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Search Results to Miklos Sahin-Toth, MD, PhD

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One or more keywords matched the following properties of Sahin-Toth, Miklos

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Research Expertise & Professional Interests Expertise in the role of proteases in pancreatitis. Our laboratory studies how various proteases and their inhibitors in the pancreas contribute to the pathogenesis of pancreatitis. Pancreatitis is believed to occur due to inappropriate, intrapancreatic activation of digestive enzymes (e.g. trypsin, chymotrypsin, elastase), which are normally synthesized and stored in their inactive forms in the pancreas. Our long-term objectives are to understand the molecular mechanisms of human pancreatitis, using genetically determined pancreatitis (e.g. hereditary pancreatitis) as a biochemical model. The main focus of our research program is to provide biochemical evidence that genetic alterations in the three human trypsinogen isoforms (PRSS1, PRSS2 and PRSS3 genes) and the pancreatic secretory trypsin inhibitor (SPINK1 gene) can significantly influence the susceptibility for the development of pancreatitis. Thus, gain-of-function mutations in cationic trypsinogen can cause pancreatitis, while loss of function mutations in anionic trypsinogen can actually protect against pancreatitis. Loss of the inhibitory function of SPINK1 either due to mutations or to degradation by mesotrypsin can represent another risk factor for pancreatitis onset. The following specific projects are studied. (1) The role of human mesotrypsin in pancreatitis. Mesotrypsin is a unique protease specialized for the degradation of trypsin inhibitors. Premature mesotrypsinogen activation might lower protective SPINK1 levels in the pancreas and contribute to the pathogenesis of pancreatitis. (2) Characterization of pancreatitis-associated cationic trypsinogen (PRSS1) mutants. Identification of novel mutation-dependent biochemical defects that lead to hereditary pancreatitis (3) Functional analysis of anionic trypsinogen (PRSS2) mutants that afford protection against pancreatitis. The concept that loss-of-function trypsinogen mutations can protect against pancreatitis provides independent evidence for the central role of trypsin in this disease. (4) Identification of the disease-causing biochemical defects in pancreatitis-associated SPINK1 mutants.
Self-Described Keywords Pancreatitis

One or more keywords matched the following items that are connected to Sahin-Toth, Miklos

Item TypeName
Concept Pancreatitis, Acute Necrotizing
Concept Pancreatitis, Alcoholic
Concept Pancreatitis, Chronic
Academic Article Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 --> Cys) that alters autoactivation and autodegradation of cationic trypsinogen.
Academic Article Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen.
Academic Article Human mesotrypsin defies natural trypsin inhibitors: from passive resistance to active destruction.
Academic Article Biochemical models of hereditary pancreatitis.
Academic Article Signal peptide variants that impair secretion of pancreatic secretory trypsin inhibitor (SPINK1) cause autosomal dominant hereditary pancreatitis.
Academic Article [Genetic risk factors in chronic pancreatitis].
Academic Article Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis.
Academic Article Proteolytic activation of human pancreatitis-associated protein is required for peptidoglycan binding and bacterial aggregation.
Academic Article Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen: a novel disease mechanism.
Academic Article Pancreatitis-associated chymotrypsinogen C (CTRC) mutant elicits endoplasmic reticulum stress in pancreatic acinar cells.
Academic Article Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis.
Academic Article Uncertainties in the classification of human cationic trypsinogen (PRSS1) variants as hereditary pancreatitis-associated mutations.
Academic Article Chymotrypsin C mutations in chronic pancreatitis.
Academic Article Comprehensive functional analysis of chymotrypsin C (CTRC) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk.
Academic Article Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl? channels and luminal anion exchangers.
Academic Article Functional effects of 13 rare PRSS1 variants presumed to cause chronic pancreatitis.
Academic Article Gene conversion between cationic trypsinogen (PRSS1) and the pseudogene trypsinogen 6 (PRSS3P2) in patients with chronic pancreatitis.
Academic Article Exonic variants affecting pre-mRNA splicing add to genetic burden in chronic pancreatitis.
Academic Article Variants in CPA1 are strongly associated with early onset chronic pancreatitis.
Academic Article Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis.
Academic Article Smoking and Drinking Synergize in Pancreatitis: Multiple Hits on Multiple Targets.
Academic Article Chymotrypsin Reduces the Severity of Secretagogue-Induced Pancreatitis in Mice.
Academic Article Human CPA1 mutation causes digestive enzyme misfolding and chronic pancreatitis in mice.
Academic Article EPC/HPSG evidence-based guidelines for the management of pediatric pancreatitis.
Academic Article Novel PRSS1 Mutation p.P17T Validates Pathogenic Relevance of CTRC-Mediated Processing of the Trypsinogen Activation Peptide in Chronic Pancreatitis.
Academic Article High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial.
Academic Article Genetic risk in chronic pancreatitis: the misfolding-dependent pathway.
Academic Article Genetic Risk in Chronic Pancreatitis: The Trypsin-Dependent Pathway.
Academic Article No significant enrichment of rare functionally defective CPA1 variants in a large Chinese idiopathic chronic pancreatitis cohort.
Academic Article A novel p.Ser282Pro CPA1 variant is associated with autosomal dominant hereditary pancreatitis.
Academic Article Chronic pancreatitis: Multicentre prospective data collection and analysis by the Hungarian Pancreatic Study Group.
Academic Article Misfolding cationic trypsinogen variant p.L104P causes hereditary pancreatitis.
Academic Article Genetic Analysis of Human Chymotrypsin-Like Elastases 3A and 3B (CELA3A and CELA3B) to Assess the Role of Complex Formation between Proelastases and Procarboxypeptidases in Chronic Pancreatitis.
Academic Article Prospective, Multicentre, Nationwide Clinical Data from 600 Cases of Acute Pancreatitis.
Academic Article Tighter Control by Chymotrypsin C (CTRC) Explains Lack of Association between Human Anionic Trypsinogen and Hereditary Pancreatitis.
Academic Article CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis.
Academic Article Pathogenic cellular role of the p.L104P human cationic trypsinogen variant in chronic pancreatitis.
Academic Article Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis.
Academic Article SPINK1 Promoter Variants in Chronic Pancreatitis.
Academic Article Variants in pancreatic carboxypeptidase genes CPA2 and CPB1 are not associated with chronic pancreatitis.
Academic Article Mesotrypsin Signature Mutation in a Chymotrypsin C (CTRC) Variant Associated with Chronic Pancreatitis.
Academic Article Functional significance of SPINK1 promoter variants in chronic pancreatitis.
Academic Article [Pediatric pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].
Academic Article [Autoimmune pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].
Academic Article [Chronic pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].
Academic Article [Acute pancreatitis. Evidence-based practice guidelines, prepared by the Hungarian Pancreatic Study Group].
Academic Article Alcohol disrupts levels and function of the cystic fibrosis transmembrane conductance regulator to promote development of pancreatitis.
Academic Article Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis.
Academic Article Robust autoactivation, chymotrypsin C independence and diminished secretion define a subset of hereditary pancreatitis-associated cationic trypsinogen mutants.
Academic Article Increased activation of hereditary pancreatitis-associated human cationic trypsinogen mutants in presence of chymotrypsin C.
Academic Article Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis.
Academic Article Sequence analysis of the human tyrosylprotein sulfotransferase-2 gene in subjects with chronic pancreatitis.
Academic Article Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process.
Academic Article Cathepsin L inactivates human trypsinogen, whereas cathepsin L-deletion reduces the severity of pancreatitis in mice.
Academic Article Variations in trypsinogen expression may influence the protective effect of the p.G191R PRSS2 variant in chronic pancreatitis.
Academic Article Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis.
Academic Article Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis.
Academic Article A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.
Academic Article Gene conversion between functional trypsinogen genes PRSS1 and PRSS2 associated with chronic pancreatitis in a six-year-old girl.
Academic Article Interaction between trypsinogen isoforms in genetically determined pancreatitis: mutation E79K in cationic trypsin (PRSS1) causes increased transactivation of anionic trypsinogen (PRSS2).
Academic Article Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis.
Academic Article The pathobiochemistry of hereditary pancreatitis: studies on recombinant human cationic trypsinogen.

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  • Pancreatitis