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71.
Cynthia A James Donald W Hadley Neil A Holtzman Jerry A Winkelstein 《Genetics in medicine》2006,8(4):234-242
PURPOSE: While the mode of inheritance of a genetic condition has long been considered to have not only medical, but also psychosocial consequences for families, this supposition has never been tested. METHODS: We surveyed 112 members of 51 families (59% response) with chronic granulomatous disease to determine the influence of mode of inheritance on parents', siblings', and patients' (1) knowledge of inheritance and reproductive risk; (2) concern about risk to future family-members; (3) feelings of guilt and blame; and (4) feelings of stigmatization. Ninety-six members of 51 families (49% response) with Duchenne/Becker muscular dystrophy and spinal muscular atrophy types II/III were also studied. RESULTS: X-linked families had better understanding of inheritance (P < 0.001) and reproductive risks (P < 0.01). X-linked mothers worried more about risks to future generations; other autosomal-recessive family members were as worried. X-linked mothers were more likely to feel guilty (P < 0.01) and blame themselves (P < 0.001). X-linked fathers blamed their child's mother (P < 0.05) and X-linked mothers felt more blamed by the father (P < 0.01). X-linked family-members were more likely to consider being a carrier stigmatizing (P < 0.05). CONCLUSION: When providing genetic counseling, attention should be given to guilt and blame in X-linked families and understanding reproductive risks in autosomal recessive families. 相似文献
72.
Use of herbal supplements for chronic liver disease. 总被引:3,自引:0,他引:3
Cynthia Levy Leonard D Seeff Keith D Lindor 《Clinical gastroenterology and hepatology》2004,2(11):947-956
BACKGROUND & AIMS: Complementary and alternative medicine (CAM) is becoming popular among patients with liver disease. Although there is a growing body of evidence regarding potential mechanisms of action of these and other herbs, caution must be used to interpret the results of the few clinical trials available. Our goal was to discuss the biologic rationale for the use of specific herbs (silymarin, glycyrrhizin, sho-saiko-to, Phyllanthus amarus , Picrorrhiza kurroa , Compound 861, CH-100, and LIV.52) in the treatment of chronic liver diseases, as well as the evidence for their efficacy and adverse effects according to clinical trials. METHODS: Because of the relative paucity of clinical studies using herbs, every trial published in English was reviewed. RESULTS: Although many trials suggest that these herbs can decrease serum transaminase levels, the effects on hepatic histopathology and long-term survival are either poorly studied or conflicting. LIV.52 has been withdrawn from the market because of deleterious effects in patients with liver disease. CONCLUSIONS: Based on current evidence, we cannot recommend the use of herbal supplements for the routine treatment of any chronic liver disease and further well-designed clinical trials are necessary. 相似文献
73.
74.
Journal of Neurology - REM sleep abnormalities are frequently encountered in disorders with alpha-synuclein pathology including Parkinson’s disease, multiple system atrophy, and dementia with... 相似文献
75.
76.
p53 mutation and protein accumulation during multistage human esophageal carcinogenesis. 总被引:22,自引:0,他引:22
W P Bennett M C Hollstein R A Metcalf J A Welsh A He S M Zhu I Kusters J H Resau B F Trump D P Lane 《Cancer research》1992,52(21):6092-6097
Preinvasive lesions of squamous cell carcinoma are well defined morphologically and provide a model for multistage carcinogenesis. Since alterations in the p53 tumor suppressor gene occur frequently in invasive esophageal squamous cell carcinoma, we examined a set of preinvasive lesions to investigate the timing of p53 mutation. Surgically resected tissues from nine patients with esophageal squamous cell carcinoma contained precursor lesions which had not yet invaded normal tissues. Immunohistochemistry showed high levels of p53 protein in both preinvasive lesions and invasive carcinomas in six cases; sequence analysis of all invasive tumors identified p53 missense mutations in two cases. Preinvasive lesions from both tumors with mutations plus one wild-type tumor were microdissected and sequenced. In one patient there were different mutations in the invasive carcinoma (codon 282, CGGarg > TGGtrp) and a preinvasive lesion (codon 272, GTGval > T/GTGleu/val). In a second case, an invasive carcinoma had a mutation in codon 175 (CGCarg > CAChis), and adjacent preinvasive lesions contained a wild-type sequence. A carcinoma and preinvasive lesion from the third case contained high levels of protein and a wild-type DNA sequence. Therefore, p53 mutation may precede invasion in esophageal carcinogenesis, and multifocal esophageal neoplasms may arise from independent clones of transformed cells. The timing of p53 protein accumulation is favorable for an intermediate biomarker in multistage esophageal carcinogenesis. 相似文献
77.
V. Leroy Young Mary K. Seaton Christine A. Feely Cynthia Arfken Dorothy F. Edwards Carolyn M. Baum Samuel Logan 《American journal of industrial medicine》1995,27(3):419-431
On-site testing of 157 poultry processors disclosed that 50% had three or more abnormal upper extremity findings out of a total of 22 possibles. The average worker had five to six abnormal findings. Impaired pinch strength, decreased vibration sensitivity in the fingertips, and reports of current numbness were the most prevalent. Of workers with signs, 25% reported no symptoms, whereas only 8% of workers reported symptoms but had no signs. The investigators concluded that this measurement method has utility for assessments of worker populations to determine prevalence of CTDs and, potentially, for preclinical detection of these disorders to permit early intervention, reduce medical costs, and minimize disability. The need for accurate measurement to enhance early detection and prevention is discussed. 相似文献
78.
Dorsoventral patterning of the Drosophila embryo requires Nudel, a large mosaic protein with a protease domain. Previous studies have implicated Nudel's protease domain as the trigger of a proteolytic cascade that activates the Toll signaling pathway to establish dorsoventral polarity in the embryo. However, the function of other regions of Nudel has been unclear. By using two-dimensional gel electrophoresis and site-directed mutagenesis, we have obtained evidence that the N-terminal region of Nudel contains a site for glycosaminoglycan (GAG) attachment that is required for dorsoventral patterning. Disruption of this site blocks a disulfide-based association between N- and C-terminal Nudel polypeptides and proteolytic activation of Nudel's protease domain. We discuss how a GAG chain on Nudel might be required for Nudel protease activation. 相似文献
79.
Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the α2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence. 相似文献
80.
Maya Koronyo-Hamaoui Eva Gak Daniel Stein Amos Frisch Yardena Danziger Shani Leor Elena Michaelovsky Neil Laufer Cynthia Carel Silvana Fennig Marc Mimouni Alan Apter Boleslav Goldman Gad Barkai Abraham Weizman 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2004,(1):76-80
The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN. 相似文献