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91.
Brittney Murray Rohan Wagle Nuria Amat‐Alarcon Alisha Wilkens Paul Stephens Elaine H. Zackai Elizabeth Goldmuntz Hugh Calkins Matthew A. Deardorff Daniel P. Judge M.D. 《American journal of medical genetics. Part A》2013,161(2):371-376
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a familial form of cardiomyopathy typically caused by mutations in genes that encode an element of the cardiac desmosome. Branchio‐oculo‐facial syndrome (BOFS) is a craniofacial disorder caused by TFAP2A mutations. In a family segregating ARVD/C, some members also had features of BOFS. Genetic testing for ARVD/C identified a mutation in PKP2, encoding plakophilin‐2, a component of the cardiac desmosome. Evaluation of dysmorphology by chromosome microarray (CMA) identified a 4.4 Mb deletion at chromosome 6p24 that included both TFAP2A and DSP, encoding desmoplakin, an additional component of the cardiac desmosome implicated in ARVD/C. A family member with both the 6p24 deletion and PKP2 mutation had more severe cardiac dysfunction. These findings suggest that this contiguous gene deletion contributes to both ARVD/C and BOFS, and that DSP haploinsufficiency may contribute to cardiomyopathy. This family provides a clinical example that underscores the need for careful evaluation in clinical scenarios where genetic heterogeneity is known to exist. Finally, it suggests that individuals with unexplained cardiomyopathy and dysmorphic facial features may benefit from CMA analysis. © 2013 Wiley Periodicals, Inc. 相似文献
92.
Rohan S. Virgincar Zackary I. Cleveland S. Sivaram Kaushik Matthew S. Freeman John Nouls Gary P. Cofer Santiago Martinez‐Jimenez Mu He Monica Kraft Jan Wolber H. Page McAdams Bastiaan Driehuys 《NMR in biomedicine》2013,26(4):424-435
In this study, hyperpolarized 129Xe MR ventilation and 1H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age‐matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader‐based ventilation defect score percentage (VDS%) and a semi‐automated segmentation‐based ventilation defect percentage (VDP). Reader‐based values were assigned by two experienced radiologists and resolved by consensus. In the semi‐automated analysis, 1H anatomical images and 129Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Ventilation images were also characterized by generating signal intensity histograms from voxels within the thoracic cavity volume, and heterogeneity was analyzed using the coefficient of variation (CV). The reader‐based VDS% correlated strongly with the semi‐automatically generated VDP (r = 0.97, p < 0.0001) and with CV (r = 0.82, p < 0.0001). Both 129Xe ventilation defect scoring metrics readily separated the three groups from one another and correlated significantly with the forced expiratory volume in 1 s (FEV1) (VDS%: r = –0.78, p = 0.0002; VDP: r = –0.79, p = 0.0003; CV: r = –0.66, p = 0.0059) and other pulmonary function tests. In the healthy subject groups (HVs and AMCs), the prevalence of ventilation defects also increased with age (VDS%: r = 0.61, p = 0.0002; VDP: r = 0.63, p = 0.0002). Moreover, ventilation histograms and their associated CVs distinguished between subjects with COPD with similar ventilation defect scores, but visibly different ventilation patterns. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
93.
Romieu R; Lacabanne V; Kayibanda M; Antoine B; Bennoun M; Chouaib S; Guillet JG; Viguier M 《International immunology》1997,9(10):1405-1413
There is now good evidence that cytokines contribute to the regulation of
tumor growth. The cytokine-driven modulation of tumor growth was
investigated during the progression of a hepatocellular carcinoma (HCC) in
SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of
liver growth correlated with increased transforming growth factor
(TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis
factor (TNF)-alpha mRNA were detected earlier during tumor development.
Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2,
IL-4 and IFN-gamma mRNA production could be reported. In vitro,
hepatocyte-like tumor cell lines established at two stages, either before
or after HCC differentiation, were characterized. The early-stage-derived
cell line produced TNF-alpha mRNA, but had barely detectable expression of
TGF-beta 1 mRNA, while later-stage- derived cell lines showed the
reciprocal pattern. All cell lines displayed a lack of sensitivity to
TNF-alpha, although some degree of sensitivity to TNF-alpha could be
observed in the presence of actinomycin-D or after treatment with
IFN-gamma. The early-stage- derived cell line was sensitive to the growth
inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines
displayed a loss of sensitivity to TGF-beta 1 which correlated with the
increased expression of TGF-beta 1 mRNA. Altogether, this suggests that
tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression
patterns during HCC progression. This model of HCC could be of valuable
interest to assess the impact of various immunotherapeutic strategies on
modulation of tumor growth.
相似文献
94.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
95.
Momeni P Pittman A Lashley T Vandrovcova J Malzer E Luk C Hulette C Lees A Revesz T Hardy J de Silva R 《Neurobiology of aging》2009,30(3):388-393
We identified a case of Alzheimer's disease with a deletion of the lysine residue at codon 280 (DeltaK280) in exon 10-encoded microtubule-binding repeat domain of the tau gene (MAPT). This mutation was originally identified in a sporadic case of frontotemporal dementia (FTD) with a family history of Parkinson's disease. In the original report, the authors were careful in their assessment of the pathogenicity and suggested one could not be sure whether the mutation was pathogenic or not. The mutation has always presented a conundrum because it is the only known mutation, of assumed pathogenicity, which increases the proportion of 3-repeat tau mRNA in in vitro assays. Here we present the clinical and pathological features of a new case with this mutation and discuss whether the mutation is indeed pathogenic. 相似文献
96.
The Mouse Secretome: Functional Classification of the Proteins Secreted Into the Extracellular Environment 总被引:1,自引:0,他引:1 下载免费PDF全文
97.
Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule 下载免费PDF全文
Bianca LW Bendermacher Joep AW Teijink Edith M Willigendael Marie-Louise Bartelink Harry R Büller Ron JG Peters Jelis Boiten Machteld Langenberg Martin H Prins 《The British journal of general practice》2006,56(533):932-937
BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease. 相似文献
98.
It is well known that magnetic susceptibility variations lead to signal voids in MRI. However, recent work has shown that positive-contrast imaging of susceptibility-induced field variations can provide signal enhancements rather than signal losses. In this paper, we propose a new method for generating positive contrast from off-resonant spins with steady-state free precession (SSFP) magnetic resonance imaging. Based on theory and experiments, we demonstrate that positive-contrast images can be acquired in the presence of susceptibility-shift media with low flip angle excitations that are determined by the spin relaxation time constants of the imaging medium. Compared to other techniques, this technique is substantially faster and has low specific absorption rates, permitting high-field imaging. In addition to acquiring positive-contrast images, we also show that it is possible to suppress the imaging medium to desired levels; thereby allowing for simultaneous registration of the background details surrounding the susceptibility-shift media. Among practical applications, we anticipate that the proposed technique can potentially facilitate high field magnetic-resonance-based molecular imaging. 相似文献
99.
100.