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Biomedical subjects

E Azuma

Publications and source records attributed to E Azuma.

97 records · Page 6Linked to original sources

Successful immunization following cord blood transplantation in a child with Diamond-Blackfan anemia.

Cord blood transplantation (CBT) has been increasingly used to treat patients with hematological diseases, but active immunizations for patients have not been described. Patients certainly need immunizations following CBT, since transplanted cord blood is naive. The authors previously reported successful hematopoietic reconstitution following cord blood transplantation from an HLA-matched sibling in a transfusion-dependent child with Diamond-Blackfan anemia. No graft-versus-host disease, either acute or chronic, has been observed so far. Here, the authors report that immunological recovery of the patient has been rapid shortly after CBT and immunization has been done successfully. Vaccines (diphtheria, pertussis, tetanus, rubella, measles, and BCG) were administered during 22-34 months post-transplant. Seroconversion to these vaccines was excellent without significant adverse effects. These results indicate that both toxoid and live vaccines have been safely administered in the patient who underwent related cord blood transplantation.

Antibody Formation↗

Histochemical demonstration of peripheral autonomic innervation in canine nasal mucosa by retrograde axonal transport of horseradish perioxidase.

The peripheral autonomic nervous pathways of the nasal mucosa in dogs were investigated by the horseradish peroxidase (HRP) method. HRP was applied to the nasal mucosa, caudal nasal nerve, ethmoidal nerve, vidian nerve and pterygopalatine ganglion in 20 dogs, and retrogradely labelled neurons were observed in the superior cervical ganglion (SCG) and the pterygopalatine ganglion (PPG) by the blue reaction method. It was suggested that the vidian nerve, the maxillary branch of the trigeminal nerve, the caudal nasal nerve, the pterygopalatine nerve and the ethmoidal nerve contained the postganglionic sympathetic fibres which originated in SCG and terminated in the nasal mucosa. Moreover, other sympathetic pathways, such as those around the blood vessels, were also suggested to be a main route. It was suggested that the postganglionic parasympathetic fibers originating in PPG travelled along the caudal nasal nerve and the ethmoidal nerve.

Animals↗

Central origin of canine vidian nerve studied by the HRP method.

Central origin of the vidian nerve in the dog was investigated using the retrograde tracing technique of horseradish peroxidase (HRP). After HRP was applied to the vidian nerve, labelled neurons were found in the medulla oblongata and the geniculate ganglion but could not be found in the trigeminal ganglion. Labelled neurons in the medulla oblongata were found not only in the dorsal part but also in the ventral part to the facial motor nucleus and were maximum in number at the level of the rostral third of the facial motor nucleus. These labelled neurons were generally medium-sized multipolar neurons with well-developed dendrites.

Animals↗

Functional significance of adhesion molecules in Fas-dependent apoptotic cell death induced by interleukin-2-activated T cells.

We investigated the functional significance of the adhesion molecules CD2 and lymphocyte function-associated antigen-1 (LFA-1: CD11a/CD18) in Fas-Fas ligand (FasL) death pathway. Interleukin-2-activated T cells expressed a large amount of FasL protein and could efficiently kill a Fas-sensitive leukemic cell line, MML-1. The major part (over 80%) of MML-1 cell death was Fas-dependent. Antibodies to CD2 and CD11a/CD18 completely inhibited MML-1 target cell lysis, whereas effector to target cell binding was partially reduced or not affected at all. These results suggest that effector/target interaction via CD2/CD58 and LFA-1/CD54 systems would be essential for triggering target cell death. More interestingly, there is the discordance in the ability of anti-CD2, and particularly anti-LFA-1 antibodies, to block Fas-dependent cell death versus effector to target conjugate formation. This suggests some non-adhesive role for CD2 and LFA-1 in induction of Fas-dependent cell death. Although these antibodies were capable of inhibiting T cell proliferative response, there was no significant reduction of FasL or granzyme B expression. Thus, the signaling pathway for growth inhibition via CD2 and LFA-1 could not be linked to signaling for FasL and granzyme B expression.

Antibodies, Monoclonal↗

CD3-mediated T cell activation is inhibited by anti-CD44 monoclonal antibodies directed to the hyaluronan-binding region.

The CD44 molecule has been shown to play a role in T cell adhesion and activation. We have investigated the ability of five anti-CD44 monoclonal antibodies (MoAb) including 15C6, 18A3, BU75 (Ancell), J173 (Immunotech), and L178 (Becton Dickinson) to regulate T cell activation. Three MoAb: 15C6, BU75, and J173 were found to selectively inhibit DNA synthesis, interleukin-2 (IL-2) receptor expression, and G1-->S transition of the cell cycle in T cells stimulated with anti-CD3 MoAb. None of anti-CD44 MoAb had influence on T cell proliferation induced by IL-2 or phorbol 12-myristate 13-acetate plus ionomycin. Inhibition of the CD3 pathway by anti-CD44 MoAb occurred by binding of MoAb directly to T cells without the involvement of monocytes or Fc receptors. In addition, the inhibitory anti-CD44 MoAb clearly suppressed intracellular calcium mobilization in T cells stimulated with anti-CD3 MoAb. Interestingly, the ability of anti-CD44 MoAb to inhibit T cell activation was well correlated with their capability to block the binding of hyaluronan (HA) to CD44 molecules. These results suggest that anti-CD44 MoAb directed to HA-binding site could selectively inhibit CD3-mediated T cell activation. Furthermore, CD44-mediated inhibitory signals would be linked to the blocking of early CD3-mediated signal transduction.

Animals↗

Transient encephalopathy following a single exposure of high-dose methotrexate in a child with acute lymphoblastic leukemia.

An episode of transient encephalopathy after the first course of intravenous high-dose methotrexate (HD-MTX; 1000 mg/m2) was observed in a 4-year-old girl with acute lymphoblastic leukemia. The neurological abnormalities took place 5 days after HD-MTX therapy. She experienced complex partial seizure and left hemiparesis, which resolved spontaneously in 5 days. Cranial computed tomographic scan and magnetic resonance imaging showed multiple low-density lesions in bilateral hemispheres. It is well appreciated that neurotoxicity from MTX follows prolonged exposures, often accompanying or following radiation therapy. To our knowledge, however, there have been no reports that such neurological complications developed following a single exposure of HD-MTX in patients with ALL. Follow-up electroencephalograms showed that she had periodic lateralized epileptiform discharges (PLEDS), suggesting functional deafferentation of cortical neurons following HD-MTX. Moreover, the serum and CSF MTX levels following a second low-dose course and her clinical course suggested that she had presumably central nervous system leukemia at the time of HD-MTX therapy, which might have been related to neurological complications. The pathogenesis of MTX-induced neurotoxicity is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Ataxia telangiectasia associated with B-cell lymphoma: the effect of a half-dose of the drugs administered according to the acute lymphoblastic leukemia standard risk protocol.

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, and variable degrees of humoral and cellular immunodeficiency. Affected individuals are known to exhibit a high incidence of lymphoma and leukemia. Because of increased chemosensitivity, the treatment of A-T patients with malignancies requires extremely careful planning and caution with respect to the use of chemotherapy. The authors report on a 12-year-old boy with A-T who developed B-cell lymphoma. He received a half-dose of the drugs administered according to the acute lymphoblastic leukemia (ALL) protocol issued by our children's cancer study group (9104 Standard Risk Protocol, Tokai Pediatric Oncology Study Group). As a result, he continues to be in complete remission and free of treatment complications 32 months after the diagnosis of B-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗