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Colorectal carcinogenesis-update and perspectives

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world Journal of Gastroenterology 2014年第48期20卷 18151-18164页

作者： hans Raskov hans-Christian Pommergaard jakob Burcharth Jacob Rosenberg Speciall?gecentret ved Diakonissestiftelsen 2000 Frederiksberg Denmark Department of Surgery Herlev Hospital University of Copenhagen DK-2730 Herlev Denmark

Colorectal cancer(CRC)is a very common malignancy in the western world and despite advances in surgery,chemotherapy and screening,it is still the second leading cause of cancer deaths in this part of the *** factors are found important in the development of CRC including colonocyte metbolism,high risk luminal environment,inflammation,as well as lifestyle factors such as diet,tobacco,and alchohol *** recent years focus has turned towards the genetics and molecular biology of CRC and several interesting and promising correlations and pathways have been *** major genetic pathways of CRC are the Chromosome Instability Pathway representing the pathway of sporadic CRC through the K-ras,APC,and P53 mutations,and the Microsatellite Instability Pathway representing the pathway of he re di t ar y non-polyposis c olon c anc e r t hrough mutations in mismatch repair *** identify early cancers,screening programs have been initiated,and the leading strategy has been the use of faecal occult blood testing followed by colonoscopy in positive *** the treatment of colorectal cancer,significant advances have been made in the recent *** molecular targets of CRC include at least two important cell surface receptors:the epidermal growth factorreceptor and the vascular endothelial growth factor *** genetic and molecular knowledge of CRC has widen the scientific and clinical perspectives of diagnosing and ***,despite significant advances in the understanding and treatment of CRC,results from targeted therapy are still not *** studies will determine the role for this new treatment modality.

关键词： Colorectal carcinogenesis Risk factors Microbiology Genetics Diet Microbiome Inflammation

Philosophy and Theology in the Islamic Culture： Al-Farabis De scientiis

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Journal of Philosophy Study 2011年第1期1卷 41-51页

作者： jakob hans Josef Schneider Universidade Federal de Uberlandia

In this paper, the author refers to the Latin translation of the Kitab Ihsa ＇al＇ Ulum of Al-Frabi made by Dominicus Gundissalinus in the Xllth Century in Toledo, Spain. This text under the Latin title De scientiis was one of the most influential texts of the Arab and Persian world in the western Latin Europe. It is an introductory text into all until known sciences written for students and laymen （illiterate） who want to study one of these sciences. The text of Al-Farabi discusses the seven liberal arts, all of the works on physics of Aristotle and includes some reflexions on metaphysics, political philosophy and theology. There are two important points：（1） All sciences have a theoretical and practical aspect. All sciences are sciences of principles and causes and their application to the practical world. （2） The so called prima philosophia is the political philosophy and not metaphysics. In this respect, Al-Farabi subordinates theology as a science of the religious laws to politics as a science of civil laws. In the same respect, he combines, under the famous sentence of Plato that philosophers are the governors and the very well companions of mankind, politics with theology

关键词： Muslim philosophy political philosophy seven liberal arts medieval philosophy theology Plato Aristotle

Identification of CD13,CD107a,and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-de-pendent upregulation

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Cell Research 2005年第5期15卷 325-335页

作者： Florian HENNERSDORF,Stefan FLORIAN,Andreas jakob,Katharina BAUMGRTNER,Karoline SONNECK,Alfred NORDHEIM,Tilo BIEDERMANN,Peter VALENT,hans-Jrg BüHRING University Clinic of Tübingen Department of Internal Medicine II Division of Hematology and Immunology Tübingen Germany Medical University Clinic of Vienna Department of Internal Medicine I Division of Hematology and Hemostaseology Vienna Austria University of Tübingen Proteome Center Tübingen Germany University Clinic of Tübingen Department of Internal Medicine II Division of Hematology and Immunology Tübingen Germany Medical University Clinic of Vienna Department of Internal Medicine I Division of Hematology and Hemostaseology Vienna Austria University of Tübingen Proteome Center Tübingen Germany University Clinic of Tübingen Department of Dermatology Tübingen Germany Medical University Clinic of Vienna Department of Internal Medicine I Division of Hematology and Hemostaseology Vienna Austria University Clinic of Tübingen Department of Internal Medicine II Division of Hematology and Immunology Tübingen Germany

Using two-colour flow cytometry >200 antibodies submitted to the 8th International workshop of Human Leukocyte Differentiation Antigens (HLDA8) have been analyzed for their reactivity with resting and activated CD203c+ basophils. Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor (FcεRI). These include antibod- ies against CD164 (wS-80160, clone N6B6 and wS-80162, clone 67D2), as well as two reagents with previously unknown specificities that were identified as CD13 (wS-80274, clone A8) and CD107a (wS-80280, clone E63-880). The activation patterns followed either the “CD203c-like” or “CD63-like” activation profile. The CD203c profile is characterized by a rapid and significant upregulation (of CD13, CD164, and CD203c), reaching maximum levels after 5- 15 min of stimulation. The phosphoinositide-3-kinase (PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced a rapid and FcεRI-independent upregulation within 1-2 min. In the CD63 profile, maximum upregulation (of CD63 and CD107a) was detected only after 20-40 min, and upregulation by TPA reached maximum levels after 60 min. In summary, our data identify CD13, CD107a, and CD164 as novel basophil-activation antigens. Based on time kinetics of upregulation, we hypothesize that molecules of the “CD203c group” and the “CD63 group” are linked to two different mechanisms of basophil activation.

关键词： CD203c CD164 CD63 CD107a basophil activation basophil marker.

Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

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Cancer Biology & Medicine 2021年第1期18卷 245-255页

作者： Andreas Marx Lena Koopmann Doris Hoflmayer Franziska Büscheck Claudia Hube-Magg Stefan Steurer Till Eichenauer Till S.Clauditz waldemar wilczak Ronald Simon Guido Sauter jakob R.Izbicki Hartwig Huland hans Heinzer Markus Graefen Alexander Haese Thorsten Schlomm Christian Bernreuther Patrick Lebok Sarah Bonk Institute of Pathology Klinikum FurthFurth 90766Germany Institute of Pathology University Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Urology University Medical Center Hamburg-EppendorfHamburg 20246Germany General Visceral and Thoracic Surgery Department and ClinicUniversity Medical Center Hamburg-EppendorfHamburg 20246Germany Martini-Clinic Prostate Cancer CenterUniversity Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Urology Charité-Universit?tsmedizin BerlinBerlin 10117Germany

Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel *** expression is restricted to prostate epithelial *** exact function is *** study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa ***:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer ***7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(Pwith negative *** ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(Pwed that low ANO7 expression was linked to TMPRSS2:ERG fusions(Pwell as presence of 9 of 11 chromosomal deletions(Pw ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT ***:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in ***7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa.

关键词： ANO7 immunohistochemistry prognosis prostate cancer

Contrast enhancement of vascular walls of intracranial high flow malformations in black blood MRI indicates high inflammatory activity

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Chinese Neurosurgical Journal 2018年第2期4卷 89-93页

作者： Athanasios K.Petridis Maxine Dibue-Adjei Jan F.Cornelius Marian Preetham Suresh Lan Li Marcel A.Kamp Yousef Abusabha Bernd Turowski hans jakob Steiger Rebecca May Department of Neurosurgery Heinrich Heine UniversityDuesseldorfGermany LivaNova Deutschland GmbH(a LivaNova PLC-owned subsidiary) Lindberghstr 25D-80939 MunichGermany Diagnostic and Interventional Neuroradiology Heinrich Heine UniversityDuesseldorfGermany Department of Neurosurgery Niederrhein HospitalDuisburgGermany

Background: There are controversies concerning the natural history of arteriovenous malformations (AVMs) in literature and it is not clear which AVMs should be treated and which should be just observed. Objective criteria beyond growth in serial MRIs or angiographies are needed. The use of black blood MRI is currently under investigation for evaluating the rupture risk of cerebral aneurysms, however its use for assessment of AVMs has yet to be evaluated. we therefore conducted a feasibility study on the application of black blood MRI (bbMRI) in AVMs to assess rupture risk. Methods: Retrospective study of 10 patients with intracranial AVMs and 4 patients with arteriovenous fistulas who received a black blood MRI before treatment. Results: AVM niduses (9/10) show contrast enhancement irrespective of rupture or size. All arteriovenous fistulas (4/4) were contrast enhancing irrespective of rupture. Conclusion: High flow malformations are in a permanent stage of inflammation which does not seem to allow conclusions on their rupture risk at the current stage. BbMRI is a feasible method of identifying inflammation in AVMs and arteriovenous fistulas. However, future prospective studies are needed to evaluate whether bbMRI contrast enhancement correlates with rupture risk.

关键词： Arteriovenous malformation Arteriovenous fistula Black blood MRI Inflammation

Cavernous brain malformations and their relation to black blood MRI in respect to vessel wall contrast enhancement

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Chinese Neurosurgical Journal 2018年第2期4卷 65-68页

作者： Athanasios K.Petridis Marian P.Suresh Jan F.Cornelius Richard Bostelmann Maxine Dibué-Adjei Lan Li Marcel A.Kamp hans jakob Steiger Bernd Turowski Rebecca May Department of Neurosurgery Heinrich Heine University DüsseldorfMoorenstr 540225 DüsseldorfGermany Diagnostic and Interventional Neuroradiology Heinrich Heine University DüsseldorfDüsseldorfGermany LivaNova Deutschland(a LivaNova PLC-owned subsidiary) Lindberghstr 2580939 MunichGermany

Background: Inflammatory responses are implicated as crucial patho-mechanisms of vascular brain malformations. Inflammation is suggested to be a key contributor to aneurysm rupture; however it is unclear whether inflammation contributes similarly to bleeding of cerebral cavernous malformations (CCMs). Black blood MRI is a sequence which identifies inflammation in blood vessel walls and in the present study is used to detect inflammatory response in CCMs. Methods: Fifteen patients with 17 CCMs treated in our department in 2017 were retrospectively analysed. All patients received black blood MRIs and the results were analysed in correlation with, size and bleeding of CCMs. Results: Size and bleeding status of CCMs did not correlate with contrast enhancement in the CCM wall. One of 3 patients with bleeding displayed contrast enhancement in black blood MRI, whereas the others had non enhancing lesions. Because of the small number of cases a statistical analysis was not performed. Conclusion: In this limited cohort, inflammatory reactions in CCMs could not be detected by black blood MRI suggesting that the level of inflammation is minimal in these lesions and those different patho-mechanisms play a more important role in the rupture of CCMs.

关键词： Cavernous malformations Inflammation Black blood MRI

测定血清S100蛋白用于诊断克-雅病:前瞻性病例对照研究

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英国医学杂志中文版 1998年第1期1卷 22-27页

作者： Markus Otto Jens wiltfang Ekkehard Schtz Ingo Zerr Anke Otto Annette Pfahlberg Olaf Gefeller Manfred Uhr Armin Giese Thomas weber hans A Kretzschmar Sigrid Poser 张星虎 Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 Cttingen Germany group Leaderlaboratory diagnosis of CJD Psychiatrische Klinik und Poliklinik Georg-AugustUniversitt Gttingen senior research fellow Abteilung Klinische Chemie Georg-August-Universitt Gttingenresearch fellow Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 Cttingen Germany research fellow Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 GttingenGermany research fellow Abteilung Klinische Chemie Georg-August-Universitt Gttingen statistician Abteilung Medizinische Statistik Georg-August-Universitt Gttingen associate professor of medical statistics continued over Max-Planck lnstitut ftir Psychiatrie Kraepelinstrasse 10 D-80804 MunichGermany research fellow Institut fr Neuropathologie Georg-August-Universitt Gttingen research fellow Neurologische Abteilung Marienkrankenhaus Hamburg Alfredstrasse 9D-22087 Hamburg Germany headdepartment of neruology Institut fr Neuropathologie Georg-August-Universitt Gttingen headdepartment of neuropathology Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 Gttingen Germany headedidemiology and early diagnosis of CJD

目的:分析克-雅病(Creutzfeldt-jakob dis-ease,CJD)患者及对照组血清中脑特异性 S100蛋白浓度。设计:前瞻性病例对照研究。研究单位:国家 CJD 监测站。研究对象:224例疑为 CJD 的转诊患者及35例无痴呆的对照病例。主要结果测定:CJD 患... 详细信息

目的:分析克-雅病(Creutzfeldt-jakob dis-ease,CJD)患者及对照组血清中脑特异性 S100蛋白浓度。设计:前瞻性病例对照研究。研究单位:国家 CJD 监测站。研究对象:224例疑为 CJD 的转诊患者及35例无痴呆的对照病例。主要结果测定:CJD 患者、其他疾病引起的痴呆患者及对照组血清 S100浓度。结果:224例疑为 CJD 的患者中,65例经病理证实确诊;6例有基因突变而肯定诊断;43例很可能患 CJD;36例可能患 CJD;74例患有其他疾病。108例为肯定或很可能 CJD 患者,其血清 S100浓度中位数为395 pg/ml(SD 387 pg/ml)。这明显高于患其他疾病的74例患者(S100浓度中位数为109pg/ml,SDl77pg/ml;P=0.0001)。以213pg/ml为界值,S100测定用于 CJD 诊断的敏感性为77.8%(95%的可信区间为66.8%～85.2%),特异性为81.1%(70.3%～89.3%)。在 Kaplan-Meier 曲线上,不同浓度 S100患者的存活时间差异有显著性(P=0.023)。结论:S100血清浓度测定是一种有价值的工具,在 CJD 的鉴别诊断中,较测定脑脊液更有价值。尚需更多的研究以确定连续测定是否有助于提高此病的诊断准确性。

关键词：克-雅病 S100蛋白脑特异性存活时间差异有显著性鉴别诊断基因突变无痴截点病例对照研究