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)

We present three observations of patients with chronic calcifying pancreatitis with multiple pancreatic calculi visible on X-ray films of the abdomen. These patients were studied with plain films and sonography. On X-ray films, visible calcifications disappeared. In contrast, sonography and computerized tomography showed that the X-ray-transparent material of stones persisted. It is known that these stones are composed of different insoluble residues of PSP-S2-5, the secretory calcium stabilizer of pancreatic juice. This shows that the spontaneous or drug-induced disappearance of pancreatic stones on radiologic films is not sufficient for healing chronic calcifying pancreatitis.
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PMID:Persistence of the X-ray-transparent matrix of vanishing pancreatic stones. 203 93

Acute pancreatitis is not the cause but may be a complication of chronic pancreatitis. Different forms of chronic pancreatitis are described. The most frequent type in all climates, chronic calcifying pancreatitis, has different causes but similar pathological changes. It is a lithiasis in which a new family of molecules. PSP, a calcium stabilizer, plays a dominant role. Studies of chronic pancreatitis have now reached the stage of molecular biochemistry.
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PMID:Pathogenesis and epidemiology of chronic pancreatitis. 265 60

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

Chronic calcifying pancreatitis (CCP) is characterized by the presence of stones in pancreatic ducts. Calcium carbonate (CaCO3) is the main constituent of stones, to which is associated an organic matrix consisting primarily of one protein of Mr 14,000, the pancreatic stone protein or PSP. PSP is not present as such in pancreatic juice, but in polymorphic forms with higher molecular weights. These secretory forms (PSP S2-5, Mr 16-19,000) are synthesized in the acinar cells of the pancreas and secreted along the same secretory pathway as the exocrine enzymes. The heterogeneity of the forms of higher Mr (PSP S2-5) is probably due to different glycosylation patterns. PSP and PSP S1 are generated by the cleavage of an Arg-Ile bond in the N-terminal part of PSP S2-5. The N-terminal sequence of PSP (40 amino acids) is identical to that of PSP S1, whose complete sequence (133 amino acids) has been determined. Yet, the two proteins differ by their pI. Pancreatic juice is normally supersaturated in CaCO3, suggesting the presence of a stabilizer preventing CaCO3 precipitation. The PSP S could play that role, since an activity inhibiting the nucleation and growth in vitro of CaCO3 crystals was found in pancreatic juice, associated with these proteins. Moreover, PSP S concentration was significantly lower in the pancreatic juice of patients with CCP than in control patients. Proteins homologous to PSP S were also found in the dog, rat, swine, monkey and ox. They constitute a new family of pancreatic secretory proteins, whose biological role would be to maintain pancreatic juice in a stable state towards CaCO3.
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PMID:The human pancreatic stone protein. 314 13

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

In order to elucidate the characteristics of reg-protein, which is identical to pancreatic stone protein (PSP/reg-protein), and the relationship between the generation and evolution of chronic pancreatitis and the expression of PSP/reg-protein in the pancreas, we investigated the expression of PSP/reg-protein in normal and diseased human pancreatic tissues by immunohistochemistry. The PSP/reg-protein was expressed in all cases with normal pancreas or chronic pancreatitis, and in 70.6% of cases with pancreatic cancer. This protein was present in the cytoplasm of acinar cells and, in some cases, in the intraluminal contents of ductules in nonmalignant tissues. From the view of distribution and cellular localization, PSP/reg-protein was expressed more broadly and densely in chronic pancreatitis with mild to moderate injury than in the normal pancreas. However, the protein was less expressed in severely damaged chronic pancreatitis tissue, such as calcifying pancreatitis, than in the normal pancreas. These findings suggest that mild to moderate injury to pancreatic tissue may stimulate the synthesis of PSP/reg-protein, whereas more severe injury tends to depress it.
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PMID:The immunohistochemical evaluation of PSP/reg-protein in normal and diseased human pancreatic tissues. 845 18

Cholelithiasis is one of the most common health disorders, but biliary surgery is burdened with numerous specific complications. These reoperations may be divided into early and late reoperations in terms of their precise therapeutic and prognostic differentiation. Recently, residual stones have been successfully treated by endoscopic sphincterotomy and percutaneous or trans-T-tube tract choledochoscopy, and reoperation is not frequently required. The purpose of this study was to identify the most common complications of biliary surgery which require reoperation so as to establish the predisposing factors and suggest alternative strategies. Thus a retrospective review of biliary surgery at the Medical University of Varna, Bulgaria was performed to identify those cases which required reoperation for complications of biliary surgery and the specific complications which required additional surgery. Of 2874 biliary operations for benign conditions, 87 reoperations were performed: 34 due to early complications and 53 due to late complications. Forty-nine of the 87 patients had undergone the initial surgery in our hospital, while 38 had been in different hospitals. Residual stones were the cause for reoperation in 37 patients. Other causes were: stenosing papillitis: 22 (with or without stones and cholangitis); iatrogenic injuries (5); strictures (5); pancreatitis (7); fistulae, abscesses, and bleeding. The most commonly performed procedure during reoperation was biliodigestive anastomosis (36), followed by T-tube drainage (28), papillosphincteroplasty (4), and double drainage (PSP + BDA), which was performed in 4 patients. In order to avoid reoperation after biliary surgery, exact preoperative diagnosis (by ERCP or US), intraoperative cholangiography and choledochoscopy and accurate operative technique are of great importance.
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PMID:Studies on reoperations of extrahepatic biliary tree. 935 39

Pancreatitis-associated protein (PAP), a secretory acute-phase protein of the pancreatic acinar cell, is highly up-regulated early in acute pancreatitis. PAP expression returns to undetectable levels when the pancreas recovers. In the rat, three isoforms of PAP are known, all of which are upregulated during acute pancreatitis. Their functions remain obscure. Pancreatic stone protein (PSP/reg), which shows strong sequence homology to PAP, is secreted into pancreatic juice under physiologic and pathologic conditions. PSP/reg is highly susceptible to trypsin cleavage at its ARG11-ILE12 bond. Cleavage results in an N-terminal undecapeptide and a C-terminal peptide called pancreatic thread protein (PTP). PTP forms oligomeric fibrillar structures, which spontaneously sediment in vitro. PTP can be found in protein plugs or stones from patients with chronic pancreatitis. Rat PAP contains a trypsin cleavage site at the same position as PSP/reg. We hypothesize that PAP is susceptible to tryptic cleavage, and that the C-terminal cleavage product of PAP spontaneously precipitates at neutral pH. To test our hypothesis, we generated and purified recombinant PAP. Here we report the production of rat PAP I, II, and III in a yeast expression system using Pichia pastoris. We demonstrate in vitro the tryptic cleavage of rat PAP and the formation of a spontaneously precipitating peptide, which we call pancreatitis-associated thread protein (PATP). PATP displays pH-dependent solubility characteristics very similar to those of PTP.
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PMID:Conformational changes of pancreatitis-associated protein (PAP) activated by trypsin lead to insoluble protein aggregates. 1124 74

A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases. In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases. Scanning and transmission electron microscopy indicate that activated thread proteins polymerize into highly organized fibrillar structures with helical configurations. Through bundling, branching, and extension processes, these fibrillar structures form dense matrices that span large topological surfaces. These findings suggest that PSP/reg and PAP I and III isoforms consist of a family of highly regulated soluble secretory stress proteins, which, upon trypsin activation, convert into a family of insoluble helical thread proteins. Dense extracellular matrices, composed of helical thread proteins organized into higher ordered matrix structures, may serve physiological functions within luminal compartments in the exocrine pancreas.
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PMID:A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. 1127 30

Pancreatic stone protein (PSP; reported in 1979), pancreatitis-associated protein (PAP; 1984) and regenerating protein (Reg I; 1988) were discovered independently in the fields of the exocrine (pancreatitis) and endocrine (diabetes) pancreas. Subsequent analysis revealed that PSP and Reg I are identical and PAP belongs to the same protein family. PSP/Reg I and PAP share a selective and specific trypsin cleavage site and result in insoluble fibrils (PTP, PATP). Search for a functional role of PSP had led to the idea that it might serve as an inhibitor in pancreatic stone formation and PSP was renamed lithostathine. Inhibitory effects of lithostathine in stone formation have been questioned. Evidence so far obtained can support a lithogenic role rather than a lithostatic role of PSP. PAP and its isoforms have been investigated mainly regarding responses to inflammation and stress. Reg I and its isoforms have been examined on regeneration, growth and mitogenesis in gastrointestinal neoplastic diseases as well as diabetes. Evidence obtained can be applied in the prediction of prognosis and therapy for inflammatory and neoplastic diseases.
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PMID:Pancreatic stone protein/regenerating protein family in pancreatic and gastrointestinal diseases. 2180 74


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