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Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass

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World Journal of Gastroenterology 2017年第12期23卷 2185-2193页

作者： Peter Macinga Adela Pulkertova Lukas Bajer Jana Maluskova Martin Oliverius Martin Smejkal Maria Heczkova Julius Spicak Tomas Hucl Department of Gastroenterology and Hepatology Institute for Clinical and Experimental Medicine Department of Pathology Institute for Clinical and Experimental Medicine Department of Transplant Surgery Institute for Clinical and Experimental Medicine Department of Radiodiagnostics and Interventional Radiology Institute for Clinical and Experimental Medicine Center for experimental Medicine Institute for Clinical and Experimental Medicine

AIM To assess the occurrence of autoimmune pancreatitis(AIP) in pancreatic resections performed for focal pancreatic *** We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic *** Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients(5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma(PC) was also present in six patients with AIP(40%), all six were men. Patients with AIP + PC were significantly older(60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes(67% vs 11%, P = 0.09), and had experienced greater weight loss(15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.

关键词： Chronic pancreatitis Pancreatic cancer Ig G4related disease Autoimmune pancreatitis Malignancy

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Etiology and functional status of liver cirrhosis by ^(31)P MR spectroscopy

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World Journal of Gastroenterology 2005年第44期11卷 6926-6931页

作者： Monika Dezortova Pavel Taimr Antonin Skoch Julius Spicak Milan Hajek MR Unit institute for clinical and experimental Medicine Prague Czech Republic Department of Hepatogastroenterology institute for clinical and experimental Medicine

AIM: To assess the functional status and etiology of liver cirrhosis by quantitative 31p magnetic resonance spectroscopy (MRS).METHODS: A total of 80 patients with liver cirrhosis of different etiology and functional status described by Child-Pugh score were examined and compared to 11 healthy volunteers. MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging *** concentrations of phosphomonoesters (PME),phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were ***: MRS changes reflected the degree of liver dysfunction in all the patients as well as in individual etiological groups. The most important change was a decrease of PDE. It was possible to distinguish alcoholic,viral and cholestatic etiologies based on MR *** and viral etiology differed in PDE (alcoholic,viral, controls: 6.5±2.3, 6.5±3.1, 10.8±2.7 mmol/L,P＜0.001) and ATP (alcoholic, viral, controls: 2.9±0.8, 2.8±0.9, 3.7±1.0 mmol/L, P＜0.01) from the control *** viral etiology, patients with alcoholic etiology also differed in Pi (alcoholic, controls: 1.2±0.4, 1.6±0.6mmol/L, P＜0.05) from controls. No significant changes were found in patients with cholestatic disease and controls; nevertheless, this group differed from both alcoholic and viral groups (cholestatic, alcoholic, viral: 9.4±2.7, 6.5±2.3, 6.5±3.1 mmol/L, P＜0.005) in ***: 31p MRS can significantly help in noninvasive separation of different etiological groups leading to liver cirrhosis. In addition, MRS changes reflect functional liver injury.

关键词： Liver cirrhosis ^ 31p MR spectroscopy Absolute concentration Child-Pugh score Etiology

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Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease

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World Journal of Gastroenterology 2018年第43期24卷 4939-4949页

作者： Lukas Bajer Antonij Slavcev Peter Macinga Eva Sticova Jan Brezina Matej Roder Radim Janousek Pavel Trunecka Julius Spicak Pavel Drastich Department of Gastroenterology and Hepatology Institute for Clinical and Experimental MedicinePrague Department of Immunogenetics Institute for Clinical and Experimental Medicine Department of clinical and Transplant Pathology Institute for Clinical and Experimental MedicinePrague Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental MedicinePrague

AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical *** Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective *** De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.

关键词： Primary sclerosing cholangitis Inflammatory bowel disease Liver transplantation Acute cellular rejection Autoimmune hepatitis Human leukocyte antigen Immunosuppression

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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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Adenosine triphosphate maintenance by branched chain amino acids as a novel neuroprotective strategy for retinal neurodegenerative diseases

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Neural Regeneration Research 2019年第1期14卷 82-84页

作者： Tomoko Hasegawa Hanako Ohashi Ikeda Department of Ophthalmology and Visual Sciences Kyoto University Graduate School of Medicine Department of experimental therapeutics Institute for Advancement of Clinical and Translational Science Kyoto University Hospital

Retinal neuronal cell death is caused in many incurable eye diseases such as retinitis pigmentosa(RP)and glaucoma,which are leading causes of adult *** RP,progressive loss of photoreceptor cells leads to visual *** established treatments are available to date for this condition,although potential treatments,including regenerative medicine,gene therapy,and neurotropic factor therapy are being *** glaucoma。

关键词：眼睛疾病视网膜氨基酸基因治疗腺苷分叉维护光敏电阻器

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Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection

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World Journal of Gastroenterology 2015年第18期21卷 5496-5504页

作者： Jan Sperl Sona Frankova Renata Senkerikova Magdalena Neroldova Vaclav Hejda Miroslava Volfova Dusan Merta Ondrej Viklicky Julius Spicak Milan Jirsa Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine Laboratory of experimental Hepatology Institute for Clinical and Experimental Medicine Department of Internal Medicine Division of Gastroenterology and Hepatology Charles University Medical School and Teaching Hospital Hepato-gastroenterology 50012 Hradec Kralove Czech Republic Department of Anesthesiology Resuscitation and Intensive Care Institute for Clinical and Experimental Medicine Department of Nephrology Institute for Clinical and Experimental Medicine

AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype ***: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the *** regression was used to determine significant predictors of *** values for continuous variables were obtained from Receiver Operating Characteristic ***:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the *** IFNL4 genotype was in almost absolute linkage disequlibrium with *** proportion of patients with a low IVL(<600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the

关键词： End-stage renal disease Hepatitis C virus genotype 1 Interferon alpha IFNL4 Ribavirin

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High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

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World Journal of Diabetes 2017年第2期8卷 56-65页

作者： Maha Coucha Islam N Mohamed Sally L Elshaer Osinakachuk Mbata Megan L Bartasis Azza B El-Remessy clinical and experimental therapeutics College of PharmacyUniversity of GeorgiaAugustaGA 30912United States

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was *** High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of ob

关键词： High fat diet Palmitate Endoplasmic-reticulum-stress Inflammation Thioredoxin-interacting protein Micro-RNA 17-5p

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Sphingosine signaling and atherogenesis

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Acta Pharmacologica Sinica 2004年第7期25卷 3-8页

作者： Jacob HANSEN-SCHWARTZ,Lars EDVINSSON Department of clinical experimental Research Glostrup University Hospital Glostrup Denmark Division of experimental Vascular Research institute of Medicine Lund University Sweden

Sphingosine-1-phosphate (S1P) has diverse biological functions acting inside cells as a second messenger toregulate cell proliferation and survival, and extracellularly, as a ligand for a group of G protein-coupled receptors(GPCRs) named the endothelial differentiation gene (EDG) family. Five closely related GPCRs of EDG family(EDG1, EDG3, EDG5, EDG6, and EDG8) have recently been identified as high-affinity S1P receptors. Thesereceptors are coupled via Gi, Gq, G12/13, and Rho. The signaling pathways are linked to vascular cell migration,proliferation, apoptosis, intracellular Ca2+ mobilization, and expression of adhesion molecules. The formation of anatherosclerotic lesion occurs through activation of cellular events that include monocyte adhesion to the endothe-lium and vascular smooth muscle cell (VSMC) migration and proliferation. Thus, S1P signaling may play animportant role in the pathogenesis of atherosclerotic vascular disease. This review highlights S1P signalling invascular cells and its involvement in the formation of atherosclerotic lesions.

关键词： sphingosine 1-phosphate sphingosine kinase sphingosine-1-phosphate receptors endothelium myocardium smooth muscle arteriosclerosis

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Bridging academic science and clinical research in the search for novel targeted anti-cancer agents

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Cancer Biology & Medicine 2015年第4期12卷 316-327页

作者： Alex Matter experimental therapeutics Center & D3 A*STAR

This review starts with a brief history of drug discovery & development, and the place of Asia in this worldwide effort discussed. The conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. The importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. The most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. The factors to consider before starting a new drug discovery & development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials.

关键词： Drug discovery drug development translational R&D targeted anti-cancer agents

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Macro-or microencapsulation of pig islets to cure type 1 diabetes

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World Journal of Gastroenterology 2012年第47期18卷 6885-6893页

作者： Denis Dufrane Pierre Gianello Department of Health Sciences Institute for Experimental and ClinicalExperimental Surgery and TransplantationCatholic University of LouvainB-1200 BrusselsBelgium

Although allogeneic islet transplantation can successfully cure type 1 diabetes,it has limited *** example,organs are in short supply;several human pancreas donors are often needed to treat one diabetic recipient;the intrahepatic site may not be the most appropriate site for islet implantation;and immunosuppressive regimens,which are associated with side effects,are often required to prolong survival of the islet *** alternative source of insulinproducing cells would therefore be of major *** represent a possible alternative source of beta *** of pig islets may appear difficult because of the immunologic species barrier,but pig islets have been shown to function in primates for at least 6 mo with clinically incompatible ***,a bioartificial pancreas made of encapsulated pig islets may resolve issues associated with islet *** several groups have shown that encapsulated pig islets are functional in small-animal models,less is known about the use of bioartificial pancreases in large-animal *** this review,we summarize current knowledge of encapsulated pig islets,to determine obstacles to implantation in humans and possible solutions to overcome these obstacles.

关键词： Cell transplantation Diabetes mellitus type 1 Islets of Langerhans Porcine Xenografts

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