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Biomedical subjects

E Azuma

Publications and source records attributed to E Azuma.

At least 55 records · Page 3Linked to original sources
PubMed1997

Two cytotoxic pathways of natural killer cells in human cord blood: implications in cord blood transplantation.

Using K562 cells as a target we investigated cord blood (CB)-natural killer (NK) cytolytic pathways. The cytotoxicity of fresh CB-NK cells was significantly lower than that of peripheral blood mononuclear cells (PB MNCs). When CB was incubated with IL-2, the level of CB-NK cytotoxicity was increased and boosted to the level observed in PB-NK cells. Fresh CB-NK cells induced apoptosis in target cells. Activated CB cells induced apoptosis and necrosis in target cells, at the same level as PB MNCs. CB stem cell transplantation may also induce graft-versus-host disease (GVHD)/graft-versus-leukaemia (GVL), similar to bone marrow transplantation.

Apoptosis↗
PubMed1997

mRNA expression of Fas receptor (CD95)-associated proteins (Fas-associated phosphatase-1/FAP-1, Fas-associating protein with death domain/FADD, and receptor-interacting protein/RIP) in human leukaemia/lymphoma cell lines.

mRNA expression of Fas (CD95)-associated proteins [Fas-associating protein with death domain (FADD), receptor-interacting protein (RIP), and Fas-associated phosphatase-1 (FAP-1)] has been investigated in 26 Fas-positive human leukaemia/lymphoma cell lines. Reverse transcriptase-polymerase chain reaction analysis revealed that FADD and RIP mRNA were invariably expressed in both Fas-sensitive and Fas-insensitive cell lines. However, FAP-1 mRNA was detected in only 11 of 26 cell lines. Interestingly 7/14 cell lines in the Fas-sensitive group were positive for FAP-1 mRNA expression. 8/12 cell lines in the Fas-refractory group did not express FAP-1 mRNA, but half of these cell lines were susceptible to tumour necrosis factor alpha-induced growth inhibition. These findings suggest that the presence or absence of FAP-1 mRNA expression did not always correlate with relative sensitivity of Fas-mediated growth inhibition. Furthermore, it is assumed that leukaemia/lymphoma cells could possess structural or functional defects of Fas or Fas-associated proteins resulting in the failure to trigger apoptotic cell death.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Fas/APO-1 (CD95)-mediated cytotoxicity is responsible for the apoptotic cell death of leukaemic cells induced by interleukin-2-activated T cells.

Apoptotic cell death is induced by the cross-linking of Fas/APO-1 receptor (CD95) in acute myelogenous leukaemia (AML) cells. Since CD95 ligand (CD95L) is expressed on interleukin-2 (IL-2)-activated T cells, we investigated the involvement of CD95-CD95L pathway in T cell-mediated cytotoxicity against AML cells. Activated CD8+ T cells could efficiently kill a parental CD95-sensitive AML cell line, MML-1 and, to a lesser extent, a CD95-resistant clone, MML-1R. Neither MML-1 nor MML-1R cells were killed by activated CD4+ T cells. The blocking monoclonal antibody (MoAb) against CD95, ZB4, caused a significant inhibition of T-cell-mediated cytotoxicity against MML-1 cells but not against MML-1R cells. Interestingly, MML-1 cells underwent the classic nuclear morphologic changes and DNA fragmentation characteristic of apoptosis when cultured with activated T cells. Enumeration of apoptotic and necrotic nuclei showed that both apoptosis and necrosis were induced in MML-1 cells, whereas necrosis was exclusively observed in MML-1R cells. Apoptosis of MML-1 cells was completely blocked in the presence of ZB4 MoAb. Similarly, blocking by ZB4 MoAb significantly inhibited T-cell-mediated lysis of fresh AML cells in a CD95-sensitive group, but not in a CD95-refractory group. In addition CD8+ T cells expressed CD95L mRNA more abundantly than CD4+ T cells upon activation by IL-2. These findings suggest that T-cell-mediated cytotoxicity against AML cells requires participation of CD95-CD95L pathway for cytotoxic signal transduction leading to target apoptosis.

Apoptosis↗
PubMed1997

2',5'-Oligoadenylate synthetase activity and T cell subset in the cerebrospinal fluid and peripheral blood of aseptic meningitis.

2',5'-oligoadenylate synthetase activity, which is assumed to be induced by interferon, is reported to be one of the useful markers reflecting interferon activity. The enzyme activity of patients with aseptic meningitis and febrile convulsion were compared in order to evaluate interferon activity as one of the local immuno-defense mechanisms of aseptic meningitis. The surface antigen of mononuclear cells in cerebrospinal fluid and peripheral blood of some patients with aseptic meningitis was also measured. The enzyme activity of patients with aseptic meningitis was 191.4 pmol/dL in the cerebrospinal fluid and 395.8 pmol/dL in the serum during the acute phase, while that of patients with febrile convulsion was 45.2 pmol/dL in the cerebrospinal fluid and 326.0 pmol/dL in the serum. The enzyme activity of the former patients significantly decreased during the recovery phase in both the cerebrospinal fluid and serum. CD3 positive cells in the peripheral blood were 56.3% of the total mononuclear cells during the acute phase and 65.2% during the recovery phase, whereas in the cerebrospinal fluid mononuclear cells, they were 87.1 and 85.5%, respectively. During the acute phase, CD4 positive cells were the predominant T lymphocyte subset in the cerebrospinal fluid cells, while CD8 positive cells were predominant during the recovery phase. The relative proportions of CD4 positive and CD8 positive cells during the acute and recovery phase in the cerebrospinal fluid mononuclear cells were quite high compared to the recovery phase, although that ratio of peripheral blood mononuclear cells was not changed throughout the course. It was concluded that T lymphocytes and increased 2',5'-oligoadenylate synthetase activity in the cerebrospinal fluid may be one of the important components in the local inflammatory process independent of the systemic host defense mechanism in aseptic meningitis.

2',5'-Oligoadenylate Synthetase↗
PubMed1997

Cytotoxic T-lymphocytes recognizing P-glycoprotein in murine multidrug-resistant leukemias.

A multidrug-resistant murine lymphoid leukemia P388/ADR overexpresses P-glycoprotein (P-gp), an active transporter that pumps cytotoxic drugs out of cells and a product of mdr1 gene. Cytotoxic T lymphocytes (CTL) that showed cytotoxicity against P388/ADR were generated from mixed lymphocyte tumor cell culture. CTL do not kill drugsensitive parental P388 (P388/parent) that does not express P-gp. Monoclonal antibody against P-gp inhibited cytotoxic activity. Similar results were obtained in another multidrug-resistant cell line P388/VP-16. Cytotoxic activity was mediated by Thy1+ CD4- CD8+ T-cells. When P388/ADR was treated with murine IL-4, expression of P-gp was downregulated. Monoclonal antibody against interleukin-4 (IL-4) abrogated the IL-4-induced suppression of P-gp. Cytolytic activity of CTL against IL-4-treated P388/ADR was dose dependently inhibited. These results suggest that P-gp is immunogenic and can be a target of CTL in this murine leukemia model.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

A case of prolonged human parvovirus B19 DNA-emia associated with polyclonal B cell activation.

The current paper reports an 8 year old girl with arthralgia and polyclonal B cell activation induced by human parvovirus B19 infection (HPV B19). The infection was diagnosed by the presence of the virus genome in sera. The patient presented with transient arthritis in the wrist, ankle joint and neck and elevation of immunoglobulin IgM antibodies to HPV B19 and rubella, antibodies to Mycoplasma and antistreptolysin O but without the typical clinical features of erythema infectiosum. The polyclonal B cell activation was paralleled by the presence of the virus genome of HPV B19 in sera. In some children with arthralgia, it is important to examine the genomes of viruses that may cause arthritis as well as the antibody titers to the viruses.

Arthralgia↗
PubMed1996

Activation of human monocyte functions by tumor necrosis factor: rapid priming for enhanced release of superoxide and erythrophagocytosis, but no direct triggering of superoxide release.

Tumor necrosis factor (TNF), like granulocyte-macrophage colony-stimul ating factor (GM-CSF), rapidly primed human monocytes for enhanced release of superoxide (O-2) stimulated by receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate (PMA), which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of suspended monocytes with 10 U/mL TNF for 10 minutes at 37 degrees C. The potency of the maximal priming effect was TNF> GM-CSF, and the combined effect of TNF and GM-CSF was greater than that of each cytokine alone. GM-CSF induced an increase in cytoplasmic pH but TNF did not. These findings suggest that TNF and GM-CSF activate monocytes through different mechanisms. TNF and GM-CSF by themselves never triggered O-2 release in suspended monocytes or monocytes adherent to endothelial cells, although both cytokines triggered massive release of O-2 in human neutrophils. In additions, TNF and GM-CSF induced tyrosine phosphorylation of a 42-kD protein in neutrophils but not in monocytes. These findings suggest that the TNF-receptor- or GM-CSF-receptor-mediated signaling pathways for triggering O-(2) release is active in neutrophils but inactive or defective in monocytes. TNF also enhanced phagocytosis of sialidase-treated autologous erythrocytes by monocytes, and this effect was further potentiated in the presence of autologous fresh serum. The significant enhancement of erythrophagocytosis was obtained at 1 U/mL TNF. At this concentration of TNF, the expression of C3bi-receptor (CD11b/CD18) was upregulated. These findings show that TNF rapidly primes human monocytes for enhanced release of O-(2) and erythrophagocytosis and suggest that TNF activates monocytes through autocrine or paracrine mechanisms at the inflammatory sites inasmuch as TNF is primarily produced by activated monocytes/macrophages.

Adult↗
PubMed1996

Rhabdomyolysis following administration of cyclophosphamide: a case report in a BMT recipient.

Massive rhabdomyolysis followed by myocardial necrosis was observed in a 14-year-old patient undergoing allogeneic bone marrow transplantation for severe aplastic anemia. Rhabdomyolysis was preceded by the administration of cyclophosphamide as part of a preparative regimen for transplantation Although the specific etiology of this rhabdomyolysis is still unknown, an association with high-dose cyclophosphamide should be noted.

Bone Marrow Transplantation↗
PubMed1996

Recurrent cold hemagglutinin disease following allogeneic bone marrow transplantation successfully treated with plasmapheresis, corticosteroid and cyclophosphamide.

A 10-year-old male with severe aplastic anemia following allogeneic BMT developed a hemolytic crisis on post-BMT day 67. The diagnosis of cold hemagglutinin disease was made based on the findings of anemia, reticulocytosis, positive direct Coombs test, and markedly elevated cold agglutinins. Anti-nuclear antibody and anti-DNA antibody were also increased. Plasmapheresis was effective as an emergency measure. Corticosteroid after plasmapheresis had a transient effect. At the second episode of hemolysis 6 months after BMT, immunosuppressive therapy with cyclophosphamide plus corticosteroid was successfully administered without negative effect on engraftment.

Anemia, Aplastic↗
PubMed1995

Successful treatment of an infant with veno-occlusive disease developed after allogeneic bone marrow transplantation by tissue plasminogen activator, heparin and prostaglandin E1.

A 15-month-old boy with severe aplastic anemia developed veno-occlusive disease (VOD) after allogeneic bone marrow transplantation (BMT), in which the preparative regimen included 50 mg/kg/day cyclophosphamide and anti-lymphocyte globulin for 4 consecutive days. The diagnosis was made based on clinical symptoms and data including, hepatomegaly, right upper quadrant abdominal pain, jaundice, ascites, coagulopathy and thrombocytopenia which was refractory to transfusions of platelet concentrate. We gave 2, 3, 5 and 5 mg/day/body of recombinant tissue plasminogen activator (tPA) followed by heparin and prostaglandin E1 (PGE1) effectively and without significant side effect on days 9, 10, 13 and 14, respectively. Clinical and biochemical improvement was steady and dramatic. We suggest that tPA following continuous heparin and PGE1 infusion may be useful in the treatment of VOD even in infantile cases.

Alprostadil↗
PubMed1995

Transient low level of IgG3 induced by sepsis.

Staphylococcus aureus sepsis developed in a 14 year old girl. Immunological evaluation revealed low level of IgG3, although total IgG level was normal. The level of IgG3 increased gradually along with the recovery from sepsis. Immunoglobulin replacement therapy might have been useful in this patient, even though the total immunoglobulin level was within normal limits.

Adolescent↗
PubMed1995

An infantile case of cytomegalovirus induced idiopathic thrombocytopenic purpura with predominant proliferation of CD10 positive lymphoblast in bone marrow.

An infant with cytomegalovirus infection (CMV) developed idiopathic thrombocytopenic purpura (ITP) at 4 months of age. A bone marrow (BM) aspiration showed a remarkable increase of immature megakaryocytes and prominent proliferation of lymphoblasts. Flow cytometric analysis of the bone marrow cells showed that the predominant cells in the lymphocyte cluster were of B-lineage (CD19) with CD10 (common acute lymphoblastic leukemia antigen) positive. Virus study showed a higher titer of CMV antibody. Cytomegalovirus DNA was detected by the polymerase chain reaction (PCR) method in urine, peripheral cells and marrow cells. Low-grade fever, diarrhea and petechiae were accompanied by mild liver dysfunction. Complete remission was made with intravenous high-dose immunoglobulin (IVIg) without progression to overt acute leukemia. The percentage of CD10+/CD19+ lymphocytes in bone marrow also diminished. We postulated that the proliferation of immature lymphocytes and megakaryocytes in bone marrow was caused by maturation arrest that might result from CMV infection.

Antigens, CD↗
PubMed1995

Acute hemolysis during cyclosporine therapy successfully treated with vitamin E.

The immunosuppressant cyclosporine induces acute hemolysis (hemolytic uremic syndrome) in some patients after transplantation, possibly because of its effects on the vascular endothelium. We report a case of Coombs-negative, non-immune severe hemolytic anemia during cyclosporine therapy after allogeneic bone marrow transplantation for severe aplastic anemia. Uremia was not observed. Vitamin E was effective in treating the intravascular hemolysis.

Acute Disease↗
PubMed1995

[The first case in Japan of unstable hemoglobin, Hb Buenos Aires [beta 85 (F1) Phe-->Ser], with parvovirus B19 infection (first case in Japan)].

A 9-year-old girl was admitted to Mie University Hospital June 25, 1992, complaining of fever, skin rash and pallor. Physical examination revealed anemia and hepatosplenomegaly. Laboratory findings showed normocytic normochromic anemia, increased reticulocyte counts and remarkably decreased haptoglobin level. Red blood cells had no morphological abnormality. Bone marrow examination showed erythroid hyperplasia without abnormal cells. Hemoglobin electrophoresis showed an abnormal band. The amino acid structure and sequence of the abnormal hemoglobin was determined to be an unstable hemoglobin, Hb Buenos Aires [beta 85 (F1) Phe-->Ser]. Sequence of genomic DNA and cDNA was compatible to Hb Buenos Aires. Parvovirus B19 infection was thought to have caused severe anemia due to hemolytic crisis in this patient because its IgM antibody was positive on admission. She recovered soon without any treatment and has been followed in the outpatient clinic. Her parents and brother showed no hemoglobin abnormality.

Base Sequence↗
PubMed1995

Successful bone marrow transplantation in a child with combined IgG subclass deficiency and neutropenia.

An 8-year-old boy with combined IgG1 deficiency and neutropenia underwent allogeneic BMT from his HLA-identical, MLC-negative sister, because immunoglobulin (Ig) infusions and prophylactic antibiotics failed to prevent life-threatening infections. Conditioning was with busulfan and cyclophosphamide, MTX and CYA were given for the prophylaxis of GVHD. For 16 months after BMT no serious infections have occurred and serum IgG1 levels have returned to the normal range without Ig replacement. BMT may be appropriate treatment for patients with IgG subclass deficiency who rarely respond to conservative therapy.

Bone Marrow Transplantation↗
PubMed1994

Consecutive cerebral MRI findings of acute relapsing disseminated encephalomyelitis.

A seven year old girl with acute relapsing disseminated encephalomyelitis (ARDEM) was observed with serial magnetic resonance imaging (MRI) examination. She had the first encephalomyelitis episode at the age of 2 years 9 months. She entered remission with steroid therapy. She suffered a recurrence at the age of 7. Steroid therapy was instituted and consecutive magnetic resonance imaging (MRI) was performed. In spite of rapid improvement of neurological abnormality with steroid and steroid pulse therapy, disseminated high intensity lesions in T2-weighted imaging which were considered as demyelination remained for a long time. Magnetic resonance imaging seems to be most suitable for evaluating the clinical condition and long-term follow-up of ARDEM.

Adrenal Cortex Hormones↗