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Biomedical subjects

F Koba

Publications and source records attributed to F Koba.

At least 19 recordsLinked to original sources

Effects of exposure to hypobaric-hypoxia on body weight, muscular and hematological characteristics, and work performance in rats.

The metabolic activities of skeletal muscles were studied in male rats exposed to hypobaric-hypoxia at about 550 Torr for 8 h per day for 2 weeks. Rats were divided into three groups; control (normoxic control), diurnal hypoxic (DH) exposure, and nocturnal hypoxic (NH) exposure groups. The changes in body weight and daily diet intake of the NH group were lower than the other groups (p < 0.01). The weights of fat in the abdominal cavity of both NH and DH groups were less than that of the control group. The red blood cell count, hemoglobin concentration, and hematocrit values were significantly increased in the hypoxic groups. The plasma glucose level in the NH group was significantly less than the control group (p < 0.05). The lactate dehydrogenase/citrate synthase (LDH/CS) activity ratios in the skeletal muscle tended to be lower in both hypoxic groups than in the control group. The swimming times to exhaustion at mild and high intensities that were measured after 2 weeks, loaded with a weight equivalent to 2.5% of the body weight, improved in the DH group. There were insignificant differences in the metabolic activity of skeletal muscles and blood characteristics between the NH and DH groups, but endurance swimming times in the DH group tended to be improved as compared to the NH group. We conclude that the DH group became competent in endurance work, which is believed to be driven from the combined effects of increased O2 transport capacity of the blood and enhanced O2 utilization capability by mitochondrial enzyme activity.

Animals↗

Expression of ornithine decarboxylase mRNA in gastric carcinoma.

BACKGROUND: Ornithine decarboxylase (ODC) is a key rate-limiting enzyme in polyamine biosynthesis. Several studies using an enzyme assay revealed that the ODC activity was higher in tumor tissue than in normal tissue. However, there is little information on the mRNA status of ODC in surgical specimens. ODC is a transcriptional target gene of c-myc. METHODS: cDNA was obtained by reverse transcription (RT) from fresh specimens of 56 surgical pairs of primary gastric carcinomas and corresponding normal tissue specimens. The ODC and c-myc mRNAs were subsequently detected by means of the polymerase chain reaction. The tumor/normal (T/N) ratio of ODC expression was calculated after correcting for glyceraldehyde-3-phosphate dehydrogenase as an internal control. The T/N ratio of ODC was plotted against that of c-myc. RESULTS: The corrected expression levels of ODC mRNA in the tumor were greater than those of the normal mucosa in 36 of 56 cases (64%). The cases of tumor with vascular vessel invasion showed a higher T/N ratio than those without vascular invasion (P < 0.01). Similarly, female patients showed a higher T/N ratio than male patients (P < 0.01). There was a significant correlation between the expressions of both ODC and c-myc genes (P < 0.05). CONCLUSIONS: The findings imply that (1) overexpression of ODC mRNA in tumor tissue may correlate with aggressive biologic behavior, such as vascular vessel invasion, and (2) there is an intimate correlation between ODC and c-myc genes.

Base Sequence↗

Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma.

The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (greater than or equal to 43%) was significantly better, as compared to that of patients with low cytotoxicity (less than 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL2 (greater than or equal to 1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection.

Cytotoxicity, Immunologic↗

[Combination chemo-endocrine therapy of metastatic and stage IV breast cancer with cyclophosphamide, adriamycin, prednisolone and tamoxifen (CAPT)--with special reference to management of brain and liver metastasis].

Sixty-three evaluable patients with metastatic and stage IV breast cancer who had not previously undergone chemo-endocrine therapy were treated with a combination chemoendocrine therapy regimen consisting of cyclophosphamide 100 mg p.o. every day, adriamycin 10 mg i.v. on day 1 to 5, prednisolone 10 mg or 20 mg (20 mg was given on day 1 to 5) p.o. every day, and tamoxifen 20 mg p.o. every day. Adriamycin on day 1 to 5 was repeated three times every two weeks. After a total dose of 150 mg of adriamycin, the patients were changed to maintenance therapy consisting of cyclophosphamide 100 mg p.o., prednisolone 10 mg p.o. and tamoxifen 20 mg p.o. every day. After 72 months of the treatment there were 61 patients good for evaluation, 13 patients achieved a complete response (21.3%) with a median survival of 30.5 months and 18 patients had a partial response (29.5%) with a median survival of 21.0 months, and 30 patients failed to respond (49.2%) with a median survival of 8.5 months. There was a significant difference in survival time between responders (CR + PR) and non-responders (NC + PD) (p less than 0.001). Responses by site were seen in lung 10/18 (55.6%), liver 3/6 (50.0%), brain 2/4 (50.0%), bone 6/17 (35.3%) and soft tissue 14/24 (56.3%). A Satisfactory response for brain and liver metastasis, which are usually viewed as a sign of grim prognosis, was obtained similar to other sites of metastasis. Retreatment with CAPT, which was attempted in patients with secondary brain metastasis who responded to CAPT for initial brain metastasis, was uniformly effective. High ration of androgen to corticosteroid, positive estrogen receptors, long disease-free survival (over two years), premenopausal, high Broca' index (above 110) resulted from the chemo-endocrine therapy regimen CAPT. Toxicity was minimal and consisted of nausea, vomiting, alopecia and leucopenia.

Adult↗

Cell-mediated cytotoxic activity of spleen cells from patients with gastric carcinoma.

The cell-mediated cytotoxic activities of cells from the spleens (SP cells) of patients with gastric carcinoma were assayed in comparison with the activities of peripheral blood mononuclear cells (PBM cells) from the same patients, and from patients with benign lesions. The natural killer cell (NK) activity of the SP cells and their capacity to generate allogeneic cytotoxicity in mixed lymphocyte culture (MLC) were very similar to those of the PBM cells. The cytotoxic activity of SP cells induced by alloactivation in MLC, however, was significantly higher than that of the PBM cells from the same patient as well as from patients with benign lesions. The production of interleukin 2 (IL 2) and the ability to induce cytotoxic cells after activation with IL 2 (LAK) were therefore examined. Both the ability to produce IL 2 and to generate LAK cells were shown to be significantly increased in SP cells when compared to PBM cells. These results indicate that the spleen may be a potential reservoir for the precursors of these activated killer cells in patients with gastric carcinoma. Furthermore, it may play an important role in the defence against tumors in these patients.

Antibodies, Monoclonal↗

A trial of postoperative adjuvant combination chemo-immunotherapy for stage IV gastric carcinoma.

A chemo-immunotherapy program was designed on the basis of our clinical findings, which revealed that the ability to generate cell-mediated cytotoxicity was remarkably augmented after adriamycin (AM) administration in cancer patients. Twenty patients with stage IV gastric carcinoma who had undergone noncurative resections were treated with the above regimen that consisted of active immunotherapy with autologous tumor cells, in combination with 30 mg of AM, given 7 days before the immunization, followed by long-term tegafur (FT) and immunomodulators. The survival of these patients was compared to that of 3 other groups of patients, namely; 30 patients treated with another chemo-immunotherapy regimen which comprised autologous tumor cells in combination with several anticancer drugs followed by long-term FT and immunomodulators (CCI1), 17 patients treated with mitomycin C followed by long-term FT and immunomodulators (CI), and 24 patients with comparable histories (HC). The first treatment group had significantly improved survival, as compared to the HC group (p less than 0.01) and the survival tended also to be more favorable, when compared to the CCI1 group (p less than 0.2) or the CI group (p less than 0.2). Moreover, the survival rate at 9 months was significantly higher than that of either the CCI1 group (p less than 0.01) or the CI group (p less than 0.01).

Adjuvants, Immunologic↗

'Two-route chemotherapy' using intra-arterial cisplatin and intravenous sodium thiosulfate, its neutralizing agent, for hepatic malignancies.

Seventeen patients with primary or metastatic malignancy in the liver were treated with 'two-route chemotherapy' (TRC). One course of this TRC consisted of hepatic artery infusion of cisplatin, 120 mg/m2, in combination with concurrent intravenous administration of sodium thiosulfate, its neutralizing agent, at a dose of 9.0 g/m2 by a rapid push, followed by 1.2 g/m2/h by continuous infusion for 6 h. Five of 11 (45%) hepatocellular carcinoma and two of six (33%) metastatic tumors achieved partial response. Although almost all patients experienced nausea or vomiting, severe side-effects, including nephrotoxicity, peripheral neuropathy or ototoxicity, were not encountered. Myelosuppression was observed in one patient after seven courses of this TRC. The results indicate that TRC may be relatively effective against hepatic malignancies in patients without severe toxicity.

Aged↗

Cell-mediated cytotoxic activity of regional lymph node cells from patients with gastric carcinoma.

The cell-mediated cytotoxic activities of cells from the perigastric lymph nodes (LNC) were assayed in patients with gastric carcinoma. These activities were compared with those of the peripheral blood mononuclear cells (PBM), and also with the LNC of patients with benign lesions. The capacity of LNC to be converted to cytotoxic cells in mixed cell culture was significantly impaired in the cancer patients as compared to that of either the PBM from the same patient, or the LNC from patients with benign lesions. The natural killer cell (NK) activity of LNC was significantly lower than that of the PBM in both groups of patients. The cytotoxic activity induced by phytohemagglutinin activation (PAK) in the LNC from patients with carcinoma, as well as from those with benign lesions was also significantly decreased, when compared to that of the PBM, although the ability of LNC to produce interleukin 2 (IL 2) was significantly increased. The ability of these cells to generate cytotoxicity after activation with IL 2 (LAK) was therefore examined, and a decreased capacity in LNC was observed. These results indicated that the ability of T cells in LNC to develop into cytotoxic cells in patients with gastric carcinoma was impaired, and that the nonspecific cytotoxicity, including NK or PAK, as well as LAK activity, was essentially low in the perigastric lymph nodes.

Carcinoma↗

Production of interleukin 2 by human lymph nodes.

Perigastric lymph node cells (LNC) from patients with gastric carcinoma or benign lesions were tested for interleukin 2 (IL 2) production upon stimulation with phytohemagglutinin (PHA), in comparison with that of peripheral blood mononuclear cells (PBM) or spleen cells (SPC). IL 2 activity in the supernatants of LNC cultures from patients with either carcinoma or benign lesions was significantly higher than that of PBM cultures from the same person. There was no significant difference in IL 2 activity between PBM cultures or LNC cultures from patients with carcinoma and patients with benign lesions. Supernatants from LNC cultures were also more active than those obtained from SPC cultures. The production of interleukin 1 (IL 1) in LNC was lower than that in PBM. In LNC, the proportion of OKT3+ cells was similar to that found in PBM, with a prevalence of OKT4+ cells over OKT8+ cells. No differences were found between lymphatic cells from patients with carcinoma and from patients having benign lesions.

Humans↗

Natural killer cell activity in the perigastric lymph nodes from patients with gastric carcinoma or benign lesions.

Natural killer cell (NK) activity against K-562 myeloid cell line was evaluated in the perigastric lymph nodes from 60 patients with gastric carcinoma and from 35 patients with benign lesions. Lymph node cells (LNC) in either group of patients showed significantly lower level of NK activity when compared to that in peripheral blood mononuclear cells (PBM) from the same patient. In LNC, the proportions of Leu-7+ and Leu-11+ cells were significantly lower than those in PBM. In addition, LNC contained a cell population, presumably nonadherent and OKT3+ cells, which exhibit suppressor function toward NK activity of autologous PBM. These results indicate that the relative inactivity in the perigastric lymph nodes may be partially attributable to the low level of mature effector cell population mediating NK activity and, at least in part, to a coexistent population of suppressor cells.

Carcinoma↗

Activated killer cell activity of spleen cells from patients with gastric carcinoma.

The activated killer cell activity of spleen cells (SPC) from patients with gastric carcinoma were assayed in comparison with those of peripheral blood mononuclear cells (PBM) from the same patient or patients with benign lesions. The cytotoxic activity induced by alloactivation in mixed lymphocyte culture (MLC) of SPC was significantly higher than that of PBM from the same patient as well as from patients with benign lesions. The cytotoxicity induced by phytohemagglutinin (PHA) activation of SPC was also significantly higher than that of PBM from the same patient. Therefore, the productibility of interleukin 2 (IL2) and the ability to generate cytotoxic cells after activation with IL 2 (LAK) were examined. Subsequently, it was found that the ability of SPC to produce IL 2 and to induce LAK cells was significantly greater than that of PBM. The results indicate that the spleen may be a potential reservoir of the precursors of these activated killer cells in patients with gastric carcinoma.

Carcinoma↗

Activated killer cell activity in lymph nodes.

The activated killer cell activity of cells from the perigastric lymph nodes (LNC) in patients with gastric carcinoma or benign lesions was assayed in comparison with that of peripheral blood mononuclear cells (PBM). The cytotoxic activity induced by phytohemagglutinin (PHA) activation in LNC from patients with either carcinoma or benign lesions was significantly decreased as compared to that in PBM, although the ability to produce interleukin 2 (IL 2) in LNC was significantly increased. Therefore, the ability to generate cytotoxic cells after activation with IL 2 was examined, and decreased capacity in LNC was observed. In LNC, the proportion of OKT3+ cells was similar to that in PBM, with a prevalence of OKT4+ cells over OKT8+ cells. Also, the percentage of Leu-11+ cells was remarkably reduced. The results indicated that decreased levels of the activated killer cell activity, which might be partially attributable to the composition of lymphocyte subsets, existed in lymph nodes, and this might facilitate tumor metastasis to the regional lymph nodes.

Cytotoxicity Tests, Immunologic↗

Depression of the generation of cell-mediated cytotoxicity in regional lymph nodes of patients with gastric carcinoma.

The capacity to generate cytotoxic cells in mixed cell culture was studied on the regional lymph node cells (LNC) from patients with gastric carcinoma, in comparison with that of the similar lymph node cells from patients with benign lesions. Generation of cytotoxic cells in LNC from cancer patients was significantly depressed, as compared to either that in peripheral blood mononuclear cells (PBM) from the same patient or that in LNC from patients with benign lesions, whereas no significant difference between those in PBM and LNC was observed in patients with benign lesions. The addition of LNC from cancer patients to autologous PBM did not result in suppression of the cytotoxic response. There was no significant difference between the ability to produce interleukin 2 (IL 2) in LNC from patients with carcinoma and benign lesions. However, OKT11+ and OKT3+ cells in LNC from cancer patients were significantly decreased without any alteration of the OKT4/OKT8 ratio, as compared to that from patients with benign lesions. In contrast, B-1+ cells were significantly increased. These results indicated that the relative inactivity of the generation of cytotoxic effector T cells in LNC from patients with gastric carcinoma might be partially related to the reduction of T cell population in the regional lymph nodes.

Cholelithiasis↗

Enhanced chemosensitivity of cells from malignant effusions under condition of exposure to high temperature.

Utilizing a clonogenic assay, the effects of hyperthermia and selected chemotherapeutic drugs on growth of cells from malignant effusions were studied. Fourteen of 25 samples obtained from 25 patients with various carcinomas formed at least 30 colonies per plate. Exposure of the cells to heat at 42 degrees C for 1 hr before the plating slightly inhibited the colony growth. The drugs, adriamycin (AM) and mitomycin C (MMC), were tested at 3 different concentrations. When the cells were treated with these two drugs for 1 hr at 42 degrees C, the percent of surviving colonies was significantly decreased, as compared to findings at 37 degrees C, in both groups, at 3 different concentrations. The combination of drugs and hyperthermia appeared to function synergistically in one-third of such cases. These results suggest that cells from malignant effusions in patients with various carcinomas were more sensitive to AM or MMC, under condition of a higher temperature (42 degrees C).

Ascitic Fluid↗

In vitro effect of interleukin 2 on depression of cell-mediated immune response after surgery.

Effect of exogenous interleukin 2 (IL 2) on the postoperative depression of cell-mediated immune response in vitro was studied in 8 patients with benign lesion and 11 patients with various carcinoma, undergoing major surgical procedures. When peripheral blood mononuclear cells (PBM) were obtained from patients 3 days after surgery, the proliferative response of PBM in mixed lymphocyte culture (MLC) was significantly decreased, as compared to that before operation. The depressed proliferative response was significantly increased and improved to the preoperative level, when exogenous IL 2 was added at a concentration of 50 per cent in culture. The defective generation of cytotoxic cells in MLC 3 days after operation was also significantly augmented and improved to the preoperative range by addition of 25 per cent IL 2 in culture. IL 2 produced minimal increase in these responses when PBM were obtained preoperatively. There was no significant difference between each value in these responses obtained from patients with benign lesion and carcinoma. These results show that PBM from patients who had undergone major surgery were responsive to exogenous IL 2. The postoperative depression of cell-mediated immune response may be reversible with exogenous IL 2.

Carcinoma↗

A multiple regression analysis of hemoglobin values and iron status in Japanese farmers.

The authors performed multiple regression analysis of hemoglobin values and the parameters related to iron dynamics. The subjects consisted of 37 farmers whose Hb, Ht, GB, SI, %-St, SFR and FEP was examined once a month for one year. 19.2% of the female farmers had anemia of which 73.8% was iron-deficiency anemia, 13.7% being latent iron deficiency. Hb, GB and FEP in males and SI, %-St, SFR, FEP in females revealed clear seasonal variations. Multiple correlation coefficient between Hb and SI, %-St, SFR, FEP as independent variables was significant in females but not in males, and the ratio of contribution (38.7%) was not very high, however, the multiple correlation coefficient was significantly high (0.622). Standard regression coefficients between Hb and SFR, FEP were significantly high (p less than 0.01). When Ht and GB were added to these 4 variables, multiple correlation coefficients (male, 0.906; female, 0.957) were remarkably high, which means serum-related variables such as Ht and GB have an undeniably important role as explanatory variables of hemoglobin levels. These standard regression coefficients showed seasonal changes.

Adult↗