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71.
72.
Gai McMichael Santhosh Girirajan Andres Moreno-De-Luca Jozef Gecz Chloe Shard Lam Son Nguyen Jillian Nicholl Catherine Gibson Eric Haan Evan Eichler Christa Lese Martin Alastair MacLennan 《European journal of human genetics : EJHG》2014,22(1):40-45
Recent studies have established the role of rare copy number variants (CNVs) in several neurological disorders but the contribution of rare CNVs to cerebral palsy (CP) is not known. Fifty Caucasian families having children with CP were studied using two microarray designs. Potentially pathogenic, rare (<1% population frequency) CNVs were identified, and their frequency determined, by comparing the CNVs found in cases with 8329 adult controls with no known neurological disorders. Ten of the 50 cases (20%) had rare CNVs of potential relevance to CP; there were a total of 14 CNVs, which were observed in <0.1% (<8/8329) of the control population. Eight inherited from an unaffected mother: a 751-kb deletion including FSCB, a 1.5-Mb duplication of 7q21.13, a 534-kb duplication of 15q11.2, a 446-kb duplication including CTNND2, a 219-kb duplication including MCPH1, a 169-kb duplication of 22q13.33, a 64-kb duplication of MC2R, and a 135-bp exonic deletion of SLC06A1. Three inherited from an unaffected father: a 386-kb deletion of 12p12.2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25.3, and a 265-kb duplication of DAAM1. This is the first systematic study of CNVs in CP, and although it did not identify de novo mutations, has shown inherited, rare CNVs involving potentially pathogenic genes and pathways requiring further investigation. 相似文献
73.
Jillian R. Hufgard Jenna L.N. Sprowles Emily M. Pitzer Sheryl E. Koch Min Jiang Qin Wang Xiang Zhang Jacek Biesiada Jack Rubinstein Alvaro Puga Michael T. Williams Charles V. Vorhees 《Journal of applied toxicology : JAT》2019,39(4):603-621
Polychlorinated biphenyls (PCBs) are toxic environmental pollutants. Humans are exposed to PCB mixtures via contaminated food or water. PCB exposure causes adverse effects in adults and after exposure in utero. PCB toxicity depends on the congener mixture and CYP1A2 gene activity. For coplanar PCBs, toxicity depends on ligand affinity for the aryl hydrocarbon receptor (AHR). Previously, we found that perinatal exposure of mice to a three‐coplanar/five‐noncoplanar PCB mixture induced deficits in novel object recognition and trial failures in the Morris water maze in Cyp1a2?/?::Ahrb1 C57BL6/J mice compared with wild‐type mice (Ahrb1 = high AHR affinity). Here we exposed gravid Cyp1a2?/?::Ahrb1 mice to a PCB mixture on embryonic day 10.5 by gavage and examined the F1 and F3 offspring (not F2). PCB‐exposed F1 mice exhibited increased open‐field central time, reduced acoustic startle, greater conditioned contextual freezing and reduced CA1 hippocampal long‐term potentiation with no change in spatial learning or memory. F1 mice also had inhibited growth, decreased heart rate and cardiac output, and impaired fertility. F3 mice showed few effects. Gene expression changes were primarily in F1 PCB males compared with wild‐type males. There were minimal RNA and DNA methylation changes in the hippocampus from F1 to F3 with no clear relevance to the functional effects. F0 PCB exposure during a period of rapid DNA de‐/remethylation in a susceptible genotype produced clear F1 effects with little evidence of transgenerational effects in the F3 generation. While PCBs show clear developmental neurotoxicity, their effects do not persist across generations for effects assessed herein. 相似文献
74.
Jillian Price Carey Escheik Ali Weinstein Patrice Winter Lynn Gerber Zobair Younossi 《Journal of clinical hypertension (Greenwich, Conn.)》2020,22(10):1915
People with Hepatitis C (HCV) and non‐alcoholic fatty liver disease (NAFLD) in the United States follow national trends toward a sedentary lifestyle and are increasingly at risk for hypertension. The intent of this study was to identify potential correlates of exercise tolerance in people with two types of chronic liver disease (CLD)‐NAFLD and HCV. Measures included cardiac output, oxygen consumption and stroke volume, blood pressure, distance walked in 6 minutes, clinical laboratory tests, and medications influencing the autonomic nervous system, patient self‐reports of activity, fatigue, and health‐related quality of life (HRQL). A total of 67 patients completed the 6‐minute walk test [45.1% Female, Age 51.7 ± 8.0 years, Body Mass Index 32.8 ± 5.9, 60% HCV]. At baseline, 70% had either diastolic (DBP) or systolic blood pressure outside normal range. Performance and cardiorespiratory measures correlated strongly with one another, but not with activity. Patients with abnormal DBP reported significantly lower maximum activity (MAS; r = −.254, P = .041, CI = −0.51 to −0.010; MAS 70.6 vs 82.5), significantly higher DBP post‐6‐minute walk test (r = .524, P = .0001, CI = 0.287‐0.762) and significantly lower overall HRQL items related to physical domains (r = .273, P = .029, CI = −0.518 to −0.029). Mental‐domain HRQL and depression measures did not correlate significantly with blood pressure. This study reports a significant correlation between both pre‐hypertensive and hypertensive DBP, poor physical‐domain self‐reports, HRQL, and performance in CLD patients. 相似文献
75.
76.
Sheedy D Say M Stevens J Harper CG Kril JJ 《Alcoholism, clinical and experimental research》2012,36(1):55-60
Background: Postmortem brain tissue provides an important resource to investigate various brain disorders, including those resulting from the effects of alcohol abuse. Unlike the traditionally recognized confounders to tissue quality (e.g., coma, hypoxia), our understanding of the effects of liver disease is incomplete. The aim of this study was to determine the effects of liver pathology, and in particular cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem brain tissue quality markers, brain pH and RNA integrity. Methods: We measured tissue quality markers in a cohort of alcohol abuse and control cases collected by the NSW Tissue Resource Centre. Cerebellar tissue was used to evaluate both brain pH and RNA quality (as indicated by the RNA integrity number: RIN). A histological assessment was performed on each case to exclude coexisting pathologies (e.g., cerebrovascular disease, hypoxic encephalopathy, neurodegenerative disease) and to assess the presence or absence of HE. Autopsy reports were reviewed for liver pathology and toxicology. Results: Analysis revealed that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46 (±0.3) as compared with the control mean 6.64 (±0.2). The mean RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66 (±0.5). The severity of liver pathology affected both brain pH (p < 0.0001) and RIN (p < 0.0001). The comparison between cirrhotic cases highlighted increased degradation of RNA in cases with cirrhosis resulting in HE (p = 0.0095). A similar effect was seen on brain pH (p = 0.0019). Conclusions: The results show that the presence of cirrhosis and, more so, HE reduces the pH and RIN of postmortem brain tissue. 相似文献
77.
Dignan FL Amrolia P Clark A Cornish J Jackson G Mahendra P Scarisbrick JJ Taylor PC Shaw BE Potter MN;Haemato-oncology Task Force of British Committee for Standards in Haematology;British Society for Blood Marrow Transplantation 《British journal of haematology》2012,158(1):46-61
A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of chronic graft-versus-host disease (GvHD). This guideline includes recommendations for the diagnosis and staging of chronic GvHD as well as primary treatment and options for patients with steroid-refractory disease. The goal of treatment should be the effective control of GvHD while minimizing the risk of toxicity and relapse. 相似文献
78.
Diagnosis and management of acute graft-versus-host disease 总被引:1,自引:0,他引:1
Dignan FL Clark A Amrolia P Cornish J Jackson G Mahendra P Scarisbrick JJ Taylor PC Hadzic N Shaw BE Potter MN;Haemato-oncology Task Force of British Committee for Standards in Haematology;British Society for Blood Marrow Transplantation 《British journal of haematology》2012,158(1):30-45
A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of acute graft-versus-host disease. This guideline includes recommendations for the diagnosis and grading of acute graft-versus-host disease as well as primary treatment and options for patients with steroid-refractory disease. The goal of treatment should be effective control of graft-versus-host disease while minimizing risk of toxicity and relapse. 相似文献
79.
Harvey J Green A Cornish J Steward C Cummins M Keen L Culliford S Poles A Hunt L Breslin P Li Y Moppett J 《Bone marrow transplantation》2012,47(10):1294-1300
We present the first detailed study analysing OS in BMT for paediatric ALL following the introduction of high-resolution (HR) HLA matching. A total of 356 consecutive paediatric ALL stem cell transplants performed between 1988 and 2007 were reviewed; 80 of them were performed following the introduction of HR HLA class I and class II matching to the transplant programme in 2002. Comparisons of matched unrelated donor (MUD) transplant outcomes before and after this period were made. Matching at the HR level for HLA-A, -B, -C, -DRB1 and -DQB1 (HR-MUD) correlated with a greater than 25% improvement in 2- and 5-year OS in paediatric ALL patients transplanted with MUDs (P=0.009, P=0.005, respectively). Two-year OS for contemporaneous HLA-matched sibling transplants (80.8%) and HR-MUD transplants (78.8%) was equivalent. At 6%, non-relapse mortality (NRM) in MUD transplants since 2002 was significantly reduced compared with previous epochs. Changes in treatment and epoch-dependent improvements in outcome were reviewed for possible confounders to the influence of HR typing using univariate and multivariate analysis. 相似文献
80.
Tracy L. Rowan Jillian L. Drouin 《The Journal of the Canadian Chiropractic Association》2013,57(4):301-309