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Zinc deficiency in patients with chronic pancreatitis

World Journal of Gastroenterology 2019年第5期25卷 600-607页

作者： Miroslav Vujasinovic AleksANDra Hedstr?m Patrick Maisonneuve Roberto Valente Henrik von Horn J-Matthias l?hr stephan l haas Department for Digestive Diseases Karolinska University Hospital Division of Epidemiology and Biostatistics IEO European Institute of Oncology IRCCS Department for Digestive Diseases Sapienza University of Rome Division of Clinical Chemistry Department of Molecular Medicine and Surgery Karolinska Institutet Karolinska University Hospital Department of Clinical Science Intervention and Technology (CLINTEC)Karolinska Institute

BACKGROUND Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis(CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency(PEI),which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting *** To investigate serum zinc levels in patients with CP of various *** Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the MANNHEIM classification system into the following etiological subcategories:alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal(fecal elastase 1 > 200 μg/g), mildly reduced(100-200μg/g) and severely reduced(fecal elastase 1 lTS A total of 150 patients were included in the analysis. Zinc deficiency(l/l) was present in 39(26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency(FE-1 lder age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients 0.002]. Smoking and number of packyears were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher

关键词： Zinc Pancreas Pancreatic exocrine insufficiency Chronic pancreatitis Malnutrition

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Enhanced expression of interleukin-18 in serum and pancreas of patients with chronic pancreatitis

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World Journal of Gastroenterology 2006年第40期12卷 6507-6514页

作者： Alexander Schneider stephan l haas Ralf Hildenbrand Sren Siegmund Iris Reinhard Helmut Nakovics Manfred V Singer Peter Feick Department of Medicine II (Gastroenterology Hepatology and Infectious Diseases) Univer-sity Hospital of Heidelberg at Mannheim Mannheim Germany Institute of Pathology University Hospital of Heidelberg at Mannheim Mannheim Germany Central Institute of Mental Health Mannheim Germany

AIM： To investigate interleukin-18 （Il-18） in patients with chronic panreatitis （CP）. METHODS： We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells （PBMC） were isolated and incubated with 50 mmol/l ethanol, lipopolysaccharide （lPS）（doses 25 g/l, 250 g/l, 2500 g/l） and both agents for 24 h. levels of Il-18 in the supernatants, and levels of Il-18, Il-12, interferon （IFN）-T and soluble CD14 in the serum were analysed by EI_ISA technique. Expression of Il-18 in PBMC was investigated by reverse-transcription （RT）-PCR. Il-18 protein levels in CP tissue and in normal pancreas were studied by ElISA technique. Il-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Immunohistochemistry for pancreatic Il-18 expression was performed.RESUlTS： In patients, Il-18 serum levels were significantly enhanced by 76% （mean： 289.9 ± 167.7 ng/l） compared with controls （mean： 165.2 ± 43.6 ng/l; P 〈 0.0005）. Il-12 levels were enhanced by 25% in patients （18.3 ± 7.3 ng/l） compared with controls （14.7 ± 6.8 ng/l, P = 0.0576） although not reaching the statistical significance. IFN-γ, and soluble CD14 levels were not increased. In vitro, lPS stimulated significantly and dosedependently Il-18 secretion from PBMC. Incubation with ethanol reduced lPS-stimulated Il-18 secretion by about 50%. The mRNA expression of Il-18 in PBMC and the response of PBMC to ethanol and lPS was similar in CP patients and controls. In PBMC, no significant differences in Il-18 protein levels were detected between patients and controls. Il-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. Il-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONClUSION： Il-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.

关键词： Chronic pancreatitis Cytokines Interleukin- 18 Pancreatic fibrosis

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Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation

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World Journal of Gastroenterology 2006年第30期12卷 4843-4849页

作者： stephan l haas Ralf Jesnowski Michael Steiner Frank Hummel Jrg Ringel Christine Burstein Horst Nizze Stefan liebe J Matthias lhr Department of Medicine II University of Heidelberg at Mannheim Germany Department of Clinical Chemistry and Pathobiochemistry University of Rostock Rostock Germany Department of Pathology University of Rostock Rostock Germany Department of Medicine University of Rostock Rostock Germany

AIM： To study expression of tissue factor （TF） in pancreatic cancer and its role in the development of thromboembolism.METHODS： TF expression was studied in eight human pancreatic carcinoma cell lines by Northern blot and indirect immunofluorescence. Expression of alternatively spliced TF （asTF） was assessed by RT-PCR. In addition, TF expression was determined by immunofluorescence in pancreatic tissues of 19 patients with pancreatic adenocarcinoma （PCa）, 9 patients with chronic pancreatitis （CP） and 20 normal controls. Plasma samples （30 PCa-patients, 13 CP-patients and 20 controls） were investigated for soluble TF levels and coagulation activation markers [thrombin-antithrombin Ⅲ complex （TAT）, prothrombin fragment 1 ＋ 2 （F1 ＋ 2）]. RESUlTS： All pancreatic carcinoma cell lines expressed TF （8/8） and most of them expressed asTF （6/8）. TF expression at the protein level did not correlate with the differentiation of the carcinoma cell line. All but two pancreatic cancer tissue samples stained positive for TF （17/19）. In all samples of CP weak staining was restricted to pancreatic duct cells, whereas only a few subendothelial cells were positive in 9/20 of normal controls. TF and TAT levels in PCa patients were significantly elevated compared to controls whereas elevated F1 ＋ 2 levels did not reach statistical significance compared to controls. In CP patients TAT and F1 ＋ 2 levels proved to be significantly elevated compared to controls, although TAT elevation was less pronounced than in PCa patients. CONClUSION： We conclude that in addition to the upregulated expression of TF on the cell membrane, soluble TF might contribute to activation of the coagulation system in pancreatic cancer.

关键词： Coagulation activation Pancreatic carcinoma Thromboembolism Thrombosis Tissue factor

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Can a polymorphism in the thalassemia gene and a heterozygote CFTR mutation cause acute pancreatitis?

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World Journal of Clinical Cases 2014年第3期2卷 62-66页

作者： J-Matthias l?hr stephan haas Gastrocentrum Karolinska Institutet and University Hospital Division of Molecular Gastroenterology Department of Medicine Ⅱ Medical Faculty Mannheim University of Heidelberg

The case of a 32-year-old black woman of African descent who suffered from repeated episodes of acute pancreatitis, initially triggered when flying on airplanes, is reported. She did not drink alcohol or smoke. Genetic analysis was negative for cationic trypsinogen, serine protease inhibitor Kazal type 1 and chymotrypsin C. However, hemoglobin F was elevated. Sequencing of the thalassemia gene revealed a novel alteration in the 5' region indicative of a functional abnormality of the molecule. Sequencing the cystic fibrosis transmembrane conductance regulator(CFTR) gene revealed a heterozygote sequence variant. The combination of a hemoglobin gene mutation known for thalassemia in conjunction with the hitherto undescribed CFTR mutation is suggested to pave the road for initial and repetitive pancreatitis attacks. This will be discussed.

关键词： Acute pancreatitis Hypoxia Flying Thalassemia Hemoglobin Cystic fibrosis transmembrane conductance regulator Hereditary persistence of fetal hemoglobin

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H pylori infection causes chronic pancreatitis in Mongolian gerbils

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World Journal of Gastroenterology 2007年第29期13卷 3939-3947页

作者： Gabriele Rieder Arno Karnholz Mechthild Stoeckelhuber Juanita l Merchant Rainer haas Max von Pettenkofer-Institute for Hygiene and Medical Microbiology Ludwig-Maximilians-University 80336 Munich Germany Institute of Anatomy Ludwig- Maximilians-University 80336 Munich Germany University of Michigan Departments of Internal Medicine and Molecular and Integrative Physiology Ann Arbor Michigan United States

AIM： To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS： Mongolian gerbils were infected with wild type （WT） H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ （defective type Ⅳ secretion）. After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction （PCR）. Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESUlTS： The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas CONClUSION： H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

关键词： H pylori Mongolian gerbil Pancreatitis Gastritis Penetrating ulcer

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The role of radiotherapy in the management of localized soft tissue sarcomas

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Cancer Biology & Medicine 2016年第3期13卷 373-383页

作者： Siaw Sze Tiong Colleen Dickie Rick l.haas Brian O'Sullivan Department of Radiation Oncology Princess Margaret Cancer Center University of Toronto Department of Radiotherapy The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital

The combination of radiotherapy(RT) and function-preserving surgery is the most usual contemporary approach in the management of soft tissue sarcomas(STS). Pre- and postoperative RT result in similar local control rates, as shown by a landmark trial in extremity STS. In this review, the role of RT in the management of extremity STS will be discussed, but STS in other sites,including retroperitoneal STS, will also be addressed. The focus will consider various aspects of RT including strategies to reduce the volume of tissue being irradiated, dose, scheduling, and the possible of omission of RT in selected cases. Finally, technology advances through the use of intensity-modulated radiotherapy(IMRT), image-guided IMRT, intraoperative radiotherapy(IORT)and particle therapy will also be discussed.

关键词： Sarcoma radiotherapy retroperitoneal sarcoma surgery extremity sarcoma

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Recent results from HERA

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Chinese Physics C 2010年第9期34卷 1254-1258页

作者： T.haas Deutsches Elektronensynchrotron

After the end of data taking in 2007,the experiments H1 and ZEUS have entered into an intense phase of data *** results of this effort on neutral （NC） and charged current （CC） cross sections at high Q 2,the longitudinal structure function F l,inclusive diffraction,heavy flavour production and on searches for glueballs are *** shown are results of a combined analysis on inclusive NC and CC cross sections performed by H1 and ZEUS using HERA-I data.

关键词： lepton-proton scattering structure functions QCD glueballs

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High Speed Rail learning System(HSRlS)-Taking Advantage of Online Technologies in Railway Education

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International Journal of Transportation Science and Technology 2015年第2期4卷 179-196页

作者： Pasi T.lautala Peter J.haas John l.Velat Michigan Technological University Michigan Tech Transportation Institute Michigan Technological University

The United States has taken initial steps toward developing a high speed rail(HSR)network,but the domestic workforce experience and institutional knowledge necessary for the planning,design,construction,and operations of HSR is *** paper describes and provides preliminary assessment of the High Speed Rail learning System(HSRlS),a demonstration project that seeks to address gaps in HSR knowledge and skills in the *** HSRlS developers designed an online education system to serve as a clearinghouse for railrelated information and content,connect teachers,trainers,and students at pre-,and postgraduate levels,and to collect demographic and professional information on groups and individuals interested in *** paper explores the technology review,selection process,and content *** visits and demographic information from over 4,000 unique individuals and 600 HSRlS course registrations are analyzed and assessed.

关键词： Higher education Workforce demand High Speed Rail Railroad education On-line education Web-based teaching and learning

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Disposition and Metabolism of 1 -Nitropropane in Rats and Chimpanzees

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Biomedical and Environmental Sciences 1989年第3期2卷 249-264页

作者： MARGRET haas-JOBElIUS FRIEDHElM KORTE F.COUlSTON Gesellschaft Gesellschaft Technische Universit t München Institut für Chemie lehrstuhl für kologische Chemie Am l wentor D-8050 FreisingWeihenstephan Federal Republic of Germany and White Sands Research Center 2512 Christina Place Alamogordo New Mexico 88310 für Strahlen-und Umweltforschung mbH München Institut für kologische Chemie Ingolst dter landstrasse 1 D-8042 Neuherberg Federal Republic of Germany

The metabolic fate of 1 -nitropropane (1-NP) has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-^(14)C]NP, respectively. The quantitative extent of urinary and fecal elimination was similar in both species. The rats excreted 16.5% ofthedosein urine and 1.7% in feces. For chimpanzees the respective values were 14.8 and 1.2%. Experiments with rats demonstrated that the major route of elimination was by exhalation. With a total elimination via the lungs of 72.6%, rats expired 10.3% of the dose as unchanged 1-NP. Five polar metabolites were isolated from the urine of chimpanzees. The two major metabolites were identified as 3-hydroxypropionic acid and 7V-methyl-N-2-(methylsulfinyl)ethylpropionic acid amide (NMPA). Both substances were also excreted in rat urine. The two identified metabolites indicate that 1-NP was degraded to propionic acid, part of which was modified to 3-hydroxypropionic acid or NMPA. A hypothetical pathway for the biochemical generation of NMPA is suggested.(c)1989 Academic Press, Inc.

关键词： ppm Nitropropane in Rats and Chimpanzees Disposition and Metabolism of 1

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铁燧岩球团的软熔特性

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烧结球团 1991年第6期16卷 35-43页

作者： l.A.haas 宾晓燕

过去,美国约95%的铁矿石球团都产自苏必利尔湖地区,1988年,有22%的铁矿石由国外进口。为了对付国外的竞争,美国矿山局研究了能够生产优质氧化球团的各种技术方案,以提高本国铁矿石球团的竞争力。本研究的出发点是确定各试验变量对球团... 详细信息

过去,美国约95%的铁矿石球团都产自苏必利尔湖地区,1988年,有22%的铁矿石由国外进口。为了对付国外的竞争,美国矿山局研究了能够生产优质氧化球团的各种技术方案,以提高本国铁矿石球团的竞争力。本研究的出发点是确定各试验变量对球团高温软熔特性的影响,目的是:1)

关键词：铁燧岩球团矿软熔特性

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