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World Journal of g.stroenterolog. 2005年第35期11卷 5521-5524页

作者： Matthias Ocker Marion g.nslmayer Steffen Zopf Susanne g.hr Christopher Janson eckhart g. hahn Christoph Herold Department of Medicine I University Erlang.n-Nuernberg Ulmenweg 18 Erlangen 91054 Germany

MM： To investig.te if and to what extent antiviral therapy influenced a broad panel of quantitative testing.of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg.interferon/ribavirin （n = 23）. Quantitative testing.of liver function, including.aminopyrine breath test （ABT）, g.lactose elimination capacity （g.C）, sorbitol clearance （SCI） and indocyanine g.een clearance （ICg. was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were neg.tive for HCVRNA, 14 patients did not respond to therapy. ABT and g.C as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICg. were not affected by antiviral therapy. In the 14 non-responders, no chang.s in QTLF values were observed during.the treatment period. CONCLUSION： ICg.and SCI remained unaffected in patients with chronic hepatitis C, while ABT and g.C were sig.ificantly compromised. ABT and g.C normalized in responders to antiviral therapy. Early determination of ABT and g.C may differentiate responders from non-responders to antiviral treatment in hepatitis C.

关键词： Aminopyrine breath test g.lactose eliminationcapacity Indocyanine g.een clearance Sorbitol clearance Hepatitis C Interferon Ribavirin

Helicobacter pylori upreg.lates prion protein expression in g.stric mucosa: A possible link to prion disease

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World Journal of g.stroenterolog. 2005年第48期11卷 7651-7656页

作者： Peter C Konturek Karolina Bazela Vitally Kukharskyy Michael Bauer eckhart g.hahn Detlef Schuppan Department of Medicine

AIM： Patholog.cal prion protein （PrP^sc） is responsible for the development of transmissible spong.form encephalopathies （TSE）. While PrPc enters the org.nism via the oral route, less data is available to know about its uptake and the role of g.strointestinal inflammation on the expression of priori precursor PrPc, which is constitutively expressed in the g.stric ***： We studied PrPc expression in the g.stric mucosa of 10 Helicobacter pylori-positive patients before and after successful H pylori eradication compared to non-infected controls using.RT-PCR and Western blotting. The effect of central mediators of g.stric inflammation, i.e., g.strin, prostag.andin E2 （Pg.2）, tumor necrosis factor alpha （TNF-α） and interleukin 1 beta （IL-1β） on PrPc expression was analyzed in g.stric cell ***： PrPc expression was increased in H pyloriinfection compared with non-infected controls and decreased to normal after successful eradication. g.strin, Pg.2, and IL-1β dose-dependently upreg.lated PrPc in g.stric cells, while TNF-α had no ***： H pylori infection leads to the upreg.lation of g.stric PrPc expression. This can be linked to H pylori induced hyperg.strinemia and increased mucosal Pg.2 and IL-1β synthesis. H pylori creates a milieu for enhanced propag.tion of prions in the g.strointestinal tract.

关键词： Prions Helicobacter pylori, g.strin Proinflammatory cytokines

Double-balloon-enteroscopy-based endoscopic retrog.ade cholang.opancreatog.aphy in post-surg.cal patients

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World Journal of g.stroenterolog. 2011年第18期17卷 2302-2314页

作者： Martin Raithel Harald Dormann Andreas Naeg.l Frank Boxberg.r eckhart g.hahn Markus F Neurath Juerg.n Maiss Department of Medicine 1 University of Erlangen-Nürnberg Emerg.ncy Unit City Hospital Fürth Dean of the University Witten-Herdecke

AIM: To evaluate double balloon enteroscopy (DBE) in post-surg.cal patients to perform endoscopic retrog.ade cholang.opancreatog.aphy (ERCP) and interventions. METHODS: In 37 post-surg.cal patients, a stepwise approach was performed to reach normal papilla or enteral anastomoses of the biliary tract/pancreas. When conventional endoscopy failed, DBE-based ERCP was performed and standard parameters for DBE, ERCP and interventions were recorded. RESULTS: Push-enteroscopy (overall, 16 procedures) reached enteral anastomoses only in six out of 37 post-surg.cal patients (16.2%). DBE achieved a hig. rate of luminal access to the biliary tract in 23 of the remaining.31 patients (74.1%) and to the pancreatic duct (three patients). Among.all DBE-based ERCPs (86 procedures), 21/23 patients (91.3%) were successfully treated. Interventions included ostium incision or papillotomy in 6/23 (26%) and 7/23 patients (30.4%), respectively. Biliary endoprosthesis insertion and reg.lar exchang. was achieved in 17/23 (73.9%) and 7/23 patients (30.4%), respectively. Furthermore, bile duct stone extraction as well as ostium and papillary dilation were performed in 5/23 (21.7%) and 3/23 patients (13.0%), respectively. Complications during.DBE-based procedures were bleeding.(1.1%), perforation (2.3%) and pancreatitis (2.3%), and minor complications occurred in up to 19.1%. CONCLUSION: The appropriate use of DBE yields a hig. rate of luminal access to papilla or enteral anastomoses in more than two-thirds of post-surg.cal patients, allowing.important successful endoscopic therapeutic interventions.

关键词： Double balloon enteroscopy Endoscopic retrog.ade cholang.opancreatog.aphy Choledochojejunostomy Hepaticojejunostomy Pancreaticojejunostomy Percutaneous cholang.odrainag.

Non-compliance in surveillance for patients with previous resection of larg. (≥ 1 cm) colorectal adenomas

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World Journal of g.stroenterolog. 2006年第45期12卷 7313-7318页

作者： Wolfg.ng.M Brueckl Berit Fritsche Brig.tte Seifert FrankBoxberg.r Heinz Albrecht Roland S Croner Axel Wein eckhart g.hahn Department of Medicine 1 University Hospital of Erlangen91054 Erlangen Germany Department of Surg.ry University Hospital ofErlangen 91054 Erlangen Germany

AIM: To assess the extent and reasons of non- compliance in surveillance for patients underg.ing.polypectomy of larg. (≥ 1 cm) colorectal adenomas. METHODS: Between 1995 and 2002, colorectal adenomas ≥ 1 cm were diag.osed in 210 patients and subsequently documented at the Erlang.n Reg.stry of Colorectal Polyps. One hundred and fi fty-eig.t patients (75.2%) could be contacted by telephone and ag.eed to be interviewed. Additionally, records were obtained from the treating.physicians. RESULTS: Fifty-four out of 158 patients (34.2%) neg.ected any surveillance. Reasons for non-compliance included lack of knowledg. concerning.surveillance intervals (45.8%), no symptoms (29.2%), fear of examination (18.8%) or old ag./severe illness (6.3%). In a multivariate analysis, the factors including.female g.nder (P = 0.036) and ag. > 62 years (P = 0.016) proved to be sig.if icantly associated with non-compliance in surveillance. CONCLUSION: Efforts to increase compliance in surveillance are of utmost importance. This applies particularly to women’s compliance. Effective strateg.es for avoiding.metachronous colorectal adenoma and cancer should focus on both the improvement in awareness and knowledg. of patients and information about physicians for surveillance.

关键词： Colorectal adenoma Colorectal cancer Surveillance colonoscopy, Non-compliance

Jejunitis and brown bowel syndrome with multifocal carcinog.nesis of the small bowel

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World Journal of g.stroenterolog. 2015年第36期21卷 10461-10467页

作者： Martin Raithel Tilman T Rau Alexander F Hag.l Heinz Albrecht Thomas de Rossi Thomas Kirchner eckhart g.hahn Department of Medicine 1 Friedrich-Alexander-University Erlangen-Nuremberg Department of Patholog. Friedrich-Alexander University Erlangen-Nuremberg Department of Patholog. Ludwig-Maximilians-University Munich

This is the first report describing.a case where prolong.d,severe malabsorption from brown bowel syndrome prog.essed to multifocally spread small bowel adenocarcinoma. This case involves a female patient who was initially diag.osed with chronic jejunitis associated with primary diffuse lymphang.ectasia at the ag. of 26 years. The course of the disease was clinically,endoscopically,and histolog.cally followed for 21 years until her death at the ag. 47 due to multifocal,metastasizing.adenocarcinoma of the small bowel. Multiple lipofuscin deposits(so-called brown bowel syndrome) and severe jejunitis were observed microscopically,and sections of the small bowel showed dense lymphoplasmacytic infiltration of the lamina propria as well as blocked lymphatic vessels. After several decades,multifocal nests of adenocarcinoma cells and extensive,flat,neoplastic mucosal proliferations were found only in the small bowel,along.with a loss of the mismatch repair protein MLH1 as a long.term consequence of chronic jejunitis with malabsorption. No evidence was found for hereditary nonpolyposis colon carcinoma syndrome. This article demonstrates for the first time multifocal carcinog.nesis in the small bowel in a malabsorption syndrome in an enteritis-dysplasia-carcinoma sequence.

关键词： Brown bowel syndrome Carcinog.nesis of the small b

Sclerosing.cholang.tis following.severe trauma: Description of a remarkable disease entity with emphasis on possible pathophysiolog.c mechanisms

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World Journal of g.stroenterolog. 2005年第27期11卷 4199-4205页

作者： Johannes Benning.r Rainer g.obholz Yurdag.el Oeztuerk Christoph H.Antoni eckhart g.hahn Manfred V.Sing.r Richard Strauss Department of Medicine Ⅰ Department of Patholog. Department of Medicine II Department of Medicine Ⅱ

MM： Persistent cholestasis is a rare complication of severe trauma or infections. Little is known about the possible pathomechanisms and the clinical ***： Secondary sclerosing.cholang.tis was diag.osed in five patients with persistent jaundice after severe trauma （one burn injury, three accidents, one power current injury）. Medical charts were retrospectively reviewed with reg.rd to possible trig.er mechanisms for cholestasis, and the clinical course was ***： Diag.osis of secondary sclerosing.cholang.tis was based in all patients on the primary sclerosing.cholang.tis （PSC）-Iike destruction of the intrahepatic bile ducts at cholang.og.aphy after exclusion of PSC. In four patients, arterial hypotension with subsequent ischemia may have caused the bile duct damag., whereas in the case of power current injury direct thermal damag. was assumed to be the trig.er mechanism. The course of secondary liver fibrosis was rapidly prog.essive and proceeded to liver cirrhosis in all four patients with a follow-up 〉2 years. Therapeutic possibilities were ***： Posttraumatic sderosing.cholang.tis is a rare but rapidly prog.essive disease, probably caused by ischemia of the intrahepatic bile ducts via the peribiliary capillary plexus due to arterial *** should be aware of this disease in patients with persistent cholestasis after severe trauma.

关键词： Life-threatening.trauma Arterial hypotension Cholestasis Ischemia of intrahepatic bile ducts Secondary sclerosing.cholang.tis Posttraumatic sclerosing.cholang.tis

Piog.itazone, a specific lig.nd of peroxisome proliferator-activated receptor-g.mma, protects pancreas ag.inst acute cerulein-induced pancreatitis

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World Journal of g.stroenterolog. 2005年第40期11卷 6322-6329页

作者： Peter C Konturek Artur Dembinski Zyg.unt Warzecha g.zeg.rz Burnat Piotr Ceranowicz eckhart g.hahn Marcin Dembinski Romana Tomaszewska Stanislaw J Konturek Department of Physiolog.

AIM： To determine the effect of piog.itazone, a specific peroxisome proliferator-activated receptor-y （PPART） lig.nd, on the development of acute pancreatitis （AP） and on the expression of heat shock protein 70 （HSP70） in the pancreas. METHODS： AP was induced in rats by subcutaneous infusion of ceruw was measured by laser Dopplein for 5 h. Pancreatic blood floler flowmetry. Plasma lipase activity, intedeukin-1β （IL-1β） and IL-10 were determined. Pancreatic weig.t and histolog. were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with piog.itazone alone or in combination with cerulein. RESULTS： Piog.itazone administered （10-100 mg.kg.i.g.） 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damag. in cerulein-induced pancreatitis （tiP） as demonstrated by the improvement of pancreatic histolog., reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its g.ne expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by piog.itazone treatment. CONCLUSION： Piog.itazone attenuates CIP and the beneficial effect of this piog.itazone is multifactorial probably due to its anti-infiammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPART lig.nds could represent a new therapeutic optionin the treatment of AP.

关键词： Cerulein-induced pancreatitis PPARy, lig.nd Heat shock protein 70

The Root Cap Determines Ethylene-Dependent g.owth and Development in Maize Roots

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Molecular Plant 2008年第2期1卷 359-367页

作者： Achim hahn Roman Zimmermann Dierk Wanke Klaus Harter Hans g. Edelmann Botanisches Institut Universitfit zu Koin Gyrhofstr. 15 D-50931 Koin Germany Present address: ZMBP Pflanzenphysiolog.e University TQbingen Auf der Morgenstelle 1 D-72076 TQbingen Germany Institut fur Entwicklung.biolog.e Universitat zu Koin Gyrhofstr. 17 D-50931 Koin Germany Institut fur Entwicklung.biolog.e Universitat zu Koin Gyrhofstr. 17 D-50931 Koln Germany ZMBP Pflanzenphysiolog.e Universitat Tubingen Auf der Morgenstelle 1 D-72076 Tubingen Germany Present address: Biolog.e und ihre Didaktik Universitat Siegen D-57068 Siegen Germany

Besides providing.protection ag.inst mechanical damag. to the root tip, the root cap is involved in the perception and processing.of diverse external and internal stimuli resulting.in altered g.owth and development, The transduction of these stimuli includes hormonal sig.aling.pathways such as those of auxin, ethylene and cytokinin. Here, we show that the root cap is essential for the ethylene-induced reg.lation of elong.tion g.owth and root hair formation in maize. Exog.nously applied ethylene is no long.r able to inhibit elong.tion g.owth when the root cap has been surg.cally removed prior to hormone treatment. Reconstitution of the cap positively correlates with the developing.capacity of the roots to respond to ethylene ag.in. In contrast, the removal of the root cap does not per se affect g.owth inhibition controlled by auxin and cytokinin. Furthermore, our semi-quantitative RT-PCR results support earlier finding. that the maize root cap is a site of hig. g.ne expression activity with respect to sensing.and responding.to hormones such as ethylene, From these data, we propose a novel function of the root cap which is the establishment of competence to respond to ethylene in the distal zones of the root.

关键词： AUXIN BIOSYNTHESIS INSENSITIVE MUTANTS CELL ELONg.TION

g.apefruit-seed extract attenuates ethanol-and stress-induced g.stric lesions via activation of prostag.andin, nitric oxide and sensory nerve pathways

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World Journal of g.stroenterolog. 2005年第41期11卷 6450-6458页

作者： Tomasz Brzozowski Peter C Konturek Danuta Drozdowicz Stanislaw J Konturek Oxana Zayachivska Robert Pajdo Slawomir Kwiecien Wieslaw W Pawlik eckhart g.hahn Department of Physiolog. Jag.ellonian University Medical Colleg. CracowPoland Department of Medicine Ⅰ University of Erlang.n-Nuremberg ErlangenGermany Oxana Zayachivska National Medical University LvivUkraine

AIM： g.apefruit-seed extract （g.E） containing.flavonoids, possesses antibacterial and antioxidative properties but whether it influences the g.stric defense mechanism and g.stroprotection ag.inst ethanol- and stress-induced g.stric lesions remains unknown. METHODS： We compared the effects of g.E on g.stric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress （WRS） with or without （A） inhibition of cyclooxyg.nase （COX）-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, （B） suppression of NO-synthase with L-NNA （20 mg.kg.ip）, and （C） inactivation by capsaicin （125 mg.kg.sc） of sensory nerves with or without intrag.stric （ig. pretreatment with g.E applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of g.stric lesions were measured by planimetry, the g.stric blood flow （g.F） was assessed by H2-g.s clearance technique and plasma g.strin levels and the g.stric mucosal g.neration of Pg.2, superoxide dismutase （SOD） activity and malonyldialdehyde （MDA） concentration, as an index of lipid peroxidation were determined. RESULTS： Ethanol and WRS caused g.stric lesions accompanied by the sig.ificant fall in the g.F and SOD activity and the rise in the mucosal MDA content. Pretreatment with g.E （8-64 mg.kg.i g. dose- dependently attenuated g.stric lesions induced by 100% ethanol and WRS; the dose reducing.these lesions by 50% （ID50） was 25 and 36 mg.kg. respectively, and this protective effect was similar to that obtained with methyl Pg.2 analog.（5 μg.kg.i g.. g.E sig.ificantly raised the g.F, mucosal g.neration of Pg.2, SOD activity and plasma g.strin levels while attenuating.IVlDA content. Inhibition of Pg.2 g.neration with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the g.E-induced protection and the accompanying.hyperemia. Cotreatment of exog.nous calcitonine g.ne-rel

关键词： g.apefriut-seed extract g.stroprotection g.stric blood flow Superoxide dismutase Prostag.andin Calcitonine g.ne-related peptide

Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

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World Journal of g.stroenterolog. 2006年第23期12卷 3716-3721页

作者： Johannes Hansler Thaddaus Till Wissniowski Detlef Schuppan Astrid Witte Thomas Bernatik eckhart g.org.hahn Deike Strobel Department of Medicine 1 Friedrich Alexander University Erlangen NurembergGermany Experimental Hepatolog. and Ontolog. Nikolaus Fiebiger Center Friedrich AlexanderUniversity Erlangen Nuremberg Germany Division of g.stroenterolog. Beth IsraelDeaconess Medical Center Harvard Medical School Boston MAUnited States

AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malig.ant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antig.ns were autolog.us liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon g.mma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ neg.tive T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and Hepg. HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells ag.inst nonmalig.ant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells ag.inst autolog.us tumor tissue. Four weeks after RFA SI ag.inst tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells ag.inst HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalig.ant tumor tissue at all time points. Before RFA cytolytic activity ag.inst the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a sig.ificant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.

关键词： CD4 CD8 Cytotoxic Immune response Immunolog. Immunotherapy Interferon g.mma T cells NK Therapeutic vaccination