Search PubMed⌕ Search

Biomedical subjects

Y Morishima

Publications and source records attributed to Y Morishima.

At least 217 records · Page 12Linked to original sources

[In vitro manipulation of bone marrow cells for bone marrow transplantation].

Recently, in vitro manipulations of bone marrow cells have been developed for the prevention of relapse in autologous bone marrow transplantation (BMT) and for the prevention of graft versus host disease in allogeneic BMT. Two methods were mainly employed clinically for the depletion of cells from transplanted bone marrow cells. Firstly, bone marrow cells were treated in vitro with monoclonal antibodies reactive to leukemia cells or T cells using complement, immunotoxin or magnetic bead. Secondly, bone marrow cells were incubated with cancer drugs such as 4-HC or mafosfamide. Our results and other reports using in vitro purging of leukemia or lymphoma cells suggest that these autologous BMTs are effective modes of cancer therapy in patients with hematological malignancies.

Acute Disease↗

Use of cyclophosphamide and total lymphoid irradiation combined with cyclosporine in bone marrow transplantation for transfused severe aplastic anemia.

Between February 1984 and August 1987, 10 patients with severe aplastic anemia were treated with bone marrow transplantation from HLA-identical sibling donors after preparation with cyclophosphamide (CY) 200 mg/kg and total lymphoid irradiation (TLI) 750 cGy. Ages ranged from 5 to 28 years (median 14 years). All patients were previously transfused. Median number of transfusions was 16 (range, 3-886). For post-transplant immunosuppression all patients were given cyclosporine and the last three patients received additional immunosuppression with short-term methotrexate. All patients had initial engraftment and survived for more than 3-46 months after transplantation. One patient developed significant acute graft-versus-host disease (GVHD) and three of nine recipients who survived more than 100 days developed chronic GVHD. One male patient who had received 21 transfusions from his marrow donor before transplantation suffered from persistent granulocytopenia. Otherwise all have Karnofsky performance scores of 90-100%. Although the number of patients is small, it appears that allogeneic bone marrow transplantation with the regimen of CY + TLI for preparation combined with cyclosporine (+ short-term methotrexate) for post-transplant immunosuppression is a promising modality for treatment of previously transfused patients with severe aplastic anemia.

Adolescent↗

[Application of monoclonal antibodies to bone marrow transplantation].

For the last several years, monoclonal antibodies (MoAbs) have been applied to clinical bone marrow transplantation (BMT). In allogeneic BMT, anti-T cell MoAbs have been used for in vitro depletion of T cells from transplanted bone marrow. This treatment has remarkably reduced the incidence of acute graft versus host disease. However, the high rate of graft rejection and leukemia relapse remains to be resolved. Autologous BMT has also been performed in leukemia and malignant lymphoma. MoAbs have been used for in vitro purging of contaminated tumor cells from preserved bone marrow. These clinical trials have resulted in a significant increase in the number of disease-free long-term survivors.

Antibodies, Monoclonal↗

Analysis of immunophenotype, genotype, and lineage fidelity in blastic transformation of chronic myelogenous leukemia: a study of 20 cases.

We have examined the immunophenotype and genotype of leukemic cells from 20 patients with the blastic phase of chronic myelogenous leukemia (CML), which is known to arise from a pluripotential hematopoietic stem cell. The phenotypic analysis of surface antigens with a panel of lineage-specific monoclonal antibodies revealed that six of 20 cases expressed phenotypes of lymphoid blastic transformation with pre-B cell markers. One of these cases was shown to coexpress cluster designation 2 of T cell marker on the same cells by two-color immunofluorescence analysis. Eight cases, including two cases that also had a megakaryocytic component, showed phenotypes expressing differentiation antigens of myeloid series. Three expressed a phenotype of megakaryoblastic transformation. The remaining three cases had no surface marker characteristic of any cellular lineage. The genotypic analysis by Southern blot hybridization showed that immunoglobulin heavy chain genes were rearranged in all of six lymphoid blastic transformations and that rearrangement of a T cell receptor beta chain gene was present in only one lymphoid blastic transformation that had no T cell surface marker. DNA samples in all cases of nonlymphoid blastic transformation were retained in the germ line configuration for both immunoglobulin and T cell receptor genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Detection of cross-reactive antibody to BLV p24 in sera of human patients infected with HTLV.

For detection of antibody to bovine leukemia virus (BLV) major core protein of p24 and cross-reactive antibody in human patients infected with human T cell leukemia virus type I (HTLV-I), monoclonal antibody, D432 against BLV p24 was used by competitive binding enzyme-linked immunoadsorbed assay (ELISA). In sera from cattle with enzootic bovine leukosis (EBL) which were positive for BLV antibodies by immunodiffusion test, 109 out of 112 (97.3%) were positive for BLV p24 antibody by competitive binding ELISA. By using the same procedures, 21 samples from adult T cell leukemia (ATL) patients and healthy carriers with HTLV-I were tested for cross-reactive antibody to BLV p24. All 21 samples were positive for HTLV-I antibodies by immunofluorescence test and/or ELISA. By competitive binding ELISA using non-treated BLV antigens, none of these 21 samples inhibited the binding of the D432. When the BLV antigen was treated by several different denaturation procedures, several HTLV-I positive samples showed the inhibition of the D432 binding and the most effective treatment was by 2-mercaptoethanol (2-ME). Sixteen out of 21 samples showed the presence of cross-reactive antibody against 2-ME-treated BLV antigens. The cross-reactivity of human sample to BLV p24 antigen was further confirmed by Western blotting of the 2-ME-treated BLV antigens. None of the 28 samples from leukemia patients other than ATL which were negative for HTLV-I antibodies showed inhibition of the D432 by the competitive binding ELISA.

Antibodies, Viral↗

Activity of platelet-derived growth factor (PDGF) in platelet concentrates and cryopreserved platelets determined by PDGF bioassay.

The bioassay of platelet-derived growth factor (PDGF) in platelets was established using the rat fibroblast cell line 3Y1. 3Y1 cells (5 X 10(3)/well) were cultured in 24-well microculture plates with RPMI 1640 medium using 1% of PDGF-free serum and 5% of platelet extracts for 4 days. Cell proliferation was measured by the increase of DNA content. This assay made it possible to measure the biological PDGF activity. PDGF activity of platelet concentrates kept the same level as that of fresh platelet samples during preservation for up to 120 h at 22 degrees C; cryopreserved platelets also retained PDGF activity well.

Biological Assay↗

Phorbol ester induces interleukin-2 receptor on the cell surface of precursor thymocyte leukemia with no rearrangement of T cell receptor beta and gamma genes.

The early event of thymocyte maturation has been analyzed using acute lymphoblastic leukemia (ALL) cells. A group of ALL cells whose cell surface phenotype was CD2 (SRBC receptor) negative and CD7 (T cell antigen) positive has been considered as precursor thymocyte ALL (pre-T-ALL). No rearrangements of the T cell receptor beta-gene (TCR beta) and gamma-gene (TCR gamma) were found in three of four pre-T-ALL patients. Stimulation of these pre-T-ALL cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) induced only CD25 (Tac) antigen but no other T cell antigens. These findings suggest that the activation pathway of interleukin 2 (IL-2) receptor already exists in the most immature precursor thymocytes. Pre-T-ALL cells from the fourth patients showed the expression of CD3 antigen, and both TCR beta and TCR gamma rearrangement. TPA induced the differentiation of the more mature pre-T-ALL cells of this case in vitro, and not only CD25 (Tac) antigen but also CD4 and CD8 antigens appeared on the cell surface. The low affinity binding of 125I-IL-2 to TPA-stimulated leukemia cells was observed in the three cases of pre-T-ALL tested, and the addition of recombinant IL-2 to TPA-stimulated cells showed no effect on cell proliferation.

Antibodies, Monoclonal↗

Detection of multidrug resistance markers, P-glycoprotein and mdr1 mRNA, in human leukemia cells.

We have examined the expression of P-glycoprotein in clinical leukemic cell samples by using a monoclonal antibody (MRK16) against P-glycoprotein. We found that leukemia cells isolated from 3 out of 6 patients with blast crisis of chronic myelogenous leukemia were reactive to MRK16. These 3 cell lines expressed high levels of mdr1 mRNA, which codes for P-glycoprotein. The present result indicates that the clinically refractory state of the tumor may be predicted in part by determining P-glycoprotein expression using the monoclonal antibody against P-glycoprotein, and the mdr1 probe.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Treatment of adult T cell leukemia with mega-dose cyclophosphamide and total body irradiation followed by allogeneic bone marrow transplantation.

A 43-year-old patient with adult T cell leukemia (ATL) was treated with mega-dose cyclophosphamide and total body irradiation (TBI) followed by bone marrow transplantation (BMT) from his HLA-identical sibling who was not a carrier of ATL virus. After BMT, ATL cells rapidly decreased and disappeared, and the engraftment of marrow was confirmed on day 20. The patient showed normal hematologic recovery. However, he died on day 205 with interstitial pneumonitis caused by cytomegalovirus infection. Neither autopsy findings nor serologic and cytologic examinations showed any evidence of ATL relapse after BMT. This pilot study suggests that mega-dose chemotherapy and TBI followed by allogeneic BMT should be considered for such treatment of ATL.

Adult↗

Ultrastructural observation of nerve fibers containing both substance P and calcitonin gene-related peptide in the nucleus tractus solitarii of the rat: a combination of immunofluorescence and PAP methods.

Nerve fibers and their axon terminals with substance P (SP)-like and calcitonin gene-related peptide (CGRP)-like immunoreactivity in the nucleus tractus solitarii were ultrastructurally characterized by a combination of immunofluorescent double staining and the PAP method. The axon terminals formed asymmetrical synaptic contacts with other non-reactive neuronal elements (perikarya, dendritic shafts and dendritic spines). Some terminals received synaptic inputs from non-reactive axon terminals. This suggests that some, if not all, afferents containing SP and CGRP are affected presynaptically by other afferents.

Animals↗

Relationships between catecholaminergic neurons and cholecystokinin-containing neurons in the caudal part of the dorsomedial medulla oblongata of the rat: light and electron microscopic observations by the 'mirror technique'.

The 'mirror technique' was used in immuno-electron microscopy to examine the synaptic relationships between neuronal structures containing catecholamines and cholecystokinin (CCK) in the caudal part of the dorsomedial medulla oblongata in the rat, using antisera against tyrosine hydroxylase and CCK. CCK-immunoreactive axon terminals made synaptic contacts with catecholaminergic neurons. Some of these catecholaminergic neurons contained CCK.

Animals↗

Histaminergic axons in the neostriatum and cerebral cortex of the rat: a correlated light and electron microscopic immunocytochemical study using histidine decarboxylase as a marker.

Histaminergic nerve fibers and their axonal varicosities in the neostriatum and cerebral cortex were light and electronmicroscopically examined by means of peroxidase-antiperoxidase immunocytochemistry with histidine decarboxylase (HDC) as a marker. A majority of HDC-like immunoreactive axonal varicosities observed in serial thin sections for electron microscopy exhibited no synaptic contacts in either the neostriatum or cerebral cortex. The remaining small proportion of immunoreactive axonal varicosities formed synaptic contacts with non-immunoreactive dendritic shafts and spines.

Animals↗