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Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 289 records · Page 16Linked to original sources

Conformations of cyclo(L-orD-Phe-L-Pro-Aca) and cyclo(L-Pro-L- or D-Phe-Aca). Cyclized dipeptide models for specific types of beta-bends.

Conformational analyses on four cyclic model peptides of the beta-bend, cyclo(L- or D-Phe-L-Pro-epsilon-aminocaproyl(Aca] and cyclo(L-Pro-L- or D-Phe-Aca), were carried out both experimentally and theoretically. Cyclo(D-Phe-L-Pro-Aca) was shown to exist as a single conformer taking the type II' beta-bend. The comparison of its CD spectra with those of cyclo(L-Ala-L-Ala-Aca) revealed that type I and II' beta-bends, both with alpha-helix-like CD spectra, can be distinguished. Cyclo(L-Phe-L-Pro-Aca) was shown to exist as a single conformer with a cis L-Phe-L-Pro peptide bond, taking the type VI beta-bend. Its CD spectrum has thus been observed for the first time for the bend containing a cis peptide bond. Cyclo(L-Pro-L-Phe-Aca) was shown to exist as a mixture of two conformers, the major one taking the type I beta-bend with a trans Aca-L-Pro peptide bond and the minor one with a cis Aca-L-Pro peptide bond. Cyclo(L-Pro-D-Phe-Aca) was suggested to exist as a mixture of two conformers, the major one taking the type II beta-bend with a trans Aca-L-Pro peptide bond and the minor one with a cis Aca-L-Pro peptide bond.

Dipeptides↗

Studies on prodrugs. 5. Synthesis and antimicrobial activity of N-(oxoalkyl)norfloxacin derivatives.

Several N-(oxoalkyl)norfloxacin derivatives (3a-g) were synthesized and evaluated for antibacterial activity in vitro and in vivo. Most of the compounds exhibited in vitro activity comparable to that of norfloxacin for Gram-positive bacteria, whereas their activity was lower than for Gram-negative bacteria. N-(2-Oxopropyl)norfloxacin (3b) liberated norfloxacin in the blood after oral administration in mice, and the serum level of norfloxacin was about 3-fold higher than that of norfloxacin itself. Thus, 3b showed high antibacterial activity in vivo.

Animals↗

Gamma-interferon production capacity and T lymphocyte subpopulation after allogeneic bone marrow transplantation.

T cell phenotypes after bone marrow transplantation (BMT) were investigated using monoclonal antibodies (moAbs) reactive to lymphocyte cell surface antigens. Patients' T cells showed decreased percentages of OKT4, 4A and 9.3-positive T cells, and increased percentages of OKT8, human Ia, and Leu-7-positive T cells. These changes in T cell phenotype persisted for a long period after BMT and had no correlation with the occurrence of graft-versus-host disease (GVHD). No lymphocyte activation antigens such as TIA (Tac) or transferrin receptor (5E9) were detected after BMT. The capacity of the patients' lymphocytes to produce gamma-interferon (IFN-gamma) was measured after incubation of lymphocytes with mitogen. Patients' lymphocytes produced significantly lower levels of IFN-gamma than the normal controls. This failure of IFN-gamma production showed no correlation with stimulation index of mitogen blastogenesis or changes of T cell population. Thus, not only T cell phenotype but also measurement of IFN-gamma production of lymphocyte may be useful in detecting immunological abnormalities in patients who receive BMT.

Adolescent↗

[Immunotherapy of acute myelogenous leukemia (AML) in adults with the Nocardia rubra cell wall skeleton].

The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on the remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (p = 0.080) and on survival length (p = 0.098). When the data were analyzed at 42 months after entry, there was a borderline significant difference in remission duration (p = 0.066) between the two groups, prolonging the 50% remission period by 120 days, but no significant differences in survival length (p = 0.306), although the 50% survival was 168 days longer in the chemoimmunotherapy group. Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.

Adult↗

Ester-exchange catalyzed by lipase modified with polyethylene glycol.

Lipoprotein lipase was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine; forty-six percent out of seven amino groups in the molecule were substituted. The modified lipase catalyzed ester-exchange reactions between an ester and an alcohol, between an ester and an acid, and between two esters. The modified enzyme catalyzed these reactions not only in organic solvents, but also in straight hydrophobic substrates. As the modified enzyme was extremely stable at elevated temperature, for example at 70 degrees C, this can find many practical applications.

Caproates↗

Augmentation of generation of human allospecific cytotoxic T lymphocyte by PPD in in vitro sensitization culture.

PPD augmented human lymphocyte blastogeneic response to allogeneic lymphocytes in the mixed lymphocyte reaction (MLR) and generation of human cytotoxic lymphocytes against allogeneic human lymphocytes in in vitro sensitization (IVS) culture. The augmenting effect of PPD in the MLR was unequivocally synergistic at its lower concentrations (0.05 and 0.01 microgram/ml). The augmentation of MLR was observed following addition of a supernatant of culture medium of lymphocytes which had been precultured with PPD for 24 h then washed free of PPD and recultured without PPD for another 24 h. PHA and Con A, in contrast, suppressed both MLR and the generation of alloreactive cytotoxic cells. The alloreactive cytotoxic lymphocytes whose generation was augmented by PPD belonged to the SRBC-rosette forming fraction and passed through a nylon-wool column. The NK cell-like activities of the alloreactive cytotoxic lymphocytes were not augmented by PPD. Analysis of the alloreactive cytotoxic lymphocytes whose generation was augmented by PPD by competitive inhibition assay with unlabeled cells indicated that the same allogeneic lymphocytes used as sensitizing cells in IVS culture inhibited the cytotoxicity, while MOLT-4 cells, which are frequently used as target cells for the human NK-cell assay, did not. When lymphocytes with known HLA-A and HLA-B were used in the IVS culture and the cytotoxicity assay, PPD was found to augment the cytotoxicity only against the target lymphocytes that possessed the same HLA as the sensitizing lymphocytes in IVS.

Cells, Cultured↗

Treatment of plasma cell neoplasm with recombinant leukocyte A interferon and human lymphoblastoid interferon.

Thirty cases of plasma cell neoplasms (24 multiple myeloma, one plasma cell leukemia, and three primary macroglobulinemia) were treated with two kinds of highly purified alpha-interferons, recombinant human leukocyte interferon (rIFN-alpha A) (16 cases) and human lymphoblastoid interferon (HLBI) (14 cases). Partial remission (PR) was obtained in two of 16 evaluable cases treated with rIFN-alpha A and in two of 12 evaluable cases treated with HLBI. If minor response (MR) was included, responses were observed in seven (31.3%) and six (50%), respectively. Response (PR + MR) was noted in 38% of 21 previously treated patients and 71% of seven previously untreated patients. Side-effects were noted in more than two-thirds of the patients. They included fever, malaise, nausea/anorexia and myelosuppression. Thus, these two kinds of highly purified alpha-interferon were effective in plasma cell neoplasm, producing unequivocal response in 14.3% of the cases without unacceptable side-effects.

Aged↗

[Prognostic factors influencing the improvement of allogeneic bone marrow transplantation in acute leukemia based on a national survey in Japan].

The records of 115 patients with acute leukemia who underwent allogeneic bone marrow transplantation from 1975 through August 1984 were collected by a national survey in Japan. One-year survival significantly improved from 9% in group I (before 1980) to 52% in group II (after 1981). Multivariate analysis indicated that selection of the patients in remission without infection at the time of transplant, as well as progress in technology of total body irradiation and selection of a platelet donor with negative cytomegalovirus titer resulted in the significant improvement in survival after 1981.

Acute Disease↗

Serological study for in vitro use of monoclonal antibody for autologous bone marrow transplantation in null cell-type acute lymphocytic leukemia.

In connection with autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) patients, the optimal conditions for in vitro elimination of leukemia cells from transplanted bone marrow cells with monoclonal antibodies (MoAb) plus rabbit complement (C) were investigated. Three monoclonal antibodies, NL-1, NL-22 and HL-47, which were produced in our laboratories and shown to react predominantly to Null-ALL cells, were used. In most cases, 10 micrograms/ml of MoAb and 50% of C were required for optimal killing of leukemia cells. Combined use of MoAbs and multiple treatments were studied, but generally no significant increase in the cytotoxicity to the target leukemia cells was observed as compared with a single treatment with the most effective single MoAb. Selection of C was very important, because some lots had lower C activity from the beginning or after incubation with normal bone marrow mononuclear cells. Nonspecific cytotoxicity to human hematopoietic cells was also observed in some lots of C. Under the optimal conditions thus defined, the three MoAbs did not inhibit the growth of granulocyte-macrophage colony-forming units (CFU-GM) or three other types of hematopoietic stem cells. Modulation of the antigens was also examined, and NL-1 antigen showed mild modulation, whereas NL-22 and HL-47 antigen did not. The results obtained indicated that these three MoAbs may be useful for eliminating Null-ALL cells in vitro from bone marrow in autologous BMT.

Antibodies, Monoclonal↗

Preliminary clinical trial of autologous bone marrow transplantation after in vitro monoclonal antibody and complement treatments in null cell-type acute lymphocytic leukemia.

Autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) was carried out after depletion of leukemia cells from transplanted bone marrow. Patients' autologous bone marrow cells were harvested during remission and treated in vitro with complement and three monoclonal antibodies (NL-1, NL-22 and HL-47) reactive to Null-ALL cells, and then cryopreserved. Three patients were transplanted with the antibody-treated bone marrow cells during the first remission period after preconditioning with intensive chemotherapy and total body irradiation, while transplantations in two other patients, who were in poor clinical condition, were done during the fourth remission period and the third relapse, respectively. Good preservation of hematopoietic stem cells after antibody treatment and cryopreservation of bone marrow cells was demonstrated in all five cases studied. Clinically, prompt recovery of white blood cells and platelets was observed in the three patients who received BMT during the first remission period; two of them have continued remission (2 and 15 months), while the other relapsed after 7 months of remission. these results suggested that autologous BMT with these three antibodies may be an effective mode of therapy for Null-ALL patients.

Antibodies, Monoclonal↗