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S Hashino

Publications and source records attributed to S Hashino.

81 records · Page 5Linked to original sources

Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess.

Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminated Candida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.

Adult↗

[The control of GVHD and immunodeficiency].

Graft-versus-host disease (GVHD) is caused by the disorder of self-tolerance mechanisms in the thymus and of peripheral tolerance mechanisms. Several cytokines also modulate GVHD, thus inducing complicated clinical features; therefore, it is important to determine which cytokines are mainly involved in the induction of GVHD in order to suppress the production of such cytokines for controlling GVHD. GVHD is closely related to immunodeficiency through T cell and B cell dysfunction. Although cytokines can potentiate these immunological dysfunction, GVHD may be simultaneously augmented by exogenous administration of cytokines. On the contrary, cytokines regulate hematopoiesis as well. Therefore, we should analyze the kinetics of cytokines and their receptor expressions as well as the influences of these factors on immune system and hematopoiesis to control GVHD and immunodeficiency.

Bone Marrow Transplantation↗

In vivo administration of cytokine in allogeneic bone marrow chimeras.

When we analyzed the in vivo efficacy of cytokine administration in murine allogeneic bone marrow chimeras, mitogen-induced responses to ConA, PHA, LPS, or PWM were increased by the in vivo administration of human recombinant granulocyte colony-stimulating factor (rG-CSF), human recombinant interleukin 2 (rIL-2), or WEHI-3B conditioned medium (CM). Furthermore, we found increased alloreactive mixed lymphocyte reactions (MLRs) against donor and/or host type alloantigens in spleen cells from (BALB/c----C3H/He) chimeras, although cytotoxic activity against BALB/c or C3H/He target cells was not detected in spleen cells from these chimeras. Since no significant increase of T cells or Ia positive cells was observed, some functional activation, rather than changes in the cell count, appeared to relate to increase immunoreactivity. An increased IL-2 production in spleen cells from chimeras injected with cytokine was observed shortly after the cessation of cytokine administration. Thereafter, an IL-2 production in these chimeras decreased around 45 days after bone marrow transplantation and then recovered nearly to the control level. An increased IL-2 responsiveness was also observed in spleen cells from these chimeras. These findings suggest that the in vivo administration of rG-CSF as well as rIL-2 or WEHI-3B CM (IL-3) can modulate the immunoreactivity in chimeras via the network of immune systems.

Animals↗

[Allogeneic bone marrow transplantation after the treatment of alpha-IFN and high-dose SNMC in two cases of acute myeloblastic leukemia with post-transfusional non-A, non-B hepatitis].

Two patients of acute myeloblastic leukemia (M2) with post-transfusional hepatitis (non-A, non-B) were treated with alpha-IFN and high-dose SNMC before allogeneic bone marrow transplantation. Bone marrow transplantation from HLA identical and MLR negative sibling donor was carried out when their hepatic functions were almost normalized. In the early phase after bone marrow transplantation, the hepatic function in both two cases has been stable, thus indicating that this treatment should be tried for reducing hepatic dysfunction and for safety bone marrow transplantation.

Adult↗

Non-specific suppressor cells in murine bone marrow chimeras: their possible role in GVHD-associated immunodeficiency.

Suppressor cells against several mitogen-induced responses were detected in the spleen of murine bone marrow chimeras, regardless of intravenous (i.v.) or intrasplenic (i.s.) bone marrow transplantation (BMT). According to the time-course of the suppressor activity against Con A, PHA, and PWM, they were readily detected at 11-21 days after BMT and thereafter, either gradually decreased or remained at a plateau level. In contrast, the suppressor activity against the LPS-stimulated response increased at 39-52 days as compared to 24-34 days after BMT. Characterization studies of suppressor cells early (11-21 days) after BMT revealed that those in the i.v. and i.s. chimeras were composed of host-derived plastic dish adherent and/or anti-Thy 1.2 antibody-insensitive spleen cells in general. On the contrary, those in the i.v. and i.s. chimeras that possessed severer GVHD were mainly composed of host-derived plastic dish non-adherent spleen cells. Since the suppressor activity was higher in chimeras with severe graft-versus-host disease (GVHD) than in conventional chimeras, suppressor cells against the mitogen-induced responses may be related to the immunodeficiency associated with GVHD. Particularly, plastic dish non-adherent suppressor cells may closely relate to GVHD-associated immunodeficiency as compared with plastic dish adherent suppressor cells.

Animals↗

Suppressor activity in the supernatant of T cell clones derived from chimeric mouse spleen cells.

The supernatant from cultures of T cell clones derived from (BALB/c----C3H/He) chimeras suppresses BALB/c anti-C3H/He or BALB/c anti-C57BL/6 MLRs. When we studied the alloantigen specificity of the suppressor activity in culture supernatant, we observed three types of the suppressor activity (i.e., the suppressor activity against BALB/c anti-C3H/He MLR, against BALB/c anti-C57BL/6 MLR, and against both MLRs) on day 3 after stimulation of the T cell clones with 20% crude IL2 and feeder cells. Since the alloantigen specificity fluctuated somewhat with time, we considered that a time-course study was needed to determine it correctly. We thought it unlikely that any IFN-gamma or PGE2 in the culture supernatant of the T cell clones would have mediated the suppression. Our results suggest that alloantigen specific and non-specific suppressor T cells exist in bone marrow chimeras. The former appears to play an important role in inducing and maintaining transplantation tolerance, while the latter seems to have a rather harmful effect upon chimeras.

Animals↗