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Biomedical subjects

H Kodo

Publications and source records attributed to H Kodo.

At least 37 records · Page 2Linked to original sources

Role of T-cell antigens in the cytolytic activities of large granular lymphocytes (LGLs) in patients with LGL lymphocytosis.

By analyzing surface antigens and cytolytic functions of proliferating large granular lymphocytes (LGLs), three types of T cell LGL lymphocytosis were delineated. The first, most commonly encountered type exhibited CD3+4-8+16+, WT31+ phenotype, low or undetectable non-major histocompatibility complex (MHC)-restricted cytotoxicity, and moderate to strong antibody-dependent cellular cytotoxicity (ADCC) and lectin-dependent cellular cytotoxicity (LDCC). Because these LGLs carried T cell antigen receptor (Ti) recognized by WT31 monoclonal antibody (MoAb), and treatment with anti-Ti, anti-CD3 MoAbs and phytohemagglutinin elicited non-MHC-restricted cytotoxicity, they may have developed from populations of in vivo primed cytotoxic T lymphocytes with unknown antigen specificity. The second, rare type of LGL lymphocytosis exhibited CD3+4-8-16+, WT31 phenotype, and strong non-MHC-restricted, ADCC and LDCC cytotoxicities. These cells were probably derived from the lymphocytes of the same phenotype found in small numbers in normal peripheral blood. Because anti-CD3 MoAb inhibited non-MHC-restricted cytotoxicity of the LGLs, a Ti not detected by WT31 MoAb, but putatively present seemed to serve as a specific receptor for target tumor cell recognition. The third type of LGL lymphocytosis showed CD3+4+8-16+, WT31+ phenotype, and lacked cytolytic activities and parallel tubular arrays. These LGLs probably evolved from cells with the same characteristics selectively located in the germinal centers of lymphoid tissues. Taken together, in patients with LGL lymphocytosis, T cell-associated antigens expressed on LGLs were shown to be involved in the regulation of LGL-mediated cytolytic activities. In addition, studies of surface antigens and the effects of MoAbs and lectins on cytolytic activities may be useful in clarifying the normal counterpart of LGLs from which leukemic or reactively proliferating LGLs originate.

Adult↗

Phase I clinical study for recombinant human granulocyte colony-stimulating factor.

The pharmacokinetics, the safety and the efficacy of purified recombinant human granulocyte colony-stimulating factor (rh G-CSF) expressed in Chinese hamster ovary (CHO) cells were studied in normal healthy adults. Following the single subcutaneous dose, G-CSF levels in sera elevated in a dose-dependent way, with C-max of approximately 140 pg per ml, T-max of 4 hours and T-half of 5 hours at a dose of 10 micrograms per ml. In accord with the elevation, blood neutrophil counts rose promptly and transiently without any changes in the other blood cell counts. Degree and duration of the neutrophilia were apparently proportional to the rh G-CSF dose and, in turn, the G-CSF levels in sera. Single daily injections of rh G-CSF at a dose of 10 micrograms per body per day for 7 consecutive days did not bring on any accumulation of rh G-CSF in sera, and repeatedly induced neutrophilias following every injection. During the course of the injections, the chemiluminescence generating ability of blood neutrophils also rose. Peak value of the transient neutrophilias and level of the abilities tended to go down after 3 or 4 consecutive injections, presumably due to the limited number of mature neutrophils which can be released from the bone marrow in response to rh G-CSF. However, it was found that the M/E ratio becomes higher after the repeated dosing with an increased proportion of myeloid immature cells as well as increase in the levels of both erythroid and myeloid precursor cells in the bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Colony-Forming Units Assay↗

Expression of IgD on B cell malignancy. An immunopathological study of 50 cases.

Expression of IgD was studied immunopathologically on 50 cases of B cell lymphomas (B MLs), together with various B cell markers including IgM, kappa and lambda chains, B1, B2, (OK)B2, (OB)B7, (OK)T10, NUB1, Leu 1, Leu 14, and PCA. IgD was demonstrated on 19 cases heavily and on 8 weakly. It associated well with expression of two antigens, B2 (C3d receptor molecule) and Leu1 (pan-T antigen), besides IgM, while, B2 was closely related in expression on B MLs to (OK)B2, (OK)B7, and NUB1. lambda chain was dominant on IgD heavily-stained cases. Histopathologically, IgD positive MLs were distributed in various types. All of diffuse intermediate type were shown to be IgD positive (4/4, 3 heavily). As cases of this type were shown to express most of other B cell antigens present on non-tumorous primary follicle B cells or mantle zone B cells, this type of MLs is speculated to be a neoplastic counterpart of such non-tumorous B cells. Eight out of 18 cases of diffuse large cell type were IgD heavily positive, suggesting some unusual mechanisms in IgD expression on these neoplastic large cells, as non-tumorous B cells lose most of their surface IgD soon after blastoid transformation. Other types of MLs were discussed with special emphasis on expression of IgD.

B-Lymphocytes↗

Suppression of mixed lymphocyte reaction by cells of human first trimester pregnancy endometrium.

In order to identify an immunological role for decidual tissue in pregnancy we have prepared single cell suspensions from the tissues of normal pregnant women and examined the effects of these cells on one-way mixed-lymphocyte reactions (MLR). The separated cells were heterogeneous, containing classical decidual cells, glandular epithelial cells, granular endometrial cells, macrophages and small lymphoid cells. [3H]Thymidine incorporation at day 6 of the MLR was suppressed by addition of the cells at the initiation of the cultures and the degree of suppression was inversely correlated to the gestational age of the decidual tissue, apparently through inhibition of the antigen recognition phase of the MLR. These findings support the view that the cells of the human first trimester pregnancy endometrium may play an important role in protecting the feto-placental unit from rejection, at least in the early phase of pregnancy.

Antigens, Surface↗

Dose-response effects of 4-hydroperoxycyclophosphamide on human T and B cell function in vitro.

4-Hydroperoxycyclophosphamide (4-OOH-CYP) is spontaneously converted in aqueous solution to 4-hydroxycyclophosphamide (4-OH-CYP), the major active metabolic of cyclophosphamide. We studied the dose related effects of in vitro treatment with 4-OOH-CYP on human T- and B cell-mediated immune responses. T-cell proliferation to mitogens and alloantigens was only partially inhibited even relatively high-doses of 4-OOH-CYP (greater than 6-12 micrograms/ml). In contrast cytotoxic functions of activated T-cells and natural killer (NK) cells were inhibited at lower doses (3-6 micrograms/ml). PWM induced in vitro synthesis of IgG by B-cells was inhibited at less than 3 micrograms/ml of 4-OOH-CYP. These data indicate that 4-HOO-CYP has selective, dose-dependent effects on human T and B cells in vitro.

B-Lymphocytes↗

Antibody synthesis by bone marrow cells in vitro following primary and booster tetanus toxoid immunization in humans.

Normal volunteers received either initial or booster immunization with tetanus toxoid. Bone marrow and peripheral blood mononuclear cells were obtained for up to 28 d after immunization and were analyzed for synthesis of total Ig and specific antibodies to tetanus toxoid. Cells were cultured in vitro for 3 or 7 d with or without pokeweed mitogen (PWM). Synthesis of IgG and IgM antibodies to tetanus (IgG-Tet and IgM-Tet) and total IgG and IgM was determined by radioimmunoassay. Four functional B cell subpopulations were detected in the bone marrow after booster tetanus immunization: (a) B cells that spontaneously synthesized IgG-Tet appeared on day 7 after immunization but were undetectable by day 21; (b) B cells that synthesized IgG-Tet after stimulation with PWM appeared after day 21 and persisted for greater than 1 mo; (c) B cells that synthesized IgM-Tet in the presence of PWM were detectable before and after immunization; and (d) B cells that spontaneously synthesized IgM-Tet appeared on day 7 and were undetectable by day 21. In contrast to the other three types of bone marrow B cells described, this fourth subpopulation of PWM-independent IgM-Tet-synthesizing B cells was not detected in the peripheral blood. After primary immunization, no spontaneous antibody-producing cells were detected in the blood or bone marrow, although there was a small rise in IgM-Tet in two of three subjects. In the bone marrow, only IgM-Tet PWM-inducible cells were seen, although mitogen-responsive IgM and IgG-Tet cells were detected in the circulation. The IgM-Tet PWM-reactive cells were present even before primary antigen exposure and appear to represent the initial B cells involved in the antibody response. These data indicate that there are specific times after immunization when different functional classes of anti-Tet-synthesizing B cells and memory B cells appear in human bone marrow. Knowledge of these data may be important in developing a strategy for the transfer of immune memory from donors to recipients in the setting of bone marrow transplantation.

Adult↗