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Reduced expression of Ca^(2+)-regulating proteins in the upper gastrointestinal tract of patients with achalasia

World Journal of Gastroenterology 2006年第37期12卷 6002-6007页

作者： Harald Fischer Judith Fischer Peter Boknik Ulrich Gergs Wilhelm Schmitz Wolfram Domschke Jan W Konturek Joachim neumann Medizinische Klinik und Poliklinik B Universittsklinikum Mnster 48129 Mnster Germany Institut fr Pharmakologie und Toxikologie Universittsklinikum Mnster 48149 Mnster Germany Institut fr Pharmakologie und Toxikologie Martin-Luther-Universitt Halle-Wittenberg 06112 Halle (Saale) Germany Klinik fr Innere Medizin/Gastroenterologie Elbe Klinikum Stade 21682 Stade Germany

AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profi les of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed. RESULTS: SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were signif icantly reduced in patients with achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus mightbe of lesser importance for regulation of SERCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.

关键词： Esophageal and gastric motility Esophagus Calsequestrin Calreticulin

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Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats

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Hepatobiliary & Pancreatic Diseases International 2017年第5期16卷 506-511页

作者： Tom Florian Ulmer Anne Weiland Georg Lurje Christian Klink Anne Andert Hamid Alizai Christoph Heidenhain Ulf neumann Department of General Visceral and Transplantation Surgery RWTH Aachen University Hospital Aachen Germany Department of Urology Helios Hospital Berlin-Buch Germany

BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and ***: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically ***: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of live

关键词： liver regeneration liver failure terlipressin splenectomy hepatectomy

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First detection of viruses in Africanized honey bees from Peru

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Virologica Sinica 2014年第5期29卷 321-323页

作者： Orlando Yaez Graciano Tejada Peter neumann Institute of Bee Health University of Bern Schwarzenburgstrasse 161Bern CH-3003Switzerland Swiss Bee Research Centre Federal Department of Economic Affairs EVD.Research Station Agroscope-Haras Liebefeld-Posieux ALP Schwarzenburgstrasse 161Bern CH-3003Switzerland Servicio Nacional de Sanidad Agraria del Peru(Senasa) Av.La Molina 1915 La MolinaLimaPeru Social Insect Research Group Zoology and Entomology DepartmentUniversity of Pretoria Private Bag X20 HatfieldPretoria 0028South Africa

Dear Editor,The ability of the Western honey bee,Apis mellifera,to adapt to most climates of the world and the ongoing standardization of colony management has made this species of honey bees the most important species for crop *** recent years,Peru emerged as a main exporter of industrial *** industry is mainly concentrated in the Peruvian coastal region,because the local climate permits off-season production

关键词： honey mellifera Apis season colony adapt coastal crops emerged concentrated

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Loco-regional hepatocellular carcinoma treatment services as a bridge to liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2019年第3期18卷 228-236页

作者： Sophia Schmitz Georg Lurje Florian Ulmer Anne Andert Philipp Bruners Maximilian Schulze-Hagen Ulf neumann Wenzel Schoening Department of General- Visceral- and Transplantation Surgery University Hospital of RWTH Aachen Aachen Germany Department of Diagnostic and Interventional Radiology University Hospital of RWTH Aachen Aachen Germany Department of Surgery Maastricht University Medical Center (MUMC) Maastricht Netherlands Department of Surgery Charité– University Medicine at Berlin Germany

Background: Liver transplantation remains the main curative treatment option for hepatocellular carcinoma(HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points(exceptional MELD, ex MELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional(neoadjuvant) treatment(LRT) is used. For patients unlikely to timely receive an organ via primary allocation,“extended critera donor(ECD) organs” are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. Methods: Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42(84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients(82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. Results: One-and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached( P = 0.487). LRT had no impact on overall survival( P = 0.629). Median waiting time was shorter if no LRT was performed(4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival( P = 0.663). Conclusions: Patients with an expected waiting time to transplantation of > 6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.

关键词： Hepatocellular carcinoma Liver transplantation Therapeutic embolization Liver neoplasms Organ transplantation

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Epo/EpoR signaling in osteoprogenitor cells is essential for bone homeostasis and Epo-induced bone loss

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Bone Research 2021年第4期9卷 549-556页

作者： Martina Rauner Marta Murray Sylvia Thiele Deepika Watts Drorit neumann Yankel Gabet Lorenz C.Hofbauer Ben Wielockx Department of Medicine III&Center for Healthy Aging Technische Universitat DresdenDresdenGermany lnstitute for Clinical Chemistry and Laboratory Medicine Technische Universitat DresdenDresdenGermany Department of Cell and Developmental Biology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Anatomy&Anthropology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

High erythropoietin(Epo)levels are detrimental to bone health in adult *** mice receiving high doses of Epo lose bone mass due to suppressed bone formation and increased bone *** humans,high serum Epo levels are linked to fractures in elderly *** earlier studies indicated that Epo modulates osteoblast activity;however,direct evidence that Epo acts via its receptor(EpoR)on osteoblasts in vivo is still ***,we created mice lacking EpoR in osteoprogenitor cells to specifically address this *** of EpoR in osteoprogenitors(EpoR:Osx-cre,cKO)starting at 5 weeks of age did not alter red blood cell parameters but increased vertebral bone volume by 25%in 12-week-old female *** was associated with low bone ***(osteoblast number,bone formation rate)and serum(P1NP,osteocalcin)bone formation parameters were all reduced,as were the number of osteoclasts and TRAP serum *** of osteoblast precursors isolated from cKO versus control mice resulted in lower expression of osteoblast marker genes including Runx2,Alp,and Col1a1 on day 21,whereas the mineralization capacity was ***,the RANKL70PG ratio,which determines the osteoclast-supporting potential of osteoblasts,was substantially decreased by 50%.Similarly,coculturing cKO osteoblasts with control or cKO osteoclast precursors produced significantly fewer osteoclasts than coculture with control ***,exposing female mice to Epo pumps(10 U-d_1)for 4 weeks resulted in trabecular bone loss(-25%)and increased osteoclast numbers(1.7-fold)in control mice only,not in cKO *** data show that EpoR in osteoprogenitors is essential in regulating osteoblast function and osteoblast-mediated osteoclastogenesis via the RANKI70PG ***,osteogenic Epo/EpoR signaling controls bone mass maintenance and contributes to Epo-induced bone loss.

关键词： progenitor homeostasis doses

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First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

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World Journal of Gastroenterology 2015年第45期21卷 12963-12969页

作者： Raja Atreya Ulrike Billmeier Timo Rath Jonas Mudter Michael Vieth Helmut neumann Markus F Neurath Markus F Neurath Medical Clinic 1 Friedrich-Alexander University Erlangen-Nürnberg Medical Department Hospital Ostholstein Institute of Pathology Klinikum Bayreuth

We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.

关键词： Ulcerative colitis Interleukin-6 Epithelial barrie

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Low SARS-CoV-2 seroprevalence but high perception of risk among healthcare workers at children’s hospital before second pandemic wave in Germany

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World Journal of Pediatrics 2021年第5期17卷 484-494页

作者： Marietta neumann Annette Aigner Eileen Rossow David Schwarz Maria Marschallek Jorg Steinmann Ralf Stucker Ingo Koenigs Philippe Stock Department of Paediatrics Altona Children's HospitalUniversitat HamburgAltonaer KinderkrankenhausBleickenallee 3822763 HamburgGermany Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin Institute of Biometry and Clinical Epidermiology BerlinCharite-Universitatsmedizin BerlinBerlinGermany Department of Neonatology and Paediatric Intensive Care Medicine Altona Children's HospitalHamburgGermany Department of Paediatric Surgery Altona Children's HospitalHamburgGermany Labor Dr.Fenner and Colleagues Hamburg.Germany Department of Paediatric Orthopaedics Altona Children's HospitalHamburgGermany Department of Paediatric Surgery University Medical Centre Hamburg Eppendorf(UKE)HamburgGermany Department of Paediatrics Altona Children's HospitalHamburgGermany

Background Healthcare workers are considered a particularly high-risk group during the coronavirus disease 2019(COVID-19)*** workers in paediatries are a unique subgroup:they come into frequent contact with children,who often experience few or no symptoms when infected with severe acute respiratory syndrome coronavirus 2(SARS CoV-2)and,therefore,may transmit the disease to unprotected *** Germany,no studies exist evaluating the risk of COVID-19 to healthcare workers in paediatric *** We tested the staff at a large children's hospital in Germany for immunoglobulin(Ig)G antibodies against the nucle-ocapsid protein of SARS CoV-2 in a period between the first and second epidemic wave in *** used a questionnaire to assess each individual's exposure risk and his/her own perception of having already been infected with *** We recruited 619 participants from all sectors,clinical and non-clinical,constituting 70%of the entire *** seroprevalence of SARS CoV-2 antibodies was 0.325%(95%confidence interval 0.039-I.168).Self-perceived risk of a previ-ous SARS-CoV-2 infection decreased with age(odds ratio,0.81;95%confidence interval,0.70-0.93).Having experienced symptoms more than doubled the odds of a high self-perceived risk(odds ratio,2.18;95%confidence interval,1.59--3.00).There was no significant difference in self perceived risk between men and *** Seroprevalence was low among healtheare workers at a large children's hospital in Germany before the second epidemic wave,and it was far from a level that confers herd ***-perceived risk of infection is often overestimated.

关键词： Health personnel SARS CoV-2 Seroepidemiologic studies Pediatrics

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Performance of silver nanoparticles in the catalysis of the oxygen reduction reaction in neutral media： Efficiency limitation due to hydrogen peroxide escape

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Nano Research 2013年第7期6卷 511-524页

作者： Christopher C. M. neumann Eduardo Laborda Kristina Tschulik Kristopher R. Ward Richard G. Compton Department of Chemistry Physical and Theoretical Chemistry Laboratory Oxford University South Parks Road Oxford OXl 3QZUnited Kingdom

The electrocatalytic activity for oxygen reduction reaction （ORR） at neutral pH of citrate-capped silver nanoparticles （diameter = 18 nm） supported on glassy carbon （GC） is investigated voltammetrically. Novelly, the modification of the substrate by nanoparticles sticking to form a random nanoparticle array and the voltammetric experiments are carried out simultaneously by immersion of the GC electrode in an air-saturated 0.1 M NaC104 solution （pH = 5.8） containing chemically-synthesized nanoparticles. The experimental voltammograms of the resulting nanoparticle array are simulated with homemade programs according to the two-proton, two-electron reduction of oxygen to hydrogen peroxide where the first electron transfer is rate determining. In the case of silver electrodes, the hydrogen peroxide generated is partially further reduced to water via heterogeneous decomposition. Comparison of the results obtained on a silver macroelectrode and silver nanoparticles indicates that, for the silver nanoparticles and particle coverages （0.035%-0.457%） employed in this study, the ORR electrode kinetics is slower and the production of hydrogen peroxide larger on the glassy carbon-supported nanoparticles than on bulk silver.

关键词： oxygen reduction reaction silver nanoparticles nanoelectrocatalysis hydrogen peroxide escape fuel cells

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Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1632-1647页

作者： Katharina Joechle Jessica Guenzle Claus Hellerbrand Pavel Strnad Thorsten Cramer Ulf Peter neumann Sven Arke Lang Visceral and Transplantation Surgery University Hospital Rheinisch-Westfalisch Technische Hochschule AachenAachen 52074Germany Department of General and Visceral Surgery Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Institute of Biochemistry Friedrich-Alexander University Erlangen-NurnbergErlangen 91054Germany Department of Internal Medicine Ⅲ University Hospital Rheinisch-Westfalisch Technische Hochschule AachenAachen 52074Germany

The mammalian target of rapamycin(mTOR)acts in two structurally and functionally distinct protein complexes,mTOR complex 1(mTORC1)and mTOR complex 2(mTORC2).Upon deregulation,activated mTOR signaling is associated with multiple processes involved in tumor growth and *** with mTORC1,much less is known about mTORC2 in cancer,mainly because of the unavailability of a selective ***,existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so *** is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth,cell survival,metabolism,and cytoskeletal *** is not only implicated in tumor progression,metastasis,and the tumor microenvironment but also in resistance to ***,the central subunit of mTORC2,was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad ***,AKT,the main downstream regulator of mTORC2/Rictor,is one of the most highly activated proteins in *** and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment,emphasizing the need for further therapeutic *** review,therefore,summarizes the role of mTORC2/Rictor in cancer,with special focus on primary liver cancer but also on liver metastases.

关键词： Mammalian target of rapamycin Mammalian target of rapamycin complex 2 Rictor Liver cancer Liver metastases Hepatocellular carcinoma Cholangiocellular carcinoma

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Diagnosis of Laron syndrome using monoplex-polymerase chain reaction technology with a whole-genome amplification template: A case report

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World Journal of Clinical Cases 2019年第23期7卷 4029-4035页

作者： Adina neumann Miguel Angel Alcantara-Ortigoza Ariadna Gonzalez-del Angel Felipe Camargo-Diaz Esther Lopez-Bayghen Laboratorio de Investigacion y Diagnostico Molecular Instituto de Infertilidad y Genetica Mexico SCINGENESMexico City 05320Mexico Instituto Nacional de Pediatria Torre de InvestigacionMexico City 04530Mexico Laboratorio de Biologia Molecular Departamento de Genetica HumanaInstituto Nacional de PediatriaMexico City 04530Mexico Departamento de Toxicologia Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional(CINVESTAV-IPN)Mexico City 07360Mexico

BACKGROUND Laron syndrome(LS)is an autosomal recessive hereditary condition affecting only 1/1000000 *** cause is associated with mutations in the growth hormone(GH)receptor(GHR),leading to GH *** patients typically present with severe growth retardation,obesity,and abnormal sexual ***,LS diagnosis is performed ***,we assessed the efficiency of Pre-implantation Genetic Testing(PGT)coupled with monoplex-polymerase chain reaction(PCR)technology for detecting this monogenic disease in embryos from a couple confirmed as LS heterozygous carriers CASE SUMMARY The couple LS-carriers were confirmed by the presence of a first child born with *** couple underwent a standard in vitro fertilization(IVF)*** was collected from trophectoderm cells from day 5 *** genome amplification(WGA)was performed using a Sureplex DNA Amplification System and analyzed by PCR,targeting the deletion of the exons 5 and 6 in the GHR gene as well as PGT by Next-generation Sequencing(Illumina).Eleven embryos were collected and analyzed.27.3%were the wild type for GHR,45.5%were heterozygotes,and 18.2%homozygous *** embryo yielded no *** 2-embryos transfers were performed;2 normal homozygous and four heterozygous carriers were selected for *** first two transfers were unsuccessful,whereas the final transfer with two heterozygous embryos resulted in clinical *** genomic composition of the fetus was verified,applying the same techniques using amniocytes,extracted after 21 wk of the ongoing *** fetus was confirmed as GHR deletion in exon 5-6,carrier.A non-affected baby was *** Here,we present a case demonstrating that using WGA as a template in addition to PCR targeting specific gene regions,exons 5 and 6 on the GHR gene,could identify LS carrier *** provides evidence that WGA and PCR serve as an excellent tool to detect this specific monogenic disease in IVF e

关键词： Growth hormone insensitivity Growth hormone receptor mutations Intragenic deletions Molecular diagnosis Embryo diagnosis Laron syndrome Case report

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