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111.
112.
Doppler K Lindner A Schütz W Schütz M Bornemann A 《Brain pathology (Zurich, Switzerland)》2012,22(1):32-40
Sporadic inclusion body myositis (sIBM) contains non-necrotic myofibers that are surrounded and/or invaded by inflammatory cells. In this study we aimed to identify selective molecules that are present at this site. Myofibers of four biopsies of sIBM that were surrounded and/or invaded by inflammatory cells were microdissected, pooled and profiled by proteomic studies using mass spectrometry. Normal skeletal muscle tissue served as control. Based on the table of proteins that were detected in sIBM only, we selected nine extracellular matrix molecules and validated the results performing immunofluorescence. Seven out of nine proteins that were detected in sIBM by mass spectrometry showed different immunohistochemical results in myositis and normal controls. Of these, the small leucine-rich repeat proteins proline arginine-rich end leucine-rich repeat protein (PRELP) and biglycan were deposited precisely at myofibers surrounded and/or invaded by inflammatory cells both in sIBM and polymyositis. The basement membrane (BM) molecules merosin, perlecan, nidogen-2 and collagen IV were variably destroyed or increased at these sites. P component, which ensheathed all myofibers in normal controls, was absent from invaded myofibers. Similar to BM remodeling, the specific deposition of PRELP and biglycan may represent a mechanism to defend against immune attack. Loss of P component may affect the anchorage of the myofiber in the endomysium. 相似文献
113.
Inga Ebermann Jennifer B. Phillips Max C. Liebau Robert K. Koenekoop Bernhard Schermer Irma Lopez Ellen Sch?fer Anne-Francoise Roux Claudia Dafinger Antje Bernd Eberhart Zrenner Mireille Claustres Bernardo Blanco Gudrun Nürnberg Peter Nürnberg Rebecca Ruland Monte Westerfield Thomas Benzing Hanno J. Bolz 《The Journal of clinical investigation》2010,120(6):1812-1823
Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease. 相似文献
114.
Asja Maaz Tanja Hitzblech Peter Arends Antje Degel Sabine Ludwig Agata Mossakowski 《Medical teacher》2018,40(5):453-460
AbstractAim: Undergraduate medical education is currently in a fundamental transition towards competency-based programs around the globe. A major curriculum reform implies a dual challenge: the change of the curriculum and the delivering organization. Both are closely interwoven. In this article, we provide practical insights into our approach of managing such a fundamental reform of the large undergraduate medical program at the Charité – Universitätsmedizin Berlin.Methods: Members of the project management team summarized the key features of the process with reference to the literature.Results: Starting point was a traditional, discipline-based curriculum that was reformed into a fully integrated, competency-based program. This change process went through three phases: initiation, curriculum development and implementation, and sustainability. We describe from a change management perspective, their main characteristics, and the approaches that were employed to manage them successfully.Conclusions: Our report is intended to provide practical insights and guidance for those institutions which are yet considering or have already started to undergo a major reform of their undergraduate programs towards competency medical education. 相似文献
115.
Voigt A Elgeti T Durmus T Idiz ME Butler C Beling M Schilling R Klingel K Kandolf R Stangl K Taupitz M Kivelitz D Wagner M 《European radiology》2011,21(5):925-935
Objective
To assess active myocardial inflammation by cardiovascular magnetic resonance (CMR) and endomyocardial biopsy (EMB) amongst adult patients with dilated cardiomyopathy (DCM).Methods
We evaluated 23 adults with chronic DCM, who had successfully undergone both CMR and EMB within 3.5?±?2.6?days. EMB was considered the gold standard. CMR assessment of myocardial inflammation used the following parameters as recommended by the recently published ??Lake Louise Criteria??: global myocardial oedema, global relative enhancement (RE), and late gadolinium enhancement (LGE). According to ??Lake Louise Criteria??, myocardial inflammation was diagnosed if two or more of the three above-mentioned parameters were positive.Results
Myocardial inflammation was confirmed by immunohistology in 12 patients (52.2%). Sensitivity, specificity, and diagnostic accuracy of CMR to detect immunohistologically confirmed myocardial inflammation were 75.0%, 72.7%, and 73.9%, respectively. Sensitivity, specificity, and diagnostic accuracy of the individual CMR parameters to detect myocardial inflammation were as follows: global myocardial oedema, 91.7%, 81.8%, and 87.0%, respectively; global RE, 58.3%, 63.6%, and 60.9%, respectively; LGE, 58.3%, 45.4%, and 52.2%, respectively.Conclusion
Global myocardial oedema was identified as a promising CMR parameter for assessment of myocardial inflammation in patients with DCM. In these patients, global myocardial oedema yielded superior diagnostic performance compared to ??Lake Louise Criteria??. 相似文献116.
Alina Pulzer Ulrich Seybold Ulf Schönermarck Manfred Stangl Antje Habicht Johannes R. Bogner Jörg Franke Michael Fischereder 《Transplant international》2013,26(3):254-258
Kidney transplantation in HIV‐infected patients is associated with a higher rate of graft rejection as well as an increased toxicity of the immunosuppressive therapy. Specifically, the use of the calcineurin inhibitor tacrolimus is problematic because of a narrow therapeutic range, a high interindividual variability of trough levels, and multiple interactions with combination antiretroviral therapy (cART). Our objective was to establish the optimal individual immunosuppressive dose for the time after kidney transplantation. We administered a temporary course of immunosuppressive therapy in three HIV‐infected patients with end‐stage renal disease (ESRD) after wait‐listing and prior to transplantation for deceased donor kidney transplantation. Starting with a tacrolimus dose of 1 mg twice daily, the dose was titrated to reach a tacrolimus trough level of 8–12 ng/ml. HIV had been diagnosed 7–14 years prior. All patients had no detectable HIV‐1 RNA while on cART. All three patients had been on chronic dialysis for 4, 7, and 10 years. In two patients, the intended tacrolimus trough levels of 8–12 ng/ml were achieved within a month. The required tacrolimus dose ranged from 0.5 mg thrice weekly to 10 mg daily. In one case, ventricular tachycardia occurred, so the immunosuppressive therapy was switched to cyclosporine A. So far, two patients have been transplanted successfully. In summary, dose‐finding of immunosuppressive therapy with tacrolimus in patients on cART before renal transplantation is feasible and appears useful to minimize immunosuppressive therapy‐related complications in the post‐transplantation period. 相似文献
117.
Rempp H Hoffmann R Roland J Buck A Kickhefel A Claussen CD Pereira PL Schick F Clasen S 《European radiology》2012,22(5):1091-1100
Objective
To evaluate different cut-off temperature levels for a threshold-based prediction of the coagulation zone in magnetic resonance (MR)-guided radiofrequency (RF) ablation of liver tumours.Methods
Temperature-sensitive measurements were acquired during RF ablation of 24 patients with primary (6) and secondary liver lesions (18) using a wide-bore 1.5?T MR sytem and compared with the post-interventional coagulation zone. Temperature measurements using the proton resonance frequency shift method were performed directly subsequent to energy application. The temperature maps were registered on the contrast-enhanced follow-up MR images acquired 4?weeks after treatment. Areas with temperatures above 50°, 55° and 60°C were segmented and compared with the coagulation zones. Sensitivity and positive predictive value were calculated.Results
No major complications occurred and all tumours were completely treated. No tumour recurrence was observed at the follow-up examination after 4?weeks. Two patients with secondary liver lesions showed local tumour recurrence after 4 and 7?months. The 60°C threshold level achieved the highest positive predictive value (87.7?±?9.9) and the best prediction of the coagulation zone.Conclusions
For a threshold-based prediction of the coagulation zone, the 60°C cut-off level achieved the best prediction of the coagulation zone among the tested levels.Key Points
? Temperature monitoring can be used to survey MR-guided radiofrequency ablation ? The developing ablation zone can be estimated based on post-interventional temperature measurements ? A 60°C threshold level can be used to predict the ablation zone ? The 50°C and 55°C temperature zones tend to overestimate the ablation zone 相似文献118.
Ute Henniges Merima Hasani Antje Potthast Gunnar Westman Thomas Rosenau 《Materials》2013,6(5):1584-1598
The irradiation of pulp is of interest from different perspectives. Mainly it is required when a modification of cellulose is needed. Irradiation could bring many advantages, such as chemical savings and, therefore, cost savings and a reduction in environmental pollutants. In this account, pulp and dissociated celluloses were analyzed before and after irradiation by electron beaming. The focus of the analysis was the oxidation of hydroxyl groups to carbonyl and carboxyl groups in pulp and the degradation of cellulose causing a decrease in molar mass. For that purpose, the samples were labeled with a selective fluorescence marker and analyzed by gel permeation chromatography (GPC) coupled with multi-angle laser light scattering (MALLS), refractive index (RI), and fluorescence detectors. Degradation of the analyzed substrates was the predominant result of the irradiation; however, in the microcrystalline samples, oxidized cellulose functionalities were introduced along the cellulose chain, making this substrate suitable for further chemical modification. 相似文献
119.
Thomas MK Völkl Diemud Simm Antje Körner Wieland Kiess Jürgen Kratzsch Helmuth G Dörr 《Acta paediatrica (Oslo, Norway : 1992)》2009,98(5):885-891
Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control.
Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI.
Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 μg/L) compared to the matched controls (6.7 μg/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage.
Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients. 相似文献
Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI.
Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 μg/L) compared to the matched controls (6.7 μg/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage.
Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients. 相似文献
120.
Growth curves of “normal” serum total IgE levels throughout childhood: A quantile analysis in a birth cohort
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