46 results on '"Faller G"'
Search Results
2. Beschäftigung in Privathaushalten unter den Bedingungen der Covid-19-Pandemie
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Geiger, L, Faller, G, Geiger, L, and Faller, G
- Published
- 2022
3. STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett’s adenocarcinomas
- Author
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Timme, S, Ihde, S, Fichter, C D, Waehle, V, Bogatyreva, L, Atanasov, K, Kohler, I, Schöpflin, A, Geddert, H, Faller, G, Klimstra, D, Tang, L, Reinheckel, T, Hauschke, D, Busch, H, Boerries, M, Werner, M, and Lassmann, S
- Published
- 2014
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4. An extract of Pelargonium sidoides (EPs 7630) inhibits in situ adhesion of Helicobacter pylori to human stomach
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Wittschier, N., Faller, G., and Hensel, A.
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Medical research -- Analysis ,Medicine, Experimental -- Analysis ,Helicobacter pylori -- Analysis -- Research ,Geraniums -- Research -- Dosage and administration -- Analysis ,Biological sciences ,Health ,Science and technology - Abstract
Abstract Root extract from Pelargonium sidoides DC is used therapeutically as antimicrobial agent against infections of the respiratory system. In order to elucidate possible modes of actions we investigated the [...]
- Published
- 2007
5. Long-term acid suppression by omeprazole in gastro-oesophageal reflux disease patients does not lead to anti-gastric autoantibody production
- Author
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BERGMAN, M. P., KLINKENBERG-KNOL, E. C., FALLER, G., VAN DER AAR, A., LAKHAI, W., VANDENBROUCKE-GRAULS, C. M. J. E., KUIPERS, E. J., and APPELMELK, B. J.
- Published
- 2005
6. Juvenile idiopathic arthritis flare due to rice bodies in the knee of a 10-year-old girl
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Faller, G, primary, Haagensen, M, additional, and Barrow, M, additional
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- 2018
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7. Unklarer Tumor der Keilbeinhöhle bei einer Patientin mit Horner-Syndrom
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Runge, S, Dimmler, A, Faller, G, and Mertens, J
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Einleitung: Tumoren der Nasennebenhöhlen sind mit 0,2–0,8% aller Malignome selten und lediglich ein kleiner Anteil hiervon sind Fernmetastasen anderer Tumorentitäten. Das Mammakarzinom wird in der Literatur als der dritthäufigste Tumor, der in die Nasennebenhöhlen fernmetastasiert, beschrieben. Fallbeschreibung: Berichtet wird von einer 60-jährigen Patientin die uns durch die Augenklinik des Hauses mit einem Horner-Syndrom vorgestellt wurde. Seit einer Woche bestünden Doppelbilder, eine subjektive Sehminderung sowie eine Lidschwäche des rechten Auges, des Weiteren diffuse Kopfschmerzen. In der Vorgeschichte bestand ein 2005 erstdiagnostiziertes pT1 pN0 M0 ductal-invasives Mammakarzinom, seit 2011 kam es zum Auftreten von Fernmetastasen, ohne Befall des Schädels bis dato. Die Bildgebung erbrachte eine beidseitige Verlegung der Keilbeinhöhle sowie der hinteren Siebbeinzellen, die in Kombination mit den angegebenen Kopfschmerzen initial auf einen eher entzündlichen Prozess schließen ließen. Des Weiteren war eine inhomogene Knochenbinnenstruktur im Bereich des Clivus auffällig. Im Rahmen einer endonasalen Siebbein- und Keilbeinhöhlenoperation ergaben sich histologisch ausgedehnte Mammakarzinominfiltrate beidseits. Schlussfolgerungen: Symptome bei Metastasen der Nasennebenhöhlen sind meistens unspezifisch und können eine akute Sinusitis mit begleitender orbitaler Komplikation vortäuschen. Neben der arteriellen hämatogenen Metastasierung erfolgt ein möglicher Tumorbefall der Keilbeinhöhle über Venenplexus im Bereich des Clivus, wie auch in unserem Fall denkbar. Schlussfolgernd sollte bei bekannter Tumorerkrankung in der Vorgeschichte und unklarer Sinusitis bzw. Nasennebenhöhlenverschattung in der Bildgebung immer auch an eine mögliche Fernmetastasierung gedacht werden. Der Erstautor gibt keinen Interessenkonflikt an., GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 11:Doc107; ISSN 1865-1038
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- 2015
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8. Anspruch und Wirklichkeit: Zum aktuellen Stand der betrieblichen Gesundheitsförderung
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Faller, G, Faller, G ( G ), Bauer, Georg F, Jenny, Gregor James; https://orcid.org/0000-0002-9946-3667, Faller, G, Faller, G ( G ), Bauer, Georg F, and Jenny, Gregor James; https://orcid.org/0000-0002-9946-3667
- Published
- 2010
9. Work-Life-Balance – ein Thema für die betrieblich Gesundheitsförderung
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Faller, G, Faller, G ( G ), Hämmig, O, Bauer, G, Faller, G, Faller, G ( G ), Hämmig, O, and Bauer, G
- Published
- 2010
10. Vereinbarkeit von Beruf und Privatleben - ein wichtiges Thema der Betrieblichen Gesundheitsförderung
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Faller, Gudrun, Faller, G ( Gudrun ), Hämmig, Oliver, Bauer, Georg F, Faller, Gudrun, Faller, G ( Gudrun ), Hämmig, Oliver, and Bauer, Georg F
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- 2016
11. Gastrin mediated down regulation of ghrelin and its pathophysiological role in atrophic gastritis
- Author
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Rau, T. T., Sonst, A., Rogler, A., Burnat, G., Neumann, H., Oeckl, K., Neuhuber, W., Dimmler, A., Faller, G., Brzozowski, T., Hartmann, A., and Konturek, P. C.
- Published
- 2013
12. Solitary fibrous tumor in the tongue. Case report and review of the literature [Solitärer fibröser tumor der zunge. Fallbericht und literaturübersicht]
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Nkenke, E. Fenner, M. Lell, M. Vairaktaris, E. Neukam, F.W. Faller, G.
- Abstract
Solitary fibrous tumors (SFT) are rare, mostly fibroblastic tumors usually situated in the pleura. Extrapleural manifestations have been described. However, the oral cavity is an uncommon localisation of this tumor. We report the very unusual case of an SFT affecting the tongue that could be removed completely because of its clear delineation. Intraoperative incisional biopsies were used to exclude malignancy. For definitive classification of the tumor, additional histopathologic examinations had to be carried out. Because SFT exhibit malignant behavior only in exceptional cases and their recurrence after complete removal has never been encountered, surgery can focus on the preservation of undisturbed function of the tongue. © 2006 Springer Medizin Verlag.
- Published
- 2007
13. Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis
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Schmaus, A, primary, Klusmeier, S, additional, Rothley, M, additional, Dimmler, A, additional, Sipos, B, additional, Faller, G, additional, Thiele, W, additional, Allgayer, H, additional, Hohenberger, P, additional, Post, S, additional, and Sleeman, J P, additional
- Published
- 2014
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14. STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett’s adenocarcinomas
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Timme, S, primary, Ihde, S, additional, Fichter, C D, additional, Waehle, V, additional, Bogatyreva, L, additional, Atanasov, K, additional, Kohler, I, additional, Schöpflin, A, additional, Geddert, H, additional, Faller, G, additional, Klimstra, D, additional, Tang, L, additional, Reinheckel, T, additional, Hauschke, D, additional, Busch, H, additional, Boerries, M, additional, Werner, M, additional, and Lassmann, S, additional
- Published
- 2013
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15. Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: Results from a population-based case-control study.
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Heuschmann PU, Neureiter D, Gesslein M, Craiovan B, Maass M, Faller G, Beck G, Neundoerfer B, Kolominsky-Rabas PL, Heuschmann, P U, Neureiter, D, Gesslein, M, Craiovan, B, Maass, M, Faller, G, Beck, G, Neundoerfer, B, and Kolominsky-Rabas, P L
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- 2001
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16. Demographics and presenting clinical features of childhood systemic lupus erythematosus
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Faller, G, primary, Kala, U K, additional, Thomson, P D, additional, and Hahn, D, additional
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- 2005
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17. Mimétisme moléculaire entre Helicobacter pylori et l'hôte
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Appelmelk, B.J., Straver, S., Verboom, T., Kuipers, E.J., Claeys, D., Faller, G., Kirchner, T., Negrini, R., Krakowka, S., Pont, J.J.H.H.M. de, Simoons-Smit, I., Maaskant, J.J., Broucke-Grauls, C.M.J.E. van de, Appelmelk, B.J., Straver, S., Verboom, T., Kuipers, E.J., Claeys, D., Faller, G., Kirchner, T., Negrini, R., Krakowka, S., Pont, J.J.H.H.M. de, Simoons-Smit, I., Maaskant, J.J., and Broucke-Grauls, C.M.J.E. van de
- Abstract
Item does not contain fulltext
- Published
- 1998
18. Mineral exploration and investment possibilities in Hungary.
- Author
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Bardossy G., Faller G., Fodor B., Foldessy J., Havasi Z., Horvath J., Polgar I., Szabo K., Szots T., Bardossy G., Faller G., Fodor B., Foldessy J., Havasi Z., Horvath J., Polgar I., Szabo K., and Szots T.
- Abstract
There are seven main sections. Section 1, Hungarian mining industry - past, present and future, discusses mineral production, government policies, corporate structures and privatisation for petroleum, gas, carbon dioxide, geothermal energy, thermal water, coal, uranium, bauxite, manganese, base and precious metals, industrial minerals and construction materials. Section 2, Mineral resources and exploration, discusses geology, mineral resources, tonnage and grade, exploration expenditure and the structure and methods of exploration. Section 3, Legal framework of mining, discusses the Concession Act, the Company Act, the Foreign Investment Act and the Mining Act. Section 4, The taxation system, banks, financing and mining, considers the national economy, accounting, taxes, royalties, concession fees, foreign investment, currency and banking. Section 5, Data files, includes details of geological archives, the National Geological Data File, data access, land registries and maps. Section 6, Exploration and mining licences, covers licencing procedures, ownership and royalties. Section 7, Nature and environment versus exploration and mining, discusses the legal framework of environmental protection. Useful addresses and a subject index are included., There are seven main sections. Section 1, Hungarian mining industry - past, present and future, discusses mineral production, government policies, corporate structures and privatisation for petroleum, gas, carbon dioxide, geothermal energy, thermal water, coal, uranium, bauxite, manganese, base and precious metals, industrial minerals and construction materials. Section 2, Mineral resources and exploration, discusses geology, mineral resources, tonnage and grade, exploration expenditure and the structure and methods of exploration. Section 3, Legal framework of mining, discusses the Concession Act, the Company Act, the Foreign Investment Act and the Mining Act. Section 4, The taxation system, banks, financing and mining, considers the national economy, accounting, taxes, royalties, concession fees, foreign investment, currency and banking. Section 5, Data files, includes details of geological archives, the National Geological Data File, data access, land registries and maps. Section 6, Exploration and mining licences, covers licencing procedures, ownership and royalties. Section 7, Nature and environment versus exploration and mining, discusses the legal framework of environmental protection. Useful addresses and a subject index are included.
- Published
- 1993
19. Hierarchic model for considering mining risks in making economical analysis, with special regard to environmental effects.
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Faller G., 15th World mining congress Madrid 25-May-9229-May-92, Fodor B., Toth I., Vojuczki P., Faller G., 15th World mining congress Madrid 25-May-9229-May-92, Fodor B., Toth I., and Vojuczki P.
- Abstract
A concept is described which systematically takes account of all the factors of risk on a uniform basis. The problem of environmental risk is discussed using the example of Hungarian coal and bauxite mines with a karstic water hazard., A concept is described which systematically takes account of all the factors of risk on a uniform basis. The problem of environmental risk is discussed using the example of Hungarian coal and bauxite mines with a karstic water hazard.
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- 1992
20. Estrogen inhibits the response-to-injury in a mouse carotid artery model.
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Sullivan, T R, primary, Karas, R H, additional, Aronovitz, M, additional, Faller, G T, additional, Ziar, J P, additional, Smith, J J, additional, O'Donnell, T F, additional, and Mendelsohn, M E, additional
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- 1995
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21. HAB-1, a new heteromyeloma for continuous production of human monoclonal antibodies
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Faller, G, primary, Vollmers, HP, additional, Weiglein, I, additional, Marx, A, additional, Zink, C, additional, Pfaff, M, additional, and Müller-Hermelink, HK, additional
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- 1990
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22. Antrum- and corpus mucosa-infiltrating CD4(+) lymphocytes in Helicobacter pylori gastritis display a Th1 phenotype.
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Sommer, F, Faller, G, Konturek, P, Kirchner, T, Hahn, E G, Zeus, J, Röllinghoff, M, and Lohoff, M
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In this study, cytokine patterns produced by CD4(+) T cells isolated from antrum or corpus gastral biopsy specimens of 10 patients with Helicobacter pylori-positive gastritis were compared. To this end, expression of intracellular cytokines (interleukin-4 [IL-4] and gamma interferon) and of CD4 was assessed by flow cytometry. Ten to 60% of the isolated CD4(+) T cells produced gamma interferon upon stimulation. With the exception of one patient, IL-4-positive CD4(+) cells were not detected. Therefore, CD4(+) cells infiltrating antrum and corpus stomach mucosa during H. pylori infection show a Th1 phenotype. This polarized Th1-type response may contribute to the inability of the immune system to eradicate H. pylori infection.
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- 1998
23. Some development tendencies of mining technologies under heterogeneous geological conditions.
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Faller G., 14th World mining congress Beijing 14-May-9018-May-90, Gal I., Gebhardt J., Szuts H., Toth M., Vojuczki P., Faller G., 14th World mining congress Beijing 14-May-9018-May-90, Gal I., Gebhardt J., Szuts H., Toth M., and Vojuczki P.
- Abstract
Coal and bauxite reserves in Hungary are often situated in difficult geological conditions, below the karstic water level. A monitoring system has been set up to help preserve the karstic water reservoir and protect the mines against water inrush. Gas and rock outbursts are also a problem and a rock mechanics measuring system is working at the Veszprem coal mine. Block caving with suspended roofs are used in some bauxite mines., Coal and bauxite reserves in Hungary are often situated in difficult geological conditions, below the karstic water level. A monitoring system has been set up to help preserve the karstic water reservoir and protect the mines against water inrush. Gas and rock outbursts are also a problem and a rock mechanics measuring system is working at the Veszprem coal mine. Block caving with suspended roofs are used in some bauxite mines.
24. Work-Life-Balance – ein Thema für die betrieblich Gesundheitsförderung
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Hämmig, O, Bauer, G, University of Zurich, and Faller, G
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610 Medicine & health ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) - Published
- 2010
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25. Early progression and transformation of a splenic diffuse red pulp small B-cell lymphoma with NOTCH1, ARID2, CREBBP, and TNFRSF14 gene mutations.
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Lopedote P, Nawaiseh AA, Malek A, Faller G, Hattar M, Dow E, and Kozyreva O
- Abstract
Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare entity. Diagnosis is typically achieved with splenectomy and most patients remain in remission after this intervention. Hemoglobin value less than 10 g/dL and NOTCH1, TP53, and MAP2K1 gene mutations at diagnosis have been associated with worse outcome. Progression after splenectomy of SDRPL is possible, although transformation to aggressive lymphoma has rarely been reported. We herein report the case of a patient formerly diagnosed with SDRPL with gene mutations involving CREBBP, NOTCH1, ARID2, and TNFRSF14 who transformed to diffuse large B-cell lymphoma six months after splenectomy., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript., (© 2023 The Authors. Published by Elsevier Ltd.)
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- 2023
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26. Future Challenges for Work-Related Health Promotion in Europe: A Data-Based Theoretical Reflection.
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Faller G
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- Europe, Health Promotion, Workplace
- Abstract
This contribution is a theoretical reflection based on statistical and empirical data as well as concepts proposed by other authors or institutions. Based on the thesis that the respective social developments equally influence and limit the orientation and design of workplace health promotion, this article deals with the challenges that arise from the contemporary social, political and economic developments for a needs-oriented and effective workplace health promotion. On the basis of a historical review of the lines of development in workplace health promotion, beginning with the Ottawa Charter in 1986, the field of tension in which work-related health promotion approaches generally operate is first outlined. Based on the results of a keyword search in relevant European statistics databases and specialized databases on the topics of demographic change, labor migration and digitalization and flexibilization of work, current development trends in the world of work are traced, priority desiderata for a future design of health promotion are derived from these, and their chances of realization are reflected upon. On the basis of the data collected, it becomes clear that today's world of work is characterized by multidimensional diversification processes, which are accompanied by the risk of worsening social inequalities. The conclusion is that future concepts of workplace health promotion must be more universal than previous approaches, which are often limited to the focus of individual behavioral prevention. The attempt to promote workplace health promotion with economic benefit arguments also runs the risk of reinforcing social inequality. The task of effective workplace health promotion, conversely, must be to initiate critical reflection on current priorities.
- Published
- 2021
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27. Stigmatization from Work-Related COVID-19 Exposure: A Systematic Review with Meta-Analysis.
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Schubert M, Ludwig J, Freiberg A, Hahne TM, Romero Starke K, Girbig M, Faller G, Apfelbacher C, von dem Knesebeck O, and Seidler A
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- Health Personnel, Humans, SARS-CoV-2, Stereotyping, COVID-19, Occupational Exposure, Occupational Health
- Abstract
Stigmatization from work-related COVID-19 exposure has not been investigated in detail yet. Therefore, we systematically searched three databases: Medline, Embase, and PsychInfo (until October 2020), and performed a grey literature search (until February 2021). We identified 46 suitable articles from 24 quantitative and 11 qualitative studies, 6 systematic reviews, 3 study protocols and 1 intervention. The assessment of stigmatization varied widely, ranging from a single-item question to a 22-item questionnaire. Studies mostly considered perceived self-stigma (27 of 35 original studies) in healthcare workers (HCWs) or hospital-related jobs (29 of 35). All articles reported on stigmatization as a result of work-related COVID-19 exposure. However, most quantitative studies were characterized by convenience sampling (17 of 24), and all studies-also those with an adequate sampling design-were considered of low methodological quality. Therefore, it is not possible to determine prevalence of stigmatization in defined occupational groups. Nevertheless, the work-related stigmatization of occupational groups with or without suspected contact to COVID-19 is a relevant problem and increases the risk for depression (odds ratio (OR) = 1.74; 95% confidence interval CI 1.29-2.36) and anxiety (OR = 1.75; 95% CI 1.29-2.37). For promoting workers' health, anti-stigma strategies and support should be implemented in the workplace.
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- 2021
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28. Right-Sided Diverticulosis and Disparities from Left-Sided Diverticulosis in the Vietnamese Population Living in Boston, Mass., USA: A Retrospective Cohort Study.
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Mehrzad R, Mishra S, Faller G, Memon B, and Fiore J
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- Age Factors, Aged, Boston epidemiology, Colonoscopy, Female, Humans, Male, Middle Aged, Prevalence, Retrospective Studies, Risk Factors, Sex Factors, Vietnam ethnology, White People, Asian, Diverticulosis, Colonic ethnology, Diverticulosis, Colonic pathology
- Abstract
Objective: To report the prevalence, clinical differences and complications of right-sided diverticulosis (RD) and to investigate the potential disparities from left-sided diverticulosis (LD) in the Vietnamese population., Subjects and Methods: A retrospective cohort study was conducted using medical records of Vietnamese-born patients from 2000 to 2013 in a community teaching hospital in Boston, Mass., USA. By simple randomization, a randomized control group of 299 Caucasian patients was also selected from the same time frame [167 males (M) and 132 females (F)]. Colonoscopy reports were reviewed for demographics (age and gender), indication and anatomical location of the colonic diverticulosis (CD), concomitant colonic findings, symptoms, and endoscopic complications., Results: A total of 207 patients were included in the Vietnamese cohort (mean age 61.6 ± 8.9 years). The mean age at first screening colonoscopy was 58.2 ± 7.2 years (114 F/92 M, 55.7/44.4%). Our study identified 104 (50.5%) patients with LD (57 M/47 F), 65 (31.1%) with RD (35 M/30 F) and 38 (18.4%) with both LD and RD (23 M/15 F); 133 (64%) were asymptomatic. A total of 21 (33%) patients with RD were symptomatic. The mean age of the control group was 61.6 ± 8.1 years. The average age at first screening colonoscopy was 52.8 ± 6.4 years. Of the 299 in the Caucasian group, 254 (84.9%) had LD (114 M/140 F), 9 (3.0%) had RD (2 M/7 F) and 36 (12%) had both LD and RD (16 M/20 F); 225 (75%) were asymptomatic and came in for screening colonoscopies. A total of 2 patients (22%) with RD were symptomatic., Conclusion: RD was common in this Vietnamese population, and the prevalence was higher than in the Caucasian control group., (© 2015 S. Karger AG, Basel.)
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- 2015
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29. Juvenile dermatomyositis in South African children is characterised by frequent dystropic calcification: a cross sectional study.
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Faller G, Mistry BJ, and Tikly M
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- Adolescent, Age of Onset, Arthritis etiology, Blood Sedimentation, C-Reactive Protein analysis, Child, Contracture etiology, Creatine Kinase, MM Form blood, Cross-Sectional Studies, Disease Management, Exanthema etiology, Female, Humans, Male, Muscle Weakness etiology, Risk Factors, South Africa, Calcinosis etiology, Dermatomyositis blood, Dermatomyositis complications, Dermatomyositis diagnosis, Dermatomyositis epidemiology, Staphylococcal Infections epidemiology, Vasculitis etiology
- Abstract
Background: To describe Juvenile dermatomyositis (JDM) that has rarely been reported in Sub-Saharan Africa in children., Methods: Retrospective record review of children with JDM attending a tertiary hospital in South Africa., Results: Twenty-one children (16 female, five male) with JDM had a mean (SD) age at presentation of 9.8 (3.3) years. Mean follow-up period was 2.6 (2.2) years. The commonest presenting features were skin rash (71%), muscle weakness (71%), inflammatory arthritis (42%) and calcinosis (29%). The cumulative frequency of calcinosis was 71%. Skin vasculitis was present in 9(43%), and 7 (33%) had Staphylococcus aureus infections. Calcinosis was strongly associated with vasculitis; 11/15 (73.3%) with calcinosis had vasculitis versus 0/6 without vasculitis (p = 0.003). Patients with calcinosis had significantly lower creatinine kinase (CK) levels compared to those without calcinosis [mean (SD) 272 U/L (401) vs. 2414 U/L (3201), respectively, p = 0.016]. All children with calcinosis had Staphylococcus aureus infection, but there was no significant difference in their duration of symptoms to presentation. Joint contractures, occurring in eight patients (38%), were associated with a significantly lower age at presentation [mean (SD) 6.8(2.8) vs. 11.6(2.1) years (no contractures) p = 0.0003], and significantly higher CRP and ESR levels. Three patients were lost to follow-up, two died. In the remaining 16 patients: 10 (47%) experienced remission, 2 relapsed and 4 persistent active disease., Conclusion: African children with JDM have increased vasculitic disease and high levels of calcinosis with low muscle enzymes, particularly CK. Younger children are at higher risk of contractures and disability. Patients are at high risk of developing Staphylococcus aureus infection. Rapid and aggressive therapy is necessary.
- Published
- 2014
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30. Gastrin mediated down regulation of ghrelin and its pathophysiological role in atrophic gastritis.
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Rau TT, Sonst A, Rogler A, Burnat G, Neumann H, Oeckl K, Neuhuber W, Dimmler A, Faller G, Brzozowski T, Hartmann A, and Konturek PC
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- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Child, Child, Preschool, Down-Regulation, Duodenum metabolism, Esophagus metabolism, Female, Gastric Mucosa metabolism, Humans, Infant, Male, Middle Aged, Rats, Rats, Wistar, Receptor, Cholecystokinin B metabolism, Stomach Neoplasms metabolism, Young Adult, Autoimmune Diseases metabolism, Gastrins metabolism, Gastritis, Atrophic metabolism, Ghrelin metabolism
- Abstract
The gastric hormone ghrelin is known as an important factor for energy homeostasis, appetite regulation and control of body weight. So far, ghrelin has mainly been examined as a serological marker for gastrointestinal diseases, and only a few publications have highlighted its role in local effects like mucus secretion. Ghrelin can be regarded as a gastroprotective factor, but little is known about the distribution and activity of ghrelin cells in pathologically modified tissues. We aimed to examine the morphological changes in ghrelin expression under several inflammatory, metaplastic and carcinogenic conditions of the upper gastrointestinal tract. In particular, autoimmune gastritis showed interesting remodeling effects in terms of ghrelin expression within neuroendocrine cell hyperplasia by immunohistochemistry. Using confocal laser microscopy, the gastrin/cholecystokinin receptor (CCKB) could be detected on normal ghrelin cells as well as in autoimmune gastritis. Functionally, we found evidence for a physiological interaction between gastrin and ghrelin in a primary rodent cell culture model. Additionally, we gathered serological data from patients with different basic gastrin levels due to long-term autoimmune gastritis or short-term proton pump inhibitor treatment with slightly reactive plasma gastrin elevations. Total ghrelin plasma levels showed a significantly inverse correlation with gastrin under long-term conditions. Autoimmune gastritis as a relevant condition within gastric carcinogenesis therefore has two effects on ghrelin-positive cells due to hypergastrinemia. On the one hand, gastrin stimulates the proliferation of ghrelinpositive cells as integral part of neuroendocrine cell hyperplasia, while on the other hand, plasma ghrelin is reduced by gastrin and lost in pseudopyloric and intestinal metaplastic areas. Ghrelin is necessary for the maintenance of the mucosal barrier and might play a role in gastric carcinogenesis, if altered under these pre neoplastic conditions.
- Published
- 2013
31. Methylation-dependent activation of CDX1 through NF-κB: a link from inflammation to intestinal metaplasia in the human stomach.
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Rau TT, Rogler A, Frischauf M, Jung A, Konturek PC, Dimmler A, Faller G, Sehnert B, El-Rifai W, Hartmann A, Voll RE, and Schneider-Stock R
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- Adult, Aged, Aged, 80 and over, Azacitidine pharmacology, Base Sequence, Chromatin metabolism, Conserved Sequence genetics, CpG Islands genetics, DNA Methylation drug effects, Female, Gastric Mucosa metabolism, Gastritis genetics, Gastritis pathology, Gene Expression Regulation, Neoplastic drug effects, Homeodomain Proteins metabolism, Humans, Inflammation genetics, Intestinal Mucosa metabolism, Male, Metaplasia, Middle Aged, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding drug effects, Stomach Neoplasms genetics, Stomach Neoplasms pathology, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha pharmacology, Young Adult, DNA Methylation genetics, Homeodomain Proteins genetics, Inflammation pathology, Intestines pathology, NF-kappa B metabolism, Stomach pathology
- Abstract
The caudal homeobox factor 1 (CDX1) is an essential transcription factor for intestinal differentiation. Its aberrant expression in intestinal metaplasia of the upper gastrointestinal tract is a hallmark within the gastritis-metaplasia-carcinoma sequence. CDX1 expression is influenced by certain pathways, such as Wnt, Ras, or NF-κB signaling; however, these pathways alone cannot explain the transient expression of CDX1 in intestinal metaplasia or the molecular inactivation mechanism of its loss in cases of advanced gastric cancer. In this study, we investigated the epigenetic inactivation of CDX1 by promoter methylation, as well as the functional link of CDX1 promoter methylation to the inflammatory NF-κB signaling pathway. We identified methylation-dependent NF-κB binding to the CDX1 promoter and quantified it using competitive electrophoretic mobility shift assays and chromatin immunoprecipitation. A methylated CDX1 promoter was associated with closed chromatin structure, reduced NF-κB binding, and transcriptional silencing. Along the gastritis-metaplasia-carcinoma sequence, we observed a biphasic pattern of tumor necrosis factor-α (TNF-α) protein expression and an inverse biphasic pattern of CDX1 promoter methylation; both are highly consistent with CDX1 protein expression. The stages of hyper-, hypo-, and hyper-methylation patterns of the CDX1 promoter were inversely correlated with the NF-κB signaling activity along this sequence. In conclusion, these functionally interacting events drive CDX1 expression and contribute to intestinal metaplasia, epithelial dedifferentiation, and carcinogenesis in the human stomach., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
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32. The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells.
- Author
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Brabletz S, Bajdak K, Meidhof S, Burk U, Niedermann G, Firat E, Wellner U, Dimmler A, Faller G, Schubert J, and Brabletz T
- Subjects
- Base Sequence, Calcium-Binding Proteins genetics, Calcium-Binding Proteins metabolism, Calcium-Binding Proteins physiology, Cells, Cultured, DNA-Binding Proteins antagonists & inhibitors, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Feedback, Physiological physiology, Gene Knockdown Techniques, Homeodomain Proteins antagonists & inhibitors, Homeodomain Proteins genetics, Humans, Intercellular Signaling Peptides and Proteins genetics, Intercellular Signaling Peptides and Proteins metabolism, Intercellular Signaling Peptides and Proteins physiology, Jagged-1 Protein, Membrane Proteins genetics, Membrane Proteins metabolism, Membrane Proteins physiology, MicroRNAs genetics, Models, Biological, Nuclear Proteins antagonists & inhibitors, Nuclear Proteins genetics, Nuclear Proteins metabolism, Receptors, Notch genetics, Serrate-Jagged Proteins, Signal Transduction genetics, Signal Transduction physiology, Trans-Activators, Transcription Factors antagonists & inhibitors, Transcription Factors genetics, Transcription Factors metabolism, Zinc Finger E-box-Binding Homeobox 1, Homeodomain Proteins physiology, MicroRNAs physiology, Neoplasms genetics, Receptors, Notch metabolism, Transcription Factors physiology
- Abstract
Notch signalling is important for development and tissue homeostasis and activated in many human cancers. Nevertheless, mutations in Notch pathway components are rare in solid tumours. ZEB1 is an activator of an epithelial-mesenchymal transition (EMT) and has crucial roles in tumour progression towards metastasis. ZEB1 and miR-200 family members repress expression of each other in a reciprocal feedback loop. Since miR-200 members target stem cell factors, ZEB1 indirectly induces stemness maintenance and associated drug resistance. Here, we link ZEB1 and its cancer promoting properties to Notch activation. We show that miR-200 members target Notch pathway components, such as Jagged1 (Jag1) and the mastermind-like coactivators Maml2 and Maml3, thereby mediating enhanced Notch activation by ZEB1. We further detected a coordinated upregulation of Jag1 and ZEB1, associated with reduced miR-200 expression in two aggressive types of human cancer, pancreatic adenocarcinoma and basal type of breast cancer. These findings explain increased Notch signalling in some types of cancers, where mutations in Notch pathway genes are rare. Moreover, they indicate an additional way how ZEB1 exerts its tumour progressing functions.
- Published
- 2011
- Full Text
- View/download PDF
33. An extract of Pelargonium sidoides (EPs 7630) inhibits in situ adhesion of Helicobacter pylori to human stomach.
- Author
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Wittschier N, Faller G, and Hensel A
- Subjects
- Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Bacterial Adhesion drug effects, Helicobacter Infections drug therapy, Helicobacter pylori physiology, Humans, Microbial Sensitivity Tests, Plant Extracts administration & dosage, Plant Extracts therapeutic use, Plant Roots, Stomach microbiology, Anti-Bacterial Agents pharmacology, Helicobacter pylori drug effects, Pelargonium, Phytotherapy, Plant Extracts pharmacology
- Abstract
Root extract from Pelargonium sidoides DC is used therapeutically as antimicrobial agent against infections of the respiratory system. In order to elucidate possible modes of actions we investigated the influence of P. sidoides root extract on microbial adhesion with Helicobacter pylori as model microorganism, a germ with a strong adherence to human stomach tissue. In an in-situ anti-adhesion assay intact human stomach tissue from patient resectates was incubated with fluorescent-labelled bacteria. Epithelial adhesion occurred in untreated samples and was quantified by fluorescent microscopy. Pre-treatment of the bacteria with Pelargonium extract showed good anti-adhesive activity. The antiadhesive effect was clearly dose-dependent in a range from 0.001 to 10 mg/ml. Within agar diffusion-test the extract had no direct cytotoxicity against H. pylori. The results show that the root extract from Pelargonium sidoides is a potent anti-adhesive agent against H. pylori and could therefore be a useful choice to avoid the first step of a bacterial infection.
- Published
- 2007
- Full Text
- View/download PDF
34. Demographics and presenting clinical features of childhood systemic lupus erythematosus.
- Author
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Faller G, Thomson PD, Kala UK, and Hahn D
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Kidney Diseases etiology, Lupus Erythematosus, Systemic diagnosis, Male, Retrospective Studies, South Africa epidemiology, Lupus Erythematosus, Systemic epidemiology, Lupus Erythematosus, Systemic physiopathology
- Abstract
Objectives: To review the presentation and characteristics of children with systemic lupus erythematosus (SLE)., Methods: The records of children with sufficient American College of Rheumatology (ACR) criteria for SLE treated by the renal units of the Johannesburg and Chris Hani Baragwanath hospitals, and the arthritis clinic of the Johannesburg Hospital between January 1974 and March 2000 were reviewed. The clinical presentation, age distribution and race were examined., Results: A total of 36 children met the criteria. There were 26 girls and 10 boys, with a mean age of 11.5 and 10.2 years respectively. The male-to-female ratio was 1:2.6 overall, with a ratio of 1:1.2 under 10 years and 1:4 over 10 years. There were 15 white, 2 Indian and 5 coloured patients. The 14 black patients all presented after 1986. Rashes were found to be the commonest clinical feature present at the time of diagnosis, followed by polyarthritis and renal pathology. Constitutional symptoms were common, as were generalised lymphadenopathy and hepatosplenomegaly, while neurological, pulmonary and cardiac signs and symptoms were less common. Renal disease was present in 58% of patients on presentation., Conclusion: There is a diverse array of presenting features in childhood SLE. There has been increased recognition of the disease in young black South Africans since 1986.
- Published
- 2005
35. Down-regulation of the homeodomain factor Cdx2 in colorectal cancer by collagen type I: an active role for the tumor environment in malignant tumor progression.
- Author
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Brabletz T, Spaderna S, Kolb J, Hlubek F, Faller G, Bruns CJ, Jung A, Nentwich J, Duluc I, Domon-Dell C, Kirchner T, and Freund JN
- Subjects
- Adenocarcinoma genetics, Animals, Colorectal Neoplasms genetics, Cytoskeletal Proteins biosynthesis, Cytoskeletal Proteins genetics, Disease Progression, Down-Regulation, Homeodomain Proteins biosynthesis, Homeodomain Proteins genetics, Integrin beta1 physiology, Male, Mice, Mice, Nude, Signal Transduction physiology, Trans-Activators biosynthesis, Trans-Activators genetics, beta Catenin, Adenocarcinoma metabolism, Adenocarcinoma pathology, Avian Proteins, Collagen Type I physiology, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Homeodomain Proteins antagonists & inhibitors
- Abstract
The homeobox transcription factor Cdx2 specifies intestinal development and homeostasis and is considered a tumor suppressor in colorectal carcinogenesis. However, Cdx2 mutations are rarely found. Invasion of colorectal cancer is characterized by a transient loss of differentiation and nuclear accumulation of the oncoprotein beta-catenin in budding tumor cells. Strikingly, this is reversed in growing metastases, indicating that tumor progression is a dynamic process that is not only driven by genetic alterations but also regulated by the tumor environment. Here we describe a transient loss of Cdx2 in budding tumor cells at the tumor host interface, and reexpression of Cdx2 in metastases. Cell culture experiments show that collagen type I, through beta(1) integrin signaling, triggers a transient transcriptional down-regulation of Cdx2 and its intestine-specific target gene sucrase isomaltase, associated with a loss of differentiation. These data indicate an active role for the tumor environment in malignant tumor progression.
- Published
- 2004
- Full Text
- View/download PDF
36. Images in cardiovascular medicine. Giant true aneurysms of saphenous vein bypass grafts: a rare cause of tumor-like mediastinal masses.
- Author
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Ropers D, Kuhlmann A, Weyand M, Faller G, Flachskampf FA, Daniel WG, Baum U, Anders K, Achenbach S, Ludwig J, and Garlichs CD
- Subjects
- Aged, Aortic Aneurysm, Abdominal complications, Aortic Rupture complications, Diagnosis, Differential, Fatal Outcome, Humans, Male, Saphenous Vein transplantation, Tomography, X-Ray Computed, Transplantation, Heterotopic, Venous Thrombosis etiology, Aneurysm diagnostic imaging, Coronary Artery Bypass, Mediastinal Neoplasms diagnosis, Mediastinum diagnostic imaging, Postoperative Complications diagnostic imaging, Saphenous Vein pathology
- Published
- 2004
- Full Text
- View/download PDF
37. Systemic Th1 immunization of mice against Helicobacter pylori infection with CpG oligodeoxynucleotides as adjuvants does not protect from infection but enhances gastritis.
- Author
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Sommer F, Wilken H, Faller G, and Lohoff M
- Subjects
- Animals, Antibodies, Bacterial blood, Female, Immunization, Interleukin-12 physiology, Mice, Mice, Inbred C57BL, Adjuvants, Immunologic pharmacology, Bacterial Vaccines immunology, Gastritis etiology, Helicobacter Infections prevention & control, Helicobacter pylori immunology, Oligodeoxyribonucleotides pharmacology, Th1 Cells immunology
- Abstract
Recent reports have suggested that oral vaccination of mice against Helicobacter pylori is dependent on a Th1-mediated immune response. However, oral vaccination in mice neither induces sterilizing immunity nor leads to complete protection from disease. Therefore, in this study we investigated whether a systemic subcutaneous immunization against H. pylori by using CpG oligodeoxynucleotides as a Th1 adjuvant could achieve protection in a mouse model of H. pylori infection. CpG oligodeoxynucleotides are known for their ability to induce nearly entirely Th1-biased immune responses and may be approved for human use in future. Immunization of mice with H. pylori lysate and CpG induced a strong local and systemic Th1 immune response. Despite this strong Th1 response, mice were not protected from infection with H. pylori yet had a 10-fold reduction in the number of H. pylori in the gastric mucosa compared to nonimmunized mice. Of note, reduction of the bacterial density in immunized mice was accompanied by a significantly enhanced gastritis. Hence, systemic Th1 immunization of mice, even though being able to reduce the bacterial load in the stomach, is associated with aggravated pathology.
- Published
- 2004
- Full Text
- View/download PDF
38. Gastric PDX-1 expression in pancreatic metaplasia and endocrine cell hyperplasia in atrophic corpus gastritis.
- Author
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Buettner M, Dimmler A, Magener A, Brabletz T, Stolte M, Kirchner T, and Faller G
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers analysis, Cell Transdifferentiation, Enteroendocrine Cells enzymology, Enteroendocrine Cells pathology, Female, Fluorescent Antibody Technique, Gastric Mucosa chemistry, Gastritis, Atrophic enzymology, Gastritis, Atrophic pathology, Humans, Hyperplasia, Immunohistochemistry, Male, Metaplasia, Middle Aged, Pancreas enzymology, Pancreas pathology, Pyloric Antrum chemistry, Sodium-Potassium-Exchanging ATPase analysis, Stomach enzymology, Stomach pathology, Up-Regulation, Enteroendocrine Cells chemistry, Gastritis, Atrophic metabolism, Homeodomain Proteins analysis, Pancreas chemistry, Stomach chemistry, Trans-Activators analysis
- Abstract
The homeodomain transcription factor PDX-1 plays a key role in endocrine and exocrine differentiation processes of the pancreas. PDX-1 is also essential for differentiation of endocrine cells in the gastric antrum. The role of PDX-1 in the pathogenesis of endocrine cell hyperplasia and pancreatic metaplasia in corpus and fundus gastritis has not been evaluated. By immunohistochemistry and double-immunofluorescence, we investigated the expression of PDX-1 in 10 tissue specimens with normal human gastric mucosa, nonatrophic and atrophic gastritis and in pancreatic metaplasia, respectively. In normal corpus mucosa and in nonatrophic corpus gastritis, PDX-1 was mainly absent. In pancreatic metaplasia, PDX-1 was found in metaplastic cells and in adjacent gastric glands. In contrast to normal gastric corpus mucosa, PDX-1 could be strongly detected in the cytoplasm of the parietal cells surrounding metaplastic areas. Furthermore, PDX-1 expression was found in hyperplastic endocrine cells and in the surrounding gastric glands in chronic atrophic gastritis. Hyperplastic endocrine cells coexpressed the beta-subunit of the gastric H,K-ATPase. We conclude that PDX-1 represents a candidate switch factor for glandular exocrine and endocrine transdifferentiation in chronic gastritis and that an impaired parietal cell differentiation might play a key role in disturbed gastric morphogenic processes.
- Published
- 2004
- Full Text
- View/download PDF
39. Transcription of sonic hedgehog, a potential factor for gastric morphogenesis and gastric mucosa maintenance, is up-regulated in acidic conditions.
- Author
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Dimmler A, Brabletz T, Hlubek F, Häfner M, Rau T, Kirchner T, and Faller G
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma pathology, Cell Line, Tumor metabolism, Fluorescent Antibody Technique, Indirect, Gastric Mucosa pathology, Gastritis, Atrophic genetics, Gastritis, Atrophic pathology, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Humans, Hydrogen-Ion Concentration, Membrane Proteins genetics, Membrane Proteins metabolism, Morphogenesis, Patched Receptors, RNA, Messenger metabolism, RNA, Neoplasm analysis, Receptors, Cell Surface, Reverse Transcriptase Polymerase Chain Reaction, Stomach pathology, Stomach Neoplasms genetics, Stomach Neoplasms pathology, Trans-Activators genetics, Up-Regulation, Adenocarcinoma metabolism, Gastric Mucosa metabolism, Gastritis, Atrophic metabolism, Stomach Neoplasms metabolism, Trans-Activators metabolism
- Abstract
Gastric body mucosa atrophy predisposes one to gastric cancer. Disturbances in the gastric differentiation process might play a role in the evolution of gastric atrophy. Sonic hedgehog (Shh) has recently been implicated as a crucial factor in gastric organogenesis and gland differentiation. In this study we investigated the expression of key factors in the Shh pathway, namely Shh and its receptor Patched (Ptc), in normal and pathologic stomach mucosa. Furthermore, the potential role of pH for Shh dysregulation was analyzed. Ten gastric biopsy specimens each from normal gastric mucosa, chronic nonatrophic gastritis, atrophic gastritis, and gastric cancer were included. Expression of Shh and Ptc was analyzed by immunohistochemistry. In normal body mucosa and in nonatrophic body gastritis, Shh was strongly expressed in parietal cells. Ptc was also expressed in gastric chief cells. Shh expression was almost completely lost in atrophic gastritis and in gastric cancer and absent in intestinal metaplasia. Ptc was markedly reduced in atrophy and only weakly positive in intestinal metaplasia and gastric cancer. In in vitro experiments, gastric cancer cell line 23132 was found positive for Shh. In long-term culture as well as in culture conditions with low pH, transcription of Shh in 23132 was significantly increased in quantitative reverse transcription PCR analyses. We concluded that the decreased expression of the Shh pathway in atrophic gastritis and gastric cancer might reflect altered differentiation processes within the gastric unit and contributes to the development of gastric atrophy. The increase of gastric pH might play a role in the development of gastric mucosa atrophy via reduction of Shh transcription.
- Published
- 2003
- Full Text
- View/download PDF
40. Colonization of C57BL/6J and BALB/c wild-type and knockout mice with Helicobacter pylori: effect of vaccination and implications for innate and acquired immunity.
- Author
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Panthel K, Faller G, and Haas R
- Subjects
- Administration, Oral, Animals, Bacterial Vaccines administration & dosage, Female, Gastritis immunology, Gastritis microbiology, Gastritis pathology, Helicobacter Infections immunology, Helicobacter Infections pathology, Helicobacter pylori genetics, Helicobacter pylori growth & development, Humans, Immunity, Active, Immunity, Innate, Immunization, Interleukins deficiency, Interleukins genetics, Membrane Glycoproteins genetics, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Receptors, Cell Surface genetics, Species Specificity, Stomach microbiology, Stomach pathology, Toll-Like Receptor 2, Toll-Like Receptors, Bacterial Vaccines immunology, Drosophila Proteins, Gastritis prevention & control, Helicobacter Infections prevention & control, Helicobacter pylori pathogenicity
- Abstract
The gram-negative bacterial pathogen Helicobacter pylori is a major cause of peptic ulcer disease and a risk factor for gastric cancer in humans. Adapted H. pylori strains, such as strain SS1, are able to infect mice and are a useful model for gastric colonization and vaccination studies. In this study we used a streptomycin-resistant derivative of H. pylori SS1 to analyze the colonization behavior and the success of vaccination in wild-type (wt) and various knockout mice of the BALB/c and C57BL/6J genetic backgrounds. We here report that BALB/c interleukin-4 knockout (IL-4(-/-)) mice are weakly overcolonized compared to the wt strain but that the IL-12(-/-) knockout results in a strong overcolonization (500%). Unexpectedly, in the C57BL/6J background the same knockouts behaved in diametrically opposed manners. The IL-4(-/-) mutation caused a 50% reduction and the IL-12(-/-) knockout caused a 95% reduction compared to the wt colonization rate. For C57BL/6J mice we further analyzed the IL-18(-/-) and Toll-like receptor 2 knockout mutations, which showed reductions to 66 and 57%, respectively, whereas mice with the IL-10(-/-) phenotype were hardly infected at all (5%). In contrast, the tumor necrosis factor receptor knockout (p55(-/-) and p55/75(-/-)) mice showed an overcolonization compared to the C57BL/6J wt strain. With exception of the low-level infected C57BL/6J IL-10(-/-) and IL-12(-/-) knockout mice, all knockout mutants were accessible to a prophylactic vaccination and their vaccination behavior was comparable to that of the wt strains.
- Published
- 2003
- Full Text
- View/download PDF
41. Generation and characterization of human monoclonal scFv antibodies against Helicobacter pylori antigens.
- Author
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Reiche N, Jung A, Brabletz T, Vater T, Kirchner T, and Faller G
- Subjects
- Aged, Aged, 80 and over, Antibodies, Bacterial genetics, Antibodies, Bacterial immunology, Antibodies, Monoclonal genetics, Antibodies, Monoclonal immunology, Antigens, Bacterial immunology, Female, Helicobacter Infections blood, Helicobacter pylori enzymology, Humans, Immunoglobulin Fragments genetics, Immunoglobulin Fragments immunology, Immunoglobulin Heavy Chains biosynthesis, Immunoglobulin Heavy Chains genetics, Immunoglobulin Heavy Chains immunology, Immunoglobulin Variable Region genetics, Immunoglobulin Variable Region immunology, Immunoglobulin kappa-Chains biosynthesis, Immunoglobulin kappa-Chains genetics, Immunoglobulin kappa-Chains immunology, Immunoglobulin lambda-Chains biosynthesis, Immunoglobulin lambda-Chains genetics, Immunoglobulin lambda-Chains immunology, Urease immunology, Antibodies, Bacterial biosynthesis, Antibodies, Monoclonal biosynthesis, Helicobacter Infections immunology, Helicobacter pylori immunology, Immunoglobulin Fragments biosynthesis, Immunoglobulin Variable Region biosynthesis
- Abstract
Infection with Helicobacter pylori is chronic despite a vigorous cellular and humoral immune response and causes severe pathology in some patients. In this study, phage display was used as a new approach in order to investigate the role of the host's humoral immune response in the pathogenesis of H. pylori gastritis. Human monoclonal single-chain Fv (scFv) antibody fragments against H. pylori cell lysate and the H. pylori urease were isolated from an immune phage display library, constructed from peripheral blood lymphocytes of an H. pylori-infected patient. After affinity selection, 23% of the clones tested showed binding activity against a lysate of the H. pylori Sydney strain in enzyme-linked immunosorbent assay (ELISA) and 9% bound the H. pylori urease. Further characterization by PCR-fingerprint analysis and sequencing revealed that two closely related H. pylori binders and one antiurease scFv could be isolated. The selected scFvs were highly specific as analyzed by ELISA and immunoblots using various bacterial lysates and recombinant proteins. Analysis of the humoral immune response following H. pylori infection using human monoclonal antibodies might contribute to a better understanding of the pathogenesis of the disease. Moreover, using immune phage display libraries, it might be possible for relevant epitopes of H. pylori antigens to be determined, which might be of use for vaccine development.
- Published
- 2002
- Full Text
- View/download PDF
42. Lewis X structures in the O antigen side-chain promote adhesion of Helicobacter pylori to the gastric epithelium.
- Author
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Edwards NJ, Monteiro MA, Faller G, Walsh EJ, Moran AP, Roberts IS, and High NJ
- Subjects
- Bacterial Adhesion, Carbohydrate Sequence, Gastric Mucosa microbiology, Humans, Latex, Lewis X Antigen metabolism, Lipopolysaccharides chemistry, Lipopolysaccharides metabolism, Molecular Sequence Data, Mutation, Nucleotidyltransferases genetics, Nucleotidyltransferases metabolism, Epithelial Cells microbiology, Helicobacter pylori chemistry, Helicobacter pylori physiology, Lewis X Antigen chemistry, O Antigens chemistry
- Abstract
Helicobacter pylori NCTC11637 expresses a lipopolysaccharide (LPS) that comprises an O antigen side-chain with structural homology to the human blood group antigen Lewis X (Le(x)). The role of this molecule in adhesion of H. pylori to gastric epithelial cells was investigated. Mutants expressing truncated LPS structures were generated through insertional mutagenesis of rfbM and galE; genes encode GDP mannose pyrophosphorylase and galactose epimerase respectively. Compositional and structural analysis revealed that the galE mutant expressed a rough LPS that lacked an O antigen side-chain. In contrast, an O antigen side-chain was still synthesized by the rfbM mutant, but it lacked fucose and no longer reacted with anti-Le(x) monoclonal antibodies (Mabs). The ability of these mutants to bind to paraffin-embedded sections from the antrum region of a human stomach was assessed. Adhesion of the wild type was characterized by tropic binding to the apical surface of mucosal epithelial cells and cells lining gastric pits. In contrast, both the rfbM and galE mutants failed to demonstrate tropic binding and adhered to the tissue surface in a haphazard manner. These results indicate that LPS and, more specifically, Le(x) structures in the O antigen side-chain play an important role in targeting H. pylori to specific cell lineages within the gastric mucosa. The role of Le(x) in this interaction was confirmed by the tropic binding of synthetic Le(x), conjugated to latex beads, to gastric tissue. The observed pattern of adhesion was indistinguishable from that of wild-type H. pylori.
- Published
- 2000
- Full Text
- View/download PDF
43. Expression of nuclear beta-catenin and c-myc is correlated with tumor size but not with proliferative activity of colorectal adenomas.
- Author
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Brabletz T, Herrmann K, Jung A, Faller G, and Kirchner T
- Subjects
- Adenoma pathology, Antigens, Nuclear, Cell Division, Colorectal Neoplasms pathology, Humans, Immunoenzyme Techniques, Nuclear Proteins metabolism, beta Catenin, Adenoma metabolism, Cadherins biosynthesis, Cell Nucleus metabolism, Colorectal Neoplasms metabolism, Cytoskeletal Proteins biosynthesis, Proto-Oncogene Proteins c-myc biosynthesis, Trans-Activators
- Abstract
Most colorectal cancers have loss-of-function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to the accumulation of nuclear beta-catenin, which, together with the DNA-binding protein TCF-4, functions as a transcriptional activator. The recently defined target genes c-myc, cyclin D1, and matrilysin are responsible for tumor proliferation or malignant progression and explain the oncogenic potential of nuclear beta-catenin. To investigate its role in early colon carcinogenesis, we analyzed the expression of beta-catenin, its target gene c-myc, and the proliferative activity in 88 colorectal adenomas of varying size and grade of dysplasia. The results revealed i) the most significant correlation of nuclear beta-catenin and c-myc expression was not with the grade of dysplasia but with the size of the colon adenoma; ii) perfect correlation of nuclear beta-catenin and c-myc expression; iii) no significant correlation of adenoma size with the proliferative activity; and iv) no significant correlation of proliferative activity and the nuclear expression of beta-catenin and c-myc. These results imply that APC mutations have additional beta-catenin-independent functions; APC mutations alone are not sufficient for nuclear overexpression of beta-catenin; and nuclear beta-catenin has additional important functions for exceeding a threshold tumor size.
- Published
- 2000
- Full Text
- View/download PDF
44. Genetic and functional characterization of the alpAB gene locus essential for the adhesion of Helicobacter pylori to human gastric tissue.
- Author
-
Odenbreit S, Till M, Hofreuter D, Faller G, and Haas R
- Subjects
- Algorithms, Amino Acid Sequence, DNA Primers, Epithelial Cells metabolism, Escherichia coli metabolism, Fluorescein-5-isothiocyanate metabolism, Genotype, Humans, Immunoblotting, Lipoproteins metabolism, Models, Genetic, Molecular Sequence Data, Palmitic Acid metabolism, Protein Structure, Secondary, RNA isolation & purification, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Bacterial Adhesion physiology, Bacterial Outer Membrane Proteins genetics, Escherichia coli Proteins, Helicobacter pylori physiology, Stomach microbiology, Transcription Factors genetics
- Abstract
In this study, we isolated and characterized a chromosomal locus of Helicobacter pylori previously identified by transposon shuttle mutagenesis as being involved in the adhesion of the pathogen to gastric epithelial cells. Two closely homologous genes were identified, designated as alpA and alpB, encoding outer membrane (OM) proteins of 518 amino acids each. They are members of the outer membrane protein supergene family identified in the H. pylori 26695 complete genome sequence. AlpA carries a functional lipoprotein signal sequence. AlpB carries a putative standard N-terminal signal sequence and shows a strong amino-acid sequence identity to AlpA. Transposon insertion mutagenesis, immunoblotting and primer extension studies indicate that both genes are organized in an operon, but no obvious consensus promoter sequence was found upstream of the transcriptional start site. The C-terminal portion of both proteins is predicted to form a porin-like beta-barrel in the outer membrane, consisting of 14 transmembrane amphipathic beta-strands. Adhesion experiments with defined isogenic mutants indicate that both proteins are necessary for specific adherence of H. pylori to human gastric tissue. The pattern of AlpAB-dependent adherence of H. pylori to the gastric epithelial surface shows a clear difference to the BabA2-mediated adherence to Lewis, suggesting that a different receptor is involved.
- Published
- 1999
- Full Text
- View/download PDF
45. The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy.
- Author
-
Claeys D, Faller G, Appelmelk BJ, Negrini R, and Kirchner T
- Subjects
- Adult, Aged, Aged, 80 and over, Atrophy, Autoantibodies analysis, Chronic Disease, Female, Gastric Mucosa pathology, Gastritis pathology, Humans, Isoantigens analysis, Lewis Blood Group Antigens immunology, Male, Middle Aged, Parietal Cells, Gastric immunology, Autoantigens immunology, Gastritis immunology, Gastritis microbiology, H(+)-K(+)-Exchanging ATPase immunology, Helicobacter Infections immunology, Helicobacter pylori, Stomach enzymology
- Abstract
Background & Aims: A subgroup of Helicobacter pylori-infected patients develops autoantibodies to gastric parietal cell canaliculi. The aim of this study was to define the unknown autoantigen., Methods: We screened 72 H. pylori-infected patients, 5 patients with autoimmune gastritis, and 36 healthy controls for immunoglobulin G autoantibodies to canaliculi by immunohistochemistry. The antigen specificity was determined by immunoprecipitation of the murine gastric H+,K+-adenosine triphosphatase (H+,K+-ATPase) expressed in oocytes and by immunoblotting on human gastric membranes from the body mucosa., Results: Autoantibodies specific for the conformational peptides of the H+,K+-ATPase were detected in 3% (1/36) of controls, in all patients with autoimmune gastritis (5/5), in 25% (18/72) of H. pylori-infected patients, and in 47% (15/32) of the infected patients with anticanalicular autoantibodies. No other major autoantigen was identified. Atrophy in the gastric body mucosa was found in 60% (9/15) of infected patients with both anticanalicular and anti-H+,K+-ATPase antibodies, but only in 13% (5/37) of infected patients lacking both autoantibodies (P < 0.01)., Conclusions: The gastric H+,K+-ATPase is a major autoantigen in H. pylori-associated antigastric autoimmunity. Thus, anti-H+,K+-ATPase autoantibodies, which are closely linked to classical autoimmune gastritis, are also significant indicators for body mucosa atrophy in chronic H. pylori gastritis.
- Published
- 1998
- Full Text
- View/download PDF
46. Expression of the transcriptional regulator Egr-1 in experimental glomerulonephritis: requirement for mesangial cell proliferation.
- Author
-
Rupprecht HD, Hoffer G, de Heer E, Sterzel RB, Faller G, and Schoecklmann HO
- Subjects
- Animals, Base Sequence, Cell Division, Cells, Cultured, DNA-Binding Proteins metabolism, Early Growth Response Protein 1, Gene Expression drug effects, Glomerular Mesangium drug effects, Glomerulonephritis, Membranoproliferative metabolism, Male, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense pharmacology, Platelet-Derived Growth Factor pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Thymidine metabolism, Transcription Factors metabolism, Zinc Fingers genetics, DNA-Binding Proteins genetics, Glomerular Mesangium metabolism, Glomerular Mesangium pathology, Glomerulonephritis, Membranoproliferative genetics, Glomerulonephritis, Membranoproliferative pathology, Immediate-Early Proteins, Transcription Factors genetics
- Abstract
The early growth response gene-1 (Egr-1), a zinc finger transcriptional regulator, was induced in a rat model of mesangioproliferative glomerulonephritis (GN). Northern blot analysis revealed a maximal 14.9-fold increase in glomerular Egr-1 mRNA at day 6 of GN. By immunohistochemistry Egr-1 protein expression was demonstrated to be mainly confined to glomerular mesangial cells (MC). To test whether Egr-1 directly regulates MC proliferation, cultured MCs were stimulated with platelet-derived growth factor (PDGF) after preincubation with different Egr-1 antisense oligonucleotides (ASOs). PDGF-induced rise in 3H-thymidine uptake by 83% and almost completely abrogated increase in MC number. We conclude that Egr-1 induction is of critical importance for PDGF-induced mitogenic signaling in MCs, and inhibition of Egr-1 in vivo may offer an approach to oppose glomerular MC proliferation in glomerular inflammatory disease.
- Published
- 1997
- Full Text
- View/download PDF
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