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)

Chronic pancreatitis is defined by a persistent destruction of the pancreatic parenchyma replaced by fibrosis. The lesions generally start in the exocrine gland, islets being attacked later in the fibrosis. The two most frequent forms are: 1. Chronic calcifying pancreatitis which is a pancreatic lithiasis responsible for more than 95% of chronic pancreatitis. In its most frequent form, calculi are built up of more than 98% calcium salts together with fibres of a degraded residue of lithostathine, a secretory protein. This disease is related (i) in most countries to alcohol, protein, fat and tobacco and (ii) in certain tropical countries to malnutrition (low-fat, low-protein diet) for some generations. A causative role for cassava and kwashiorkor is improbable. The mechanism of calcium precipitation is partly explained by the calcium-saturation of pancreatic juice and the decreased biosynthesis of lithostathine S, the secretory protein preventing crystallization. As a rule, diabetes (and steatorrhoea) appear after a clinical evolution characterized by recurrent attacks of upper abdominal pain, generally lasting some days with transiently increased concentrations of pancreatic enzymes in serum. When diabetes appears, pain frequently disappears. Complications are mostly observed in the first 10 years of clinical evolution. 2. Obstructive pancreatitis is due to an obstacle (tumours, scars) in the pancreatic duct. It is rarely a cause of diabetes. Diabetes due to chronic pancreatitis is characterized by the low incidence of ketosis and the high incidence of insulin-induced hypoglycaemia. Patients are generally thin. Serum insulin levels, either basal or stimulated, are decreased. Glucagon is less affected. Angiopathies and retinopathies are less frequent than in non-insulin-dependent diabetes. Neural complications are fairly frequent. The diagnosis is generally easy because diabetes appears at a late stage of the disease. The treatment generally requires insulin.
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PMID:Chronic pancreatitis and diabetes. 144 67

A human pancreatic cDNA library was screened with the cDNA encoding rat "pancreatitis-associated protein" (PAP). The selected clone encoded a secretory protein structurally related to rat PAP. The protein had the same size as rat PAP and showed 71% amino acid identity, the six half-cystines being in identical positions. Domains of the proteins showing homologies with calcium-dependent lectins were also conserved. In addition, expression in pancreas of the genes encoding the human protein and rat PAP showed similar characteristics: both were expressed at very low levels in control tissue and overexpressed during the acute phase of pancreatitis, contrary to most secretory products. The human protein was therefore named human pancreatitis-associated protein (PAP-H). Antibodies raised to a synthetic peptide of PAP-H detected a single band with an M(r) compatible with PAP-H in Western blot analysis of proteins extracted from a pancreas presenting with acute pancreatitis. In that tissue, the protein could be immunolocalized to the apical regions of acinar cells. An immunoassay was also constructed to quantify the protein in serum. Elevated PAP-H levels were observed in patients with acute pancreatitis and in some patients with chronic pancreatitis. Values were close to background in healthy subjects and in patients with other abdominal diseases. These results confirm that PAP-H synthesis increases during inflammation and suggest a possible use of the protein as biological marker of acute pancreatitis.
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PMID:Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases. 146 87

The exact aetiology of chronic calcifying pancreatitis is unknown; several factors that lead to the development of this well-defined disease have been identified. Epidemiologic studies and careful analysis of nutritional data played an important role in precising the risk represented by alcohol consumption and dietary habits, and characterized the geographical distribution of the disease. At the same time, biochemical modifications of the pancreatic juice were described in alcoholics; later on, a new family of pancreatic secretory protein, the so-called "Pancreatic Stone Protein" was discovered. While its secretory form (PSP S2-5) prevents calcium crystal formation from the supersaturated pancreatic juice, its partially degraded form (PSP S1) is insoluble and probably the main protein of intraductal and intraacinar precipitates. Recent studies have confirmed that in chronic calcifying pancreatitis patients the mRNA encoding the synthesis of PSP S2-5 is decreased, and the protein is diminished both in the zymogen granules and in the pancreatic juice.
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PMID:Chronic calcifying pancreatitis: epidemiology and current concept of the lithogenesis. 269 18

In recent studies performed on pancreatic stones from patients with alcoholic pancreatitis, a novel secretory protein was identified: the pancreatic stone protein (PSP Mr 14,000). This protein suppresses CaCO3 precipitation, and could therefore stabilize normally supersaturated pancreatic juice. Crystallographic analysis of stones from patients with nutritional pancreatitis (NP), as well as alcoholic pancreatitis (AP), revealed that the main constituent was calcite (CaCO3). In the present study, we investigated the organic matrix of NP stones. In the 14 cases studied, the organic matrix was rendered soluble after mineral dissolution with EDTA + citrate. Analysis of the isolated matrix revealed the presence of one major protein (Mr 14,000), and of a minor protein (Mr 30,000), which is in fact an aggregate form of the 14,000 Mr protein. Using PSP antibodies, complete immunological identity was found between PSP, the immunoreactive form of PSP present in nonactivated pancreatic juice, and the protein matrix of NP stones. Moreover, protein matrix of NP stones also inhibited the nucleation of CaCO3 crystal, and decreased their growth rate in vitro. The presence of PSP in all AP and NP stones suggests that it plays a key role in stone formation during the course of chronic pancreatitis. These results also suggest the existence of some pathophysiological links between these two apparently different etiological forms of calcifying pancreatitis.
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PMID:Organic matrix of pancreatic stones associated with nutritional pancreatitis. 338 20

Lactoferrin is a nonenzymatic secretory protein of human pancreas specifically increased in the external pancreatic secretion of patients with chronic calcifying pancreatitis. The possibility of an elevated concentration of plasma lactoferrin level in these patients needed to be explored even if the low pancreatic concentration of the protein did not favor this hypothesis. As expected, no increase could be observed between the plasma lactoferrin level of 16 patients with chronic calcifying pancreatitis (131 +/- 15 micrograms/l), compared to 17 controls (166 +/- 11 micrograms/l) and 15 patients with different organic diseases (187 +/- 18 micrograms/l).
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PMID:Plasma lactoferrin levels in patients with chronic calcifying pancreatitis. 662 44

Lactoferrin is a non-enzymatic secretory protein present in the acinar cells of human pancreas, and specifically increased in the pancreatic juice of chronic calcifying pancreatitis patients. Immunocytochemical localization of lactoferrin demonstrates its presence in the zymogen granules of the pancreatic acinar cell as well as in the endoplasmic reticulum cisternae. On the same section, only a few acini are positive but all cells within individual acini are similarly either positive or negative. The intensity of the reaction and the number of stained acini are greater in chronic calcifying pancreatitis patients.
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PMID:Immunocytochemical localization of lactoferrin in human pancreas. 734 87

PAP is a pancreatic secretory protein expressed in the pancreas during the acute phase of pancreatitis. We have investigated the effect of the serum from rats with acute pancreatitis (SAP) on the expression of the PAP mRNA in AR-42J cells. PAP mRNA is strongly induced by SAP in a dose-dependent manner. This induction is abolished by preheating the SAP or diminished by treating the cells with cycloheximide. In addition, amylase but not actin mRNA expression was induced by a different SAP factor. We transfected the AR-42J cells with a chimeric gene containing 1.2 kbp 5'-flanking region of the PAP promoter linked to the CAT reporter gene. The CAT activity was significatively increased in the cells, on treating them with SAP. Our results show: first, SAP contains factors responsible for the PAP mRNA expression and secondly, the cis-acting elements are localized within the 1.2 kbp upstream region of the transcription initiation site.
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PMID:Serum from rats with acute pancreatitis induces expression of the PAP mRNA in the pancreatic acinar cell line AR-42J. 794 66

Pancreatitis-associated protein (PAP) is a secretory pancreatic protein present in small amounts in normal pancreas and overexpressed during the acute phase of the pancreatitis. In this paper, we describe the cloning, characterization, and chromosomal mapping of the human PAP gene. The gene spans 2748 bp and contains six exons interrupted by five introns. The gene has a typical promoter containing the sequences TATAAA and CCAAT 28 and 52 bp upstream of the cap site, respectively. We found striking similarities in genomic organization as well as in the promoter sequences between the human and rat PAP genes. The human PAP gene was mapped to chromosome 2p12 using rodent-human hybrid cells and in situ chromosomal hybridization. This localization coincides with that of the reg/lithostathine gene, which encodes a pancreatic secretory protein structurally related to PAP, suggesting that both genes derived from the same ancestral gene by duplication.
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PMID:Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene. 818 10

The pancreatitis-associated protein (PAP) is a lectin-related secretory protein present in small amounts in the rat pancreas and rapidly overexpressed during the acute phase of pancreatitis. We demonstrate in this report that PAP is also expressed in rat intestine. A cDNA library from rat jejunum was probed with pancreatic PAP cDNA. The inserts of the selected recombinant clones corresponded to a transcript whose nucleotide sequence was identical to that of pancreatic PAP mRNA. The transcript was detected in duodenum, jejunum, ileum, and colon. A protein with same molecular mass (16 kDa) and pI (8.2) as pancreatic PAP was actually immunodetected in ileum homogenate after separation by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Intestinal PAP was immunolocalized to the epithelial cells of the lower part of the villi. The protein accounted respectively for 0.02, 0.05, and 0.1% of soluble proteins in duodenum, jejunum, and ileum homogenates, as measured by enzyme-linked immunosorbent assay, and could not be detected in stomach and colon. Influence of fasting and feeding on PAP mRNA concentration was analyzed in ileum. Concentration decreased by 81 and 94% after animals were fasted for 24 and 48 h, respectively. Feeding restored the initial content within 6 h. On the other hand, intestinal PAP mRNA concentration was not altered during acute pancreatitis.
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PMID:PAP, a pancreatic secretory protein induced during acute pancreatitis, is expressed in rat intestine. 823 45

The pancreatitis-associated protein (PAP) is a lectin-related secretory protein present in small amounts in the rat pancreas and overexpressed during the acute phase of pancreatitis. On the other hand, PAP is constitutively expressed in the intestinal tract but not in other tissues. We cloned from a pancreatic cDNA library two overlapping cDNAs encoding a protein structurally related to PAP. This second PAP, which was called PAP II, was the same size as the original PAP (PAP I) and showed 74.3% amino acid homology. Studies on gene expression demonstrated that PAP II mRNA concentration increased within 6 h following induction of pancreatitis, reached maximal levels (> 200 times control values) at 24-48 h, and decreased thereafter, similar to PAP I. However, PAP II mRNA could not be detected in the intestinal tract or in other tissues. We also isolated a PAP II genomic DNA fragment which was characterized over 2.7 kb of gene sequence and 1.9 kb of 5' flanking sequence. The 5' end of the coding sequence was determined by primer extension of the PAP II mRNA. The PAP II coding sequence spanned six exons separated by five introns. Several potential regulatory elements were identified in the promoter region, including two glucocorticoid-response elements and one IL-6-response element. Antibodies raised to a synthetic peptide of PAP II detected a single band in Western blot analysis of the pancreatic secretory proteins from rats with pancreatitis, with a M(r) compatible with the theoretical M(r) of PAP II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of a second rat pancreatitis-associated protein. Messenger RNA cloning, gene structure, and expression during acute pancreatitis. 836 91


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