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)

In order to reproduce what might occur during the initial phase in some cases of acute alcohol-induced pancreatitis, rabbits were infused with diluted ethanol and low-dose cerulein. The duct permeability was assessed by recovery of fluoresceinated dextran (molecular weight 19,500) in central venous blood following orthograde duct perfusion with this substance in the anesthetized animal. Serum ethanol, lipase, and amylase were measured; pancreatic duct morphology was examined by light microscopy and electron microscopy. ATP and glutathione were measured, as were amylase, trypsinogen/trypsin, cathepsin B, and DNA levels in differential centrifugates. As expected, acinar amylase and trypsinogen showed a significant decrease in the experimental group; cathepsin B activity was similarly diminished. Compared with the control group, the activity of serum amylase and lipase in the experimental group demonstrated a significant increase. However, no differences between saline-infused control animals and the treated group regarding pancreatic duct permeability, continuity of lumen-lining epithelium, ATP and glutathione levels, and the relative subcellular distribution of pancreatic digestive and lysosomal enzymes were observed. Thus, our findings do not support the relevance of some of the most common hypotheses on the pathophysiology of acute pancreatitis in its early stage for at least a certain subgroup of patients with acute alcohol-induced pancreatitis.
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PMID:Glutathione and ATP levels, subcellular distribution of enzymes, and permeability of duct system in rabbit pancreas following intravenous administration of alcohol and cerulein. 814 53

To examine whether the gut is a source of infection in acute pancreatitis, bacterial translocation and alterations of intestinal microecology and morphology were studied in 16 dogs. Dogs were colonized with a strain of Escherichia coli (E. coli 6938K) bearing the plasmid pUC4K, which confers kanamycin resistance. In eight dogs (group I), pancreatitis was induced by sodium taurocholate/trypsin injection. Eight other dogs (group II) underwent laparotomy only. The pancreas, mesenteric lymph nodes, peritoneal fluid, liver, and spleen were harvested 7 days later for culturing and histologic analysis. Identification of E. coli 6938K was accomplished by plasmid DNA analysis. Group I dogs had severe pancreatitis and ischemic changes in small bowel mucosa. Group II dogs had no changes. Translocation to the pancreas occurred in five dogs and to mesenteric lymph nodes in six dogs with pancreatitis. No translocation occurred in group II dogs (p < 0.05). In addition to E. coli 6938K, other gram-negative kanamycin-resistant species were isolated, including E. coli (other than 6938K) and Enterobacter cloacae. Enteric origin of these strains was confirmed by antibiography and plasmid DNA analysis. No overgrowth of cecal gram-negative bacteria was found. This study suggests that the gut is a primary source of infection in pancreatitis and that ischemic damage of intestinal mucosa may promote bacterial translocation.
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PMID:Plasmid labeling confirms bacterial translocation in pancreatitis. 831 Nov 34

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

NORs (Nucleolar Organizer Regions) are loops of DNA encoding ribosomal RNA, which reflect cellular activity. The Ag-NORs staining was applied to paraffin sections of 10 normal pancreas, 10 chronic pancreatitis and 23 pancreatic cancer, with 17 gastric and 18 colonic cancers. We calculated the mean Ag-NORs number and Ag-NORs index, and defined T/N ratio. The mean Ag-NORs number was compared with the data obtained by Flow cytometry (FCM) in pancreatic carcinoma. A significant difference in Ag-NORs index was found between benign (normal: 1.86 +/- 0.38, pancreatitis: 2.14 +/- 0.53) and malignant tissues (4.02 +/- 1.19) of the pancreas (p < 0.01). Compared with the data by FCM, there was a significant correlation between the mean Ag-NORs number and the percentage of S-phase cells in pancreatic carcinoma (r = 0.59, p < 0.01). Ag-NORs index in pancreatic carcinoma showed significantly lower value than that in cancer of stomach (6.35 +/- 1.32) and colon (7.66 +/- 1.35), but there was no difference in T/N ratio among them. In conclusion, the Ag-NORs staining is useful for analyzing proliferating activity in pancreatic carcinoma. The proliferating potential in pancreatic carcinoma is lower than that in gastric and colonic ones. This may be due to the low proliferating potential of the background mucosa from which pancreatic carcinoma will arise.
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PMID:[Study on proliferating potential by Ag-NORs staining in human pancreatic carcinoma]. 843 56

We present a case of a 27-year-old female suffering from chronic calcifying pancreatitis with diabetes mellitus. Radiographic examinations and exocrine pancreatic function tests revealed considerable dilatation of pancreatic ducts with large intraductal calculi and exocrine pancreatic insufficiency, respectively. Recent literature indicates that a decrease in the activity of pancreatic stone protein (PSP), which inhibits CaCO3 crystal formation in pancreatic juice, is closely related to the development of chronic calcifying pancreatitis. The patient had no apparent cause or family history of pancreatitis. We therefore investigated the possibility that alterations in the PSP gene might explain the chronic pancreatitis seen in this patient. Six exons of the PSP gene amplified by polymerase chain reaction were directly sequenced, but there was no apparent base mutation observed. Furthermore, Southern blot analysis revealed neither rearrangement nor deletion of the PSP gene in the genomic DNA of this case. However, this genetic approach will be useful for future study of the etiology of hereditary pancreatitis.
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PMID:Idiopathic chronic calcifying pancreatitis with diabetes mellitus. Analysis of pancreatic stone protein gene. 848 98

Normal pregnancy is associated with a two- to threefold increase in plasma triglyceride levels, particularly in the third trimester, due both to the overproduction of VLDLs and to the possible suppression of lipoprotein lipase (LPL) activity. Numerous mutations in the human LPL gene causing complete LPL deficiency have been described, but naturally occurring mutations that result in defective LPL with partial activity have not yet been reported. Here we describe a 30-yr-old woman who was first diagnosed with LPL deficiency during pregnancy after she developed pancreatitis. Her plasma triglyceride levels remained mildly elevated at approximately 300 mg/dl (3.4 mmol/liter) after the first pregnancy but rose significantly after she became pregnant again (1800 to 2000 mg/dl) (20.2 to 22.5 mmol/liter). DNA sequence analysis of the LPL gene showed that the patient is homozygous for a Ser172-->Cys missense mutation in exon 5. In vitro mutagenesis revealed that the Ser172-->Cys mutation caused a mutant LPL protein that had residual activity higher than that seen in all eight other missense mutations in patients with LPL deficiency identified in our laboratory. We propose that some mutations in the LPL gene produce a defective LPL with partial activity, which usually leads to mild hypertriglyceridemia.
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PMID:Gene-environment interaction in the conversion of a mild-to-severe phenotype in a patient homozygous for a Ser172-->Cys mutation in the lipoprotein lipase gene. 848 65

The kinetics of rat macrophage proliferation in the inflamed pancreas was analysed using a duct-ligation pancreatitis model. We performed a double immunostaining of pancreatic cryosections using a panel of monoclonal antibodies to either macrophage-specific (ED1, ED2) or macrophage-related (CR3 and Ia) antigens in combination with a cell marker of DNA synthesis (5-bromo-2'-deoxyuridine, BrdU). One hour labeling with BrdU revealed each recorded macrophage phenotype to have a very high labeling index (12-28%), peaking on day 2 after induction of pancreatitis. The percentage of each proliferating phenotype also reached 20-40% of the total BrdU+ cells on day 2. The proliferating macrophages consisted of heterogeneous subpopulations including monocyte-like cells and resident macrophages. Their growth occurred in a relatively synchronized fashion, and seemed to be triggered by common proliferative signals.
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PMID:Proliferation kinetics of macrophage subpopulations in a rat experimental pancreatitis model. 849 27

A 15-year-old girl had severe Raynaud's phenomenon and arthralgias. A high ANA-IF titer was found and undifferentiated connective tissue disease was diagnosed. After 7 years of moderately flaring disease the patient deteriorated and presented with congestive heart failure, pleuropericardial effusion, hemolytic uremic syndrome, proteinuria and moderate hypertension. Autoantibodies against DNA, Sm-protein, and very high titers against U1RNP were detected. Therapy with high steroid doses, a cyclophosphamide pulse and 4 weeks of plasmaphresis with plasma exchange improved the heart, but not the renal condition. Symptomatic pancreatitis became the dominant problem of a progressively consuming process that resulted in the death of the patient. Post-mortem examination revealed widespread vasculopathy with intima proliferation and only minimal fibrosis involving the kidneys, heart and other main organs, including the pancreas. Taken together, the clinical picture was of an overlap between scleroderma and systemic lupus erythemathosus; the serologic and histopathologic findings suggest a diagnosis of a severe form of mixed connective tissue disease (MCTD).
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PMID:Widespread vasculopathy with hemolytic uremic syndrome, perimyocarditis and cystic pancreatitis in a young woman with mixed connective tissue disease. Case report and review of the literature. 851 21

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was tricirbine 20 mg/m2 per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m2 per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m2 until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed. The maximum dose was 40 mg/m2. Two patients died, one each at the 35 and 40 mg/m2 levels, respectively, 3 months and 6 weeks after their last course, one without intervening disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of > or = 35 mg/m2 has unacceptable toxic effects.
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PMID:Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer. 852 86

Alpers' syndrome is a progressive neurodegenerative disorder with liver disease that usually presents in the first few years of life. Only rarely have patients presented later in life with delayed onset of Alpers' syndrome. Herein we present a case of a 17-year-old male with a progressive 8-month course of severe headaches, multiple stroke-like episodes with visual deficits, and seizures that concluded with acute hemorrhagic pancreatitis. Neuropathological findings were characteristic for Alpers' syndrome: neurodegeneration and astrogliosis of the occipital cortices including the striate cortices, similar but less advanced changes in the parietal cortices, right Ammons horn sclerosis, degeneration of the posterior columns, and mild cerebellar Purkinje cell loss. Examination of the liver revealed extensive centrilobular hepatocyte necrosis. Skeletal muscle did not contain ragged red fibers, nor were there mitochondrial DNA point mutations characteristic for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).
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PMID:Alpers' syndrome presenting with seizures and multiple stroke-like episodes in a 17-year-old male. 860 37


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