Takao Taniguchi

Circulating naïve and CD4+CD25high regulatory T cells in patients with autoimmune pancreatitis.

Objective: Autoimmune pancreatitis (AIP) is a new clinical entity of pancreatic disorder. There are several immunologic and histological abnormalities specific for the disease, including increased levels of serum IgG4 and infiltration of lymphocytes and IgG4-positive plasmacytes. The role of IgG4 is unclear. Recently, regulatory T cells (Tregs) have been reported to be involved in the development of various autoimmune diseases as well as B cell shifting to IgG4-producing plasmacytes. To clarify the role of Tregs in the pathophysiology of AIP, we analyzed circulating Tregs in AIP. Methods: We recruited 27 patients with AIP for this study. For comparison, we also recruited 23 patients with other pancreatic disease and 32 healthy subjects as controls. We analyzed Tregs as CD4+CD25high and CD4+CD25+CD45RA+ (naïve) from peripheral blood by flow cytometry. Results: In peripheral blood, CD4+CD25high Tregs were significantly increased in AIP patients (3.01% ± 1.77%) compared with alcoholic chronic pancreatitis (CP) (1.65% ± 0.58%), idiopathic CP (1.53% ± 0.56%), and healthy control (1.72% ± 0.81%, P < 0.05). Naïve Tregs significantly decreased in AIP (0.32% ± 0.22%) compared with healthy control (0.83% ± 0.65%) and CP group (alcoholic and idiopathic CP; 0.52% ± 0.40%, P < 0.05). In untreated AIP patients, the number of CD4+CD25high Tregs and IgG4 are correlated (R = 0.53, P < 0.05). Conclusions: Increased numbers of CD4+CD25 high Tregs may influence IgG4 production in AIP, whereas decreased numbers of naïve Tregs may be involved in the pathogenesis of AIP.

Effects of the anti‐ICAM‐1 monoclonal antibody on dextran sodium sulphate‐induced colitis in rats

Increased expression of intercellular adhesion molecule‐1 (ICAM‐1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM‐1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti‐ICAM‐1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti‐ICAM‐1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM‐1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti‐ICAM‐1 therapy in IBD, our findings encourage experiments using therapies that target ICAM‐1 in rats with already developed disease.

High Prevalence of Autoantibodies Against Carbonic Anhydrase II and Lactoferrin in Type 1 Diabetes : Concept of Autoimmune Exocrinopathy and Endocrinopathy of the Pancreas

Introduction Dysfunction of the exocrine as well as the endocrine pancreas has been reported in type 1 diabetes. Lymphocytic infiltration of the exocrine pancreas is observed in approximately half of Japanese type 1 diabetic patients. Aims To investigate the involvement of autoimmunity against the exocrine pancreas in type 1 diabetes. Methodology We examined autoantibodies against human carbonic anhydrase II (ACA) and lactoferrin (ALF), antigens in the pancreatic duct cells and the pancreatic acinus, respectively, in 43 type 1 diabetic patients and 20 type 2 diabetic patients using the enzyme-linked immunosorbent assay method. Results Of 43 type 1 diabetic patients, ACA was detected in 28 patients (65%) and ALF was detected in 29 patients (67%). One or both of the antibodies were detected in 33 type 1 diabetic patients (77%). In contrast, neither ACA nor ALF were detected in type 2 diabetic patients. Conclusions The high prevalence of both ACA and ALF strongly suggests the involvement of autoimmunity against the exocrine pancreas as well as the endocrine pancreas in some type 1 diabetic patients. We propose that these conditions be referred to as autoimmune exocrinopathy and endocrinopathy of the pancreas.

Autoimmune pancreatitis detected as a mass in the tail of the pancreas

A mass in the tail of the pancreas was detected in a 62‐year‐old male patient who had hypergammaglobulinaemia, and was positive for antinuclear antigen and anti‐SS‐A antibody. Endoscopic retrograde pancreatography revealed focal irregular narrowing of the main pancreatic duct in the tail of the pancreas. Dynamic computed tomography showed swelling of the pancreatic tail, which was enhanced on delayed phase. Autoimmune pancreatitis was suspected and corticosteroid therapy was commenced. This led to significant resolution of the pancreatic stricture. It is important to recognize this clinical entity as corticosteroid therapy may avoid unnecessary surgery.

Diffusion-weighted magnetic resonance imaging in autoimmune pancreatitis

PurposeThe aim of this study was to investigate the usefulness of diffusion-weighted magnetic resonance imaging (DWI MRI) for the diagnosis and evaluation of autoimmune pancreatitis (AIP).Materials and methodsA total of 4 consecutive patients with AIP, 5 patients with chronic alcoholic pancreatitis (CP), and 13 patients without pancreatic disease (controls) were studied. DWI was performed in the axial plane with spin-echo echo-planar imaging single-shot sequence. Apparent diffusion coefficients (ADCs) were measured in circular regions of interest in the pancreas. In AIP patients, abdominal MRI was performed before, and 2–4 weeks after steroid treatment. Follow-up study was performed chronologically for up to 11 months in two patients. The correlation between ADCs of the pancreas and the immunoglobulin G4 (IgG4) index (serum IgG4 value/serum IgG4 value before steroid treatment) was evaluated.ResultsIn the AIP patients, DWI of the pancreas showed high signal intensity, and the ADCs of the pancreas (mean ± SD: 0.97 ± 0.18 × 10−3 mm2/s) were significantly lower than those in patients with CP (1.45 ± 0.10 × 10−3 mm2/s) or the controls (1.45 ± 0.16 × 10−3 mm2/s) (Mann-Whitney U-test, P < 0.05). In one AIP patient with focal swelling of the pancreas head that appeared to be a mass, DWI showed high signal intensity throughout the pancreas, indicating diffuse involvement. The ADCs of the pancreas and IgG4 index were significantly inversely correlated (Spearman’s rank correlation coefficient, rs = −0.80, P < 0.05).ConclusionAutoimmune pancreatitis showed high signal intensity on DWI, which improved after steroid treatment. ADCs reflected disease activity. Thus, diffusion-weighted MRI might be useful for diagnosing AIP, determining the affected area, and evaluating the effect of treatment.

Autoimmune pancreatitis detected as a mass in the head of the pancreas without hypergammaglobulinemia, which relapsed after surgery: case report and review of the literature.

Autoimmune pancreatitis is a recently proposed clinical entity characterized by diffuse swelling of the pancreas, irregular narrowing of the main pancreatic duct on endoscopic retrograde pancreatography, hypergammaglobulinemia, and the presence of autoantibodies, together with responsiveness to corticosteroid therapy (1, 2). There are some reports of cases with focal swelling, which simulates pancreatic cancer or lymphoma (3–6), as well as cases that begin with focal swelling and progress to diffuse swelling (7–10 ). Here, we report a case of autoimmune pancreatitis that presented with obstructive jaundice and a mass in the head of the pancreas, which progressed to diffuse swelling 4 months after surgery. We also review the clinical features of reported cases of autoimmune pancreatitis.

CASE REPORT: Autoimmune Pancreatitis Detected as a Mass in the Head of the Pancreas with Contiguous Fibrosis Around the Superior Mesenteric Artery

Several cases of chronic pancreatitis associated with autoimmunity have been reported (1–3), and the concept of autoimmune pancreatitis was recently proposed (4, 5). This clinical entity is characterized by diffuse or focal swelling of the pancreas, irregular narrowing of the main pancreatic duct on endoscopic retrograde pancreatography (ERP), hypergammaglobulinemia, and the presence of autoantibodies, together with remarkable responsiveness to corticosteroid therapy. Some cases showing focal swelling or multiple focal masses that simulate pancreatic cancer or lymphoma have been reported by us and others (3, 6–10). Here, we report a case of autoimmune pancreatitis, detected as a mass in the head of the pancreas with a contiguous mass around the superior mesenteric artery, that was treated successfully with corticosteroid.

Effects of a Thromboxane A2 Receptor Antagonist in an Animal Model of Inflammatory Bowel Disease

BACKGROUND/AIMS We evaluated the effects of an antagonist of the thromboxane A2 receptor (ONO-NT-126) in an animal model of inflammatory bowel disease (IBD). METHODS Colitis was induced by intracolonic instillation of trinitrobenzenesulfonic acid/ethanol in male Wistar rats. ONO-NT-126 or vehicle alone was administered intraluminally via anus once a day. The rats were killed after 7 days for assessment of colonic damage by the colonic damage score. RESULTS AND CONCLUSION ONO-NT-126 markedly reduced the colonic damage. Our findings suggest that the thromboxane-thromboxane receptor system plays an important role in this model of IBD and that antagonism of the thromboxane A2 receptor may prove useful for the treatment of IBD.

Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon

We have investigated the effects of adrenomedullin (AM) on mucosal ion transport using the Ussing method and smooth muscle contraction using the Magnus method in rat. Our results indicate that AM increases Isc (short-circuit current) for Cl- secretion (100 nM:170.0 +/- 41.2%, 1 microM:193.8 +/- 45.5%, 100% Isc:28.2 +/- 3.1 microA/cm2) with an initial small decrease of Isc, inhibiting Na+ absorption. Tetrodotoxin (TTX) inhibits the Isc response elicited by AM (86%). In addition, AM relaxes potassium-induced contraction (10 nM:11.1 +/- 8.51%, 100 nM:33.4 +/- 12.7%, 100% contraction: 1.8 +/- 0.22 g), and TTX inhibits the response elicited by AM (90%). We conclude that AM modulates water and ion transport as well as bowel movement, mainly through the colonic nervous system.

7084 Endoscopic aspiration mucosectomy using a bipolar snare for gastric neoplasms.

PURPOSE: Although tissue damage is minimized using the bipolar snare, it is not widely used for endoscopic mucosal resection of the stomach because of slippage. The purpose of this study is to determine whether a bipolar snare can be used effectively for endoscopic mucosal resection of the stomach if aspiration is added to avoid slippage of the snare. METHODS: Patients with gastric adenoma or early gastric intestinal type adenocarcinoma were enrolled. Depressed lesions which were ulcerated or greater than 10 mm in diameter and elevated lesions greater than 20 mm in diameter were excluded. The utility of endoscopic aspiration mucosectomy using a bipolar snare (EAM-B) was examined retrospectively and compared with respect to specimen size, rate of complete resection, and occurrence of complication with endoscopic mucosal resection with a capfitted panendoscope using a monopolar snare (EMRC-M). RESULTS: EAM-B was performed in five lesions of five patients and EMRC-M was performed in five lesions of four patients. The resected specimen size was 20.0 ± 0.9 mm after EAM-B and 16.2 ± 4.5 mm after EMRC-M. There was no significant difference in the resected specimen size (P=0.0611) after EAM-B and EMRC-M. Complete resection was achieved in all cases. There were no complications. CONCLUSIONS: A bipolar snare can be used effectively for endoscopic mucosal resection of the stomach if aspiration is added to avoid slippage of the snare.