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A potential role of karyopherin a2 in the impaired maturation of dendritic cells observed in glioblastoma patients

Neuroimmunology and Neuroinflammation 2015年第1期2卷 8-14页

作者： Konstantinos Gousias Alexander von Ruecker Gerrit H.Gielen Pitt Niehusmann Andreas Waha Hartmut Vatter Matthias Simon Department of Neurosurgery University Hospital of BonnSigmund-Freud-Strasse 2553105 BonnGermany Department of Neurosurgery University Hospital of BochumBergmannsheilBürkle-de-la-Camp-Platz 144789 BochumGermany Department of Pathology University Hospital of BonnSigmund-Freud-Strasse 2553105 BonnGermany Department of Neuropathology University Hospital of BonnSigmund-Freud-Strasse 2553105 BonnGermany

Aim:Patients with glioblastomas demonstrate well‑documented immunological impairments including decreased numbers of mature dendritic cells(DCs).Recent data identified karyopherin a2(KPNA2),a nucleocytoplasmic shuttling receptor,as diagnostic and prognostic biomarker for *** aim of this ongoing study is to correlate parameters of immunity and nucleocytoplasmic transport in glioblastoma ***:We preoperatively collected serum from 17 patients with glioblastomas and determined DC subsets(HLA DR+Lin-,CD34-,CD45+,CD123+,CD11+were analyzed)using a 6‑color flow cytometry *** levels of KPNA2 and nuclear accumulation of p53 were evaluated semi‑quantitatively by immunohistochemistry.O6‑methylguanine DNA methyltransferase(MGMT)and isocitrate dehydrogenase‑1(IDH‑1)status were assessed by pyrosequencing and immunohistochemistry,***:Median expression levels for both KPNA2 and p53 were 5-10%.IDH‑1‑R132H mutation and MGMT promoter hypermethylation was detected in 3/16 and 1/9 patients,*** counts of total mature DCs,myeloid DCs and plasmacytoid DCs were 9.6,2.1,3.4 cells/μL.A preliminary analysis suggests an association between low KPNA2 nuclear expression and increased numbers of mature ***,this correlation did not reach statistical significance so far(P=0.077).Conclusion:Our preliminary data may indicate a role of KPNA2 in the impaired maturation of DCs observed in glioblastoma patients.

关键词： Glioblastomas isocitrate dehydrogenase‑1 karyopherin a2 mature dendritic cells O6‑methylguanine DNA methyltransferase p53

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肝细胞癌TGF-β受体表达的改变——一种组成性活性TGF-βI型受体突变体的效应

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世界核心医学期刊文摘（胃肠病学分册） 2005年第9期1卷 14-15页

作者： Musch A. Rabe C. Paik M.-D. 张诗峰 sigmund-freud-strasse 25 DE-53105 Bonn Germany

Background/Aims: Hepatocellular carcinomas (HCC) often show resistance to the effects of transforming growth factor-β(TGF-β). This study focuses on molecular mechanisms of this resistance to explore ways to overcome it. Methods: Transcription and protein expression of TGF-βtype I and type II receptors (TGF-βRI/RII) were analyzed in clinical HCCs and the human hepatoma cell lines HuH-7 and HepG2. HuH-7 cells were transiently and stably transfected with a constitutively active TGF-βRI mutant (CATGF-βRI). Resulting growth kinetics, integrin expression, invasiveness, TGF-β-mediated activation of human plasminogen activator inhibitor type-1 (PAI-1) promoter and Smad expression were determined. Results: In clinical HCCs, there was less TGF-βRII (6/10 cases) and more TGF-βRI (8/10 cases) protein expression detectable in tumor compared to adjacent liver tissue. In HuH-7 cells, TGF-βRII expression was likewise decreased. Cells transiently transfected with CA TGF-βRI exhibited strong TGF-β-related PAI-1 promoter activation. Stably transfected cells showed an attenuated response of the PAI-1 promoter, but increased Smad7 expression. Proliferation of stable clones was decreased. There was no change in integrin expression or invasiveness. Conclusions: Decreased TGF-βRII protein expression might cause TGF-βresistance in a subset of clinical HCCs. Stable transfection with CA TGF-βRI reverses this in HuH-7 cells without increasing invasiveness.

关键词： TGF-β受体肝细胞癌 I型受体突变体种组侵袭力瞬时转染整联蛋白稳定转染抑制作用

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甲氨蝶呤治疗43例顽固性皮肤红斑狼疮患者的有效性和安全性回顾研究

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世界核心医学期刊文摘（皮肤病学分册） 2005年第10期1卷 32-33页

作者： Wenzel J Brhler S Bauer R 罗素菊 Department of Dermatology University of Bonn Sigmund-Freud-Strasse 25 53105 Bonn Germany

Background:The therapy of cutaneous lupus erythematosus (CLE) is often challenging, especially in patients resistant to topical treatment and established first-line systemic drugs such as antimalarials. Systemic corticosteroids are effective, but their use is limited due to well-known side-effects, especially in long-term treatment. In recent years several other immunosuppressive agents have been successfully applied in CLE. However, there are no large studies or explicit guidelines on the use of these drugs in CLE. Objectives:To perform a retrospective investigation of the efficacy of low-dose methotrexate (MTX) in the treatment of CLE. Methods:One hundred and thirty-nine patients with CLE were seen at our department between 2001 and 2003, of whom 43 patients required low-dose MTX. All had histologically confirmed CLE lesions. Clinical data including disease activity, additional treatment, laboratory parameters and side-effects were recorded carefully at the time of presentation. Statistical analyses were performed by paired nonparametric Wilcoxon test and Student’s t-test using SPSS 11 software. Results:MTX led to a highly significant (P < 0.01) decline in disease activity. An improvement of the cutaneous lesions was recorded in nearly all patients treated with MTX (42 of 43; 98%). Severe side-effects necessitating discontinuation of MTX treatment were recorded in seven patients (16%), which quickly resolved when MTX was discontinued. Life-threatening complications were not observed. Intravenous application was tolerated better than oral administration. Interestingly, we observed a significant increase in circulating lymphocyte numbers in patients with lymphopenia ( < 1.0×109 cells L-1) prior to MTX treatment. Conclusions:Our study supports earlier findings reporting the efficacy of low-dose MTX in CLE lesions, particularly in recalcitrant clinical courses. MTX treatment appears to be safe if patients are carefully selected and monitored, with particular attention

关键词：皮肤红斑狼疮甲氨蝶呤回顾研究淋巴细胞减少症抗疟药指导方案免疫抑制剂大样本研究疾病活动度及已

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癫痫发作的可预测性研究

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世界核心医学期刊文摘（神经病学分册） 2005年第8期1卷 25-26页

作者： Mormann F. Kreuz T. Rieke C. 高中宝 Department of Epileptology University of Bonn Sigmund-Freud-Strasse 25 53105 Bonn Germany

Objective: An important issue in epileptology is the question whether informat ion extracted from the EEG of epilepsy patients can be used for the prediction o f seizures. Several studies have claimed evidence for the existence of a pre-se izure state that can be detected using different characterizing measures. In thi s paper, we evaluate the predictability of seizures by comparing the predictive performance of a variety of univariate and bivariate measures comprising both li near and non-linear approaches. Methods: We compared 30 measures in terms of th eir ability to distinguish between the interictal period and the pre-seizure pe riod. After completely analyzing continuous inctracranial multi-channel recordi ngs from five patients lasting over days, we used ROC curves to distinguish betw een the amplitude distributions of interictal and preictal time profiles calcula ted for the respective measures. We compared different evaluation schemes includ ing channelwise and seizurewise analysis plus constant and adaptive reference le vels. Particular emphasis was placed on statistical validity and *** sults: Univariate measures showed statistically significant performance only in a channelwise, seizurewise analysis using an adaptive baseline. Preictal changes for these measures occurred 5-30 min before seizures. Bivariate measures exhib ited high performance values reaching statistical significance for a channelwise analysis using a constant baseline. Preictal changes were found at least 240 mi n before seizures. Linear measures were found to perform similar or better than nonlinear measures. Conclusions: Results provide statistically significant evide nce for the existence of a preictal state. Based on our findings, the most promi sing approach for prospectiveseizure anticipation could be a combination of biva riate and univariate measures. Significance: Many measures reported capable of s eizure prediction in earlier studies are found to be insignificant i

关键词：发作间期预测性研究癫痫病非线性关系参考水平评价计划有效性评估双变量试验结果单变量

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Bone cement adhesion on ceramic surfaces—Surface activation of retention surfaces of knee endoprostheses by atmospheric pressure plasma *** surface treatment

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Journal of Advanced Ceramics 2016年第2期5卷 137-144页

作者： B.MARX C.MARX R.MARX U.REISGEN D.C.WIRTZ ISF Welding and Joining Institute RWTH Aachen University Pontstrasse 49 52062 Aachen GermanyCC&A Medical Components Ltd. Center for Biomedical Engineering Pauwelsstrasse 17 52074 Aachen Germany CC&A Medical Components Ltd. Center for Biomedical Engineering Pauwelsstrasse 17 52074 Aachen Germany ISF Welding and Joining Institute RWTH Aachen University Pontstrasse 49 52062 Aachen Germany Orthopaedics and Traumatology Clinic University Hospital Bonn Sigmund-Freud-Strasse 25 53127 Bonn Germany

CoCrMo alloys are contraindicated for allergy sufferers. For these patients, uncemented and cemented prostheses made of titanium alloy are indicated. Knee prostheses machined from that alloy, however, may have poor tribological behavior. Therefore, for allergy sufferers, knee replacements in form of cemented high-strength oxide ceramic prostheses which reveal excellent tribological behavior are suitable. In addition, the rate of particle induced aseptic loosening may be reduced. For adhesion of bone cement, the smooth ceramic surface, however, exposes inefficient mechanical retention spots as compared with a textured metal surface. Undercuts generated by corundum blasting, which in the short and intermediate term are highly efficient on a CoCrMo surface, are not appropriate on a ceramic surface due to the brittleness of ceramics. The corresponding textures may initiate cracks which will weaken the strength of a ceramic prosthesis. Due to the lack of textures, mechanical retention is poor or even not existent. Micromotions are facilitated and early aseptic loosening is predictable. Instead silicoating of the ceramic surface will allow specific adhesion and result in better hydrolytic stability of bonding, thereby preventing early aseptic loosening. Silicoating, however, presupposes a clean and chemically active surface which may be achieved by atmospheric plasma or thermal surface treatment. In order to evaluate the effectiveness of silicoating, the bond strengths of atmospheric plasma versus thermal surface treated and silicoated ZPTA (zirconia platelets toughened alumina) surfaces were compared with “as-fired” surfaces by utilizing TiAlV probes (diameter: 6 mm) for traction–adhesive strength test. After preparing samples for traction–adhesive strength test (sequence: ceramic substrate, silicate layer and penetrated silane, protective lacquer (PolyMA), bone cement, TiAlV probe), they were aged up to 150 days at 37°C in Ringer’s solution. The bond strengths observed

关键词： total knee replacement out of oxide ceramics aseptic loosening allergenic potential atmospheric plasma treatment silicoating hydrolytic stability

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具有尿失禁临床症状的病人3T动态骨盆底MRI——初步结果

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国际医学放射学杂志 2009年第1期32卷 91-92页

作者： N. Morakkabati -Spitz J. Gieseke W.A. Willinek P.J. Bastian B. Schmitz F. Trber 鞠志国 Department of Radiology University of BonnSigmund - Freud-Strasse 25D-53105BonnGermany

前瞻性评估尿失禁病人3T动态骨盆底MRI的可行性、影像质量及诊断正确性．并与1．5T MRI表现对照。10例诊断为尿失禁的病人（具有临床症状、临床检查、盆腔超声）在同一天随机先后分别行1．5T和3．0T动态平衡FFE（B-FFE）序列检查。3．0T... 详细信息

前瞻性评估尿失禁病人3T动态骨盆底MRI的可行性、影像质量及诊断正确性．并与1．5T MRI表现对照。10例诊断为尿失禁的病人（具有临床症状、临床检查、盆腔超声）在同一天随机先后分别行1．5T和3．0T动态平衡FFE（B-FFE）序列检查。3．0T和1．5T采用相同的空间分辨率（1．5mm×1．5mm×8mm）和时间分辨率（0．44s）。

关键词：高场盆底 MRI

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儿童颞叶癫痫手术后的功能恢复更好

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世界核心医学期刊文摘（神经病学分册） 2006年第6期2卷 55-56页

作者： Gleissner U. Sassen R. Schramm J. 周永 Department of Epileptology University of Bonn Sigmund-Freud Strasse 25 53105 Bonn Germany Dr.

The purpose of our study is to evaluate whether children recover better than adults from memory deficits as a consequence of temporal lobe surgery. We compared 3 and 12 month outcomes obtained in children and adults with medically refractory epilepsy. Each candidate underwent temporal lobe resection for seizure control and children were matched with regard to pathology, onset of epilepsy, side of surgery and type of surgery with adults (N = 30 for each group, mean age at surgery 13 versus 30 years). Three months after surgery, both left-resected groups displayed a significant decline in verbal learning capacity. During the following 9 months, only the children recovered and were able to reach their preoperative level 1 year after surgery. The left-resected adults remained, for the most part, on their low level and one year after surgery, they were still significantly worse than at the time of their preoperative examination. The right-resecte d adults experienced a deterioration in visual memory 1 year after surgery relative to the results of the short-term follow-up; the children improved. The children also had a better outcome with regard to attentional functions and, as a trend, a better seizure outcome (Engel Outcome 1-1 year after surgery: 63%adult s, 80%paediatric patients). Our neuropsychological data provide evidence of greater plasticity and compensational capacity in childhood. The results can be taken as a strong argument for early surgical intervention.

关键词：儿童患者颞叶癫痫手术后功能恢复颞叶切除术语言学习能力癫痫患者成人药物成人患者早期手术治疗

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Design,delivery and efficacy testing of therapeutic nucleic acids used to inhibit hepatitis C virus gene expression in vitro and in vivo

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World Journal of Gastroenterology 2000年第5期6卷 626-629页

作者： Wolfgang H.Caselmann Matthias Serwe Thomas Lehmann János Ludwig Brian S.Sproat Joachim W.Engels Department of Medicine I University of BonnSigmund-Freud-Str.25D-53105 BonnGermany Institute for Organic Chemistry University of FrankfurtD - 60439 Frankfurt/MainGermany Innovir GmbH D - 37124 RosdorfGermany

Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated *** this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental *** oligodeoxynucleotides(ODN) are

关键词： hepatitis C-like viruses/therapy gene expression in vitro in vivo nucleic acids/therapeutic use cytomegalovirus

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在皮肤型红斑狼疮中趋化因子受体CCR4及其配体胸腺和活化调节趋化因子/CCL17对淋巴细胞的趋化作用

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世界核心医学期刊文摘（皮肤病学分册） 2005年第11期1卷 6-7页

作者： Wenzel J. Henze S. Wrenkmper E. 刘安 Dr. Department of Dermatology University of Bonn Sigmund-Freud-Strasse 25 53105 Bonn Germany

Skin-infiltrating T lymphocytes are thought to play a major role in the pathogenesis of cutaneous lupus erythematosus (CLE). In this study, we investigated the role of the chemokine receptor 4 (CCR4) and its ligand thymus-and activation-regulated chemokine (TARC/CCL17) for the recruitment of T cells in inflamed skin of patients with CLE. We found significant numbers of CCR4+T lymphocytes in the skin of all patients with CLE. Interestingly, a subset of patients with disseminated scarring skin involvement were characterized by both lesional and circulating CD8+T cells expressing CCR4. Destruction of epidermal and adnexal structures was histomorphologically associated with CCR4+cytotoxic T cells invading basal layers of the epidermis where keratinocytes showed apoptotic death. The CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and elevated in the serum of CLE patients. The functional relevance of lymphocytic CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration assays. Our investigations suggest that CCR4 and TARC/CCL17 play a role in the pathophysiology of CLE. In particular, cytotoxic CD8+T cells expressing CCR4 appear to be involved in scarring subtypes of CLE.

关键词：皮肤型红斑狼疮 CCL17 趋化因子受体趋化作用角质形成细胞皮肤浸润瘢痕性表皮基底层组织形态学病理生理学

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Role of rumination in the relationship between metacognition and shyness

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World Journal of Psychiatry 2018年第4期8卷 108-113页

作者： Sara Palmieri Giovanni Mansueto Simona Scaini Francesca Fiore Sandra Sassaroli Giovanni M Ruggiero Rosita Borlimi Bernardo J Carducci Studi Cognitivi Cognitive Psychotherapy School and Research Center Department of Psychology Sigmund Freud University Psicoterapia Cognitiva e Ricerca Cognitive Psychotherapy School Shyness Research Institute Indiana University Southeast

AIM To explore the association between metacognitive beliefs, rumination and shyness in a non-clinical sample of adults. METHODS One hundred and three healthy subjects from the general population were enrolled in the study. Shyness was evaluated using the Revised Cheek and Buss Shyness Scale, rumination was assessed using the Ruminative Response Scale, metacognition was evaluated using the MetaCognitions Questionnaire 30, and anxiety levels were measured using the State Trait Anxiety Inventory form Y. Correlation analyses, mediation models and 95% bias-corrected and accelerated(BCaCI) bootstrapped analyses were performed. Mediation analyses were adjusted for sex and anxiety. RESULTS Shyness, rumination and metacognition were significantly correlated(P < 0.05). The relationship between metacognition and shyness was fully mediated by rumination(Indirect effect: 0.20; 95% BCaCI: 0.08-0.33).CONCLUSION These findings suggest an association between metacognition and shyness. Rumination mediated the relationship between metacognition and shyness, suggesting that rumination could be a cognitive strategy for shy people. Future research should explore the relationship between these constructs in more depth.

关键词： Social anxiety Shyness Rumination Postevent Metacognitive beliefs

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