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Biomedical subjects

T Akiyoshi

Publications and source records attributed to T Akiyoshi.

At least 145 records · Page 8Linked to original sources
PubMed1990

'Two-route chemotherapy' using cisplatin and its neutralizing agent, sodium thiosulfate, for intraperitoneal cancer.

The pharmacokinetics of intraperitoneal cisplatin (DDP) administered with simultaneous intravenous sodium thiosulfate (STS) were investigated by a bioassay system using the phytohemagglutinin (PHA) stimulation assay of human peripheral blood mononuclear cells (PBM). Active DDP in the plasma, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. However, the peak level of active DDP in the peritoneal cavity was not significantly decreased. Fourteen patients with intraperitoneal carcinoma were treated with intracavitary DDP chemotherapy in combination with STS in this setting. Of 8 patients with malignant ascites who were evaluable for response, 4 patients experienced complete disappearance of ascites and the remaining 4 patients responded with apparent decrease in the volume of their ascites. No serious drug-associated toxicity was encountered.

Adult↗
PubMed1989

Rearrangement of T-cell receptor delta chain gene as a marker of lineage and clonality in T-cell lymphoproliferative disorders.

We analyzed the rearrangement of T-cell receptor (TcR) delta chain gene in 88 cases of lymphoproliferative disorders; 31 acute lymphoblastic leukemias/lymphoblastic lymphomas (ALL/LBL); 27 adult T-cell leukemias/lymphomas, 9 angioimmunoblastic lymphoadenopathies (AILD); 10 T-cell lymphomas (non-Hodgkin's lymphoma); and 11 Hodgkin's disease. All of 9 T-ALL/LBL cases, of which 4 cases have neither beta nor gamma gene rearrangement, had a new rearranged band of TcR delta locus. Ten of 16 B-lineage ALL/LBL had rearranged band(s) or deletion of TcR delta locus. The rearranged bands were recognized in 2 cases of AILD and 1 case of T-cell lymphoma. All cases of adult T-cell leukemias/lymphomas, 4 of AILD, 4 of T-cell lymphoma, and 8 of Hodgkin's disease had deleted TcR delta locus. Heterogeneous findings of TcR delta locus analysis were observed in AILD, T-cell lymphoma, and Hodgkin's disease. In 16 cases with TcR delta rearrangement, the J delta 1 region was frequently used and the J delta 2 region was rearranged in one AILD. It is suspected that J delta 3 was used in one T-ALL/LBL. There was no correlation between the phenotypic pattern of CD3, CD4, CD8 in T-cell disorders and the rearrangement of the TcR delta gene. These findings suggest that the newly identified TcR delta chain gene rearranges at a very early stage of T-cell ontogeny; prior to the other TcR genes and perhaps at almost the same stage with CD7 expression. The TcR delta gene is useful in assessing clonality for the most immature T-cell neoplasms not showing rearrangement of the other TcR genes. This gene is not lineage specific; however, when used in conjunction with immunoglobulin heavy chain gene, it may be a useful tool to distinguish lymphoid lineage of ALL/LBL.

Gene Rearrangement, T-Lymphocyte↗
PubMed1989

Augmentation of the generation of lymphokine-activated killer cells after a single dose of mitomycin C in cancer patients.

The effect of mitomycin C administration on the generation of cytotoxic cells, induced by in vitro activation of peripheral blood mononuclear cells (PBM) with interleukin-2, was studied in patients with various carcinomas. The ability of PBM to generate lymphokine-activated killer (LAK) cell activity against Raji cell targets was significantly augmented 5 and 7 days after a single intravenous dose of 12 mg/m2 mitomycin C, when compared to that of PBM obtained before mitomycin C injection. Further, LAK cell activity against autologous tumor cells was also significantly increased after the drug administration. The distribution of lymphocyte subsets exhibited a significant increase in the percentage of CD3+ cells after injection, with the elevation of the CD4/CD8 ratio. Furthermore, the proportion of the CD4+ Leu8+ subpopulation, which identifies inducers of suppression, was significantly reduced. Thus, the decrease in the proportion of suppressor-inducer subsets of PBM might be at least partially, responsible for the augmented generation of LAK cells after mitomycin C administration.

Antigens, Differentiation↗
PubMed1989

[Secondary leukemia (AML) with TcR beta rearrangement].

A 60-year-old female with fever and general lymphadenopathy was admitted to our hospital in 1979. By histological examination of cervical lymph node, she was diagnosed as B-cell malignant lymphoma, diffuse, large, stage IV B (Ann Arbor classification). In 1984, the complete remission of malignant lymphoma was observed after MOPP, COPP and VAPP chemotherapies. After 3 years, she was readmitted because of leukocytosis in which 64% immature abnormal cells were detected. By conventional cytological and cytochemical evaluations, the immature abnormal cells were identified as secondary AML cells with M 2 type (FAB), peroxidase (+), My 7 (+) and chromosomal abnormality; 48, X, -X, +4, -9, +21, del (1) (p 34), i (17 q), + M 1, + M 2. Analysis of Ig and TcR genes showed TcR-beta rearrangement. It has been reported that secondary leukemia frequently causes chromosomal abnormalities and therapy resistance. Ig gene and TcR gene analysis of secondary leukemia combined with chromosome examination, which has reported little, may be useful in predicting prognosis and therapy resistance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

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↗
PubMed1988

The prevention of experimental cholesterol gallstones by ileectomy in mice.

After a lithogenic diet containing 0.5 per cent cholesterol and 0.25 per cent sodium cholate was fed to a group of normal Crj-ICR male mice for 10 days, cholesterol gallstones developed. No formation of gallstones occurred, however, in a group of mice from which 20 cms of terminal ileum had been removed prior to the feeding of the lithogenic diet. The biliary concentrations of cholesterol, phospholipids and bile acids were markedly lower in the ileectomized mice, with the decrease in cholesterol concentration being most significant. On the other hand, fecal excretion of sterols and bile acids increased in the ileectomized mice. The pool size of bile acids increased after the feeding of the lithogenic diet, but ileectomy decreased the pool size in mice fed the ordinary or lithogenic diets. The biliary concentration of cholic acid increased after the feeding of the lithogenic diet, but decreased with ileectomy. The biliary concentration and fecal excretion of deoxycholic acid markedly increased, while those of beta-muricholic acid and its secondary bile acids, omega-muricholic acid and hyodeoxycholic acid, decreased. The increase in plasma and liver cholesterol levels after the feeding of the lithogenic diet was prevented by ileectomy. These data suggest that ileectomy prevents the formation of cholesterol gallstones after the feeding of a lithogenic diet due to a decrease in cholic acid absorption.

Animals↗
PubMed1988

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↗
PubMed1988

Augmentation of the generation of OK-432 activated killer cells after a single dose of mitomycin C in cancer patients.

Effect of mitomycin C (MMC) administration on the generation of cytotoxic cells induced by in vitro activation of peripheral blood mononuclear cells (PBM) with OK-432, a bacterial immunopotentiator, was studied in patients with various carcinomas. Following i.v. injection of a single dose of 12 mg/m2 MMC, the ability of PBM to generate OK-432 activated killer cells was markedly increased. Thus, the cytotoxic activity observed 7 days after MMC administration was significantly augmented as compared to that before treatment. Therefore, the ability to generate lymphokine activated killer (LAK) cells was examined, and significantly increased capacity was observed 5 and 7 days after MMC injection. Then, the OK-432 activated killer cell activity significantly correlated with the LAK activity. After treatment, the distribution of lymphocyte subsets exhibited a significant decrease in the percentage of OKT8+ cells. Leu-11+ cells were also reduced. The results appear to indicate that the imbalance in T-cell subsets and the increase in the ability to induce LAK cells may be related to the augmenting effect of MMC administration on the generation of OK-432 activated killer cells in cancer patients.

Biological Products↗
PubMed1988

'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↗
PubMed1988

A simplified tritiated thymidine incorporation assay for chemosensitivity testing of human tumors.

Chemosensitivity testing was performed using a simplified rapid assay based on tritiated thymidine incorporation. In this assay, 1.5 X 10(5) tumor cells were cultured for 72 h in double-layer agarose in 25 mm plastic dishes, which had a Millipore membrane sealed to the underside. After 24 h labeling of the cells with tritiated thymidine, cells were collected on the membrane by evacuating the solubilized medium through the filter sealed to the underside of the dish, which was placed in a boiling water bath. The radioactivity of the collected cells was counted by liquid scintillation. We found that 65% of 68 malignant tumors gave evaluable chemosensitivity results. Overall, chemotherapeutic drugs caused a 38% response rate in vitro. Twenty instances were evaluable for in vitro-in vivo correlations. The predictive accuracies were 93% for resistance and 67% for sensitivity. The results indicate that, with technical simplicity and shorter time course (4 days), this assay may be useful for chemosensitivity testing in human tumors.

Antineoplastic Agents↗
PubMed1987

Antibody-dependent cell-mediated cytotoxicity using a murine monoclonal antibody against human colorectal cancer in cancer patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by a murine monoclonal antibody against human colorectal carcinoma, antibody 19-9, with human effector cells was tested in 33 patients with various carcinomas, 16 patients with benign lesions, and 13 normal controls, using a 12-h 51Cr release assay using human colorectal cancer cells as targets. Peripheral blood mononuclear cells (PBM) from these groups of patients and normal controls achieved moderate levels of target cell lysis in the presence of the monoclonal antibody at the high effector to target cell ratio of 200:1. The ADCC activity of PBM in cancer patients was significantly higher than that in either normal persons or patients with benign lesions. Since the ADCC was shown to be mainly mediated by adherent monocytes in the PBM, ADCC activity of monocytes from cancer patients was compared to those from control groups at an effector to target cell ratio of 30:1. The results also showed that the lytic capacity of monocytes was significantly higher in cancer patients than that in the control populations.

Adult↗
PubMed1987

Augmentation of the generation of cell-mediated cytotoxicity in culture by mitomycin C.

The effects of mitomycin C (MMC) on the generation of cell-mediated cytotoxicity in primary stimulation culture of human peripheral blood mononuclear cells (PBM) with the B lymphoblastoid Raji cell line were assessed. The cell-mediated cytotoxicity induced in culture was significantly augmented when MMC was added to cultures on day -1 to day 3 for 24 h at concentrations of 2.5 X 10(-2) micrograms/ml and 2.5 X 10(-3) micrograms/ml. To identify the cell populations affected by MMC, PBM were separated by adherence to plastic after treatment with MMC for 24 h (day -1). The two populations were recombined with untreated separated cells and stimulated with antigen. The ability to develop an augmented cell-mediated cytotoxicity was associated with the adherent cell fraction of MMC-treated PBM. Therefore, the ability of MMC-treated adherent cells to produce interleukin 1 (IL 1) was examined. Significantly higher levels of IL 1 were produced by treated cells as compared to untreated adherent cells. The results appear to indicate that the selective effects of MMC on the adherent cell fraction, especially the modification of IL 1 production, may be involved in the mechanisms of MMC-induced augmented cell-mediated cytotoxicity.

Cells, Cultured↗
PubMed1987

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↗
PubMed1987

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↗