Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to study the mechanisms leading to fibrosis in chronic pancreatitis, an in situ immunohistochemical investigation of lymphocytes and of class II major histocompatibility complex expression (HLA-DR) by epithelial cells has been designed. Samples of normal pancreas (n = 8), chronic calcifying pancreatitis (n = 4), chronic obstructive pancreatitis (n = 6), and diffuse fibrosing pancreatitis (n = 6) have been studied. In normal pancreas, T-lymphocytes were rare and were located in the epithelial layer of pancreatic ducts and in the periductal connective tissue. Duct cells were constantly HLA-DR negative. In chronic calcifying pancreatitis and chronic obstructive pancreatitis, T cells were numerous and were located around ducts and in the spreading areas of fibrous septa. In chronic obstructive pancreatitis, the duct cells strongly expressed the HLA-DR antigen. In diffuse fibrosing pancreatitis, fibrous tissue was devoid of lymphocytes and duct cells never expressed the HLA class II antigen. These results suggest that lymphocytes are involved in the fibrosing process occurring in chronic calcifying pancreatitis and chronic obstructive pancreatitis but not in diffuse fibrosing pancreatitis. The significance of de novo expression of HLA-DR antigen by duct cells is discussed.
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PMID:Lymphocyte subsets and HLA-DR expression in normal pancreas and chronic pancreatitis. 197 51

We assessed HLA-DR types and investigated serum samples for islet-cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin-dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin-dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta-cell dysfunction in insulin-dependent diabetes in chronic pancreatitis differs from that of classical insulin-dependent diabetes.
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PMID:Insulin-dependent diabetes mellitus secondary to chronic pancreatitis is not associated with HLA or the occurrence of islet-cell antibodies. 226 74

An autopsy case of chronic pancreatitis associated with unusual chronic thyroiditis in a 54-year-old woman is presented. Microscopically, the pancreas was densely infiltrated by lymphocytes and its exocrine parenchyma was completely replaced by sclerotic tissue. The thyroid gland was also infiltrated by lymphocytes, but no lymphoid follicles were observed. These morphological changes are rare findings with respect to the severity of inflammation and the association of the affected organs. Further findings suggested involvement of an autoimmune mechanism in the pathogenesis of these lesions. Using the avidin-biotin-conjugate technique and antibodies (Abs) against T lymphocyte and HLA-DR antigens (Ags), immunological aspects of the lesions were studied. Most of these infiltrating lymphocytes were revealed to be T lymphocytes, and HLA-DR Ags were observed on the epithelial cells of the pancreatic ducts and thyroid follicles. As a control, 45 surgical specimens of pancreas and thyroid gland were studied for detection of HLA-DR expression on the epithelial cells. One case of chronic pancreatitis was revealed to express HLA-DR Ag on the epithelium. The patient was a 44-year-old woman who had silently developed pancreatic cyst due to chronic inflammation. This finding also suggests a role of autoimmunity in the pathogenesis of chronic idiopathic pancreatitis.
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PMID:Expression of histocompatibility antigen HLA-DR on the epithelial cells of the pancreatic duct and thyroid follicle. An autopsy case. 239 38

The immunohistochemical features of pancreatic grafts in eight patients with pancreatic transplants were analyzed and compared with pancreases from five patients with chronic pancreatitis and with three pancreatic tissues without histological abnormalities. There was a significant increase in glucagon producing cells in patients with transplanted pancreases compared with those with chronic pancreatitis (P less than 0.05). A significant decline in insulin-producing cells was seen in the transplanted pancreases with rejection in comparison with normal pancreatic tissue. Immunohistochemical staining for HLA-DR (Ia) antigens revealed expression of HLA-DR by endothelial cells, mononuclear cells, and by some ductal epithelial cells, but not by the endocrine islet cells. These results suggest that significant changes in insulin and glucagon production occur in the transplanted pancreas with rejection and that HLA-DR is not expressed by islet cells during graft rejection or with chronic inflammation.
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PMID:Pancreas transplantation: an immunohistochemical analysis of pancreatic hormones and HLA-DR expression. 256 35

A possible immunogenetic basis for diabetes in chronic pancreatitis was explored by studying 19 patients with both disorders, most of whom required treatment with insulin. In contrast to patients with insulin-dependent (Type 1) diabetes, patients with diabetes and chronic pancreatitis had residual beta cell function but blunted C-peptide responses to intravenous glucagon, absence of circulating islet cell antibodies, and HLA-DR types similar to control subjects and patients with chronic pancreatitis without diabetes. Diabetes complicating chronic pancreatitis is therefore not associated with the biochemical or immunogenetic markers characteristic of Type 1 diabetes.
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PMID:Evidence against an immunogenetic basis for diabetes in chronic pancreatitis. 332 10

This study was prospectively carried out in order to clarify if an aberrant expression of HLA-DR molecules could take part in the pathogenesis of chronic pancreatitis. Pancreatic specimens from 12 chronic pancreatitis patients and nine controls were examined. Strong HLA-DR expression was observed in 6/12 chronic pancreatitis patients and in 1/9 controls. Moreover, lymphocytic foci with large numbers of activated cells were found only in chronic pancreatitis. The four HLA-DR - patients had a marked increase of fibrous tissue with small portions of acinar tissue, whereas the six patients with strong positivity had the greatest dilatation and hyperplasia of the ducts. These findings are similar to those observed in immune diseases, such as thyroiditis and primary biliary cirrhosis (PBC), and suggest that autoimmune phenomena are involved in chronic pancreatitis.
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PMID:HLA molecule expression on chronic pancreatitis specimens: is there a role for autoimmunity? A preliminary study. 349 62

The hypothesis was tested that islet autoimmunity is induced by ongoing islet cell destruction in subjects with susceptibility genes HLA-DR 3 and/or DR 4. Sixty-one patients with confirmed chronic pancreatitis were analysed, 30 of whom expressed HLA-DR 3 and/or DR 4. Electron microscopy studies in 10 patients showed that the inflammatory process also affected islets, as recognisable from islet cell lysis, intrainsular fibrosis and immune cell infiltrates. None of the sera tested contained any of three markers of islet autoimmunity, ICA, IAA or GAD antibodies. A correlation was seen between the loss of exocrine function, as determined by the ALTAB-test, and of beta-cell function, as determined by the C-peptide response to i.v. glucagon. However, there was no preferential loss of beta-cell function in patients with HLA-DR 3 and/or DR 4. We conclude that islet cell destruction occurs during chronic pancreatitis, but does not trigger islet autoimmunity, even in the presence of HLA-DR 3 and/or DR 4.
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PMID:Inflammatory islet damage in patients bearing HLA-DR 3 and/or DR 4 haplotypes does not lead to islet autoimmunity. 805 84

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p < 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.
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PMID:Expression of major histocompatibility antigens in human chronic pancreatitis. 779 37

Acinar regression in chronic pancreatitis may be due to immune attack in parenchymal areas neoexpressing HLA-DR molecules. CD4+Th1 cytotoxic T cells induce apoptosis of their targets via oligomerizing CD95 (APO-1/Fas) death receptors on target cells by their CD95 ligand (CD95L). We determined the expression of CD95 and CD95L in epithelia of normal and chronically inflamed pancreatic tissues. We applied RT-PCR and Western blotting for CD95L expression profiles, serial frozen section immunohistochemistry to detect CD95, CD95L, and HLA-DR molecules, CD3, CD4, CD11c, and S-100 protein (S100p). Normal pancreases and chronic pancreatitis contain CD95L message and protein. Immunohistochemistry revealed a mutually exclusive expression of CD95 and CD95L. Physiologically, acini were CD95-/CD95L+, ducts were CD95-/CD95L-, and islets were CD95-/CD95L+. In areas of lymphohistiocytic infiltration, mainly consisting of CD3+CD4+ T cells and CD11c+, CD4+/-, S100p+ interstitial dendritic cells, and in areas of initial fibrosis, acini and ducts were HLA-DR+, acini CD95+/CD95L-, and ducts CD95+/CD95L-. Islet cells were CD95-/CD95L+ in both conditions. IFNgamma levels in protein lysates, as measured by an immunoassay, were significantly higher in chronic pancreatitis than in normal pancreas (p < 0.0003). In vitro, IFNgamma down-modulated CD95L message and protein in ASPC1 and BxPc3 pancreatic carcinoma cells. In conclusion, pancreatic epithelia differentially express CD95 and CD95L in a mutually exclusive manner. In chronic pancreatitis the CD95-/CD95L+ status is conserved in islet cells even in the vicinity of lymphohistiocytic infiltrates, whereas it is lost in acini coexpressing HLA-DR. As a potential consequence, and possibly triggered by local release of IFNgamma, CD4-Th1 cells may cognately interact with and successfully attack exocrine cells by triggering CD95 on their target without being killed by epithelial, CD95L-mediated, counterattack.
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PMID:Differential and mutually exclusive expression of CD95 and CD95 ligand in epithelia of normal pancreas and chronic pancreatitis. 1131 Aug 25

Autoimmune pancreatitis (AIP) is defined histologically by periductal and interacinar lymphocytic infiltration. Immunohistochemically, the majority of these lymphocytes are identified as T cells. Epithelial HLA-DR antigen expression was also described as a marker of autoimmunity in this type of chronic pancreatitis. We report 2 cases, a 56-year-old man and a 29-year-old woman, with AIP associated with immune-mediated inflammation of the main duodenal papilla (MDP). Serologically, antinuclear antibody positivity was detected in the male patient. The female patient, treated medically for ulcerative proctitis, had no serological evidence of autoimmune disease. Macroscopic papillitis was present only in the male patient, and endoscopic biopsy samples were taken from this swollen MDP. Since we could not exclude malignancy, a pancreatic head resection was performed in both patients. The histologic and immunohistochemical studies of the resected specimens showed periductal T-lymphocytic infiltration in the pancreatic and papillary tissues. Furthermore, HLA-DR-antigen expression was also demonstrated in epithelial cells of the pancreas and MDP. The immunohistological features of endoscopic biopsy samples from the swollen MDP were identical as in the surgically resected specimens. Immune-mediated inflammation of the MDP may be associated with AIP.
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PMID:Autoimmune pancreatitis associated with immune-mediated inflammation of the papilla of Vater: report on two cases. 1525 9


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