Cholecystokinin (CCK) binding to its receptors on guinea pig gastric chief cell membranes was characterized with 125I-COOH terminal octapeptide of CCK (125I-CCK8). Specific binding of 125I-CCK8 to chief cell membranes was maximal at pH 6.0 and 30°C after 180min of incubation and reversible upon the addition of 10-7M unlabeled CCK8. CCK analogs such as CCK8, gastrin-I, and COOH-terminal tetrapeptide of CCK (CCK4) competitively inhibited the labeled CCK8 binding with the half maximal inhibitory concentration of 10-10M, 3×10-7M and 10-6M, respectively. Furthermore, guanine nucleotide analogs such as GTPγS and Gpp(NH)p also inhibited the labeled CCK8 binding to chief cell membranes. Scatchard analysis of the binding data at pH6.0 revealed two orders of the binding sites and GTPγS decreased the binding by converting two binding sites of the receptors to only one site of lower affinity. These results suggest that there are specific receptors for CCK, which are coupled to a guanine nucleotide regulatory protein on guiea pig gastric chief cell membranes.
Specific type of early gastric cancer based on the cancer surface area and the degree of invasion were studied by measuring digital values of the cancer surface area in early gastric cancer patients. The results indicated that the pen and super type of early gastric cancer had many clinicopathological characteristics as compared with common type of early gastric cancer. An immunohistochemical study also revealed that the pen type of early gastric cancer had a high growth activity. Moreover, it was suggested that EGF was involved in its specific invasion and growth, and that EGF and TGF-β affected its scirrhous growth. The possibility that the poorly differentiated pen type is an early lesion of linitis plastica type gastric cancer was also considered. From these findings, it was assumed that the immunological staining of EGF and TGF-β in biopsy specimens might be useful in the diagnosis of the pen type of early gastric cancer and also in diagnosis of early lesion of linitis plastica type gastric cancer.
DNA polymerase α is an endogenous DNA replication enzyme expressed in all cells in a proliferation cycle. An immunoperoxidase method and the monoclonal antibody to DNA polymerase α were used to identify proliferating cells in colorectal carcinomas (n=35) and adenomas (n=43). The labeling index (L.I.) in colorectal carcinomas was 51.6%, being significantly higher than 28.6% in adenomas. The L.I. in colorectal carcinomas correlated with clinical staging (stage I: 33.1%, stage II and III: 49.5%, stage IV and V: 66.9%). Furthermore, the L.I. had a tendency to elevate as carcinoma deeply invaded (pm: 25.8%, ss-s or a1-a2: 52.2%, si or ai: 67.5%). The L.I. in adenoma was related to the degree of atypia. The L.I. in adenomas with mild atypia, with moderate atypia, and cancer in adenoma were 18.3%, 31.5%, and 47.0%, respectively. And the L.I. of cancer in adenoma had no significant defference in advanced carcinomas (47.0% vs 51.6%). These results suggest that the L.I. is useful as a marker for evaluating the degree of biological malignancy of human colorectal caricnomas and the degree of histopathological atypia of adenomas.
A new autoantibody to 210kDa microtubule associated protein (MAP) obtained from rabbit liver excrude was detected in the serum with various liver diseases and SLE. As there were no reports concerning autoantibodies to MAPs in animals and human, it may say that anti-210kDa MAP autoantibody we detected was a new cytoskeleton antibody. Using western blotting method, the anti-210kDa MAP autoantibody was frequently found in the patients with alcoholic liver diseases (52.5%), PBC (55.6%), autoimmune hepatitis (83.3%), SLE (71.4%) but rarely in the patients with viral liver diseases (26.4%) and none in normal controls at a serum dilution of 1:10. In addition, at a serum dilution of 1:100, the anti-210kDa MAP autoantibody was found in the patients with alcoholic liver diseses (22.5%), PBC (44.4%), autoimmune hepatitis (66.7%), SLE (71.4%), viral liver diseases (17.0%) and none in normal controls. It was confirmed that the anti-210kDa MAP autoantibody was frequently detected in cases of alcoholic liver diseases, PBC, autoimmune hepatitis and SLE than in those of viral liver diseases and normal control.
sIL2R in the sera of patients with viral liver diseases and primary biliary cirrhosis (PBC) were quantified with a solidphase enzyme immunoassay using two monoclonal antibodies against the receptor. As IL2 upregulated sIL2R release in vitro and in vivo, the serum levels of sIL2R might be a useful marker for T cell mediated immune responses. The sIL2R in patients with acute hepatitis, chronic hepatitis (CH) and PBC were significantly higher than those in control subjects. Serum sIL2R in patients with CH and PBC was capable of binding IL2 and did not affect IL2 depended immune responses of blastoid lymphocytes. These results suggest that IL2 production and sIL2R release increase significantly in patients with CH and PBC, and IL2 depended cytotoxic T cells may play a role of pathogenesis of CH and PBC.
We investigated expression of HBV markers in chronic liver disease positive for antibody to HCV (anti-HCV). Sera from 107 patients with chronic non-A, non-B liver disease, 65 HBs antigen carriers with chronic liver disease and 14 asymptomatic HBV carriers were tested for the presence of anti-HCV. Anti-HCV was detected in 83(78%) patients with chronic non-A, non-B liver disease, irrespective of the past history of blood transfusion, and anti-HCV prevalence was similar in each category of chronic liver disease. Fifty-three (64%) out of these 83 sera positive for anti-HCV has also antibodies to HBV. Anti-HBc antibody was detected frequently in liver cirrhotics with hepatocellular carcinoma than in chronic persistent hepatitis, chronic active hepatitis and cirrhotics without hepatocellular carcinoma. In addition, titers of anti-HBc antibody were significantly higher in cirrhotics with hepatocellular carcinoma than in the other groups. On the other hand, anti-HCV was detected in 7 out of 65 patients with HBV-related liver disease. Four out of these 7 were patients with HBV-related hepatocellular carcinoma. Anti-HCV was detected in none of asymptomatic HBV carriers. These findings suggest that infection with both HBV and HCV is likely to cause more serious liver disease than infection with a single agent.
We have conducted an experiment to examine the effects of a truncal vagotomy on the gallstone formation. Chosen for this experiment were ICR male mice that were given an abdominal vagotomy. While the postoperated mice were on a cholesterol-free diet, we found that, due to the vagotomy, the mole fraction of the cholesterol in the mice's gallbladder bile increased, as did the total protein concentration in their bile. When being fed foods to promoted a gallstone, the postoperated mice clearly demonstrated a higher rate of gallstones formation than without the vagotomy, and while the choresterol concentration in their bile did not show a significant increase, total protein concentraiton did increase significantly. The rate of a biliary infection also increased. Considering the above, we have concluded that a truncal vagotomy is a factor that promotes the gallstone formation.
Human bile glycosaminoglycan (GAG) was examined in eight normal controls and 87 patients with hepatobiliary diseases, in order to elucidate a role and significance of GAG in gallstone formation. Each crude mucopolysacharides (c-MP) were examined by carbohydrate analysis, additional two dimensional electrophoresis and DEAE Sephacel column chromatography. The yield of c-MP and total hexosamine concentration, a marker for mucin, were significantly higher in gallstone patients than controls both in gallbladder and hepatic bile. They were marked high values especially in cholestatic bile. Electrophoresis of GAG from normal and pathological bile identically showed single spot at unique position which mobility were simliar to standard hyaluronic acid, but lower at both run, and they resisted enzymatic digestion. More detail analysis by chromatography revealed three peaks and second peak eluted at 0.85M NaCl was thought to be the most important fraction. This fraction was rich in neutral sugar and its amino acid was composed almost entirely of glucosamine. Present results suggested that these GAG were peculiar to human bile and played a significant role in gallstone formation by quantitative change.
We investigated prognosis in 48 patients with hepatic hilar carcinoma (35 treated with percutaneous biliary drainage (PBD) and 13 without PBD) and complication associated with PBD. Survival rate in 20 patients who had no cholangitis within 1 month after PBD was significantly superior to that in 15 patients with cholangitis. The former was 51.9% at 6 months and 13.0% at 1 year. We thought that this result would be helpful in estimating prognosis in patients with hepatic hilar carcinoma treated with combined therapy. Cholangitis within 1 month after PBD was caused from inadequate drainage for separated intrahepatic bile ducts, ERC before PBD and dislodgement of drainage catheter. Survival rate in patients with PBD not accompanied by cholangitis in 1 month after was superior to that in those without PBD. So we thought that PBD could improve prognosis in patients with hepatic hilar carcinoma if they had no cholangitis within 1 month after PBD.
To explore the changes in the exocrine pancreas and the possible stimulation by gut hormones of secretion of lysosomal enzyme into the pancreatic juice, we measured the caerulein-stimulated amylase output, the cathepsin B output into the pancreatic juice and the pancreatic tissue amylase and cathepsin B contents, as well as the distribution of cathepsin B in acinar cells in both the regenerating (4 days) and recovery (8 days) stages after about 70% hepatectomy in rats. The amylase output increased significantly after hepatectomy. Cathepsin B was secreted into the pancreatic juice after stimulation by caerulein in both the control and hepatectomized groups. Four days after hepatectomy, the cathepsin B output was significantly greater than that of the control group, and redistribution of cathepsin B in acinar cells was noted. These changes in cathepsin B disappeared in the recovery stage (8 days) after hepatectomy. In addition, the pancreatic amylase content was significantly higher than in the control group, but the pancreatic cathepsin B content did not change significantly. These results suggest that caerulein stimulated the secretion of lysosomal enzyme into the pancreatic juice in the same way as digestive enzymes and that lysosomal enzymes in the pancreatic juice play an important physiological role. Furthermore, these results indicate the increased synthesis and secretion of amylase in and from acinar cells as well as the fragility of acinar cells.
We investigated whether intraduodenal (id) oligopeptide with three or four amino acids residues (pH 7.0) stimulates pancreatic exocrine secretion and release of endogenous plasma secretin and CCK in anesthetized rats. Id administration of oligopeptides in three doses (25, 100, 400mg/hr) at a speed of 4ml/hr resulted in dose-related increases in pancreatic secretion of pancreatic juice volume, bicarbonate, and amylase outputs (r=0.598, 0.673, and 0.426, P<0.05-0.001), and plasma concentrations of secretin and CCK (r=0.743, 0.425, P<0.001 and 0.05). Intravenous administration of CCK-antagonist, CR1505 (5mg/kg•hr) markedly inhibited oligopeptide-stimulated amylase output, but did not affect pancreatic juice volume and bicarbonate output. These results suggest that id oligopeptide increases pancreatic exocrine secretion and releases endogenous secretin and CCK.
We evaluated diagnostic capability and clinical usefulness of histological diagnosis of the pancreas by percutaneous biopsy controled on ultrasound image. Thirty seven patients with pancreas carcinoma and 11 with chronic pancreatitis underwent the procedure using 21 gauge-Sonopsy C1needle (Hakko co. Ltd.). Specimens of the tissue obtained were adequate for histological interpretation in 95.8% of all the 48 patients. The histological judgement referring to the nature of the lesion corresponded in 91.3% with the final diagnosis established surgical exploration, autopsy or long follow up more than one year. In cases of pancreas carcinoma with a successful procedure of the biopsy, histological type of carcinoma was confirmed in 91.4% of the tumors. It proved accordant pathologically with the conclusion based on the resected tumors in 5 of 8 patients operated on after the biopsy. Chronic pancreatitis was histologically diagnosed in 9 of the 11 patients with the biopsy. A confident diagnosis could not be obtained by imaging modalities including ultrasound, X-ray CT, ERCP and angiography in 7 of 37 patients with pancreas carcinoma and 3 of 11 with chronic pancreatitis. Biopsy by this method was so useful as to obtain the correct diagnosis in all these cases but one. Abdominal pain happend most frequently as a adverse effect during the procedure, but dissapered soon after that. There were no serious complications requiring intensive care. In conclusion, percutaneous histological biopsy controlled on ultrasound image may be recommended as a reliable method for making a definite diagnosis providing more valuable information than cytological biopsy, when diagnostic imaging modalities are unsuccessful in elucidating patholoy of the pancreas.