Liver mitochondrial membrane potential was assessed during regeneration following partial hepatectomy in rabbits. Absorbance change of safranine O per milligram of mitochondrial protein was used to evaluate mitochondrial membrane potential. Absorbance change was calibrated to the membrane potential in millivolts produced by valinomycin-induced potassium diffusion potential. At 24 hr after hepatectomy, absorbance change of safranine O per milligram of mitochondrial protein increased from 15.0 +/- 2.2 X 10(-3) to 37.4 +/- 3.3 X 10(-3) per mg (p less than 0.005). This represents a mitochondrial membrane potential increase from 77.0 +/- 4.6 to 124.4 +/- 6.7 mV. Phosphorylative activity increased from 59.9 +/- 5.0 to 106.1 +/- 7.4 nmoles ATP synthesized per mg per min (p less than 0.005). The enhancement of phosphorylative activity was closely linked to the elevation in liver mitochondrial membrane potential (r = 0.77, p less than 0.005). We suggest that elevation of mitochondrial membrane potential, coupled with enhanced oxidative and phosphorylative activities, plays an important role in the regeneration process following hepatectomy.

Adenosine Triphosphate↗

PubMedDate not supplied

[Surgical biopsy of the pancreas. Procedure and diagnostic value].

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Aged↗

PubMedDate not supplied

Clinicopathological characteristics of duodenal microgastrinomas.

Duodenal gastrinomas do not seem to behave as malignantly as sporadic pancreatic gastrinomas. Statistical analysis of 49 patients with sporadic pancreatic gastrinoma and 21 patients with sporadic duodenal gastrinoma reported since 1980 in Japan revealed that the incidence of hepatic metastasis was 57% in patients with sporadic pancreatic gastrinoma and only 9% in patients with sporadic duodenal gastrinoma (p less than 0.01). These findings suggest that there is an essential biological differences between duodenal and pancreatic gastrinoma. Five patients with sporadic duodenal microgastrinoma (tumor diameter less than 5mm) in our hospital had no hepatic metastases; however, 4 patients had lymph node metastases. Immunohistochemical study of 5 sporadic duodenal microgastrinomas and 6 sporadic pancreatic gastrinomas revealed that the sporadic duodenal gastrinomas contained significantly fewer insulin-producing or glucagon-producing cells than sporadic pancreatic gastrinomas. The cellular composition of the metastatic lymph nodes from duodenal microgastrinomas was similar to that of the primary tumor. This difference in cellular composition between the duodenal microgastrinomas and the pancreatic gastrinomas suggests that the process of development and differentiation of gastrinoma cells is different.

Adult↗

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Changes in mitochondrial redox state following an oral glucose load.

Changes in cytosol and mitochondrial redox state after an oral glucose load were studied in the liver of rats. The [NAD+]/[NADH] ratios increased 4-fold in the cytoplasm and 1.5-fold in the mitochondria 60 min after an oral glucose load, when serum IRI was maximally increased. It is suggested that an increase in mitochondrial redox state following an oral glucose load is due to an enhanced rate of removal of NADH by the respiratory chain, possibly due to an elevated level of insulin available to hepatocytes, and that an increase in cytosol redox state depends on an enhancement in mitochondrial oxidation of cytosol reducing equivalent.

Acetoacetates↗

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Cellular alterations of parotid gland of rats with acute pancreatitis induced by cerulein.

To explore the cellular and subcellular alterations of the parotid gland during acute pancreatitis, we examined the redistribution of lysosomal enzyme, cathepsin B, along with the discharge of the LDH and cathepsin B from parotid acini of rats with acute pancreatitis induced by a supramaximal dose of cerulein (5 micrograms/kg/h for 3.5 h). Both the serum amylase level and parotid-gland amylase content were increased significantly in rats with acute pancreatitis. The dry-/wet-wt ratio ratio was significantly lower than in the control. In vitro studies showed that discharge of LDH from the parotid acini and leakage of cathepsin B from lysosomes in the acini were significantly higher than in the control. In addition, there was redistribution of the cathepsin B (shifting from the lysosomal pellet to the zymogen pellet) in the parotid gland. These results indicate that in acute pancreatitis there is edema and accumulation of amylase in the parotid glands, along with increased cellular and lysosomal fragility. Thus, there seems to be a close relationship between the exocrine pancreas and the parotid glands. Gut hormones, such as cerulein, also appear to play an important role in the pathophysiology of the parotid glands.

Acute Disease↗

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Factors influencing prognosis and indications for curative pancreatectomy for ductal adenocarcinoma of the head of the pancreas.

The factors influencing prognosis and the indications for curative resection by radical pancreatectomy were evaluated in 74 patients treated with pancreatectomy for ductal cell carcinoma of the head of the pancreas. The 5-yr survival rates for patients without lymph node metastasis, capsular invasion, portal system involvement, or retroperitoneal invasion were 21.2, 20.2, 25.5, and 19.6%, respectively; the 5-yr survival rate for patients with lymph node metastasis or capsular invasion was 5.3% and 6.4%, respectively, and the 2-yr survival rate for patients with portal system involvement or retroperitoneal invasion was 0%. The 5-yr survival rate for 32 patients treated with radical pancreatectomy was 33.4%, and the 3-yr survival rate for 42 patients treated with nonradical pancreatectomy was 0%. Our results suggest that, in patients with ductal adenocarcinoma of the pancreas without factors limiting prognosis, curative resection by radical pancreatectomy is feasible; however, in patients with positive factors, particularly portal system involvement or retroperitoneal invasion, a comprehensive therapeutic program combining extensive surgery, radiation, chemotherapy and/or immunotherapy is necessary to obtain better results.

Adult↗

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Effects of synthetic kassinin on splanchnic circulation and exocrine pancreas in dogs.

Effects of intravenously administered synthetic kassinin on splanchnic circulation and exocrine pancreatic secretion were examined in six anesthetized dogs. Kassinin caused dose-related increases in the blood flow in superior mesenteric artery and portal vein, and produced an initial increase followed by a decrease in pancreatic blood flow, but did not affect the exocrine pancreatic secretion. This study demonstrates that kassinin affects splanchnic blood flow in dogs, and suggests that kassinin or a kassinin-like substance functions as a neuropeptide controlling the splanchnic circulation in mammalian species.

Animals↗

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Effects of synthetic human pancreastatin on pancreatic secretion and blood flow in rats and dogs.

Effects of synthetic human pancreastatin-52 and human pancreastatin-29 on pancreatic secretion and blood flow were examined in rats and dogs. Synthetic human pancreastatin-52 and human pancreastatin-29 were equally potent in suppressing the release of amylase stimulated by cholecystokinin in rats in vivo. However, neither human pancreastatin-52 nor human pancreastatin-29 altered basal and cholecystokinin-stimulated amylase release from isolated dispersed rat pancreatic acini. In studies in dogs, human pancreastatin-29 suppressed releases of amylase and protein stimulated by cholecystokinin, but did not alter pancreatic blood flow. These results suggest that the inhibitory effects of pancreastatin on pancreatic secretion do not involve a direct action on pancreatic acinar cells nor alteration of pancreatic blood flow. Pancreastatin probably is important in regulating exocrine pancreatic secretions as well as endocrine pancreatic secretions.

Amylases↗

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Immunohistochemical studies on the localization of cancer associated antigens DU-PAN-2 and CA19-9 in carcinomas of the digestive tract.

The immunohistochemical localization of DU-PAN-2 antigen and CA19-9 antigen in carcinomas of the digestive tract was studied using an immunoperoxidase technique. Staining for DU-PAN-2 antigen and CA19-9 antigen was observed in 104 (79%) and 96 (73%) of 131 carcinomas of the digestive tract, respectively. Diffuse staining (more than 20% of carcinoma cell stained) for DU-PAN-2 was detected in 14 of 21 (67%) pancreatic carcinomas and 11 of 19 (58%) carcinomas of the biliary tract (including cholangiocarcinoma). Diffuse staining for CA19-9 was detected in 15 (71%) of pancreatic carcinomas and nine (47%) of the carcinomas of the biliary tract. In colon carcinomas, no diffuse staining for DU-PAN-2 was observed, whereas diffuse staining for CA19-9 was found in 41%. There was a positive correlation between the differentiation degree (or grade) of the adenocarcinomas of the colon and the expression of CA19-9, but not that of DU-PAN-2. These immunohistochemical studies showed that DU-PAN-2 antigen is expressed diffusely in most cases of adenocarcinoma of the pancreas and biliary tract and is more specific for adenocarcinomas of the pancreas and biliary tract than CA19-9.

Adenocarcinoma↗

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Protection by gabexate mesilate (FOY) of the exocrine pancreas in rats with acute pancreatitis induced by a supramaximal dose of caerulein.

Earlier studies have reported that interstitial oedematous pancreatitis characterized by hyperamylasaemia can be seen during the early stage of stimulation of supramaximal dose of caerulein. The present study investigated the changes in both cellular and lysosomal fragility and the protective effects of a synthetic protease inhibitor gabexate mesilate (FOY) on this non-invasive model of experimental pancreatitis. The infusion of FOY (50 mg/kg/h) prevented the caerulein-induced increase in serum amylase and pancreatic oedema formation and reduced the elevated amylase content significantly. The administration of FOY with caerulein also reduced the increased lactic dehydrogenase (LDH) discharge significantly and inhibited the cathepsin B leakage from lysosomes in an in vitro incubation system. These results indicate that FOY plays its protective role at the subcellular level--that is, in lysosomes by inhibiting some proteases such as phospholipase A2. The importance of esterases in the pathogenesis of acute pancreatitis is demonstrated. This type of esterase inhibitor may be valuable clinically in the treatment of acute pancreatitis and these results also suggest the role of lysosomal fragility in the pathogenesis of progression of acute pancreatitis.

Acute Disease↗

PubMedDate not supplied

Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate-induced pancreatitis.

The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasaemia, high amylase activity in ascitic fluid, hyperendotoxaemia and a high serum level of fibrin degradation products (FDP) and redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. Sodium taurocholate injection into the pancreatico-biliary duct also caused the bacterial growth in the pancreas. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and Shiomarin was significantly more protective than E3123 therapy alone. These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis.

Acute Disease↗

PubMedDate not supplied

Antitumor activity of 5'-deoxy-5-fluorouridine in human digestive organ cancer xenografts and pyrimidine nucleoside phosphorylase activity in normal and neoplastic tissues from human digestive organs.

5'-Deoxy-5-fluorouridine (5'-DFUR) is believed to be metabolized to 5-fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase). PyNPase activity is reported to be higher in neoplastic tissues than in normal tissues, and this has been proposed as an explanation for the selective cytotoxicity of 5'-DFUR against tumors. In the present study, PyNPase activity was measured in 95 neoplastic and normal specimens from human digestive organ tissues. In specimens from the esophagus, stomach, intestine and pancreas, PyNPase activity was higher in neoplastic tissues than in normal tissues. However, PyNPase activity in non-malignant liver tissues, especially cirrhotic liver tissues, was much higher than in the normal tissues of the other digestive organs. PyNPase activity in non-malignant liver tissues was a high as in primary liver tumors, and PyNPase activity in metastatic liver tumors was lower than in primary tumors and non-malignant cirrhotic tissues. The in vivo antitumor activities of oral 5'-DFUR and intravenous 5-FU were also assessed in 6 human digestive organ cancer xenograft lines transplanted subcutaneously in nude mice, and the relationship between the in vivo antitumor effects of 5'-DFUR and PyNPase activity in the tumors was assessed. However, there was no statistically significant correlation between them. Although the in vivo antitumor effect of intravenous 5-FU correlated significantly with the in vitro sensitivity of the tumors to 5-FU (assessed by DNA synthesis inhibition assay), the in vivo effects of 5'-DFUR did not correlate with the in vitro sensitivity to 5-FU. It is suggested that: (a) the liver may be the major site for metabolizing 5'-DFUR to 5-FU, and (b) measuring PyNPase activity in the tumor may not be a useful indicator for chemotherapy with 5'-DFUR.

Adenocarcinoma↗

PubMedDate not supplied

The role of additional chemotherapy with oral UFT in intravenous combination chemotherapy with cisplatin and 5-fluorouracil for human gastric cancer xenograft lines of well- and poorly- differentiated adenocarcinomas transplanted in nude mice.

In order to assess the role of maintenance chemotherapy with the oral anticancer agent UFT, a mixture of uracil and futraful, in the intensive intravenous chemotherapy for gastric cancer, nude mice transplanted with human gastric cancer xenografts were treated with intravenous 5-fluorouracil (5-FU) and cisplatin (CDDP), alone or in combination, with or without the oral anticancer agent UFT. UFT was given at its maximal clinical dose of 10 mg/kg of body weight daily for 2 weeks, while 5-FU and/or CDDP was intravenously administered at the dose of 20 mg/kg and 1.8 mg/kg of body weight respectively once a week, alone or in combination, for two weeks. The results revealed that 5-FU or CDDP alone were ineffective for both GC-YN, a well differentiated adenocarcinoma line, and GC-SF, a poorly differentiated adenocarcinoma line; however, UFT was effective for GC-SF. In combinations, only the three-agent combination 5-FU + CDDP + UFT (FPU) was effective for GC-YN; however, all the two-agent combinations and FPU were effective for GC-SF. FPU significantly suppressed the growth of GC-YN much more than all the other treatment groups. In contrast, although all combinations as well as UFT alone were effective for GC-SF, there was no significant difference among these effective groups. Moreover, no side effects were noted in combined use of UFT. This study suggests that oral UFT as a maintenance treatment may be beneficial in the combination chemotherapy for human gastric cancer.

Adenocarcinoma↗

PubMedDate not supplied

Relationships for recombinant interleukin-2-stimulated mixed lymphocyte tumor extract reaction between peripheral blood lymphocytes and regional node lymphocytes in gastric cancer patients.

To investigate the relationship between "systemic" antitumor immunity and "local" antitumor immunity with respect to the histopathological stage of gastric cancer, interleukin-2 stimulated mixed lymphocyte tumor extract reactions (ILS-MLTR) of peripheral blood lymphocytes (PBL) and regional node lymphocytes (RNL) were evaluated in 59 gastric cancer patients. ILS-MLTRs of both PBL and RNL decreased with the advance of cancer stage, but ILS-MLTRs of PBL were always lower than those of RNL. Positive correlations in MLTR between PBL and RNL were found in patients with depth of invasion to muscularis propria and serosa and peritoneal dissemination. Inverse correlations between PBL and RNL were noted in patients with stage IV and distant nodal involvement. These results suggest that variations in the anticancer immunities might be effectively managed by an immunotherapy which is designed according to the responsiveness in the immune parameter ILS-MLTR.

Cells, Cultured↗