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Biomedical subjects

T Tobe

Publications and source records attributed to T Tobe.

At least 217 records · Page 12Linked to original sources
PubMed1991

Non-parallel secretion of pancreatic amylase and trypsinogen following hepatectomy in rats.

To explore the changes in exocrine pancreatic function in the stages of active regeneration and recovery after hepatectomy, we measured the caerulein-stimulated amylase and trypsinogen output in anesthetized rats 4 days and 8 days after about 70% hepatectomy. Both 4 days and 8 days after hepatectomy, the amylase output was significantly greater than in the control groups. On the other hand, 4 days after hepatectomy, the trypsinogen output was almost the same as in the control groups, and 8 days after hepatectomy, it was significantly lower than in the control groups. Thus, the secretion of amylase and trypsinogen 8 days after hepatectomy was not parallel. The amylase content of the pancreas was significantly larger after hepatectomy than in the control groups, but the trypsinogen content was significantly smaller. These results indicate a non-parallel secretion of pancreatic digestive enzymes, as well as differences in the functions of the acinar cells after partial hepatectomy, and the important role of amylase in glucose metabolism after hepatectomy.

Amylases↗
PubMed1991

[Protein-free culture of esophageal cancer cell lines].

We have established 13 esophageal cancer cell lines capable of growing in a protein-free environment. The growth of these cells was not affected by conditioned medium, but the growth of NIH3T3 cells and human fibroblasts was stimulated by conditioned medium. On the other hand, conditioned medium inhibited the growth of human endothelial cells. Amplified int-2 oncogene correlated well with the growth of cells in a protein-free environment but the number of EGF receptors and growth effect of EGF did not relate to such growth. Esophageal cancer cells grow automatically, possibly involving mesenchymal cells via the paracrine system. This results in a poor prognosis in patients.

Cell Division↗
PubMed1991

[Problems of clinical trials as viewed in the perspective of decision theory].

In this paper, the current clinical trial based on the Neyman-Pearson's principle of hypothesis testing is reviewed in the perspective of decision theory, its shortcomings are revealed and alternative methods proposed. In the current trial design, the alpha error is arbitrarily fixed at a level (e.g., 0.05), even lower than the beta error level (0.1 or 0.2). This results in failure with smaller trial size to identify the better treatment, dose-patient interaction, or optimal patient stratum for treatment. If on the other hand, the most harmless alpha error is ignored, the total number of patients expected to be cured can be substantially increased due to earlier identification of the better treatment. In case treatment, A has some disadvantages compared with B in terms of cost, toxicity etc., then the null hypothesis should be changed to "the cure rate of A is greater than that of B by delta", an adjustment for the disadvantages, which can be estimated by utility analysis. The loss to the society and target population may be further increased if improper regimen is provided including omission of the best treatment arm, suboptimal treatment intensity, selection of improper patient stratum, failure to individualize treatment plan (inflexible regimen). In order to maximize the benefit of our patients and society, radical changes of the current clinical trial design is needed using decision analytical approach.

Antineoplastic Agents↗
PubMed1991

[Effects of CR1505, a CCK antagonist, on pancreatic growth in hamsters].

The effects of CR1505, a CCK antagonist, on CCK-stimulated and normal pancreas were studied in Syrian golden hamsters. The CCK-stimulated trophic effect was inhibited by CR1505 in a dose-dependent manner, in which CR1505 100 mg/kg bw resulted in a complete inhibition of the weight of pancreas, the total pancreatic protein and DNA contents, compared to the control. Otherwise, CR1505 administration in doses of 25, 50, 100 mg/kg bw alone, didn't induce any significant changes among CR1505-treated groups and the control one. However, in the dose of 200 mg/kg bw, the weight of pancreas, the total pancreatic protein and DNA contents were significantly lower than control levels, suggesting pancreatic atrophy in the hamster. It's concluded that CR1505 is an effective CCK receptor antagonist that could inhibit the CCK-induced pancreatic trophic effect. Furthermore, CR1505 administration to normal pancreas brought out pancreatic atrophy, indicating that CCK seems to play an important role in the maintenance of normal pancreatic growth in hamsters.

Animals↗
PubMed1991

Relationship between glucose tolerance and quantitative changes of islet cells in chronic obstructive pancreatitis due to pancreatoduodenal cancer.

This study was conducted to clarify the relationship between indicators of preoperative glucose tolerance and quantitative changes of endocrine cells in the islet of Langerhans in patients with chronic obstructive pancreatitis due to pancreatoduodenal cancer. Twenty-one specimens of pancreatic tissue obtained from patients who underwent pancreatoduodenectomy or total pancreatectomy for pancreatoduodenal cancer were divided into four groups according to the degree of fibrosis (Grades 0-III). Islet cells in serial sections were stained immunohistochemically to determine the proportions of B-, A-, D-, and PP-cells in the islets of Langerhans. In patients with pancreatic tissue with the most severe fibrosis, of several preoperative glucose metabolism indices measured, it was found that the ratio of integrated value of change in serum insulin to that of serum glucose (sigma delta IRI:sigma delta BS) was significantly decreased. There was a significant positive correlation between proportion of B-cells, and both the ratio of change in insulin to that of glucose (delta IRI:delta BS) and sigma delta IRI:sigma delta BS. On the other hand, there was a significant negative correlation between proportion of A-cells and sigma delta IRI:sigma delta BS. The present data strongly suggest that it is possible to estimate the degree of fibrosis and to quantify changes of the islet cells prior to surgery in patients with obstructive pancreatitis due to pancreatoduodenal cancer by calculating these glucose metabolism indices, and that sigma delta IRI:sigma delta BS is a particularly useful index.

Chronic Disease↗
PubMed1991

[Indices of the malignancy of cancer--is it possible to predict the recurrence or metastasis of cancer?].

The following 3 points are important clinical problems to be resolved in the management of cancer: 1. Are there any useful procedures in the diagnosis, treatment or prevention of recurrence or metastasis of cancer? 2. Can the recurrence or metastasis of cancer be predicted? 3. Are there any parameters which reflect the degree or grade of malignancy of cancer? For the diagnosis of recurrence or metastasis, tumor markers and imaging MRI are useful, especially for colorectal cancer. Radical extended resection can lead to good survival even though the tumor recurs. A randomized prospective study of 1011 gastrectomized cancer patients treated with oral OK432 showed significantly good results, especially in n(+) cases with curative resection. Prognostic stratification and risk assessment by computer analysis using Akaike Information Criteria (AIC) showed that cancerous invasion of subserosal veins (Vd) was the most important risk factor for liver metastasis of colorectal cancer. In predicting the recurrence or metastasis of cancer computer analysis by AIC appears to be a useful procedure. DNA ploidy patterns demonstrated by flow cytometry and oncogene analysis of tumor tissue have been reported and discussed as possible indices of the grade of malignancy.

Digestive System Neoplasms↗
PubMed1991

[Changes in lysosomal enzyme and fragility of pancreatic acinar cells in hepatectomized rats].

To explore the cellular and lysosomal fragility of pancreatic acinar cells in both the early and recovering stages after partial hepatectomy, we evaluated the changes in the pancreatic water content, redistribution of lysosomal enzyme, lysosomal fragility in acinar cells, and lactate dehydrogenese (LDH) discharge from acinar cells 4 days and 8 days after about 70% hepatectomy in rats. In the early stage (4 days) after hepatecotmy, the pancreatic water content was significantly greater than that in sham-operated or normal rats. Both the LDH discharge and lysosomal fragility were also significantly higher than those in the sham-operated and normal rats. Redistribution of lysosomal enzyme was also found in this early stage. In the recovering stage (8 days) after hepatectomy, these parameters tended to return to the preoperative levels (normal rats). These results indicate that the cellular fragility of acinar cells is increased in the early stage after hepatectomy. Lysosomal fragility seems to be related to this cellular fragility of acinar cells in the early stage after hepatectomy.

Animals↗
PubMed1991

[A case report of liver metastasis from rectal cancer effectively treated with intravenous infusion of cisplatin alone].

A 49-year-old man with liver metastasis from rectal cancer was treated with cisplatin (CDDP) alone. Cisplatin was administered intravenously 3 times at a dose of 50 mg (31 mg/m2). He achieved an excellent PR (94% decrease) as determined by CT scanning, and plasma CEA level decreased from 37 to 2.2 ng/ml. The side effects were nausea, vomiting, and reflux esophagitis, but neither leucopenia nor renal dysfunction was observed. As a result, a radical operation could be undertaken.

Adenocarcinoma↗
PubMed1990

Differentiation-dependent expression of I and sialyl I antigens in the developing lung of human embryos and in lung cancers.

The localization of two carbohydrate antigens, I and sialyl I antigens, in the lungs of developing human embryos was investigated using specific monoclonal antibodies and compared with the distribution patterns of the known embryonic antigen, stage-specific embryonic antigen-1 (Lex hapten). When the future bronchi were actively developing from the bronchial buds in the lungs of 50- to 53-day-old embryos, the immature bronchial bud cells were I-, Lex+, while the fully differentiated epithelial cells of the larger bronchus were I+, Lex-. When the bronchiolar bud cells matured into bronchiolar epithelial cells in the lung of a 12-week-old embryo, the immature bronchiolar bud cells were I-,Lex+, while the fully differentiated epithelial cells of the bronchioles were I+,Lex-. Sialylated forms of the antigens finally appeared in the lungs of 18-week-old embryos, when the terminal bud cells actively proliferated and underwent the differentiation process into epithelial cells of alveoli and alveolar ducts. The immature terminal bud cells at this stage were I-, sialyl I-, Lex+, sialyl Lex-i+, while the fully differentiated alveolar epithelial cells were I+, sialyl I+, Lex-, sialyl Lex-i-. After 8 months, the flattened mature alveolar epithelial cells were strongly positive for both I and sialyl I antigens, the strong expression of which continued after birth and even into the adult stage. These distribution patterns indicate that the I and sialyl I antigens are specific markers for the differentiated type cells in each stage of development, while Lex and related embryonic antigens were specific to the immature bud cells in every stage. The above-described differentiation-dependent expression patterns of these antigens seem to be reflected in the distribution of these antigens in human lung cancers, i.e., I and sialyl I antigens were expressed in lung cancer cells more weakly than in normal lung cells, while the Lex and sialyl Lex-i were expressed in cancer cells much more strongly than in normal lung cells. This was further reflected in the serum levels of these antigens in the patients with respiratory disorders. The distribution pattern of the serum levels of these antigens in patients with lung cancers showed sialyl Lex-i greater than sialyl I, indicating that these serum antigens originated from the lung cancer lesion where sialyl Lex-i is much more dominant than sialyl I antigen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1990

Effect of heat treatment on tumor cells and antitumor effector cells.

We examined the effects of heat treatment on tumor cells and antitumor effector cells in order to investigate the combined effects of hyperthermia and immunotherapy including adoptive immunotherapy. Plasmacytoma MOPC104E syngeneic to BALB/c mice was used as the tumor cell line, while fresh spleen cells immunized to MOPC104E (IM-FSC) and interleukin-2-cultured lymphocytes induced in vitro from IM-FSC (CL) were used as the effector cells. Tumor cells or effector cells were heat-treated in a water bath at 42 degrees C for 30 or 60 min. Tumor cells heat-treated at 42 degrees C for 30 min grew temporarily and then regressed in the tumor transfer test, whereas untreated tumor cells showed no regression under any conditions. Furthermore, fresh spleen cells of mice inoculated with heat-treated tumor cells from regressed tumors showed marked tumor-neutralizing activity. The antitumor effects of CL were markedly inhibited by heat treatment according to the results of the tumor-neutralizing test and the 51Cr release assay, whereas heat treatment had little influence on the antitumor activity of IM-FSC. However, the neutralizing activity of effectors and the killing activity of CL against heat-treated tumor cells were both markedly augmented, since the susceptibility of the tumor cells to the antitumor effector cells was augmented by heat treatment. These results suggest that heat treatment of tumor cells augments the antitumor effects of IM-FSC and CL, hence we speculate that hyperthermia augments the effects of immunotherapy including adoptive immunotherapy.

Animals↗
PubMed1990

Lysosomal redistribution and increased fragility of pancreatic acinar cells in early stage after hepatectomy in rats.

To explore the cellular fragility of pancreatic acinar cells in the early stage after partial hepatectomy, we evaluated the subcellular redistribution of lysosomal enzyme, lysosomal fragility in acinar cells, lactate dehydrogenase (LDH) discharge from acinar cells and the pancreatic water content in rats 4 days after about 70% hepatectomy. Following hepatectomy, there was redistribution of lysosomal enzymes, and more cathepsin B in zymogen pellets (1.3 KP) and less cathepsin B in lysosomal pellets (12 KP) than in sham-operated or normal rats. Soluble cathepsin B activity and LDH discharge also increased significantly after hepatectomy. The pancreatic water content was significantly increased after hepatectomy. These results indicate that the fragility of acinar cells increased in the early stage after hepatectomy.

Animals↗
PubMed1990

Sandwich ELISA assay for quantitative measurement of SP-40,40 in seminal plasma and serum.

SP-40,40 was purified from human plasma by PEG fractionation, DEAE-Sephacel, Phenyl-Toyopearl 650M, Bio-Gel A-0.5m and hydroxylapatite chromatographies. Three monoclonal antibodies (IF12, IID9 and IVF4) to this protein were prepared: IF12 and IID9 were specific for the beta subunit and IVF4 for the alpha subunit. The concentrations of SP-40,40 in seminal plasmas and sera were determined using a sandwich ELISA method. The results showed that the average concentrations of SP-40,40 were 438 +/- 285 micrograms/ml in seminal plasmas and 111 +/- 50 micrograms/ml in sera of normal donors. SP-40,40 concentrations in seminal plasmas of Klinefelter and excretory azoospermia patients were similar to those of normal donors. However, those of oligozoospermia and idiopathic azoospermia patients were about half the normal value.

Animals↗
PubMed1990

[Changes of parotid gland in rat caerulein-induced acute pancreatitis: study on in vitro system].

To explore the relationship between exocrine pancreas and parotid gland, we measured the changes of parotid gland in in-vitro system at an acute pancreatitis induced by supramaximal dose of caerulein (5 micrograms/kg/h for 3.5 hours) in rats. Both the serum amylase levels and parotid gland amylase content in rats with acute pancreatitis increased significantly compared with normal rats. The dry/wet weight ratio also decreased significantly and LDH discharge from parotid acini as well as lysosomal enzyme leakage from lysosomes in acini increased significantly compared with normal rats. In addition, redistribution of lysosomal enzyme in parotid acini was seen in acute pancreatitis. These results indicate the edema and congestion of amylase in parotid gland, and furthermore the increased cellular and lysosomal fragility of parotid gland at an acute pancreatitis. Thus, there seems to be the intimate organ relationship between exocrine pancreas and parotid gland as well as the important roles of gut hormones such as caerulein in the pathophysiology of parotid gland.

Acute Disease↗
PubMed1990

[A double blind study to evaluate the optimal dose and its frequency for oral administration of OK-432 (picibanil) by immunological parameters (the 2nd report)].

The present study was designed to determine the optimal dose and frequency of oral administration of a biological response modifier, OK-432 (Picibanil), which has been used for cancer immunotherapy by injection. Ninety one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40KE, once or 3 times a week before operation (5KE X 1/W, 20KE X 1/W, 40KE X 1/W, or X 3/W). Misregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. In the 1st report, we already showed that 5KE X 3/W might be the optimal regimen to augment the natural killer (NK) activity of regional lymph node lymphocyte (RNL). In the 2nd report, we searched for the optimal regimen to augment the antitumor immunity of T lymphocytes. The proliferative response of RNL to SuPR (protein derived from OK-432) was augmented in all the groups administered OK-432. The responsiveness of PBL to autologous tumor extract enhanced by IL-2 was augmented by 5KE X 1/W, and that of RNL was augmented by 5KE X 3/W. The killer/suppressor (Leu2+15-/Leu2+15+) ratio in RNL increased in all the groups administered OK-432 especially in 20KE X 3/W group. Oral administration of OK-432 augmented both non-specific and the specific antitumor immunity of PBL as well as RNL, and 5KE X 3/W may be the optimal regimen to augment the antitumor immunity, especially of RNL.

Administration, Oral↗
PubMed1990

Soluble factors including proteinases released from damaged cells may trigger the wound healing process.

The wound healing process is initiated as soon as tissue is injured. Herein, we demonstrate that c-fos and c-myc mRNA transcripts are promptly increased in the wounded tissue in vivo and in vitro. A buffer solution from scraped serum-starved quiescent fibroblasts, when added to resting fibroblasts, caused the increase of c-fos and c-myc mRNA among the indicator cells. Soluble factors contained in the wounding supernatant are responsible for these phenomena and we call them wounding factors. Addition of proteinase inhibitors to the culture medium drastically reduced the c-fos mRNA induction by the wounding factors. Exogenously added trypsin or thrombin mimicked the activity of wounding factors. These results suggest that wounding causes soluble factors including various proteinases to be released from the damaged cells, which trigger the adjacent cells to respond to the injury.

Animals↗