Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum RNase (RNase I; ribonuclease 3'-pyrimidino-oligonucleotidohydrolase, EC 3.1.4.22) activity (mean +/- SD) with polycytidine as substrate was determined in normal individuals (24.9 +/- 3.0 units/ml) and in patients with pancreatic cancer (37.3 +/- 14.8), pancreatitis (38.5 +/- 12.6), nonpancreatic diseases (48.7 +/- 14.8), or renal failure (175.8 +/- 92.8). Patients with pancreatic cancer could not be distinguished from those with pancreatitis or with nonpancreatic disease, although the RNase activities in all of these differed from the activity in normal individuals. The serum RNase activities of four patients with resectable "curable") pancreatic carcinoma and two others with advanced pancreatic cancer without obstructive jaundice were normal. After total pancreatectomy, serum RNase activity remained in the high-normal range. The data presented here and data in the literature show that serum RNase cannot be of primarily pancreatic origin. The present study also demonstrates that measurement of its activity is not useful in early detection of pancreatic cancer.
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PMID:Serum RNase in the diagnosis of pancreatic carcinoma. 28 51

Serum RNase (ribonuclease) of normal persons and of patients with pancreatitis, carcinoma of pancreas, or other neoplasms was determined with poly(C) as substrate. Strikingly abnormal elevations occur in the serum RNase of patients with pancreatic cancer. There is no elevation in the serum RNase level of patients with pancreatitis. Average serum RNase values of 52 normal persons, 10 patients with pancreatitis, 30 patients with pancreatic cancer, 28 patients with breast cancer, 11 patients with lung cancer, 20 patients with colon cancer, six patients with stomach cancer, and four patients with liver cancer, respectively, were 104, 120, 383, 131, 173, 197, 194, and 152 units/ml of serum. Ninety percent of the patients with pancreatic cancer were above the level of 250 units of serum and 90% of all patients with varied cancers were below this level. In the presence of severe renal insufficiency, marked elevation of serum RNase was also observed. Serum RNase, because of its unique specificity, pancreatic origin, and its abnormal elevation in sera of patients with pancreatic cancer, serves as a reliable biochemical marker of carcinoma of the pancreas in the presence of normal renal function.
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PMID:Elevated serum ribonuclease in patients with pancreatic cancer. 106 80

The present study evaluated serum ribonuclease activity (SRA) in patients with inflammatory and neoplastic pancreatic diseases. RNase determination was carried out using t-RNA (T) from E. coli MRE 600 at pH 7.4 and polycytidylic acid (poly-C) (P) at pH 6.6 as RNA substrates with RNase A from bovine pancreas as reference enzyme. Healthy volunteers had a SRA of T: 160 +/- 12 and P: 482 +/- 24 ngeq/mL (mean +/- SEM (n]. In patients with acute interstitial pancreatitis (AIP), SRA was similar to healthy controls (T: 166 +/- 14; P: 474 +/- 30 ngeq/mL). Patients with acute necrotizing pancreatitis (ANP) had increased SRA (T: 278 +/- 49; P: 791 +/- 145 ngeq/mL, p less than 0.01, compared to controls). SRA values were also increased in patients with chronic pancreatitis (CP) with T: 224 +/- 15 ngeq/mL (p less than 0.01) and in patients with pancreatic carcinoma (PCA) with T: 331 +/- 35 (p less than 0.001 vs controls, p less than 0.01 vs CP). Increased SRA was detected in patients with renal insufficiency (T: 2576 +/- 195 ngeq/mL, p less than 0.001). Diagnostic discrimination between AIP and ANP was achieved in 69% using T-SRA (sensitivity 31%, specificity 88%), and in 78% using P-SRA (sensitivity 54%, specificity 92%). Discrimination between CP and pancreatic carcinoma was possible in 68% (sensitivity 67%, specificity 71%). The diagnostic value of serum RNase is limited because of its low sensitivity, but increased T-SRA above a cutoff of 250 ngeq/mL and increased P-SRA above a cutoff of 620 ngeq/mL are specific for detecting pancreatic necrosis in the absence of renal impairment. The kidney is a major site for SRA clearance.
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PMID:Serum ribonuclease activity in the diagnosis of pancreatic disease. 203 16

Antiserum to human urinary RNase C [ribonuclease (pancreatic), EC 3.1.27.5], developed in rabbits, was used to characterize this enzyme through studies of inhibition of RNase C-catalyzed poly(C) hydrolysis and of competition in a RIA. By either assay, the antiserum failed to cross react with human urinary RNase U (EC 3.1.27.-) or bovine pancreatic RNase A (EC 3.1.27.5). RNase C is immunologically identical to the poly(C)-active RNase in various human sera, including samples obtained from normal individuals, patients with pancreatic carcinoma, pancreatitis, or other malignant and nonmalignant diseases. This conclusion is based on the finding of superimposable antibody dose-inhibition curves for poly(C) hydrolysis and parallel competition RIA curves for RNase C and the various sera. There was a positive correlation (r = 0.73; p less than 0.001) between concentrations of RNase C as determined by poly(C) hydrolysis and competition RIA in serum samples from 102 patients. Therefore, the latter technique provides al alternative method for measuring RNase C in sera.
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PMID:Immunological studies of ribonuclease C from human urine. 727 95

The pancreatitis-associated proteins (PAPs) are major pancreatic secretory proteins during acute pancreatitis. However, mechanisms of regulation of PAP gene expression are poorly understood, and there is a lack of information regarding mouse PAP gene expression. Herein, we employed Northern blotting and RNase protection assays to measure mouse PAP-I mRNA levels in the normal pancreas and intestine, and in the pancreas during caerulein-induced acute pancreatitis. Unexpectedly, we found that mouse PAP-I mRNA levels are constitutively high in the adult pancreas, as well as in the small intestine. Furthermore, mouse pancreatic PAP-I mRNA levels are rapidly and dramatically down-regulated (3 h) after the initiation of caerulein injections, but slowly return to high levels by 72 h. Interestingly, we found that pancreatic PAP-I mRNA levels are also transiently and dramatically down-regulated after L-buthionine-[S,R]-sulfoximine administration. Thus, a correlation between PAP-I mRNA levels and glutathione levels in the mouse pancreas was demonstrated.
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PMID:Regulation of mouse pancreatitis-associated protein-I gene expression during caerulein-induced acute pancreatitis. 888 77

Plasma pancreatic-type Poly-C specific ribonuclease (P-RNase)-enzyme activity increases in patients with acute pancreatitis (AP) who develop pancreatic necrosis and severe disease course. It is considered as a marker of pancreatic tissue destruction. The aim of this study was to estimate interrelations between major inflammatory cytokines such as: interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor soluble receptors: sTNFR55 and sTNFR75 output, and plasma P-RNase activity. The study was carried out in a group of 56 patients with AP, where 20 developed pancreatic necrosis. It was found that serum P-RNase concentration and levels of all studied inflammatory cytokines significantly increase already in the first day from diagnose of the disease (2.5 folds for P-RNase, 20 for IL-8, about 200 for IL-6 and 1.5 for receptors, respectively). In the first day from admission to hospital, P-RNase activity significantly correlated with plasma concentration of studied inflammatory cytokines. The most pronounced correlation was found for P-RNase and IL-6 in days 1-4 from diagnose, manifested by Pearson correlation r coefficients amounting to 0.86, 0.79, 0.60 and 0.57 respectively (p<0.001). Dividing the studied AP patients into two groups, varying in severity of disease a significant differences in P-RNase and IL-6, IL-8 and sTNFR55/sTNFR75 were found. In patients with acute necrotizing pancreatitis P-RNase significantly correlate with levels of major inflammatory cytokines. Carried out studies suggest that activity of P-RNase reflects severity of inflammatory reaction, which is dependent on development of pancreatic injury and tissue necrosis in AP.
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PMID:Poly-C specific ribonuclease activity correlates with increased concentrations of IL-6, IL-8 and sTNFR55/sTNFR75 in plasma of patients with acute pancreatitis. 1456 81

The aim of this study was to compare diagnostic performance of C-reactive protein (CRP) and poly-C avid ribonuclease (P-RNase) levels in the prediction of a severe clinical course of acute pancreatitis (AP). The study included 36 patients with mild and 20 with severe AP. CRP concentration was measured by an immunonephelometric method and P-RNase activity by the rate of polycytidylate hydrolysis at pH 7.8. At the time of admission, both P-RNase and CRP levels were significantly increased in all patients when compared to healthy subjects (29.2 vs. 18.7 U/l and 91.1 vs. 2.89 mg/l; p < 0.001). Up to days 3 and 4 a further increase in P-RNase was observed. On the other hand, the increase in CRP continued only through days 2 and 3 (p < 0.001). Severe acute pancreatitis (SAP) and mild acute pancreatitis (MAP) differed significantly with respect to P-RNase levels on all days studied; whereas CRP levels differed significantly on days 2-5 but did not differ at admission. Receiver operating characteristic (ROC) curve function analysis yielded the best sensitivity of SAP detection for P-RNase, equaling 72.2%, at the cut-off point value 65.3 U/l on day 3 after admission. The sensitivity of CRP for detection of SAP was 85.0% at 125.7 mg/l on the 2nd day after admission. Both parameters studied were significantly associated with the severity of the AP clinical course; however, on days 1 and 2 post-admission, P-RNase was more specific for detection of SAP than CRP (94.4% vs. 77.1% on the 1st day and 94.4% vs. 55.5% on the 2nd day). In conclusion, P-RNase has shown an excellent performance for early differentiation of acute necrotizing pancreatitis.
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PMID:Comparison of sensitivity and specificity of serum poly-C avid ribonuclease activity and C-reactive protein concentration in detection of mild and severe acute pancreatitis. 1520 93

Coxsackievirus B3 (CVB3) is a causative agent of viral myocarditis, meningitis, pancreatitis, and encephalitis. Much of what is known about the coxsackievirus intracellular replication cycle is based on the information already known from a well-studied and closely related virus, poliovirus. Like that of poliovirus, the 5' noncoding region (5' NCR) of CVB3 genomic RNA contains secondary structures that function in both viral RNA replication and cap-independent translation initiation. For poliovirus IRES-mediated translation, the interaction of the cellular protein PCBP2 with a major secondary structure element (stem-loop IV) is required for gene expression. Previously, the complete secondary structure of the coxsackievirus 5' NCR was determined by chemical structure probing and overall, many of the RNA secondary structures bear significant similarity to those of poliovirus; however, the functions of the coxsackievirus IRES stem-loop structures have not been determined. Here we report that a CVB3 RNA secondary structure, stem-loop IV, folds similarly to poliovirus stem-loop IV and like its enterovirus counterpart, coxsackievirus stem-loop IV interacts with PCBP2. We used RNase foot-printing to identify RNA sequences protected following PCBP2 binding to coxsackievirus stem-loop IV. When nucleotide substitutions were separately engineered at two sites in coxsackievirus stem-loop IV to reduce PCBP2 binding, inhibition of IRES-mediated translation was observed. Both of these nucleotide substitutions were engineered into full-length CVB3 RNA and upon transfection into HeLa cells, the specific infectivities of both constructs were reduced and the recovered viruses displayed small-plaque phenotypes and slower growth kinetics compared to wild type virus.
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PMID:Altered interactions between stem-loop IV within the 5' noncoding region of coxsackievirus RNA and poly(rC) binding protein 2: effects on IRES-mediated translation and viral infectivity. 1944 5

The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer."
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PMID:Cholecystokinin and pancreatic cancer: the chicken or the egg? 2417 32