Yasuro Yamamoto

Endoscopic measurement of papillary sphincter zone and pancreatic main ductal pressure in patients with chronic pancreatitis.

To determine the significance of manometric pressure of the pancreatic duct, we used a microtransducer inserted through a duodenoscope to measure pressures in the papillary sphincter zone and pancreatic main duct in 20 control subjects and 20 patients with chronic pancreatitis, and recorded the effect of exogenous glucagon or secretin. There was no significant difference between control subjects and patients with chronic pancreatitis without papillitis in the motility of the sphincter of Oddi. The pancreatic main ductal pressure was significantly higher in the patients with chronic pancreatitis (54.5 +/- 29.9 mmHg) than in the control subjects (16.2 +/- 8.7 mmHg). The viscosity of pure pancreatic juice of patients with chronic pancreatitis [5.8 centipoise (cp)] in the basal secretory state was significantly higher than that of the control subjects (1.61 cp). These data lead to the hypothesis that increased pancreatic ductal pressure in patients with chronic pancreatitis without papillitis is due not to papillary dysfunction, but to increased viscosity or other unknown factors.

Major histocompatibility antigen-restricted cytotoxicity in inflammatory bowel disease

BACKGROUND The role of cytotoxicity mediated by peripheral blood mononuclear cells for colonic epithelial cells in inflammatory bowel disease (IBD) is still controversial. To clarify it, we studied major histocompatibility antigen (MHC)-restricted T cell-mediated cytotoxicity (CTL). METHODS Cytotoxicity was measured by 51Cr release from colonic cells after the 6-hour incubation with peripheral blood mononuclear cells in 11 IBD patients (6 with Crohns disease and 5 with ulcerative colitis). RESULTS CTL activity (E/T ratio = 200:1 or 100:1) for autologous target cells was significantly increased (22%-40%) in 5 of 6 CD and 4 of 5 UC patients (22%-64%) compared with that for allogeneic target cells. The increase in CTL activity was mainly inhibited by anti-MHC class I and CD8 monoclonal antibodies (50 micrograms/mL), while it was partially inhibited by anti-MHC class II or CD4 antibodies in some patients. Complement-mediated depletion of CD2+ cells also significantly decreased CTL activity. CONCLUSIONS The results indicate that MHC-restricted T cell cytotoxicity may play a role in mucosal damage in some patients of IBD.

Specific cellular immune responses to pancreatic antigen in chronic pancreatitis and Sjögren's syndrome

The specific cellular immune response to the partially purified pancreatic antigen was studied by the peripheral blood lymphocyte proliferation assay in patients with chronic pancreatitis, Sjögrens syndrome, and primary biliary cirrhosis. A significant positive result (stimulation index >2.0) was observed in 7 of 21 patients with idiopathic chronic pancreatitis (33%;P<0.05), 6 of 7 patients with Sjögrens syndrome-associated chronic pancreatitis (86%;P<0.0005), and 6 of 11 patients with Sjögrens syndrome (55%;P<0.01), compared to normal controls whose stimulation index was 0.94±0.28 (mean ± SD;n=14; range, 0.56–1.60). On the other hand, patients with alcoholic chronic pancreatitis (17%;n=12), stone-related chronic pancreatitis (0%;n=7), primary biliary cirrhosis-associated chronic pancreatitis (33%;n=3), primary biliary cirrhosis (0%;n=4), systemic lupus erythematosus (17%;n=6), and autoimmune thyroiditis (0%;n=6) showed no significant difference from normal controls. Furthermore, in patients with idiopathic chronic pancreatitis who had positive results, a lymphocyte proliferative response to the pancreatic antigen was observed in T cells, especially in the CD4+ T cell subpopulation. These results suggest that the pancreatic antigen plays a role in the pathogenesis of a part of idiopathic chronic pancreatitis and Sjögrens syndrome in association with T cell responses and, also, suggest that autoimmunity may be a possible etiological factor in chronic pancreatitis.

Pressure of papillary sphincter zone and pancreatic main duct in patients with alcoholic and idiopathic chronic pancreatitis

SummaryTo determine the significance of manometric pressure of the pancreatic duct in patients with alcoholic and idiopathic chronic pancreatitis, we used a microtransducer inserted through a duodenoscope to measure pressures in the papillary sphincter zone and pancreatic main duct in 20 control subjects and 31 patients with chronic pancreatitis without papillary stenosis including 10 cases of alcoholic chronic pancreatitis (ALCP) and 21 cases of idiopathic chronic pancreatitis (ICP). The pancreatic main ductal pressure was significantly higher in the patients with ALCP (55.7±28.9 mm Hg) or ICP (44.5±25.8 mm Hg) than in the controls (16.2±8.7 mm Hg), but there was no significant difference between ALCP and ICP. There was no significant difference between control subjects and ICP in the motility of the sphincter of Oddi. In ICP there no were correlationships between pancreatic ductal pressure and the motility of papillary sphincter zone. In ALCP, the frequency of the papillary sphincter waves was significantly higher than in normal subjects and there was a correlation between the pancreatic ductal pressure and the motility of the papillary sphincter zone. These data suggest that increased pancreatic ductal pressure in ALCP may be in part due to papillary dysfunction, but not in ICP.

Interspecies crossreactive antigen of the pancreatic duct cell prepared by monoclonal antibody

SummaryAn interspecies cross-reactive antigen (mol wt 60,000) for pancreatic duct cells was prepared by a monoclonal antibody (SP3-1; IgM). Homogenized pig pancreatic tissues were separated by gel filtration chromatography with Sephadex G-100 and ion-exchange column chromatography with DEAE-Sephacel and used as immunogens. Immunohistochemically, antigens against SP3-1 were distributed in duct cells of the pancreas, salivary gland, lacrimal gland, esophageal gland, bile duct, and the distal renal tubule in the pig, monkey, and human. The antigenic determinant contained protein, but not sialic acid or monosaccharide. Preliminary leukocyte migration inhibition test (n = 5) showed positive in four patients with definite Sjögren’s syndrome (SS), whereas one patient without autoantibodies similar to SS showed negative. These findings suggest that this antigen may be involved in the pathophysiology in these conditions.

Controlled trial of D-penicillamine with low dosis in the treatment of chronic liver diseases

SummaryControlled trial of D-penicillamine was carried out with low dosis in 10 patients with chronic persistent hepatitis, 11 patients with chronic aggressive hepatitis and 7 patients with liver cirrhosis. After 6 weeks and 6 months treatment mean values of transaminases improved in patients with chronic persistent hepatitis. The mean serum transaminases levels of the patients with chronic aggressive hepatitis were statistically decreased after 6 weeks treatment but not significantly lower after 6 months treatment than on entry. D-penicillamine is not effective for the treatment of patients with liver cirrhosis. Eight of 36 patients treated were withdrawn from the trial because of adverse drug toxicity side effects.

Increased production of Interleukin 1 by peripheral monocytes activated with biliary antigen immune complex in primary biliary cirrhosis.

PBCでは肝内胆管上皮に由来する特異抗原に対する自己免疫反応がその本態と想定されている.我々は先にPBCではInterleukin (IL) cascadeに異常が存在すること,障害胆管周囲のマクロファージ内に胆管上皮抗原免疫複合体が存在することを明らかにした.今回我々はPBCの6症例を対象とし末梢血単球の免疫複合体(IC)に対する反応性を培養上清中に産生されるIL-1活性の面より検討した.その結果,PBCではICに対する反応性は健常人に比し昂進傾向が見られ,殊に胆管上皮抗原免疫複合体に対しては25,100,200μg/mlの濃度で健常人に比して有意に反応性の昂進が認められるとの成績を得た.この成績より障害胆管周囲において胆管上皮抗原免疫複合体で刺激された障害胆管周囲のMΦは一方では抗原提示を行なうと共に他方IL-1産生を行い,細胞障害性T細胞を介してPBCにおける胆管病変の成立に関与している可能性が強いと考えられた.

Abnormality of serum immunoglobulins in chronic liver disease-immune complex like substances, abnormaly basic γ-globulin, secretory IgA and anti-DNA antibody

1) Serum secretory IgA was reduced in chronic liver disease while it was increased in obstructive jaundice. 2) Serum anti-dsDNA antibody was slightly increased in chronic liver disease, especially it was significantly increased in lupoid hepatitis in which its titer paralelled with the course of disease activity. 3) Serum Clq binding activity, Clq binding inhibition activity and polyclonal rheumatoid factor binding inhibition activity were increased in chronic liver disease and their disease activity was correlated with concentration of macromolecular immune complexes which were fractionated with sucrose density gradient ultracentrifugation. 4) Abnormally basic y-globulin which was dominantly found in chronic hepatitis B sera was determined to be monomeric IgG. I t was increased in aggravation of the disease but has no correlation with Clq binding monomeric IgG. 5) Liver membrane specific lipoprotein (LP-1), Espinosas liver specific antigen (LSA), Nerenbergs hepatorenal antigen (HRA) and Tamm-Horsfall glycoprotein (THGP) had positive charge, and LP-2 and F-antigen did negative charge. 6) Human liver cell membrane fraction could not be obtained by the method of Ray or aqueous two phase polymer system which have been used for rat liver.