Markus Lerch | Universität Greifswald (original) (raw)
Papers by Markus Lerch
The American journal of gastroenterology, 2014
We used data from population-based studies to determine the accuracy of the Fatty Liver Index (FL... more We used data from population-based studies to determine the accuracy of the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI) in determining individual risk of hepatic steatosis. We also developed a new risk scoring system and validated all three indices using external data. We used data from the Study of Health in Pomerania (SHIP; n=4,222), conducted in North-eastern Germany, to validate the existing scoring systems and to develop our own index. Data from the South German Echinococcus Multilocularis and Internal Diseases in Leutkirch (EMIL) study (n=2,177) were used as an external validation data set. Diagnostic performance was evaluated in terms of discrimination (area under the receiver operating characteristic curve (AUC)) and calibration plots. We applied boosting for generalized linear models to select relevant diagnostic separators. The FLI accurately discriminated patients with fatty liver disease from those without (AUC=0.817) but had poor calibration, in that p...
Nature Genetics, 2015
Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene 1 . Mutations in C... more Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene 1 . Mutations in CEL cause maturityonset diabetes of the young as well as pancreatic exocrine dysfunction 2 . Here we describe a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 × 10 −6 by two-tailed Fisher's exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 × 10 −11 ; formal metaanalysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis.
Methods: DNA sequencing was done after PCR-amplification of human leukocyte DNA followed by restr... more Methods: DNA sequencing was done after PCR-amplification of human leukocyte DNA followed by restriction fragment length polymorphism-analysis. The Cys-122 and wild type trypsinogen were expressed in E-coli. Measurements of trypsinogen activa- tion and trypsin autolysis were performed over a wide range of experimental conditions. Results: This family with hereditary pancreatitis required new diagnostic assay based on restriction enzyme digest with
Gut, Jan 18, 2014
Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription fact... more Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription factor 1 (PTF1) complex. Induction of pancreatitis leads to MAP kinase activation and transient suppression of the acinar differentiation programme. We investigated the role of MAP kinase-interacting kinase 1 (Mnk1) in mouse exocrine pancreas development and in the response to secretagogue-induced pancreatitis. Mnk1 expression was analysed using immunohistochemistry, RT-qPCR and western blotting. Ptf1a binding to Mnk1 was assessed by chromatin immunoprecipitation and qPCR. Acute pancreatitis was induced in wild type and Mnk1(-/-) mice by 7 h intraperitoneal injections of caerulein. In vitro amylase secretion and trypsinogen activation were assessed using freshly isolated acinar cells. In vivo secretion was quantified by secretin-stimulated MRI. Mnk1 is expressed at the highest levels in pancreatic acinar cells and is a direct PTF1 target. Mnk1 is activated upon induction of pancreatitis and ...
On the basis of our current knowledge about the physical properties and biological effects of low... more On the basis of our current knowledge about the physical properties and biological effects of low temperature plasmas the possibilities and prospects of plasma medicine are discussed in an interdisciplinary dialogue in order to generate hypotheses for further basic and applied research.The following possibilities are seemed feasible for the medical application of low-temperature plasmas: * Prevention and treatment of diseases (chronic wounds, skin and mucosal infectious diseases, localized tumors, keloid formation, promotion of angiogenesis, tissue ablation, hemostasis) * Inhibition of biofilm formation by surface treatment and by direct action on biofilms * Promotion of incorporation of implants into viable tissue by changing the surface (hydrophobicity, plasma steered application of antimicrobial active layers with drug delivery function) * Promotion of improved penetration of topically applied drugs with therapeutic outcome * Employment for veterinary indications * Improved clean...
Gut, Jan 24, 2014
Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). ... more Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort. We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships. Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). ...
Journal of Medical Genetics, 2003
ereditary pancreatitis (HP) is an inborn disorder which leads to recurrent episodes of pancreatit... more ereditary pancreatitis (HP) is an inborn disorder which leads to recurrent episodes of pancreatitis in children and young adults and is associated with exocrine pancreatic insufficiency and secondary diabetes. 1-3 Several germline mutations in the cationic trypsinogen (PRSS1) gene have been found to be associated with the disease phenotype, the most common of which are the R122H, N29I, and A16V
MATERIALS AND METHODS In the present study we sought to determine by Northern blot analysis and m... more MATERIALS AND METHODS In the present study we sought to determine by Northern blot analysis and mRNA in situ hybridization whether gene expression of heat shock proteins (HSPs) (HSP 89a, HSP 891~, HSP 70, and ubiquitin) is altered in pancreatic carcinoma, compared to control tissues (normal pancreas and chronic pancreatitis tissue). HSP 89a was selectively overexpressed in pancreatic carcinoma, and
Journal of Translational Medicine, 2014
Background: Individualized Medicine aims at providing optimal treatment for an individual patient... more Background: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the "Greifswald Approach to Individualized Medicine" (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice.
![Research paper thumbnail of [S3-guideline exocrine pancreatic cancer]](https://attachments.academia-assets.com/44774494/thumbnails/1.jpg)
](Zeitschrift Fur Gastroenterologie, 2013
Current Gastroenterology Reports, 2012
Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are list... more Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge. In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs.
Zeitschrift für Gastroenterologie, 2014
Diabetes Care, 2014
To determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 trial.
PLoS ONE, 2013
Introduction: Impairment of the mucosal barrier plays an important role in the pathophysiology of... more Introduction: Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis.
Physical Review C, 1985
Excitation functions have been measured for production of isotopes of Bk through Fm in bombardmen... more Excitation functions have been measured for production of isotopes of Bk through Fm in bombardments of 248 Cm with 234-to 294-MeV 40 Ca ions and with 239-to 318-MeV 48 Ca ions. The maxima of the isotopic distributions for these elements occur at only 2 to 3 mass numbers larger ...
Physical Review C, 1986
Yields for isotopes of Rn through Pu have been measured in the reaction 48Ca+248Cm at an energy o... more Yields for isotopes of Rn through Pu have been measured in the reaction 48Ca+248Cm at an energy of 248-263 MeV (1.04-1.10 times the Coulomb barrier). Despite the low bombarding energy, high and essentially constant integral yields of about 1 to 2 mb for the elements Rn through U were observed. There is evidence that these nuclides are produced with little
Pancreatology, 2001
... Samples can be taken on the basis of non-disclo-sure of research results. These samples must ... more ... Samples can be taken on the basis of non-disclo-sure of research results. These samples must be anony-mous or the samples carefully coded so as to protect the identity of the individuals and to guard against the inad-vertent release of unwanted genetic information. ...
The American journal of gastroenterology, 2014
We used data from population-based studies to determine the accuracy of the Fatty Liver Index (FL... more We used data from population-based studies to determine the accuracy of the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI) in determining individual risk of hepatic steatosis. We also developed a new risk scoring system and validated all three indices using external data. We used data from the Study of Health in Pomerania (SHIP; n=4,222), conducted in North-eastern Germany, to validate the existing scoring systems and to develop our own index. Data from the South German Echinococcus Multilocularis and Internal Diseases in Leutkirch (EMIL) study (n=2,177) were used as an external validation data set. Diagnostic performance was evaluated in terms of discrimination (area under the receiver operating characteristic curve (AUC)) and calibration plots. We applied boosting for generalized linear models to select relevant diagnostic separators. The FLI accurately discriminated patients with fatty liver disease from those without (AUC=0.817) but had poor calibration, in that p...
Nature Genetics, 2015
Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene 1 . Mutations in C... more Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene 1 . Mutations in CEL cause maturityonset diabetes of the young as well as pancreatic exocrine dysfunction 2 . Here we describe a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 × 10 −6 by two-tailed Fisher's exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 × 10 −11 ; formal metaanalysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis.
Methods: DNA sequencing was done after PCR-amplification of human leukocyte DNA followed by restr... more Methods: DNA sequencing was done after PCR-amplification of human leukocyte DNA followed by restriction fragment length polymorphism-analysis. The Cys-122 and wild type trypsinogen were expressed in E-coli. Measurements of trypsinogen activa- tion and trypsin autolysis were performed over a wide range of experimental conditions. Results: This family with hereditary pancreatitis required new diagnostic assay based on restriction enzyme digest with
Gut, Jan 18, 2014
Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription fact... more Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription factor 1 (PTF1) complex. Induction of pancreatitis leads to MAP kinase activation and transient suppression of the acinar differentiation programme. We investigated the role of MAP kinase-interacting kinase 1 (Mnk1) in mouse exocrine pancreas development and in the response to secretagogue-induced pancreatitis. Mnk1 expression was analysed using immunohistochemistry, RT-qPCR and western blotting. Ptf1a binding to Mnk1 was assessed by chromatin immunoprecipitation and qPCR. Acute pancreatitis was induced in wild type and Mnk1(-/-) mice by 7 h intraperitoneal injections of caerulein. In vitro amylase secretion and trypsinogen activation were assessed using freshly isolated acinar cells. In vivo secretion was quantified by secretin-stimulated MRI. Mnk1 is expressed at the highest levels in pancreatic acinar cells and is a direct PTF1 target. Mnk1 is activated upon induction of pancreatitis and ...
On the basis of our current knowledge about the physical properties and biological effects of low... more On the basis of our current knowledge about the physical properties and biological effects of low temperature plasmas the possibilities and prospects of plasma medicine are discussed in an interdisciplinary dialogue in order to generate hypotheses for further basic and applied research.The following possibilities are seemed feasible for the medical application of low-temperature plasmas: * Prevention and treatment of diseases (chronic wounds, skin and mucosal infectious diseases, localized tumors, keloid formation, promotion of angiogenesis, tissue ablation, hemostasis) * Inhibition of biofilm formation by surface treatment and by direct action on biofilms * Promotion of incorporation of implants into viable tissue by changing the surface (hydrophobicity, plasma steered application of antimicrobial active layers with drug delivery function) * Promotion of improved penetration of topically applied drugs with therapeutic outcome * Employment for veterinary indications * Improved clean...
Gut, Jan 24, 2014
Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). ... more Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort. We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships. Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). ...
Journal of Medical Genetics, 2003
ereditary pancreatitis (HP) is an inborn disorder which leads to recurrent episodes of pancreatit... more ereditary pancreatitis (HP) is an inborn disorder which leads to recurrent episodes of pancreatitis in children and young adults and is associated with exocrine pancreatic insufficiency and secondary diabetes. 1-3 Several germline mutations in the cationic trypsinogen (PRSS1) gene have been found to be associated with the disease phenotype, the most common of which are the R122H, N29I, and A16V
MATERIALS AND METHODS In the present study we sought to determine by Northern blot analysis and m... more MATERIALS AND METHODS In the present study we sought to determine by Northern blot analysis and mRNA in situ hybridization whether gene expression of heat shock proteins (HSPs) (HSP 89a, HSP 891~, HSP 70, and ubiquitin) is altered in pancreatic carcinoma, compared to control tissues (normal pancreas and chronic pancreatitis tissue). HSP 89a was selectively overexpressed in pancreatic carcinoma, and
Journal of Translational Medicine, 2014
Background: Individualized Medicine aims at providing optimal treatment for an individual patient... more Background: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the "Greifswald Approach to Individualized Medicine" (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice.
Zeitschrift Fur Gastroenterologie, 2013
Current Gastroenterology Reports, 2012
Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are list... more Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge. In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs.
Zeitschrift für Gastroenterologie, 2014
Diabetes Care, 2014
To determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 trial.
PLoS ONE, 2013
Introduction: Impairment of the mucosal barrier plays an important role in the pathophysiology of... more Introduction: Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis.
Physical Review C, 1985
Excitation functions have been measured for production of isotopes of Bk through Fm in bombardmen... more Excitation functions have been measured for production of isotopes of Bk through Fm in bombardments of 248 Cm with 234-to 294-MeV 40 Ca ions and with 239-to 318-MeV 48 Ca ions. The maxima of the isotopic distributions for these elements occur at only 2 to 3 mass numbers larger ...
Physical Review C, 1986
Yields for isotopes of Rn through Pu have been measured in the reaction 48Ca+248Cm at an energy o... more Yields for isotopes of Rn through Pu have been measured in the reaction 48Ca+248Cm at an energy of 248-263 MeV (1.04-1.10 times the Coulomb barrier). Despite the low bombarding energy, high and essentially constant integral yields of about 1 to 2 mb for the elements Rn through U were observed. There is evidence that these nuclides are produced with little
Pancreatology, 2001
... Samples can be taken on the basis of non-disclo-sure of research results. These samples must ... more ... Samples can be taken on the basis of non-disclo-sure of research results. These samples must be anony-mous or the samples carefully coded so as to protect the identity of the individuals and to guard against the inad-vertent release of unwanted genetic information. ...