 mg/kg p.o.) inhibited exudate formation, mononuclear cells and PMN accumulation in a dose-dependent manner during the late phase (48 and 72 hr) of carrageenan-induced pleurisy in the rat. 相似文献
29.
Elia M Martin S Price C Hallworth MJ Neale G 《Clinical nutrition (Edinburgh, Scotland)》1984,2(3-4):173-179
The effect of 4 days total starvation (water only) in five normal subjects on the circulating concentrations of various proteins was studied. Changes in plasma albumin and total protein concentrations were compared with those of six patients undergoing elective abdominal surgery with partial starvation and six patients undergoing orthopaedic surgery with adequate feeding - (0.126-0.146 MJ/kg/day and 1.2-1.4 g protein/kg/day). In a companion study hand grip strength was measured daily in ten normal subjects during starvation and in 18 patients undergoing surgery for hernia repair (n = 6), cholecystectomy (n = 6) and major abdominal surgery (n = 6). Starvation produced marked reductions (approximately 30%) in the circulating concentrations of retinol binding protein and prealbumin but did not significantly affect the plasma concentration of immunoglobulins (IgG, IgA, IgM) acute phase reactants (orosomucoid, haptoglobin, alpha(1) antitrypsin), albumin and total protein. On the other hand both types of elective surgery produced significant reductions in plasma albumin and total protein concentrations irrespective of feeding. Grip strength was not significantly altered by four days of starvation but surgery produced a temporary reduction in grip strength, the extent and duration of which was related to the severity of operation. This study helps to separate the effect of surgery and starvation on hand dynamometry and circulating protein concentrations and indicates their limitations as indicators of nutritional state. 相似文献
30.
R Neale 《Canadian Medical Association journal》1984,131(8):907-908
In 50 consecutive pregnant women at a 125-bed community hospital with 1000 deliveries annually, labour was induced with prostaglandin E2 administered intravaginally. There were no stillbirths or neonatal deaths, and complications in the mothers were few. In nine women (18%) oxytocin was subsequently administered because of a failure of labour to progress; in spite of this, cesarean section was required in two (4%) of the patients. The overall cesarean section rate was 6%. Prostaglandins have been used routinely to induce labour in the United Kingdom for several years. This noninvasive method is safe, effective and well received by women in a community hospital setting, including those wanting "natural childbirth". 相似文献