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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Graft pancreatitis and allograft rejection were both accompanied by increased serum levels of immunoreactive anionic trypsin (irAT) in a porcine pancreatic allograft transplantation model. Characterization of this immunoreactivity by gel filtration revealed different elution profiles in these conditions that can be helpful in the differentiation between them. During graft pancreatitis, a major part of the immunoreactivity was found within the high-molecular-weight fraction corresponding to the formation of complexes between trypsin and protease inhibitors. During allograft rejection, virtually all serum irAT increase could be attributed to the release of anionic trypsinogen without any evidence of activation. Since this transplantation model includes urinary diversion of the exocrine secretions, irAT and immunoreactive cationic trypsin (irCT) can also be measured in the urine. Characterization of this immunoreactivity showed that most of both irAT and irCT was found as active trypsin but a minor part was probably complexed with some protease inhibitor (possibly pancreatic secretory trypsin inhibitor [PSTI]).
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PMID:Characterization of immunoreactive trypsin as a means of differentiating graft pancreatitis and allograft rejection after porcine pancreatic transplantation. 173 80

The serum and urine concentrations of a tumour-associated trypsin inhibitor, TATI, were determined by radioimmunoassay in patients with pancreatic cancer and with benign pancreatic and biliary diseases. Elevated serum levels (greater than 20 micrograms l-1) were found in 85% of the patients with pancreatic cancer, and elevated urine levels (greater than 50 micrograms g-1 creatinine) in 96% of the patients. Thus low TATI level, especially in urine, makes the possibility of pancreatic cancer less likely. Serial assay of TATI in serum from three patients with surgically removed pancreatic cancer showed elevation of the TATI level at the time of detection of recurrence. However, high serum and urine levels were also seen in pancreatitis and in benign extrahepatic cholestasis. Thus TATI is a sensitive, although not specific, indicator of pancreatic and biliary disease, but the use of TATI as a tumour marker in the primary diagnosis of pancreatic cancer is limited. Immunohistochemical staining of pancreatic lesions showed that half of the pancreatic tumours expressed TATI, but the pancreatic tissue adjacent to a carcinoma always stained stronger than the carcinoma. It therefore seems that the main source of TATI in serum and urine of patients with pancreatic cancer are the normal acini and not the tumour tissue. In pancreatitis the staining was intense and clearly stronger than in normal pancreas.
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PMID:Tumour-associated trypsin inhibitor, TATI, in patients with pancreatic cancer, pancreatitis and benign biliary diseases. 374 64

Idiopathic chronic pancreatitis (ICP) is the leading cause of nonalcoholic chronic pancreatitis. This study examined a series of patients with ICP to determine the prevalence and role of mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). Genetic testing was done in 39 patients with ICP. In this series, 17 patients had CFTR mutations and 9 had PSTI mutations. Pancreatitis risk was increased 14-fold by having the N34S PST1 mutation, 40-fold by having two abnormal copies of CFTR, and 600-fold by having both. In patients with two CFTR mutations, extrapancreatic clinical findings and nasal bioelectric responses suggested reduced residual CFTR protein function. Thus, pancreatitis risk showed complex inheritance and was highest in individuals who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI). These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the classification, diagnosis, and pathogenesis of pancreatitis.
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PMID:Idiopathic pancreatitis related to CFTR: complex inheritance and identification of a modifier gene. 1222 54

Mutations of three major genes are associated with an increased risk of acute and chronic pancreatitis: the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the pancreatic secretory trypsin inhibitor (PSTI) or serine protease inhibitor, Kazal type 1 (SPINK1) gene. Some autosomal dominant forms of hereditary pancreatitis are associated with mutations of the PRSS1 gene, which can be readily identified by genetic testing. Mutations of the CFTR gene can lead either to cystic fibrosis or to idiopathic chronic pancreatitis, and to a variety of cystic fibrosis-associated disorders, including congenital bilateral absence of the vas deferens and sinusitis. These mutations, as with those of the SPINK1 (or PSTI) gene, are prevalent in North America; thus, the presence of such a mutation in an asymptomatic person does not confer a high risk of developing pancreatitis. Combinations of mutations of the PRSS1 and SPINK1 genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests that SPINK1 is a disease modifier. The major fear expressed by potential candidates for genetic testing is that the results could lead to insurance discrimination. Studies of the positive predictive value of genetic tests are hampered by recruitment bias and lack of knowledge of family history of pancreatitis. Genetic testing is most useful for persons for whom family members have already been found to exhibit a particular pancreatitis-associated mutation. In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing.
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PMID:Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments for the motion. 1256 Aug 56

The importance of pretest information, using an accredited DNA laboratory and interpreting the genotype on behalf of the patient and their physicians is emphasized. Care with predictive testing and the strong encouragement to involve a specialist genetic counseling service is made. A similar approach to genetic testing should be used when children are involved. Because of the incomplete pickup of PRSS1 mutations, particularly of a limited mutation panel of R122H and N291 (perhaps with A16V), a diagnosis of HP cannot be ruled out by molecular genetic testing alone. The A16V mutation has a reduced penetrance, and its contribution to pancreatitis remains unclear. The advice to patients with genetic forms of pancreatitis is a strong encouragement to avoid smoking, to avoid alcohol, and to remain in contact with clinical and research groups for their follow-up and screening trials for early pancreatic cancer. The remaining issues are of how wide to cast the net of investigation in patients with unexplained pancreatitis, particularly looking for mutations in the CFTR and lower penetrance genes such as PSTI/SPINK1.
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PMID:Genetic counseling for hereditary pancreatitis--the role of molecular genetics testing for the cationic trypsinogen gene, cystic fibrosis and serine protease inhibitor Kazal type 1. 1552 21

Hereditary pancreatitis (HP) is an autosomal dominant inherited disease characterized by recurrent episodes of pancreatitis often beginning in childhood, a family history of at least 2 other affected members, and the absence of known etiologic factors. The discovery of mutations in cationic trypsinogen gene (PRSS1) in HP not only provided insights into the molecular mechanisms of pancreatitis, but also opened a new era in the field of chronic pancreatitis. The detection of mutations in serine protease inhibitor, Kazal type 1 (SPINK1) and CFTR in patients with hereditary or idiopathic chronic pancreatitis has placed the emphasis on the importance of genetic mutations in pancreatitis. Because the estimated cumulative risk of pancreatic cancer development in hereditary pancreatitis is nearly 40%, screening tests are important in selected cases. There are no specific medical therapies recommended in patients with HP. Registration of patients with Nationwise Registries is essential if management strategies are to be improved and genetic research to be continued.
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PMID:[Hereditary pancreatitis]. 1572 18

Idiopathic chronic pancreatitis (ICP) is the leading cause of chronic pancreatitis in children and nonalcoholic adults. The risk of developing ICP is increased in individuals who have mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). In studies from the United States and France, the risk of ICP is increased about 40-fold by having two abnormal copies of the CFTR gene, about 14-fold by having the N34S PSTI mutation, and about 500-fold by having both. When ICP patients have two abnormal copies of the CFTR gene, there is also evidence of reduced residual CFTR protein function in extrapancreatic tissues based on clinical findings and nasal ion transport responses. Thus, pancreatitis risk is highest in individuals who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI). These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the diagnosis and pathogenesis of pancreatitis.
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PMID:Reduced CFTR function and the pathobiology of idiopathic pancreatitis. 1575 63

Pancreatic inflammatory disease can be classified as acute pancreatitis (AP) and chronic pancreatitis (CP) primarily by clinical criteria, with an obvious difference by restoration of normal function in the former or by permanent residual damage in the latter. Gallstones and alcohol are the most common causes of AP. Recent investigations have established that AP from all cause may disrupt normal stimulus-secretion coupling function within the acinar cell. This disruption within the acinar cell leads to an event termed 'co-localization' in which the digestive and lysosomal enzymes merge resulting in a premature activation of proteases. The mechanisms of inflammatory cells which adhere to endothelial cell are determined by a variety of mediators of cytokines released at the site of tissue damage. Cytokines hold the key for both local and systemic inflammatory response in AP. Besides, CP is a debilitating disease characterized by progressive and irreversible destruction of pancreatic tissue leading to exocrine and endocrine insufficiencies. Alcohol intake is the most common cause of CP. Mutations in the cationic trypsinogen gene were identified as causative gene for hereditary pancreatitis. The recognition of frequent cystic fibrosis transmembrane conductance regulator (CFTR) mutations and serine protease inhibitor, Kazal type 1 (SPINK1) mutations in idiopathic CP has hightened the awareness of importance of genetic mutations in CP. Pancreatic stellate cells represent the main cellular source of extracellular matrix in CP and play a key role in pancreatic fibrosis.
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PMID:[Pancreatitis--etiology and pathogenesis]. 1630 44

Trypsinogens and PSTI/TATI/SPINK1 are expressed, usually together, at high levels by the pancreas but also by many other normal and malignant tissues. The present review describes studies on the expression and putative functions of trypsinogens and PSTI/TATI/SPINK1 in the human body. The clinical aspects are discussed, including the correlations between expression of trypsinogens and PSTI/TATI/SPINK1 in tissues, serum, and urine of patients with pancreatitis or cancer and clinicopathological characteristics, i.e., the roles of trypsinogens and PSTI/TATI/SPINK1 in spontaneous and hereditary pancreatitis, tumor progression, and prognosis.
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PMID:Biochemistry and clinical role of trypsinogens and pancreatic secretory trypsin inhibitor. 1651 20

Autoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic immune-driven, inflammatory process that can involve organs such as the bile duct, salivary glands and lymph nodes, in addition to the pancreas. Many of the presenting signs and symptoms of AIP, including painless jaundice, weight loss and mild epigastric pain, are characteristic of pancreatic adenocarcinoma; thus, obtaining an accurate diagnosis to avoid unnecessary surgery is imperative. AIP responds very well to steroid treatment, although it may recur in up to 20% to 40% of cases. The diagnostic criteria for AIP are histological, radiographic, clinical and laboratory-based in nature. Although no international consensus on diagnostic criteria has yet been made, some of the diagnostic features of AIP include elevated gamma globulin, immunoglobulin, and, in particular, immunoglobulin G4 fraction (IgG4). The search for a distinct serological marker of AIP has included antibodies to a wide range of antigenic stimuli. To date, there have been studies of AIP and antibodies to lactoferrin, carbonic anhydrase isoforms II and IV, pancreatic secretory trypsin inhibitor (PSTI or SPINK) as well as to less sensitive or specific markers of autoimmunity, such as antinuclear antibody and rheumatoid factor. Although there are some preliminary strengths of association with PSTI antibodies, none of these biomarkers appears to be sensitive or specific enough to serve as distinctive evidence of AIP. At the current time, elevations of IgG4 to greater than 280 mg/dL remain the most reliable and reproducible indicator that a patient has AIP.
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PMID:Serology in autoimmune pancreatitis. 1904 79


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