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Raj P. Kapur Ian Neilson Robert M.W. Hofstra Lynda W. Holloway Ron C. Michaelis Kathleen A. Leppig 《American journal of medical genetics. Part A》2002,108(1):51-56
Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM‐mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease–associated gene to cause intestinal aganglionosis. © 2002 Wiley‐Liss, Inc. 相似文献
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Glyceraldehyde-3-phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell death 下载免费PDF全文
Akira Sawa Adil A. Khan Lynda D. Hester Solomon H. Snyder 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(21):11669-11674
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein levels increase in particulate fractions in association with cell death in HEK293 cells, S49 cells, primary thymocytes, PC12 cells, and primary cerebral cortical neuronal cultures. Subcellular fractionation and immunocytochemistry reveal that this increase primarily reflects nuclear translocation. Nuclear GAPDH is tightly bound, resisting extraction by DNase or salt treatment. Treating primary thymocytes, PC12 cells, and primary cortical neurons with antisense but not sense oligonucleotides to GAPDH prevents cell death. Because cell-death-associated nuclear translocation of GAPDH and antisense protection occur in multiple neuronal and nonneuronal systems, we propose that GAPDH is a general mediator of cell death and uses nuclear translocation as a signaling mechanism. 相似文献
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Allergy to laboratory animals: a follow up study of its incidence and of the influence of atopy and pre-existing sensitisation on its development. 总被引:1,自引:1,他引:0 下载免费PDF全文
P A Botham C T Lamb E L Teasdale S M Bonner J A Tomenson 《Occupational and environmental medicine》1995,52(2):129-133
OBJECTIVES--To investigate the incidence of allergy to laboratory animals (ALA) during the first two years of employment, and to study the effect on ALA of atopy and sensitisation. METHODS--A follow up prospective study of ALA at the Zeneca (formerly ICI) Research Laboratories. RESULTS--The incidence of the disease during the first year of employment has remained at about 10% since the mid-1980s. This compares with an incidence of 37% in the early 1980s. The reduction in incidence and its maintenance at a lower level is thought to be due to the introduction and management of improved engineering controls, working practices, and educational programmes designed to reduce exposure to allergens from laboratory animals. The underlying incidence of immunological sensitisation to animals (the presence of immunoglobulin E (IgE) antibodies to animal allergens) is much higher (40% after one and 53% after two years of exposure). Both atopic diathesis and presensitisation to laboratory animals increased the likelihood that a person would develop ALA. CONCLUSION--Neither factor predicted the disease accurately so their use should be restricted to the identification of people who may be more susceptible to the development of ALA (and thus who may need to pay particular attention to the use of personal protective equipment) rather than to their exclusion. 相似文献
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Patients' perceptions of their clinical interactions: development of the multidimensional desire for control scales 总被引:2,自引:0,他引:2
Anderson Lynda A.; DeVellis Robert F.; Boyles Barbara; Feussner John R. 《Health education research》1989,4(3):383-397
Interventions oriented toward enhancing patient-provider communicationwill benefit from having a satisfactory measure of patientsdesires for control in clinical interactions. Findings fromtwo studies are reported describing the development and validationof the Multidimensional Desire for Control (MDC) Scales. A totalof 160 patients with non-insulin-dependent diabetes (NIDDM)participated in the first study, which was designed to developand validate a measure of patients desires for control.Factor analysis yielded three subscales reflecting patientsdesires for: (i) personal, (ii) clinician, and (ii) shared controlin the interaction. Alphas for the three subscales were high( 0.750.86). Correlations with other measures of controlwere suggestive of good construct validity. The second investigationinvolves a replication study verifying the factorial compositionand validity of the scales. An independent sample of 109 patientswith NIDDM participated in this study. Findings support thereliability of the subscales (0.750.81). Furthermore,patients desires for control were significantly associatedwith patient satisfaction, with desire for personal controlnegatively related to patient satisfaction (r = 0.30,0.41, affective and behavioural dimensions, respectively)and desire for clinician control positively related to satisfaction(r = 0.44, 0.28, 0.31, affective, behavioral, and cognitivedimensions, respectively). 相似文献
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Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells 总被引:28,自引:0,他引:28
A family of five cholinergic muscarinic receptor genes (m1, m2, m3, m4, and m5) has recently been identified and cloned. In order to investigate the pharmacological properties of the individual muscarinic receptors, we have transfected each of these genes into Chinese hamster ovary cells (CHO-K1) and have established stable cell lines expressing each receptor. In the present study we have examined the antagonist binding properties of each muscarinic receptor. Antagonists were chosen that had previously been proposed to be selective for muscarinic receptor subtypes and included pirenzepine, AF-DX 116, methoctramine, dicyclomine, hexohydrodifenidol, hexahydrosiladifenidol, hexocyclium, and silahexocyclium. m1, m2, and m3 receptors express binding properties similar to those expected of high affinity pirenzepine-type receptors of cerebral cortex ("M1"), low affinity pirenzepine-type receptors of atria ("M2 cardiac type"), and the intermediate affinity pirenzepine-type receptors found in exocrine glands ("M2 glandular type"), respectively. The M1/M2 schema cannot readily accommodate the binding properties of the m4 and m5 receptors. Pirenzepine, methoctramine, and hexahydrosiladifenidol were the most selective agents for the m1, m2, and m3 receptors, respectively. None of the antagonists used in this study were uniquely selective for either the m4 or m5 receptors. The diverse binding profiles of individual cloned receptors and the widespread distribution of m1-m4 mRNAs indicate that radioligand binding studies performed on primary tissues may actually be assessing the composite properties of a heterogeneous mixture of muscarinic receptor subtypes. 相似文献