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Biomedical subjects

T Manabe

Publications and source records attributed to T Manabe.

At least 343 records · Page 19Linked to original sources
PubMed1992

Differences in cellular proteins between high and low metastatic potential sublines from the methylcholanthrene-induced rat fibrosarcoma cell line.

The purpose of the present study was to determine with two-dimensional electrophoresis whether two sublines (high and low metastatic potential to lymph nodes) of rat fibrosarcoma induced by methylcholanthrene have differences in cellular proteins. The high metastatic potential subline had a specific protein in the protein map of the whole cell lysate. Its isoelectric point was 6.4 and the molecular weight was 18,000. This specific protein appeared in maps of the precipitate of 1,000 g centrifugation and in the supernatant from treatment with 0.5% Nonidet P-40 (NP-40). But this specific protein was not stained by five lectins, concanavalin A, wheat germ agglutinin, Ulex europeus agglutinin-1, Dolichis biflorus agglutinin, and Ricinus communis agglutinin. Apparently, this high metastatic potential subline has a specific protein in the plasma membrane which has no glycochain.

Animals↗
PubMed1992

A new synthetic protease inhibitor, E-3123, prevents lysosomal and mitochondrial fragility in rat caerulein-induced pancreatitis.

The study investigated the protective effect of a new synthetic protease inhibitor, E-3123, a 4-guanidinobenzoate methanesulphonate, on the exocrine pancreas in caerulein-induced pancreatitis of rats both in vivo and in vitro. Hyperamylasaemia, pancreatic oedema and congestion of amylase, as well as cathepsin B leakage from lysosomes and malate dehydrogenase leakage from mitochondria, were prevented by infusion of 5 mg/kg.h E-3123 particularly when infused for 2 h before and during 5 micrograms/kg.h caerulein infusion for 3.5 h. The results indicate that E-3123 plays its protective roles against pancreatitis in the subcellular compartments such as lysosomes and mitochondria, and that such a low molecular weight protease inhibitor as E-3123 may be clinically useful in the treatment of acute pancreatitis.

Acute Disease↗
PubMed1992

Effect of short-termed pancreatic duct obstruction on the pancreatic subcellular organellar fragility and pancreatic lysosomal enzyme secretion in rabbits.

We studied the effect of short-term (3 h) pancreatic duct obstruction (PDO) on the exocrine pancreas and on the secretion of lysosomal enzymes into the pancreatic juice of rabbits during stimulation by pancreatic secretagogues. The following evaluations were made: serum amylase levels, pancreatic water content, pancreatic amylase, trypsinogen and cathepsin B content, and output of pancreatic enzymes and lysosomal hydrolases when stimulated by secretin and caerulein as well as the distribution of cathepsin B in subcellular fraction. Cellular fragility (LDH leakage from dispersed acini) and subcellular organellar fragility (cathepsin B leakage from lysosomes and malate dehydrogenase leakage from mitochondria) were also evaluated. PDO for 3 h plus secretin infusion caused a significant rise in serum amylase levels, pancreatic water content, and pancreatic amylase and trypsinogen content due to congestion of digestive enzymes during PDO. There was also a redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction and increased cellular and subcellular organellar fragility. In normal rabbits and in those with only secretin infusion, caerulein stimulated the secretion of cathepsin B into pancreatic juice. Just after PDO, the secretion of cathepsin B, amylase and trypsinogen significantly decreased. By 24 h after PDO, the output of cathepsin B stimulated by caerulein and secretin had increased significantly. Amylase and trypsinogen output were also significantly increased at this stage, in both the secretin and caerulein fractions. These results indicate that the secretion of lysosomal enzymes into pancreatic juice is stimulated by gut hormones, such as caerulein, in the normal physiological state and in pathological states, such as PDO. These results also show an important role of increased cellular and subcellular organellar fragility in the pathogenesis of pancreatic injuries induced by PDO and augmented secretion of both lysosomal enzymes and pancreatic digestive enzymes in the recovery stage after PDO and their important roles at this stage. Lysosome enzymes also seem to play some physiological roles in the pancreatic ductal system in normal physiological states as well as their roles in pathological states, because cathepsin B can activate trypsinogen, and trypsin can activate many other enzymes.

Amylases↗
PubMed1992

Effects of acute pancreatitis on hepatic secretion of lysosomal enzymes into bile and hepatic lysosomal fragility: protective effects of a new synthetic protease inhibitor, ONO 3307.

To evaluate the effects of acute pancreatitis on hepatic function and hepatic cellular and subcellular organellar fragility, we studied 1) the hepatic secretion of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-glucosaminidase) into bile in the isolated perfused rat liver model; 2) the aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lysosomal enzyme levels in the effluent in an isolated liver model; 3) hepatic lysosomal fragility in an in vitro incubation study; and 4) protective effects of a new low molecular weight synthetic protease inhibitor, ONO 3307, against hepatic injury in doses of 2 and 5 mg/kg.h in acute pancreatitis induced by a supramaximal dose of cerulein in rats. Decreased hepatic secretion of lysosomal enzymes into bile and accelerated hepatic lysosomal fragility were observed in acute pancreatitis induced by cerulein. ONO 3307 showed a significant protective effect against this hepatic injury in acute pancreatitis, the dose of 5 mg/kg.h showing a more potent effect than the dose of 2 mg/kg.h. These results suggest that the impaired hepatic function, including depressed hepatic secretion of lysosomal enzymes, seems to be closely related to accelerated hepatic fragility and that some unknown protease, which is present in pancreatitis and is susceptible to inhibition by ONO 3307, plays a crucial pathologic role in the development of this liver injury during acute pancreatitis.

Acute Disease↗
PubMed1992

Acute cytotoxic effect of cyclosporin A on pancreatic acinar cells in rats. Protective effect of the synthetic protease inhibitor E3123.

This study was designed to evaluate the acute toxic effects of cyclosporin A on the exocrine pancreas and the protective effects of a new potent protease inhibitor, 4-(2-succinimidoethylthio) phenyl 4-guanidinobenzoate methanesulfonate, E3123. Cyclosporin A in a dose of 5 mg/kg.h caused a significant increase in serum amylase levels, pancreatic amylase content, and interstitial edema, suggesting that it induces exocrine pancreatic injury. Cyclosporin A also caused redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction, indicating colocalization of lysosomal enzymes with pancreatic digestive enzymes. E3123 in a dose of 2 mg/kg.h prevented almost completely these changes caused by cyclosporin A. These results indicate that exocrine pancreatic injury is induced by cyclosporin A and that lysosomal enzymes play important roles in the pathogenesis of this injury and also suggest that E3123 might protect the exocrine pancreas of patients receiving cyclosporin A after organ transplantation.

Amylases↗
PubMed1992

Cytotoxic effects of cyclosporin A on the exocrine pancreas in rats.

The current study was done to evaluate the subacute toxic effects of cyclosporin A (CS) on the exocrine pancreas and the protective effect of potent protease inhibitor camostate (FOY-305). CS administration (15 milligrams, twice a day) for 14 days caused a significant increase in serum amylase levels, pancreatic amylase and cathepsin B content and mild acinar cell vacuolization and interstitial edema. CS also caused the redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction, indicating colocalization of lysosomal enzyme with pancreatic digestive enzymes. The administration of camostate (150 milligrams per kilogram, twice a day for 14 days) almost completely prevented the toxic changes induced by CS. These results indicate that CS induces exocrine pancreatic injury and that lysosomal enzymes play important roles in the pathogenesis of the injury. The results also suggest the usefulness of camostate in protecting the exocrine pancreas in patients treated with CS after organ transplantation, because it can inhibit some proteases that are closely involved in the fragility of the subcellular organelles.

Amylases↗
PubMed1992

Protective effect of nafamostat mesilate on cellular and lysosomal fragility of acinar cells in rat cerulein pancreatitis.

This in vivo and in vitro study demonstrates the protective effects of a new synthetic protease inhibitor--nafamostat mesilate, FUT-175--on increased cellular and lysosomal fragility within acinar cells during the early stage of cerulein-induced acute pancreatitis in rats. FUT-175 prevented hyperamylasemia, pancreatic edema, congestion owing to amylase, and lactic dehydrogenase (LDH) discharge from acini as well as cathepsin-B leakage from lysosomes dose-dependently in doses of 1-10 mg/kg.h. These results suggest that FUT-175 can protect against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases may well play the important role in the pathogenesis of acute pancreatitis, and such a low molecular protease inhibitor may be useful clinically in the treatment of acute pancreatitis.

Amylases↗
PubMed1992

Toxic effects of oxygen-derived free radicals on rat pancreatic acini; an in vitro study.

Isolated pancreatic acini were incubated with either a combination of xanthine and xanthine oxidase which generates superoxide (O2), or hydrogen peroxide (H2O2), and the direct cytotoxic effect of active oxygen species on the pancreatic acini was examined in vitro in the isolated pancreatic acini system of the rat. Both amylase secretion and lactic dehydrogenase discharge were increased dose-dependently by the addition of xanthine and xanthine oxidase, and suppressed by the addition of a superoxide scavenger, superoxide dismutase. In addition, amylase and lectate dehydrogenase discharge was increased dose-dependently by hydrogen peroxide and decreased by catalase. These results suggest that superoxide and hydrogen peroxide directly injure pancreatic acinar cells and that active oxygen species are involved in the pathogenesis of acute pancreatitis.

Amylases↗
PubMed1992

[The cellular and lysosomal fragility of pancreatic acinar cells after ligation of pancreatico-biliary duct in the rat and the protective effects of nafamostat mesilate].

To explore the changes of exorine pancreas in the early stage after ligation of pancreatico-biliary duct (PBD) in rat, we evaluated the changes of serum amylase levels, pancreatic water content as well as the changes of subcellular distribution of cathepsin B in the acinar cells. We also evaluated the lactic dehydrogenase (LDH) discharge from dispersed acini as an index of cellular fragility and cathepsin B leakage from lysosomes as an index lysosomal fragility in vitro study as well as the protective effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT 175) in this model. After ligation of PBD, the serum amylase levels and pancreatic water content, increased significantly compared with those of the control group, but returning to the normal levels at 18 hours. The redistribution of cathepsin B in acinar cells was found and both the cellular and lysosomal fragility increased significantly compared with those of the control groups, shown their peak changes at 12 hours after ligation of PBD. But continuous intravenous administration of FUT 175 (2mg/mg.hr) remarkably attenuated all the parameters. These results indicate the important roles of lysosomal enzyme and lysosomal fragility in the pathogenesis of acute pancreatic injuries in this modes, and the clinical usefulness of FUT 175 in the treatment acute pancreatitis.

Acute Disease↗
PubMed1992

Malignant sex-cord stromal tumor of the testis: report of a case with special reference to its unusual intracytoplasmic substructures.

A case of malignant sex-cord stromal tumor (gonadal stromal tumor) in the left testis of a 42-year-old man with no sign of hormonal abnormality is reported. Histologically, a large portion of the tumor was composed of solid nests of round cells with a moderate amount of eosinophilic cytoplasm, but some areas contained small spaces somewhat resembling Call-Exner bodies and/or the follicular structures of granulosa cell tumors. In general, however, the tumor cells did not show a clear-cut differentiation into either Sertoli cells or granulosa cells. The tumor, because of its high mitotic rate, lymphatic, venous and capsular invasion, and metastasis to the para-aortic lymph nodes, was considered to be malignant. We simply designated this tumor, therefore, as a malignant sex-cord stromal tumor. An ultrastructural study revealed unique intracytoplasmic bodies composed of multiple stacks of tubular structures which superficially mimicked annulate lamellae. No lipid droplets, Reinke's crystalloids or Charcot-Böttcher filaments were seen. The rarity of the tumor and the presence of unusual substructures prompted us to report the case.

Adult↗
PubMed1992

Hyalinizing trabecular adenoma.

A case is presented of hyalinizing trabecular adenoma in a 54-year-old Japanese female. The patient underwent a hemithyroidectomy for the diagnosis of thyroid carcinoma. An intraoperative frozen section diagnosis was medullary carcinoma. Hematoxylin and eosin stained permanent sections from the surgical specimen, a well encapsulated 3.0 x 2.0 x 1 cm nodule, also led us to suspect medullary carcinoma, but immunohistochemical staining for thyrocalcitonin, CEA, and thyroglobulin showed that it was a hyalinizing trabecular adenoma.

Adenoma↗
PubMed1992

Effect of synthetic protease inhibitors on superoxide (O2-), hydrogen peroxide (H2O2) and hydroxyl radical production by human polymorphonuclear leukocytes.

The effects of clinically used protease inhibitors (aprotinin, nafamostat mesilate, gabexate mesilate) on the production of oxygen-derived free radicals (O2-, H2O2, .OH) by human polymorphonuclear leukocytes were examined. Nafamostat mesilate and gabexate mesilate markedly and dose-dependently inhibited zymosan-stimulated O2- production by human polymorphonuclear leukocytes. However, aprotinin had a slight scavenging effect on O2- produced by the xanthine-xanthine oxidase system. All the protease inhibitors inhibited H2O2 production, but had no significant scavenging effect on H2O2. Nafamostat mesilate and gabexate mesilate slightly inhibited .OH production. These results indicate that the synthetic protease inhibitors nafamostat mesilate and gabexate mesilate inhibit the production of various activated oxygen radicals by human polymorphonuclear leukocytes, and the differences in their inhibitory effects suggest that each synthetic protease inhibitor is specific for a particular oxygen-derived free radical.

Adult↗
PubMed1992

Effect of intraarterial active oxygen species on the rat pancreas.

To explore the role of active oxygen species in the development and progression of acute pancreatitis, we studied the direct toxic effect on the rat pancreas of active oxygen species: superoxide anions generated by xanthine/xanthine oxidase (X/XO), and hydrogen peroxide (H2O2). After a continuous injection of X (10(-3)M, 0.9 ml/hour)/XO (1 U/ml, 0.3 ml/hour) into the celiac artery supplying the pancreas, hemorrhages and extensive edema developed in the pancreas. The amylase and lipase concentrations in the peritoneal fluid rose to 10.3 and 13.8 times the control values, respectively. The subsequent infusion of superoxide dismutase (SOD, 3600 U/hour) into the external jugular vein completely suppressed hemorrhages, and reduced edema and the amylase and lipase concentrations in the peritoneal fluid. After continuous injection of H2O2 (100 microM, 1.2 ml/hour), via the celiac artery, marked hemorrhages and edema appeared in the pancreas, and the amylase and lipase concentrations in the peritoneal fluid were 11.1 and 17.3 times higher than the control values, respectively. These abnormalities were significantly suppressed by the intravenous infusion of catalase (10 mg/kg/hour) or gabexate mesilate (10 mg/kg/hour). These results indicate that active oxygen species have a direct toxic effect on the pancreas and that free radicals may play an important role in the development of acute pancreatitis.

Amylases↗
PubMed1992

Augmented secretion of lysosomal enzyme into pancreatic juice after short term obstruction of the pancreatic duct in rats.

To find out if and when lysosomal enzymes are excreted into pancreatic juice in physiological and pathological conditions, the changes in the secretion of cathepsin B into pancreatic juice were investigated in 66 Wistar rats with cannulation of common pancreatic-biliary duct and common bile duct, and infusions of caerulein and secretin. In a separate experiment ducts were cannulated and secretin infused as before, but in one group the ducts were "obstructed" and in another they were allowed to remain patent. Obstruction of the pancreatic duct for three hours caused a moderate significant rise in serum amylase activity. Cathepsin B activity in the pancreatic subcellular fractions was redistributed, and the amount of cathepsin B increased. In rats with obstructed ducts the secretion of cathepsin B and other lysosomal enzymes that were stimulated by caerulein was significantly greater than in the animals in which the ducts remained patent. Lysosomal enzymes associated with zymogen granules are secreted into pancreatic juice together with digestive enzymes after stimulation by gut hormones, and they may have pathophysiological roles in pancreatic juice.

Amylases↗
PubMed1992

[A case of endobronchial fibroma associated with recurrent pneumonia].

We present a case of endobronchial fibroma in a 59-year-old man admitted for repeated pneumonia, successfully treated by endoscopic Nd-YAG laser. His chest X-ray showed an infiltrative shadow in the right lower lung field and a mass shadow within the truncus intermedius. Bronchoscopy revealed a polypoid mass with lobulated whitish surface, obstructing 90% of the lumen. A biopsy taken from the tumor was suggestive of fibroma histologically. Two previous case reports stated that endobronchial fibroma readily detaches from the bronchial wall during removal. The tumor was successfully removed without dropping any tumor fragment to obstruct the distal bronchus by means of biopsy forceps manually attached to an endoscope with endoscopic Nd-YAG laser. The resected tumor was mainly composed of collagen fibers with scanty spindle-shaped fibroblastic cells, which was considered consistent with endobronchial fibroma. Endobronchial fibroma is a rare benign lung tumor, and only seven cases have been reported in the Japanese literature. There was no recurrence at three years and nine months.

Bronchial Neoplasms↗
PubMed1992

[Radiation therapy of pancreatic cancer].

We have been using external beam radiotherapy (EBRT) and intraoperative radiotherapy (IORT) for both resectable and unresectable pancreatic cancer patients. EBRT (50-60 Gy) was combined with IORT (25-33 Gy) whenever possible, but otherwise EBRT or IORT was given alone. In patients with unresectable tumor but no distant metastasis, the median survival time (MST) was 7.5 months (M) for the EBRT group and 9 M for the EBRT+IORT group. These MST's were significantly longer than the MST of 3 M of patients who had been treated without radiation (historical control). In non-Stage IV patients undergoing non-curative resection, the MST was 12.5 M for the EBRT group, 15.5 M for the EBRT+IORT group, and 7 M for the historical control. In patients undergoing macroscopic curative resection, the MST was 14 M for the EBRT group, 10 M for the EBRT+IORT group, and 10.5 M for the historical control. In Stage IV patients (with distant metastasis), the MST was 4.5 M for the EBRT group, 4 M for the EBRT+IORT group, 2 M for the IORT group, and 2.5 M for the historical control. Thus, radiotherapy appeared useful especially in non-Stage IV patients undergoing non-curative or no resection. A decrease or relief of pain was obtained in 90% of patients with unresectable lesions. Radiotherapy seems to play an important role in the treatment of pancreatic cancer but more aggressive combined treatment seems to be necessary to further improve the dismal prognosis of pancreatic cancer patients.

Combined Modality Therapy↗
PubMed1992

[Measurement of small bowel transit time in dogs with acetaminophen and indocyanine green].

We developed an experimental method to measure the gastric and the small bowel transit times in dogs without using X-ray nor radioisotopes. The dog with the ileostomy was given food containing acetaminophen (APAP) and indocyanine green (ICG), then we sampled blood and ileal contents of the dog. We could measure the gastric transit time by detecting plasma APAP and the small bowel transit time by detecting ICG in the intestinal contents. Using this experimental system, we examined the times after feeding milk or solid meal. The gastric transit time after taking solid meal was longer than that after taking milk, but this difference was not significant, and the small bowel transit time after taking solid meal was significantly shorter than that after taking milk.

Acetaminophen↗