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791.
X Zhang T YY Lai S WY Chiang P OS Tam D TL Liu C KM Chan C P Pang C Zhao L J Chen 《Eye (London, England)》2013,27(10):1204-1213
Purpose
Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients.Methods
Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12–16, 22–32, and 38–45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses.Results
Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study.Conclusions
Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP. 相似文献792.
Lisa T. Eyler Elizabeth Prom‐Wormley Christine Fennema‐Notestine Matthew S. Panizzon Michael C. Neale Terry L. Jernigan Bruce Fischl Carol E. Franz Michael J. Lyons Allison Stevens Jennifer Pacheco Michele E. Perry J. Eric Schmitt Nicholas C. Spitzer Larry J. Seidman Heidi W. Thermenos Ming T. Tsuang Anders M. Dale William S. Kremen 《Human brain mapping》2011,32(4):641-653
Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
793.
Jernigan TL Archibald SL Fennema-Notestine C Taylor MJ Theilmann RJ Julaton MD Notestine RJ Wolfson T Letendre SL Ellis RJ Heaton RK Gamst AC Franklin DR Clifford DB Collier AC Gelman BB Marra C McArthur JC McCutchan JA Morgello S Simpson DM Grant I;CHARTER Group 《Journal of neurovirology》2011,17(3):248-257
Despite the widening use of combination antiretroviral therapy (ART), neurocognitive impairment remains common among HIV-infected (HIV+) individuals. Associations between HIV-related neuromedical variables and magnetic resonance imaging indices of brain structural integrity may provide insight into the neural bases for these symptoms. A diverse HIV+ sample (n?=?251) was studied through the CNS HIV Antiretroviral Therapy Effects Research initiative. Multi-channel image analysis produced volumes of ventricular and sulcal cerebrospinal fluid (CSF), cortical and subcortical gray matter, total cerebral white matter, and abnormal white matter. Cross-sectional analyses employed a series of multiple linear regressions to model each structural volume as a function of severity of prior immunosuppression (CD4 nadir), current CD4 count, presence of detectable CSF HIV RNA, and presence of HCV antibodies; secondary analyses examined plasma HIV RNA, estimated duration of HIV infection, and cumulative exposure to ART. Lower CD4 nadir was related to most measures of the structural brain damage. Higher current CD4, unexpectedly, correlated with lower white and subcortical gray and increased CSF. Detectable CSF HIV RNA was related to less total white matter. HCV coinfection was associated with more abnormal white matter. Longer exposure to ART was associated with lower white matter and higher sulcal CSF. HIV neuromedical factors, including lower nadir, higher current CD4 levels, and detectable HIV RNA, were associated with white matter damage and variability in subcortical volumes. Brain structural integrity in HIV likely reflects dynamic effects of current immune status and HIV replication, superimposed on residual effects associated with severe prior immunosuppression. 相似文献
794.
Schuler PJ Börger V Bölke E Habermehl D Matuschek C Wild CA Greve J Bas M Schilling B Bergmann C Trellakis S Budach W Gauler T Brandau S Lang S Whiteside TL Sorg RV Hoffmann TK 《European journal of medical research》2011,16(2):57-62
Background
Regulatory T cells (Treg) and dendritic cells (DC) play an important role in tumor immunity and immune escape. However, their interplay and the effects of anti-cancer therapy on the human immune system are largely unknown.Methods
For DC generation, CD14+ monocytes were enriched by immunomagnetic selection from peripheral blood of advanced head and neck squamous cell carcinoma (HNSCC) patients and differentiated into immature DC using GM-SCF and IL-4. DC maturation was induced by addition of TNFα. The frequency of CD4+CD25highF0XP3+ Treg in HNSCC patients was analyzed before and after radio-chemotherapy (RCT) by four-color flow cytometry.Results
In HNSCC patients, the frequency of Treg (0.33 ± 0.06%) was significantly (p = 0.001) increased compared to healthy controls (0.11 ± 0.02%), whereas RCT had variable effects on the Treg frequency inducing its increase in some patients and decrease in others. After six days in culture, monocytes of all patients had differentiated into immature DC. However, DC maturation indicated by CD83 up-regulation (70.7 ± 5.5%) was successful only in a subgroup of patients and correlated well with lower frequencies of peripheral blood Treg in those patients.Conclusion
The frequency of regulatory T cells is elevated in HNSCC patients and may be modulated by RCT. Monocyte-derived DC in HNSCC patients show a maturation deficiency ex vivo. Those preliminary data may have an impact on multimodality clinical trials integrating cellular immune modulation in patients with advanced HNSCC. 相似文献795.
Hobbs CA James SJ Jernigan S Melnyk S Lu Y Malik S Cleves MA 《American journal of obstetrics and gynecology》2006,194(1):218-224
796.
Bischoff-Grethe A Ozyurt IB Busa E Quinn BT Fennema-Notestine C Clark CP Morris S Bondi MW Jernigan TL Dale AM Brown GG Fischl B 《Human brain mapping》2007,28(9):892-903
Due to the increasing need for subject privacy, the ability to deidentify structural MR images so that they do not provide full facial detail is desirable. A program was developed that uses models of nonbrain structures for removing potentially identifying facial features. When a novel image is presented, the optimal linear transform is computed for the input volume (Fischl et al. [2002]: Neuron 33:341-355; Fischl et al. [2004]: Neuroimage 23 (Suppl 1):S69-S84). A brain mask is constructed by forming the union of all voxels with nonzero probability of being brain and then morphologically dilated. All voxels outside the mask with a nonzero probability of being a facial feature are set to 0. The algorithm was applied to 342 datasets that included two different T1-weighted pulse sequences and four different diagnoses (depressed, Alzheimer's, and elderly and young control groups). Visual inspection showed none had brain tissue removed. In a detailed analysis of the impact of defacing on skull-stripping, 16 datasets were bias corrected with N3 (Sled et al. [1998]: IEEE Trans Med Imaging 17:87-97), defaced, and then skull-stripped using either a hybrid watershed algorithm (Ségonne et al. [2004]: Neuroimage 22:1060-1075, in FreeSurfer) or Brain Surface Extractor (Sandor and Leahy [1997]: IEEE Trans Med Imaging 16:41-54; Shattuck et al. [2001]: Neuroimage 13:856-876); defacing did not appreciably influence the outcome of skull-stripping. Results suggested that the automatic defacing algorithm is robust, efficiently removes nonbrain tissue, and does not unduly influence the outcome of the processing methods utilized; in some cases, skull-stripping was improved. Analyses support this algorithm as a viable method to allow data sharing with minimal data alteration within large-scale multisite projects. 相似文献
797.
Fischer SA Graham MB Kuehnert MJ Kotton CN Srinivasan A Marty FM Comer JA Guarner J Paddock CD DeMeo DL Shieh WJ Erickson BR Bandy U DeMaria A Davis JP Delmonico FL Pavlin B Likos A Vincent MJ Sealy TK Goldsmith CS Jernigan DB Rollin PE Packard MM Patel M Rowland C Helfand RF Nichol ST Fishman JA Ksiazek T Zaki SR;LCMV in Transplant Recipients Investigation Team 《The New England journal of medicine》2006,354(21):2235-2249
798.
MI Strakhova CA Cuff AM Manelli TL Carr DG Witte JL Baranowski TA Vortherms TR Miller L Rundell MJ McPherson RM Adair AA Brito BM Bettencourt BB Yao JM Wetter KC Marsh H Liu MD Cowart JD Brioni TA Esbenshade 《British journal of pharmacology》2009,157(1):44-54
Background and purpose:
The histamine H4 receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H4 receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine).Experimental approach:
We have analysed the pharmacological profile of A-940894 at mouse native, rat recombinant and human recombinant and native, histamine H4 receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan-induced peritonitis.Key results:
A-940894 potently binds to both human and rat histamine H4 receptors and exhibits considerably lower affinity for the human histamine H1, H2 or H3 receptors. It potently blocked histamine-evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine-induced shape change of mouse bone marrow-derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell-dependent model of zymosan-induced peritonitis, A-940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D2 levels. Finally, A-940894 has good pharmacokinetic properties, including half-life and oral bioavailability in rats and mice.Conclusions and Implications:
These data suggest that A-940894 is a potent and selective histamine H4 receptor antagonist with pharmacokinetic properties suitable for long-term in vivo testing and could serve as a useful tool for the further characterization of histamine H4 receptor pharmacology. 相似文献799.
Twenty-seven preterm infants were compared to 10 full-term infants at term equivalent age using a voxel-based analysis of diffusion tensor imaging of the brain. Preterm infants exhibited higher fractional anisotropy values, which may suggest accelerated maturation, in the location of the sagittal stratum. While some earlier findings in preterm infants have suggested developmental delays, the results of this study are more consistent with accelerated white matter development, possibly as a result of increased sensorimotor stimulation in the extrauterine environment. These results are the first to suggest that the increased intensity of stimulation associated with preterm birth may advance the process of white matter maturation in the human brain. Questions remain about whether these findings reflect acceleration of the process of white matter maturation generally, or localized alterations induced specifically by activity in affected pathways. 相似文献
800.
Stephen R. Benoit MD MPH Wato Nsa MD PhD Chesley L. Richards MD MPH Dale W. Bratzler DO MPH Abigail M. Shefer MD Lynn M. Steele MS John A. Jernigan MD MS 《Journal of the American Geriatrics Society》2008,56(11):2039-2044
OBJECTIVES: To describe antimicrobial prescribing patterns in nursing homes. DESIGN: Retrospective, observational study. SETTING: Total of 73 nursing homes in four U.S. states; study period was from September 1, 2001, through February 28, 2002. PARTICIPANTS: Four thousand seven hundred eighty nursing home residents. MEASUREMENTS: Number and type of antimicrobials, indication for their use, and resident and facility factors associated with antimicrobial use in nursing homes. RESULTS: Of 4,780 residents, 2,017 (42%) received one or more antibiotic courses. Overall, residents received a mean of 4.8 courses/1,000 resident‐days (mean facility range 0.4–23.5). In multivariable analysis, higher probability of nursing home discharge and of being categorized in the rehabilitation, extensive services, special care, or clinically complex Resource Utilization Groups were associated with higher rates of antimicrobial usage. Three drug classes accounted for nearly 60% of antimicrobial courses—fluoroquinolones (38%), first‐generation cephalosporins (11%), and macrolides (10%). The most common conditions for which antimicrobials were prescribed were respiratory tract (33%) and urinary tract (32%) infections. CONCLUSION: Antibiotic use is variable in nursing homes. Targeting educational and other antimicrobial use interventions to the treatment of certain clinical diagnoses and conditions may be an appropriate strategy for optimizing antimicrobial use in this setting. 相似文献