Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.
Acute Disease ; Chronic Disease ; Cytokines/immunology* ; Human ; NF-kappa B/metabolism* ; Pancreas/metabolism* ; Pancreas/immunology* ; Pancreas/cytology ; Pancreatitis/metabolism ; Pancreatitis/immunology ; Support, U.S. Gov't, Non-P.H.S.

OBJECTIVETo analyze the clinical and laboratory features of anti-soluble liver antigen/liver-pancreas (SLA/LP) autoantibody positive patients with abnormal liver functions.

METHODSFrom July 1999 to August 2004, 4928 serum samples from patients with abnormal liver functions (ALT >40 U/L) were collected. A series of autoantibody examinations were carried out. Clinical manifestations and laboratory findings of 8 patients with anti-SLA/LP autoantibody positive were reviewed.

RESULTSAmong the 5500 serum samples, 8 cases (6 females and 2 males) with positive anti-SLA/LP autoantibodies were found with complete clinical information. The age of the patients was (27-76) years old. The case histories were from 2 years to 10 years. Of the 8 patients, 6 cases had liver cirrhosis and HBsAg-negative and anti-HCV-negative, active, 1 case had liver cirrhosis with HBsAg-positive, but HBVDNA negative; 1 case had liver cirrhosis and anti-HCV positive, but HCV RNA negative. The 8 cases were all ANA positive with titers of 31:320. Four cases were AMA positive and 2 among these 4 cases were M2 positive. The most frequent symptoms were fatigue, anorexia, nausea, jaundice, abdominal distention and edema of lower limbs. All patients had high hypergammaglobulinemia.

CONCLUSIONAnti-SLA/LP autoantibody was at a low detection rate in the study with females in preponderance, Clinical and laboratory characteristics of the 8 cases were consistent with those of the autoimmune hepatitis (AIH). Testing for anti-SLA autoantibodies helps in the diagnosis of AIH in many patients who may otherwise be misdiagnosed.

Adult ; Aged ; Autoantibodies ; immunology ; Autoantigens ; immunology ; Female ; Hepatitis, Autoimmune ; diagnosis ; immunology ; Humans ; Male ; Middle Aged ; Pancreas ; immunology ; Sequence Homology

The importance of innate immunity in host defense is becoming clear after discovery of innate immune receptors such as Toll-like receptor or Nod-like receptor. Innate immune system plays an important role in diverse pathological situations such as autoimmune diseases. Role of innate immunity in the pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome or atherosclerosis that has not been previously considered as inflammatory disorders, is also being appreciated. Here, the role of innate immunity in the development of type 1 diabetes, a classical organ-specific autoimmune disease, and type 2 diabetes will be discussed, focusing on the role of specific innate immune receptors involved in these disease processes.
Animals ; Cytokines/*immunology ; Diabetes Mellitus, Type 1/*immunology ; Diabetes Mellitus, Type 2/*immunology ; Humans ; Immunity, Innate/*immunology ; Inflammasomes/*immunology ; *Models, Immunological ; Pancreas/immunology

BACKGROUND/AIMS: Autoimmune pancreatitis is a distinctive type of chronic pancreatitis with reversibility. We analyzed the largest number of patients with autoimmune pancreatitis among the studies carried out at a single institution in Korea. METHODS: We retrospectively analyzed the clinical, radiologic, laboratory and histologic features in 17 patients who were diagnosed as autoimmune pancreatitis. RESULTS: The patients were predominately elderly men who presented with jaundice or nonspecific gastrointestinal symptoms. In most of the patients, serum pancreatic enzymes were normal or mildly elevated with an accompanying cholestatic biochemical profile. Elevated IgG levels and detection of autoantibodies were observed in 47% (8/17) and 35% (6/17), respectively. Thirteen patients showed histologic findings of lymphoplasmacytic infiltration and fibrosis, and one patient showed predominant infiltration of eosinophils. Fifteen patients revealed radiologic images of diffuse swelling of pancreas and the sclerosing pattern on direct pancreatogram. All of the features improved in response to oral steroid therapy. Two cases showed focal narrowing with upstream duct dilatation and thus, they were diagnosed as focal type. Diabetes mellitus concurred in 13 cases and primary sclerosing cholangitis and Sjogren's syndrome were present in 1 case, respectively. CONCLUSIONS: The recognition of autoimmune pancreatitis allows patients to avoid unnecessary surgery and recover with the administration of oral steroid.
Aged ; Autoimmune Diseases/*diagnosis/pathology ; Chronic Disease ; English Abstract ; Humans ; Male ; Middle Aged ; Pancreas/pathology ; Pancreatitis/*diagnosis/immunology/pathology

Transplantation would be the only way to cure the end-stage organ failure involving heart, lung, liver, kidney and pancreas. The replacement of the parts of the body damaged to lose its function or lost to trauma must be a dream of human-being. Human history is replete with chimeras, from sphinxes to mermaids, making one wonder if the ancients might actually have dreamed of what now is called 'xenotransplantation'. In the 20th century, the transplantation of organs and tissues to cure disease has become a clinical reality. The development in the fields of surgical techniques, physiology and immunology attributed to the successful transplantation in human. In the center of the successful transplantation lies the progress in understanding the cellular and molecular biology of immune system which led to the development of immunosuppressive drugs and the invention of the concept of immunological tolerance. The mandatory side effects of immunosuppressive drugs including infection and cancer forced us to search alternative approaches along with the development of new immunosuppressive agents. Among the alternative approaches, the induction of a state of immunologic tolerance would be the most promising and the most generic applicability as a future therapy. Recent reports documenting long-term graft survival without immunosuppression suggest that tolerance-based therapies may become a clinical reality. Last year, we saw the epoch making success of overcoming hyperacute rejection in porcine to primate xenotransplantation which will lead porcine to human xenotransplantation to clinical reality. In this review, I dare to summarize the development of transplantation immunology from the perspective of history.
Allergy and Immunology ; Chimera ; Graft Survival ; Heart ; Humans ; Immune System ; Immunosuppression ; Immunosuppressive Agents ; Inventions ; Kidney ; Liver ; Lung ; Molecular Biology ; Pancreas ; Physiology ; Primates ; Transplantation Immunology* ; Transplantation, Heterologous

Autoimmune pancreatitis (AIP) has two distinct subsets. Type 1 AIP or lymphoplasmacytic sclerosing pancreatitis is systemic disease with the elevation in serum levels of the IgG4. Type 2 AIP, also called duct-centric pancreatitis, features granulocyte epithelial lesions with duct obstruction in the pancreas without systemic involvement. Here, we report a case of type 2 AIP diagnosed by pathology, which is the first report in Korea. The case is a 56-year-old woman who presented with anorexia and vomiting. Computed tomography revealed mass-like lesion in the pancreatic head and the compression of the distal common bile duct and the head portion of the main pancreatic duct. Serum levels of the IgG4 were normal. Histologic examination revealed a dense neutrophil infiltration in the pancreatic parenchyme associated with extensive fibrosis, thereby confirming the diagnosis of type 2 AIP. The abnormalities in the clinical, laboratory, and radiological findings improved after oral steroid treatment.
Autoimmune Diseases/blood/immunology/*pathology ; Female ; Fibrosis ; Humans ; Immunoglobulin G/blood ; Magnetic Resonance Imaging ; Middle Aged ; Neutrophils/immunology ; Pancreas/pathology ; Pancreatitis/*drug therapy/immunology/pathology ; Steroids/*therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo summarize the treatment experience of long-term surviving patients after combined abdominal organ transplantation.

METHODSFrom October 2001 to January 2005, 19 patients received combined abdominal organ transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The periods of follow up were from 6 months to 3 years and 8 months. Summarize primary diseases of the patients, factors which impacted on patients long-term survival rate, and immunological characteristics of combined abdominal organ transplantation.

RESULTSAll of 19 transplant cases were performed successfully. Among then, 18 were followed up; 16 survived till now; 2 patients undergoing liver-kidney transplantation were dead, one of which died from myocardial infarction in the 18 months after operation, and one died from cytomegalovirus in infection of lung in 13 months; 1 liver-kidney transplantation patient and 2 pancreas-liver transplantation patients experienced acute rejection once; 2 patients were found nephrotoxicity. Among the 18 patients, 4 patients' survival time were over 3 years, 7 over 2 years, 6 over 1 year, 1 over 10 months.

CONCLUSIONSCombined abdominal organ transplantation is effective for treatment of two abdominal organ failure diseases. Factors which impact on patients long-term surviving include choosing suitable recipient, high quality of donated organ, avoidance of surgical complication, the history of myocardial infarction before operation, immunosuppressive regime and virus infection late after transplantation. Combined abdominal organ transplantation has some different immunological characteristics from single organ transplantation.

Adult ; Aged ; Duodenum ; transplantation ; Female ; Follow-Up Studies ; Humans ; Kidney Transplantation ; immunology ; methods ; mortality ; Liver Transplantation ; immunology ; methods ; mortality ; Male ; Middle Aged ; Pancreas Transplantation ; immunology ; methods ; mortality ; Treatment Outcome

OBJECTIVETo investigate clinicopathological features of fibrous mass-forming chronic pancreatitis (FMCP), to compare clinicopathological and immunohistochemical characteristics between autoimmune pancreatitis (AIP) and fibrous mass-forming non-autoimmune pancreatitis (nAIP) and to provide evidence for pathological diagnosis, differential diagnosis and clinical treatment strategy.

METHODSClinicopathological features were analyzed in 81 cases of FMCP. Infiltrating IgG4(+) plasmacytes were counted by immunohistochemical staining.

RESULTSAmong 81 cases of FMCP, 20 cases were diagnosed as AIP and 61 cases were interpreted as nAIP. AIP was more common in males over 50 years, whereas nAIP was seen in much younger patients (P = 0.001). The amount of inflammatory cells in the stroma of AIPs was remarkable higher than that in nAIPs (P = 0.002). The incidence of neuritis in AIPs (100%, 20/20) was also higher compared with that of nAIPs (75.4%, 46/61; P = 0.017). Storiformed-fibrosis was more common in AIPs (95.0%, 19/20) than in nAIPs (1.6%, 1/61;P = 0.000). Pancreatic intraepithelial neoplasia (PanIN) was observed in 50.0%(10/20) of AIPs and 32.8%(20/61) of nAIPs, with a greater severity observed in AIPs (P = 0.031). Tubular complex (TC) was more commonly observed in AIPs (65.0%, 13/20) than nAIPs (26.2%, 16/61;P = 0.002). Among 81 cases of FMCP, 61 cases had less than 11 IgG4(+) plasmacytes /HPF, 7 cases had 10-30/HPF and 13 cases had over 30/HPF.

CONCLUSIONSFMCPs include both AIP and nAIP. AIP has distinct pathological features and the presence of IgG4(+) plasmacyte is an important diagnostic parameter. FMCP appears to be an important precancerous lesion of pancreatic ductal adenocarcinoma. Surgery may be considered for patients with FMCP due to its mass-forming nature. In contrast, patients with AIP are treated medically due to its steroid-responsiveness. Therefore, accurate and timely diagnosis of AIP is of clinical relevance to avoid unnecessary surgical complications and to prevent progression of the disease.

Adult ; Aged ; Autoimmune Diseases ; immunology ; pathology ; surgery ; Carcinoma, Pancreatic Ductal ; immunology ; pathology ; surgery ; Diagnosis, Differential ; Female ; Fibrosis ; Humans ; Immunoglobulin G ; metabolism ; Male ; Middle Aged ; Pancreas ; pathology ; Pancreatic Neoplasms ; immunology ; pathology ; surgery ; Pancreatitis, Chronic ; immunology ; pathology ; surgery ; Plasma Cells ; immunology ; Precancerous Conditions ; immunology ; pathology ; surgery ; Young Adult

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Castleman Disease ; immunology ; pathology ; Cyclophosphamide ; therapeutic use ; Diagnostic Errors ; Doxorubicin ; therapeutic use ; Humans ; Immunoglobulin G ; blood ; Kidney ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Diseases ; drug therapy ; immunology ; pathology ; surgery ; Male ; Middle Aged ; Nephrectomy ; Pancreas ; Plasma Cells ; immunology ; pathology ; Prednisone ; therapeutic use ; Submandibular Gland ; Vincristine ; therapeutic use

BACKGROUNDOne of the major causes of death in severe acute pancreatitis (SAP) is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition (EIN) as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs.

METHODSSAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition (PN) or elemental enteral nutrition (EEN) or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes (MLN), liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum.

RESULTSCompared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury (ileum mocosa thickness, villus height, and crypt depth) were significantly alleviated by EIN (P < 0.05). Moreover, concerning liver function, the serum levels of alanine aminotransferase, aspartate aminotransferase and albumin were ameliorating significantly in the EIN group.

CONCLUSIONOur results suggested that EIN could maintain the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in SAP dogs. Early EIN was safe and more effective treatment for SAP dogs.

Acute Disease ; Amylases ; metabolism ; Animals ; Bacteria ; isolation & purification ; Dogs ; Endotoxins ; blood ; Enteral Nutrition ; Immunity ; Intestinal Mucosa ; metabolism ; Liver ; physiopathology ; Nutritional Support ; Pancreas ; pathology ; Pancreatitis ; immunology ; metabolism ; therapy ; Parenteral Nutrition