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Biomedical subjects

G Ohshio

Publications and source records attributed to G Ohshio.

At least 55 records · Page 3Linked to original sources

Quantitative analysis of collagen and collagen subtypes I, III, and V in human pancreatic cancer, tumor-associated chronic pancreatitis, and alcoholic chronic pancreatitis.

The collagen content in human pancreatic cancer tissue, tissue of tumor-associated chronic pancreatitis (TACP), and normal pancreatic tissue was determined in 14 patients with pancreatic cancer by measuring the amount of 4-hydroxyproline. Four patients with alcoholic chronic pancreatitis (AlCP) were also analyzed. The mean collagen content in both pancreatic cancer tissue and TACP tissue was approximately threefold higher than in normal pancreatic tissue. Cyanogen bromide peptides of type I, III, and V collagens from invasive ductal carcinomatous tissue of the pancreas and from TACP tissue of eight patients were analyzed sequentially using high-performance liquid chromatography with ion-exchange and gel-permeation columns. No difference in the proportion of type I, III, and V collagens was detected between pancreatic cancer tissue and TACP tissue. The mean collagen content in AlCP tissue was significantly lower than that in TACP tissue, but no difference in the proportion of type I, III, and V collagens was detected between these two tissues. These results indicate a similar quantity and distribution pattern of fibrillar collagen in human pancreatic cancer and TACP.

Alcoholism↗

Evaluation of pancreatic tumors with positron emission tomography and F-18 fluorodeoxyglucose: comparison with CT and US.

PURPOSE: To assess the clinical value of positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) for identification of pancreatic carcinoma. MATERIALS AND METHODS: Forty-six patients suspected of having a pancreatic neoplasm and who were to undergo surgery prospectively underwent FDG PET, computed tomography (CT), and transabdominal ultrasound (US). Endoscopic US was performed in 40 patients. Images were independently interpreted and compared with the histopathologic findings at surgery (41 patients) or with clinical follow-up findings (five patients). RESULTS: In 33 of 35 patients, foci of pancreatic carcinomas (10-100 mm in diameter) were identified as an increase in FDG uptake, whereas CT, transabdominal US, and endoscopic US depicted the foci in 31, 31, and 28, cases, respectively. Among 11 benign lesions, nine showed no increased FDG uptake (specificity = 82%). Specificities of the other modalities were lower. False-positive findings were obtained in a case of chronic active pancreatitis and in a serous cystadenoma. CONCLUSION: FDG PET, which provides "biochemical" information, is accurate in identifying pancreatic carcinoma and may be a method of choice when imaging equivocal masses detected with other "anatomic" imaging studies.

Adenocarcinoma↗

Intracellular Ca2+ dynamics and in vitro secretory response in acute pancreatitis induced by a choline-deficient, ethionine-supplemented diet in mice.

In order to approach impaired stimulus-secretion coupling in acute pancreatitis induced by a choline-deficient, ethionine-supplemented (CDE) diet in mice, the agonist-evoked intracellular Ca2+ dynamics of dispersed pancreatic acini were evaluated by microspectrofluorometry. Mice were fed a CDE diet for 24 or 48 h, and the pancreas was dispersed to the acini. The in vitro amylase secretion analysis of the CDE groups demonstrated a poor dose-response curve which was significantly lower (p < 0.01) when 100 pM cholecystokinin (CCK) was administered. Both in CDE and control groups, the application of a physiological dose of CCK-8 (10 pM) evoked intracellular Ca2+ oscillations. Periodicity and amplitude of the oscillations in the CDE groups were not significantly different. The administration of a higher dose of CCK-8 (100 pM) evoked a large, sharp, and transient rise in intracellular Ca2+, followed by a small, continuous increase above basal levels for the duration of stimulation both in CDE and control groups. The peak Ca2+ level was lower in the CDE groups, but this was not statistically significant. In conclusion, during the early phase (from 24 to 48 h) of CDE pancreatitis, the pattern of agonist-evoked intracellular Ca2+ release is less affected. Other mechanisms subsequent to the onset of intracellular Ca2+ release are likely to be involved in the inhibition of enzyme secretion.

Acute Disease↗

Value of fluorine-18-fluorodeoxyglucose and thallium-201 in the detection of pancreatic cancer.

UNLABELLED: This study compares the diagnostic value of 18F-FDG PET imaging and 201TI-SPECT imaging in patients with pancreatic cancer. METHODS: Twenty-five patients with histologically-proven pancreatic cancer were studied. Following PET transmission scanning, 3 mCi of 201TI were administered after patients had fasted overnight. Thallium-201-SPECT images were obtained 15 min later. Immediately after 201TI-SPECT imaging, 4 mCi of FDG were administered and PET images were obtained 60 min later. The PET and SPECT images were compared qualitatively and quantitatively. For quantitative analysis, 10 x 10 mm2 regions of interest (ROIs) were selected in areas of the tumor showing the highest tracer accumulation and in the normal pancreas. The tumor to nontumor activity ratio (T/N ratio) was calculated. RESULTS: Although both techniques delineated focal lesions with an increase in tracer accumulation in 16 patients, PET identified eight additional patients in whom 201TI-SPECT images did not visualize any lesion. Thus, FDG-PET provided significantly higher sensitivity (96%) than 201TI-SPECT (64%). Among the patients showing increased tracer accumulation, the T/N ratio was significantly higher with FDG-PET (3.24 +/- 1.27) than with 201TI-SPECT (1.77 +/- 0.37) (p < 0.0001). CONCLUSION: We conclude that FDG-PET has a larger clinical value for noninvasive detection of pancreatic cancer than 201TI-SPECT. If a PET camera is available, FDG-PET is considered to be the method of choice for the evaluation of patients with suspected pancreatic cancer.

Adult↗

Effect of the oral administration of sepimostat mesilate on cerulein induced acute pancreatitis in rats.

The effect of a potent protease inhibitor, sepimostat mesilate (CAS 103926-82-5, FUT-187), on acute interstitial edematous pancreatitis induced by a supramaximal dose of cerulein, a cholecystokinin (CCK) analogue, was evaluated. The serum amylase activity increased 18-fold over normal control after the infusion of cerulein at 5 micrograms/kg/h for 6 h. The serum lipase activity showed a 235-fold increase. An elevated pancreatic water content, pancreatic interstitial edema, inflammatory infiltration and vacuolization of the acinar cells were found. Redistribution of cathepsin B shifted from the lysosomal pellet fraction to the zymogen granule pellet fraction was noted in the early stages. All these parameters of pancreatitis mentioned above were inhibited by FUT-187 pretreatment at doses of 30 to 300 mg/kg. These observations suggest that FUT-187 inhibits the redistribution of cathepsin B shift from the lysosomal fraction to the zymogen fraction in cerulein-induced acute pancreatitis and improves the parameters of acute pancreatitis.

Acute Disease↗

Expression of sialosyl-Tn antigen (monoclonal antibody MLS102 reactive) in normal tissues and malignant tumors of the digestive tract.

Oncogenic transformation is often associated with changes in the glycosylation state of malignant cells. We investigated the immunohistochemical localization of sialosyl-Tn antigen [O-linked NeuAc(alpha 2-->6)GAINAc] using a novel monoclonal antibody MLS102 in normal and malignant digestive-tract tissues. In normal tissues, weak MLS102 immunoreactivity was observed in the epithelium of the esophagus, stomach and colon. However, MLS102 immunoreactivity was strong in the goblet cells of the duodenum, but not in the Brunner glands. In carcinomas of the esophagus, stomach, colon, pancreas and biliary tract, positive staining was detected with a high frequency (80%-100%). In mucinous carcinomas and signet-ring cell carcinomas, malignant cells themselves and the mucins they secreted were strongly positive for sialosyl-Tn antigen. There was no significant correlation between the frequency of expression of sialosyl-Tn antigen and the degree of differentiation (grade). However, in the case of well-differentiated adenocarcinomas, sialosyl-Tn antigen was found mainly in the supranuclear areas (Golgi area), on the apical surface and in the adjacent cytoplasm. In poorly differentiated adenocarcinomas, the antigen was often detected in the whole plasma membrane and cytoplasm. Therefore, monoclonal antibody MLS102 may be useful in further elucidating the characteristics of digestive-tract cancers, and possibly in their treatment.

Antibodies, Monoclonal↗

Assessment of the proliferative activity and radiosensitivity of human tumours using the cytokinesis-block micronucleus assay.

We established an in vitro cytokinesis-block micronucleus assay of human tumours for estimation of the proportion of cells undergoing mitosis (the dividing fraction, DF), the time for the number of nuclei to double and the radiosensitivity in terms of the micronucleus frequency, based on a concept described previously. Under certain conditions, the nuclear number doubling time (NNDT) was considered to represent the potential doubling time. Tumour specimens obtained at surgery were disaggregated into single-cell suspensions and were directly cultured in the presence of cytochalasin B with or without irradiation. At various intervals, the percentage of multinucleate cells (the plateau value represented the DF), the average number of nuclei per cell and the number of micronuclei in binucleate cells were determined. DF and NNDT values were obtained in 58 of the 73 tumours investigated, and the micronucleus frequency was obtained in 54 of these 58 tumours. The DF ranged from 4.1% to 71% and the NNDT ranged from 3.1 to 83 days. A DF > or = 20% was associated with a higher recurrence rate in patients undergoing curative operation. A correlation was found between the NNDT and the time to relapse in patients with recurrent disease. The average number of micronuclei per binucleate cell at 2 Gy of irradiation (after subtraction of the value at 0 Gy) ranged from 0.052 to 0.35. Tumours which produced more micronuclei after irradiation showed a better response to radiotherapy. This assay can be readily performed on human tumours and appears to have promise as a predictive assay for radiation therapy.

Adenocarcinoma↗

Immunohistochemical study of heparan sulfate proteoglycan in adenocarcinomas of the pancreas.

The prognosis for carcinoma of the pancreas is extremely poor. One of the characteristics of this tumor is its invasion of the surrounding tissues. Reduction of glycoprotein is considered to be conducive to invasion of the basement membrane by carcinoma cells. Heparan sulfate proteoglycan (HSPG), a kind of glycoprotein, is an important component of basement membrane. In this study, the relation between HSPG and carcinoma of the pancreas was examined by using the immunohistochemical method, and the survival rate of pancreatic adenocarcinoma was evaluated. We found that some carcinomas contained little or no HSPG. The poorer the differentiation of an adenocarcinoma of the pancreas, the lower was its content of HSPG. The level of HSPG was significantly different in carcinomatous and in noncarcinomatous cells. There was a close correlation among the content of HSPG, the degree of differentiation of carcinomas of the pancreas, and the survival time. HSPG seems to be useful in prognosis of adenocarcinoma of the pancreas.

Adenocarcinoma↗

Pancreatic exocrine secretion in short-term pancreatic duct obstruction induced acute pancreatitis in rats: an in vivo and in vitro study.

We investigated digestive enzyme release following a short-term pancreatic duct obstruction in rats. An in vivo experiment demonstrated that a 6-hour pancreatic duct obstruction reduced digestive enzyme release evoked both by endogenously released cholecystokinin (CCK) due to pancreaticobiliary diversion and by exogenous administration of CCK8. In vitro experiments also showed that pancreatic duct obstruction reduced the maximal CCK8-evoked amylase secretion. Amylase secretion evoked by the calcium ionophore A23187 and by phorbol myristate acetate was also markedly decreased. These data suggest that pancreatic duct obstruction probably interferes with the secretory process downstream of hormone receptor binding, intracellular Ca2+ release and protein kinase C activation.

Acute Disease↗

Platelet-activating factor involvement in the aggravation of acute pancreatitis in rabbits.

Platelet activating factor (PAF) was administered to anesthetized rabbits with cerulein-induced acute pancreatitis to investigate the role of PAF in the development of acute pancreatitis. In acute edematous pancreatitis, induced with cerulein 20 micrograms/kg/h i.v. for 5 h, blood flow in the gastroduodenal and superior mesenteric arteries (GDAF and SMAF) had decreased significantly by 30 min and the serum amylase and lipase levels were significantly increased in the early phase. In the cerulein+PAF group, in which PAF was injected 100 ng/kg/min i.v. for 20 min simultaneously with cerulein, GDAF and SMAF declined significantly to 52 +/- 4 and 47 +/- 3% (p < 0.05), serum amylase and lipase levels rose significantly to 1,110 +/- 150 and 1,370 +/- 190% (p < 0.01) at 300 min, much higher than in the cerulein group. Furthermore, scattered hemorrhages and more marked inflammatory cell infiltration were observed histologically. These findings suggest that PAF has an additive role in the aggravation of acute pancreatitis.

Acute Disease↗

Role of pancreatic blood flow and vasoactive substances in the development of canine acute pancreatitis.

To study the role of pancreatic blood flow and vasoactive substances in the development of acute pancreatitis, we measured portal vein blood levels of bradykinin, prostaglandin E2 (PGE2), histamine, serotonin, and pancreatic enzymes, and with an electromagnetic blood flowmeter we recorded gastroduodenal arterial flow (GDAF), superior mesenteric arterial flow (SMAF), and mean arterial blood pressure for 6 hr in dogs with acute hemorrhagic necrotizing pancreatitis induced by the retrograde injection of autologous bile (0.5 ml/kg) into the pancreatic duct. GDAF and SMAF decreased immediately in the early phase of acute pancreatitis (-17.8 +/- 6.1%** at 10 min and -15.8 +/- 7.1%* at 20 min; *P < 0.05, **P < 0.01); portal bradykinin concentration increased quickly (3.2 +/- 1.2 pM at 0 time, 16.2 +/- 5.2 pM* at 5 min, 30.4 +/- 4.8** pM** at 10 min, and 39.6 +/- 15.1 pM* at 20 min). Portal PGE2 concentration increased gradually after the induction of acute pancreatitis, and differences from the control group were significant at 20, 30, and 180 min (1426 +/- 175 pM at 0 time, 1956 +/- 273 pM* at 20 min, 2148 +/- 265 pM** at 30 min, and 3369 +/- 686 pM* at 180 min). Portal histamine and serotonin concentrations increased somewhat, but not significantly. These findings suggest that the injection of bile into the pancreatic duct causes the pancreas to quickly release a large amount of bradykinin into the portal vein, which immediately reduces the pancreatic blood flow in the early phase, thus accelerating the progress of acute pancreatitis.

Acute Disease↗

Pathogenesis of lupus dermatoses in autoimmune mice. XIX. Attempts to induce subepidermal immunoglobulin deposition in MRL/Mp- +/+ mice.

The deposition of immunoglobulin (Ig) at the dermo-epidermal junction (DEJ) of the skin, frequently observed in autoimmune mouse strains, is similar to that seen in patients with systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr (MRL/lpr) mice have an autosomal recessive mutant gene, lpr, which produces massive T-cell proliferation and accelerates the onset of autoimmune diseases. MRL/Mp- +/+ (MRL/n) mice lack the lpr gene, and do not develop autoimmune disease during the first year after birth under pathogen-free conditions. To verify the mechanisms of subepidermal Ig deposition in the skin of LE, we designed an experiment in which we could induce Ig deposition in the control MRL/n mice. Intraperitoneal injection of lymphoproliferative cells of aged MRL/lpr mice induced splenomegaly and splenic granulomatous angitis in the control MRL/n mice. Lipopolysaccharide (LPS), a polyclonal B-cell activator, induced slight splenomegaly and relatively high levels of serum Ig. Dermatopathological investigation revealed mild lymphocyte infiltration without positive Ig deposition at the DEJ of MRL/n mice treated with proliferative T cells. Injection of both proliferative T cells and LPS induced 50% positivity of subepidermal Ig deposition, and high levels of serum immunoglobulins and anti-double stranded DNA (anti-dsDNA) antibodies. These changes were not observed in MRL/n mice injected with thymocytes of newborn MRL/lpr mice. Skin lesions and lupus nephritis were not demonstrated in any of the mice tested. This study suggest that both the mild inflammatory reaction and the presence of anti-dsDNA antibodies are required for the induction Ig deposition at the DEJ in the skin of LE patients.

Animals↗

Nuclear DNA content as a prognostic predictor in carcinoma of the pancreas.

Eighty-six patients with carcinoma of the pancreas were studied retrospectively. Paraffin-embedded specimens and flow cytometry were used to evaluate the accuracy of the measurement of nuclear DNA as a predictor of the postoperative prognosis. From the series of 86 patients, 72 with a diagnosis of tubular adenocarcinoma (Japanese classification) were selected, and their DNA ploidy pattern and clinical and pathological features were correlated; 52.3% of the 86 patients and 52.8% of the 72 tubular adenocarcinoma patients showed DNA aneuploidy. Histological examinations of the tubular adenocarcinomas showed 42.9% DNA aneuploidy in well differentiated, 56.8% in moderately differentiated, and 71.4% in poorly differentiated types. The DNA ploidy showed a statistically significant positive correlation with the T category. The presence or absence of retroperitoneal invasion was thought to be the most important prognostic factor. Cumulative survival rates showed that the prognosis for patients with retroperitoneal invasion and DNA aneuploidy was significantly worse than for those with DNA diploidy or those without retroperitoneal invasion.

Adenocarcinoma↗

Bradykinin involvement in the aggravation of acute pancreatitis in rabbits.

This study was designed to investigate the role of bradykinin in the aggravation of acute pancreatitis. After injection of bradykinin 2 micrograms/kg to anesthetized rabbits with cerulein-induced acute pancreatitis, the pancreatic blood flow through gastroduodenal and superior mesenteric arteries (GDAF and SMAF) was determined with electromagnetic blood flow meters, the serum amylase level was measured, and pancreatic tissue was observed histologically. In rabbits treated with a supramaximal dose of cerulein alone (20 micrograms/kg/h), pancreatic blood flow was decreased and the serum amylase level was increased significantly by the early phase, and histological examination showed acute edematous pancreatitis. In rabbits treated with cerulein and bradykinin, GDAF and SMAF were significantly diminished at 300 min (51 +/- 5% and 50 +/- 4%, respectively, p < 0.05), and the serum amylase level rose significantly at 180 and 300 min (730 +/- 130% and 1,190 +/- 200%, respectively, p < 0.01) compared with rabbits treated with cerulein alone, and histological examination revealed pancreatic necrosis and greater inflammatory cell infiltration. These findings suggest that bradykinin has an additive role in the aggravation of acute pancreatitis.

Acute Disease↗

Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer.

To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity.

Adenocarcinoma↗

Effect of postischemic reperfusion on the pancreas.

In an examination of the effect of ischemia and reperfusion on the generation of active oxygen species during pancreatic cell damage, a short-term ischemia and reperfusion model was prepared by the occlusion and reperfusion of both the anterior mesenteric artery and the celiac artery in rats. Following 60 minutes of occlusion plus 7 hours of reperfusion of the anterior mesenteric artery and the celiac artery, the serum concentrations of amylase and lipase rose significantly to 7 and 6 times the respective control values. After 30 minutes of occlusion plus 7 hours of reperfusion, or after 7 hours of occlusion without reperfusion, amylase and lipase levels were not changed significantly. The continuous intravenous infusion of superoxide dismutase (3600 U/kg/hour) in rats receiving 60 minutes of occlusion plus 7 hours of reperfusion suppressed the rise in serum amylase and lipase values to 25 percent of the values in the non-injected group. These results suggest that the active oxygen species which are generated by the short-term ischemia and reperfusion method injure the endothelium and cause hyperamylasemia and hyperlipasemia. Inhibition of the rise in serum amylase and lipase concentrations by pretreatment with a scavenger of active oxygen, superoxide dismutase, suggests that the active oxygen species are involved in the pathogenesis of acute pancreatitis.

Amylases↗

Flow cytometric analysis of nuclear DNA content of duct cell carcinoma of the pancreas.

BACKGROUND: This study was designed to evaluate the efficacy of nuclear DNA content analysis in determining the prognosis of carcinoma of the pancreas. METHODS: Resected and paraffin-embedded specimens from 72 patients with duct cell carcinoma of the pancreas were examined, and flow cytometry was used to explore the relationship between DNA ploidy and TNM classification or histologic grade. RESULTS: DNA aneuploidy was found histologically in 42.9%, 56.8%, and 71.4% of Grade 1, 2, and 3 tumors, respectively. DNA ploidy showed a statistically significant correlation with T category and retroperitoneal invasion. The cumulative survival rate of patients with retroperitoneal invasion was shorter than that of those without retroperitoneal invasion. Among the patients with retroperitoneal invasion, those with DNA aneuploidy had a significantly shorter survival time than did those with DNA diploidy. CONCLUSIONS: The DNA ploidy pattern, in combination with the presence or absence of retroperitoneal invasion, appears to be useful in predicting the prognosis for duct cell adenocarcinoma of the pancreas.

Adult↗