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91.
A nonstop variant in REEP1 causes peripheral neuropathy by unmasking a 3′UTR‐encoded,aggregation‐inducing motif 下载免费PDF全文
Julia Mohr Lisa V. Goldberg Amir Jahic Cornelia Klisch Christian A. Hübner Saskia Biskup Christian Beetz 《Human mutation》2018,39(2):193-196
Single‐nucleotide variants that abolish the stop codon (“nonstop” alterations) are a unique type of substitution in genomic DNA. Whether they confer instability of the mutant mRNA or result in expression of a C‐terminally extended protein depends on the absence or presence of a downstream in‐frame stop codon, respectively. Of the predicted protein extensions, only few have been functionally characterized. In a family with autosomal dominant Charcot‐Marie‐Tooth disease type 2, that is, an axonopathy affecting sensory neurons as well as lower motor neurons, we identified a heterozygous nonstop variant in REEP1. Mutations in this gene have classically been associated with the upper motor neuron disorder hereditary spastic paraplegia (HSP). We show that the C‐terminal extension resulting from the nonstop variant triggers self‐aggregation of REEP1 and of several reporters. Our findings support the recently proposed concept of 3′UTR‐encoded “cryptic amyloidogenic elements.” Together with a previous report on an aggregation‐prone REEP1 deletion variant in distal hereditary motor neuropathy, they also suggest that toxic gain of REEP1 function, rather than loss‐of‐function as relevant for HSP, specifically affects lower motor neurons. A search for similar correlations between genotype, phenotype, and effect of mutant protein may help to explain the wide clinical spectra also in other genetically determined disorders. 相似文献
92.
S?nke?Detlefsen Asbj?rn?Mohr Drewes Mogens?Vyberg Günter?Kl?ppel 《Virchows Archiv : an international journal of pathology》2009,454(5):531-539
Autoimmune pancreatitis (AIP) has been established as a special entity of chronic pancreatitis (CP). However, its clinical
distinction from pancreatic cancer and other types of CP is still difficult. The aim of this study was to evaluate the efficacy
of pancreatic core needle biopsy for the diagnosis of AIP. In 44 core needle biopsy specimens, we assessed the following microscopic
features: granulocytic epithelial lesions (GELs), more than ten IgG4-positive plasma cells/HPF, more than ten eosinophilic
granulocytes/HPF, cellular fibrosis with inflammation, lymphoplasmacytic infiltration, and venulitis. All biopsies that showed
four or more of the six features (22 of 44) were obtained from 21 of 26 patients whose clinical diagnosis and follow-up were
consistent with AIP. All non-AIP CP patients (n = 14) showed three or less than three of the features in their biopsies. GELs were only observed in biopsy specimens from
AIP patients. In conclusion, our data indicate that the six criteria we applied were able to recognize AIP in 76% of biopsy
specimens using a cut-off level of four. When the specimens that revealed only three features but showed GELs were added,
the sensitivity rose to 86%. Pancreatic core needle biopsy can therefore make a significant contribution to the diagnosis
of AIP. 相似文献
93.
IntroductionSling erosion/extrusion is a complication after suburethral sling insertion for female stress urinary incontinence that occurs in approximately 6% of patients. Symptoms may include vaginal discharge, infections, postcoital bleeding, and alterations of the sexual function. Little is known about the effect of sling erosion on the sexual function of the male partner.AimThe aim of this study was to determine male sexual function in partners of women who had undergone sling insertion for stress urinary incontinence and who developed sling erosion postoperatively.Main Outcome MeasuresMain outcome measures were the Brief Male Sexual Function Inventory (BMSFI) and visual analog scale (VAS) scores.MethodsMale partners of patients who presented with sling erosion for various reasons were addressed and asked to fill in the BMSFI and assess sexual pain using the VAS before and 6 months after the sling erosion of their female partners was treated. Participants gave informed consent and those who had undergone prostate surgery during the past 12 months were excluded. For statistical analyses, SPSS version 10.0 (SPSS Inc., Chicago, IL, USA) was used.ResultsThirty-two males were included in the study and produced a full set of data. VAS scores as a measurement for “hispareunia” improved from a median score of 8 before to a median score of 1 after intervention. Some domains of male sexual function (sexual interest, sexual drive, ejaculation, and erection) were significantly improved whereas the strength of erection, problems with ejaculation, and problems with lack of interest were not statistically significantly changed.ConclusionsChanges of male sexual function and particularly pain after sling insertion in their female partners may be due to sling exposure. Sexual interest and drive may be negatively influenced. Male dyspareunia is a complaint that can be treated effectively by correcting the sling exposure. Mohr S, Kuhn P, Mueller MD, and Kuhn A. Painful Love—“Hispareunia” after sling erosion of the female partner. 相似文献
94.
M.‐T. Dieterlen H. B. Bittner A. Pierzchalski S. Dhein F. W. Mohr M. J. Barten 《Clinical and experimental immunology》2014,176(1):120-128
Extracorporeal photopheresis (ECP) has been used as a prophylactic and therapeutic option to avoid and treat rejection after heart transplantation (HTx). Tolerance‐inducing effects of ECP such as up‐regulation of regulatory T cells (Tregs) are known, but specific effects of ECP on regulatory T cell (Treg) subsets and dendritic cells (DCs) are lacking. We analysed different subsets of Tregs and DCs as well as the immune balance status during ECP treatment after HTx. Blood samples were collected from HTx patients treated with ECP for prophylaxis (n = 9) or from patients with histologically proven acute cellular rejection (ACR) of grade ≥ 1B (n = 9), as well as from control HTx patients without ECP (HTxC; n = 7). Subsets of Tregs and DCs as well as different cytokine levels were analysed. Almost 80% of the HTx patients showed an effect to ECP treatment with an increase of Tregs and plasmacytoid DCs (pDCs). The percentage of pDCs before ECP treatment was significantly higher in patients with no ECP effect (26·3% ± 5·6%) compared to patients who showed an effect to ECP (9·8% ± 10·2%; P = 0·011). Analysis of functional subsets of CD4+CD25highCD127low Tregs showed that CD62L‐, CD120b‐ and CD147‐positive Tregs did not differ between the groups. CD39‐positive Tregs increased during ECP treatment compared to HTxC. ECP‐treated patients showed higher levels for T helper type 1 (Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx patients with rejection before ECP treatment compared to patients with prophylactic ECP treatment. We recommend a monitoring strategy that includes the quantification and analysis of Tregs, pDCs and the immune balance status before and up to 12 months after starting ECP. 相似文献
95.
M. Riffelmann J. Mohr W. Hellenbrand C. H. Wirsing von Koenig 《European journal of clinical microbiology & infectious diseases》2014,33(5):805-808
We evaluated whether the results of diagnostic polymerase chain reaction (PCR) testing combined with time since last vaccine dose could be used to monitor the effectiveness of acellular pertussis vaccines. In 258 consecutive nasopharyngeal swabs from children and adolescents with typical pertussis symptoms, 80 were positive and 178 were negative in PCR for Bordetella pertussis DNA (IS 481). Time since last vaccine dose was available for 152 patients, of which 120 were fully immunised. Among the fully vaccinated patients, the median age of 41 PCR-positive patients was 8.4 years (range 0.9–12.3) and that of 79 PCR-negative cases was 3.3 years (range 0.4–14.1) (p?<?0.01). The median time since last pertussis vaccine dose was 6.05 years [95 % confidence interval (CI): 0.5–10.9] in PCR-positive cases and 2.22 years (95 % CI: 0.04–9.23) in PCR-negative cases (p?<?0.001). The use of diagnostic PCR results from pertussis cases together with time since last vaccine dose permits estimates of the duration of protection after vaccination with acellular pertussis vaccines that are in keeping with more complex studies. 相似文献
96.
In 2003 a 16-year-old boy died unexpectedly and the cause of death was determined as cardiomyopathy by the autopsy. A more precise specification of the cardiomyopathy was requested by the relatives 4 years later in particular with respect to the possible presence of an arrhythmogenic right ventricular cardiomyopathy (ARVCM) which mainly has an autosomal dominant inheritance. To diagnose an ARVCM standardized criteria have been developed based on structural, histological, electrocardigraphic and arrhythmogenic factors as well as a positive family anamnesis. At the time of the postmortem diagnostics only structural and histological criteria were available. For the histological verification an imaging analytic procedure described by Angelini et al. in 1993 was used for the quantitative evaluation of the fatty tissue and connective tissue in the myocardium. This procedure was adapted to modern technology standards so that an image analysis could be performed with a customary personal computer. Digital microphotographs of Sudan red and Elastica-van-Gieson stained slices with a 400x magnification were used. These images were processed by means of computer-aided image analysis and the respective areas of fatty tissue and connective tissue were determined. Arrhythmogenic right ventricular cardiomyopathy could be excluded by the investigations, however, an idiopathic dilated cardiomyopathy (DCM) could be diagnosed. The relatives of the deceased were recommended to undertake further physical and genetic examinations. 相似文献
97.
98.
Aya Mohr Sasson Abraham Tsur Anat Kalter Alina Weissmann Brenner Liat Gindes 《The journal of maternal-fetal & neonatal medicine》2016,29(8):1318-1321
Objective: Evaluate physiologic factors associated with reduced maternal perception of fetal movements (RFM).Methods: A historical cohort study of all women (years 2011–2013, n?=?399) that visited the maternal emergency room (ER) (gestational age 24?+?0–42?+?0) due to RFM (group A), that was compared to a control group consisted from women with normal perception of fetal movements (group B). Groups were compared for maternal characteristics (age, gravity, parity, BMI), gestational age, placental location, gestational age at birth and fetal outcomes (birth-weight and Apgar scores).Results: In a multivariate regression analysis, including maternal age, height, weight, BMI, gestational age on admission to ER, gravity, parity and placental location, only two variables remained significantly associated with RFM – nulliparity (OR?=?2.28, p?=?0.001) and anterior placenta (OR?=?1.44, p?=?0.034). Group A was not associated with lower Apgar scores (1 and 5-min, p?=?0.40 and 0.57, respectively) or low birth-weight (p?=?0.76), nor was it associated with prematurity (p?=?0.41), low (<7) 5-min Apgar score, fetal death or neonatal death.Conclusions: Reduced fetal movements are associated with anterior placenta and nulliparity. 相似文献
99.
100.
Clinical aspects of pelvic inflammatory disease 总被引:2,自引:0,他引:2
Pelvic inflammatory disease (PID) is a common and poorly managed condition.
Untreated or inadequately treated, it leads to tubal infertility, ectopic
pregnancy and chronic pelvic pain. Diagnostic difficulties are compounded
by the wide variety of clinical presentations and the insensitivity and
poor specificity of laboratory tests. Better recognition of mild and
atypical disease needs a high index of suspicion whenever young, sexually
active women present with gynaecological symptoms. Laparoscopy supplemented
by microbiological tests and fimbrial minibiopsy should be regarded as the
diagnostic 'gold standard' for research studies; new studies are required
to identify techniques which might reduce under- and over-diagnosis. Early
treatment reduces the risk of an adverse effect on fertility. Any
therapeutic regimen selected should be effective against the common
aetiological agents Chlamydia trachomatis, Neisseria gonorrhoeae, genital
mycoplasmas and aerobic and anaerobic bacteria. Since at least 60% of cases
of PID can be attributed to infection with a sexually transmitted organism,
partner notification forms an essential part of management.
相似文献