Biomedical subjects

Y Komada

Publications and source records attributed to Y Komada.

115 records · Page 7Linked to original sources

PubMed1982

[Experience with high-dose methotrexate therapy for malignant solid tumors].

Thirteen patients with malignant solid tumors, mainly osteogenic sarcomas, were treated by high-dose MTX therapy, 50-400 mg/kg, in a total of 72 cycles. It has been proved that this therapy was relatively safe provided careful clinical surveillance were assured. Of 8 patients with osteogenic sarcomas, 6 had no metastatic lesions on the chest X-rays before this therapy: three were alive without any evidence of disease for 18-25 months after high-dose MTX therapy. In some cases of other malignant solid tumors, particularly intracranial tumors, clinical efficacy was observed. Dose-time relationships, etc. should further be studied for more therapeutic efficacies of high-dose MTX therapy.

Adolescent↗

PubMedDate not supplied

A child case of CD34+, CD33-, HLA-DR-, CD7+, CD56+ stem cell leukemia with thymic involvement.

It has been reported that the CD56+/CD7+/CD3- phenotype of natural killer (NK) cells develop from the CD34+/HLA-DR- bone marrow (BM) mononuclear cell population in long-term BM culture (LTBMC). An HLA-DR-/CD33+/CD56+/CD16- myeloid/natural killer cell acute leukemia has been described. We report here a 7-year-old boy who developed stem cell acute leukemia with superior vena cava syndrome secondary to thymic involvement. Surface marker analyses revealed that the leukemia cells showed CD34+/HLA-DR-/CD33-/CD7+/CD56+ phenotype. When stimulated with phorbol ester in vitro the leukemic cells morphologically differentiated to myeloid cells developing CD13, CD15 and CD56 antigens. Our results suggest that CD34+/HLA-DR-/CD7+/CD56+ stem cell leukemia may arise from transformation of a pluripotent precursor cell, which could differentiate to both myeloid and NK cell lineages.

Antigens, CD↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Prevention of pleural effusion after hepatectomy using fibrin sealant.

Retention of pleural effusion after hepatectomy is an important complication that may affect the postoperative course. However, there are few reports on its pathogenesis or preventive measures. We evaluated the mechanism of the development of this complication and preventive measures against it. During the past 4-year period, hepatectomy was performed in 77 patients, of whom 64 underwent liver mobilization by transecting the hepatic ligaments. A fibrin sealant was sprayed on the cut surface of the hepatic ligaments in randomly selected 25 of the 64 patients to determine whether this application can prevent postoperative retention of pleural effusion. Post-operative pleural effusion was not observed in any patient treated by fibrin sealant spraying but was observed in 13 (30%) of the other 39 patients treated with this sealant (p < 0.05). In addition, none of the 23 patients in whom the liver was not mobilized during hepatectomy showed postoperative pleural effusion. These results suggest that severance of the hepatic ligaments is a major cause of pleural effusion, and application of a fibrin sealant to the undersurface of the diaphragm around the insertion of the liver ligaments is useful for preventing this complication.

Drainage↗