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)

The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis. 150 42

To investigate the effect of splenectomy on lymphocyte subpopulations we monitored changes in serum concentrations of soluble suppressor/cytotoxic (sCD8) and soluble helper/inducer (sCD4) antigen in 11 splenectomized patients. Indications for splenectomy were hereditary spherocytosis in 2, idiopathic thrombocytopenic purpura in 2, gastric carcinoma in 4, Hodgkin's disease in 2 and pancreatitis in 1 patient. Lymphocyte subpopulations were also analyzed by means of conventional immunophenotyping with monoclonal antibodies to CD4 and CD8. We consistently found an early postoperative drop of sCD8 and sCD4 levels within the first week after splenectomy, paralleling changes in the percentages of CD4+ and CD8+ lymphocytes. While alterations of lymphocyte subsets in the peripheral blood were completely reversible and sCD4 levels returned to preoperative values, sCD8 concentrations remained suppressed even 3 months after splenectomy. SCD8 levels at the nadir and those 3 months after splenectomy were significantly lower than preoperative values (P = 0.003, P = 0.149 respectively). Since sCD8 levels reflect suppressor/cytotoxic cell activity, we suggest that suppressor cell activity is reduced in splenectomized patients.
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PMID:Decrease in soluble CD8 antigen levels in splenectomized patients as an index for reduced suppressor/cytotoxic cell activity. 168 49

The E variant of encephalomyocarditis (EMC) virus causes an encephalomyelitis and coagulative necrosis of the pancreas and parotid glands in some but not all strains of inbred and outbred mice. In other models of disease caused by picornaviruses, depletion of specific lymphocyte subsets abrogates the development of tissue lesions. In this study, severe encephalomyelitis and acinar pancreatitis and parotitis developed in adult male A/J mice infected with 100 PFU of EMC virus. Depletion of the CD4+ subset of T lymphocytes in vivo with a monoclonal antibody (MAb) prior to EMC virus inoculation protects mice from developing encephalomyelitis, pancreatitis, and parotitis. This effect is also seen when animals are treated with anti-CD4 and anti-CD8 in combination, but the anti-CD8 MAb alone does not ameliorate the disease. Overall, concentrations of virus in tissues from anti-CD4-treated animals are lower than in immunologically intact control mice. Small-plaque variants of virus were also recovered from the tissues in some animals in this group. CD4+ lymphocytes are involved in the expression of EMC virus-induced pancreatitis and parotitis in A/J mice. This specific subset of T cells would appear to influence EMC viral tropism or replication in various organs.
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PMID:Immunomodulation of encephalomyocarditis virus-induced disease in A/J mice. 170 84

Starting in 1988, 72 patients with advanced human immunodeficiency virus (HIV) infection were enrolled in a phase I study of didanosine at the National Cancer Institute. Beginning in 1992, patients with decreases in CD4 cell counts could switch to a combination of zidovudine and didanosine. The estimated median survival for all patients was 28 months (95% confidence interval, 23-46). However, for patients whose entry CD4 cell counts were 100-300/mm3, the estimated 4-year survival was 80%. Baseline CD4 and CD8 cell counts, hemoglobin, lymphocytes, sedimentation rates, diagnosis of AIDS, and fever were significant predictors of overall survival. Principal toxicities were pancreatitis and peripheral neuropathy; no new toxicities were seen with extended didanosine treatment that had not been observed in shorter-term studies. This 5-year follow-up shows that didanosine can be tolerated for > 4 years in some patients with advanced HIV infection and may have particular long-term utility in patients with moderately advanced immunosuppression.
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PMID:Five-year follow-up of a phase I study of didanosine in patients with advanced human immunodeficiency virus infection. 775 92

When activated, lymphocytes secrete glycoproteins related to particular surface proteins, including soluble forms of the interleukin-2 receptor (sIL-2R) and of the surface proteins CD4 (sCD4) and CD8 (sCD8). We evaluated the release of these glycoproteins in order to assess the activation of the cellular immune system during the course of acute pancreatitis. Thirty-five patients with acute pancreatitis (22 M, 13 F, mean age 64 years, range 16-97) were studied. The diagnosis was based on typical abdominal pain associated with a twofold increase of serum lipase as well as morphological abnormalities compatible with acute pancreatitis seen at computed tomography and/or ultrasonography. The pancreatitis was of biliary origin in 22 patients, due to alcohol abuse in 8, due to pancreas divisum in 1, due to type IV hyperlipoproteinemia in 1 and of unknown origin in 3. Based on clinical outcome, 22 patients had mild pancreatitis, whereas 13 had severe disease. In all patients serum sIL-2R, sCD4 and sCD8 were determined on admission and daily for the following 5 days using enzyme immunoassay (EIA) techniques. Serum concentrations of sIL-2R and sCD8 were significantly higher in acute pancreatitis patients relative to healthy controls during the entire observation period, whereas sCD4 levels were significantly lower in acute pancreatitis patients than in the control group from the 2nd to the 6th day of observation. Serum sIL-2R concentrations were significantly higher in patients with severe pancreatitis than in those with the mild form of the disease, whereas no differences in serum concentrations of sCD8 and sCD4 were found between patients with mild pancreatitis and those with severe disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavior of serum soluble interleukin-2 receptor, soluble CD8 and soluble CD4 in the early phases of acute pancreatitis. 806 32

Circulating lymphocyte numbers and activation together with granulocyte function were measured in 20 patients in the early stages of an attack of acute pancreatitis and in 20 healthy controls. Circulating lymphocytes, T lymphocytes, and CD4 and CD8 T lymphocyte subsets were decreased in both mild pancreatitis (67-80 per cent of controls) and severe pancreatitis (22-40 per cent of controls). CD4:CD8 ratios were unchanged and median (interquartile range) interleukin 2 receptor expression was increased from less than 1 per cent in controls to 14(6) per cent in severe pancreatitis, suggesting lymphocyte activation. Median granulocyte chemiluminescence was increased to 293 per cent of controls in severe pancreatitis and random motility was reduced to 77 per cent of controls, indicating increased metabolic activity. Complement-mediated antibody-independent opsonization and chemotaxis toward endotoxin were normal. Immune function is not reduced early in acute pancreatitis. Granulocyte hyperactivity may be important in the development of multiple organ failure.
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PMID:Immune function early in acute pancreatitis. 894 82

Gene transfer into the pancreas would be useful for the treatment of a variety of disorders, including cystic fibrosis, diabetes, cancer, and immunomodulation of pancreatic allografts. A hypothesis that various cell populations in the pancreas could be targeted by recombinant adenoviruses was developed and tested. Gene transfer into the rat ductal epithelium, acinar cells, and islets of Langerhans was accomplished with a recombinant adenovirus containing bacterial beta-galactosidase by retrograde delivery of adenovirus into the pancreaticobiliary duct. Maximal gene expression was observed at 3 days and correlated with DNA blot analysis. Histologic analysis of sections from pancreatic tissue in the adenovirus-treated rats demonstrated severe pancreatitis. Immunophenotyping of the inflammatory infiltrate with rat lymphocyte-specific markers showed CD45-, CD8-, and CD4-positive cells. Tissue injury resolved as gene expression was lost, with both features absent by 21 days. Pancreatic regeneration was documented by the presence of 5-bromo-2'-deoxyuridine-positive staining cells. Pancreatic gene transfer with first-generation recombinant adenoviruses can be accomplished by techniques applicable to clinical situations. The use of first-generation recombinant adenoviruses for pancreas-directed gene transfer is limited by the development of inflammation and transient expression.
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PMID:Adenovirus-mediated in vivo gene transfer and expression in normal rat pancreas. 874 Apr 9

A 23-year-old man experiencing three episodes of acute pancreatitis of undetermined etiology is described. Repeated questioning revealed that all three events had occurred after intake of the drug pyritinol. Controlled rechallenge with a single dose of the drug led to a fourth episode of acute pancreatitis. Skin testing was negative, but lymphocyte stimulation tests and double fluorescence analysis detected pyritinol-activated CD4 and CD8 lymphocytes. Together with the clinical observation that the intervals between drug intake and start of symptoms of acute pancreatitis became shorter with repeated exposure, the data are consistent with an immune-mediated origin of the pancreatitis. Pyritinol has to be added to the list of drugs capable of inducing acute pancreatitis.
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PMID:Acute pancreatitis due to pyritinol: an immune-mediated phenomenon. 967 51

To investigate impairment of cellular immunity in severe acute pancreatitis, alterations of peripheral lymphocytes in acute pancreatitis were examined. In 48 patients with severe acute pancreatitis, the mean peripheral lymphocyte count on admission was 959 + 105/mm3, and it was significantly decreased in the patients with subsequent infection (623 +/- 90/mm3 ) in comparison to those without infection (1084 +/- 135/mm(3)). According to an analysis of lymphocyte subsets, although both B and T lymphocytes were decreased in peripheral circulation in the patients with infection, it was primarily CD8-positive lymphocytes that decreased in these subsets. Cell cycle analysis of lymphocytes collected from these patients indicated that apoptotic changes occurred after 24 hours' incubation in lymphocytes from patients with severe pancreatitis but not in lymphocytes from healthy control subjects. In a rat model of experimental necrotizing pancreatitis, total peripheral lymphocytes and T lymphocytes were significantly decreased 5 hours after induction of pancreatitis. In severe pancreatitis, peripheral lymphocytes are eliminated from systemic circulation possibly as a result of apoptosis. It has been suggested that impairment of cellular immunity due to peripheral lymphocyte apoptosis is linked to the development of subsequent infectious complications in acute pancreatitis.
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PMID:Peripheral lymphocyte reduction in severe acute pancreatitis is caused by apoptotic cell death. 1105 56

Adhesion and activation molecules as well as cytokines play an important role in an immune scenario. In acute pancreatitis, we have studied some of these in order to evaluate dysregulation. For this we took peripheral blood mononuclear cells and pancreatitis tissue cells. We analysed activation markers like CD69, CD25 and HLA-DR and found a marked elevation of CD69 as well as CD25 in both peripheral blood cells and tissue mononuclear cells when compared to controls. In PBMC-CD69: P<0.01 and CD25: P<0.01; in tissue-CD69: P<0.001 and CD25: P<0.001. The HLA-DR levels, however, were reduced in the disease state (in acute pancreatitis patient blood (P<0.01) and tissue cells (P<0.001)). The adhesion molecules showed unanimous rise in the blood and the tissue samples. In blood samples, CD11a: P<0.05 and CD11b: P<0.05 and tissue samples CD11a: P<0.01 and CD11b: P<0.01and CD54 in peripheral blood (P<0.05) and tissue (P<0.01) of AP was high as compared to controls. By simultaneous flowcytometric analysis, we determined the co-expression of a surface marker (CD4/CD8/CD14) and intracellular cytokine (TNF-alpha and IFN-gamma) in individual cells. The IFN-gamma producing CD8+T cells were elevated in pancreatic tissue (P<0.01). TNF-alpha producing cell numbers were significantly higher in tissue cells than in blood and also in CD8+ T cells (P<0.001). We conclude that monocyte function is affected in AP as shown by reduced HLA-DR numbers and lowered TNF-alpha producing cells. Moreover, the CD8+T cells appear to play an important role in cytokine synthesis at the effector site.
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PMID:Expression of activation, adhesion molecules and intracellular cytokines in acute pancreatitis. 1141 Feb 45


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