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Biomedical subjects

Y Komada

Publications and source records attributed to Y Komada.

At least 109 records · Page 6Linked to original sources

Histological, immunohistochemical, and chromosomal studies on non-adrenal neuroblastomas without increased excretion of catecholamines and their metabolites in urine.

We reviewed our records for the last 10 years and found three of the 36 patients with neuroblastoma did not excrete significantly increased quantities of catecholamine metabolites in urine. All of these tumors were histologically characterized by small round cells and possessed a few dense core granules on the electron microscopic examination. All of them were reacted with anti-neuron-specific enolase (NSE) antibodies, OKB2, PI153/3 monoclonal antibodies (MoAbs). The HNK-1, BA-1, and SJ-9A4 MoAbs reacted with two out of three. One of them demonstrated a reciprocal translocation involving the short arm deletion of chromosome 1. This multidisciplinary study has been helpful in making more accurate diagnoses for neuroblastoma without classical clinical characters.

Catecholamines↗

Leukemia-specific serum from a child showing an immunofluorescent pattern distinct from J-5 monoclonal antibody directed for CD10 (common ALL antigen).

Leukemia-specific human antibody was detected in a child with acute lymphoblastic leukemia (ALL) treated with chemoimmunotherapy. Chemoimmunotherapy consists of standard chemotherapy and subcutaneous injections of irradiated ALL cells with a biological response modifier. This ALL-specific serum reacted in 60 out of 67 (89.5%) children with ALL and was not reactive with normal cells. Furthermore, this ALL-specific serum showed a different immunofluorescent pattern on dual staining as compared with J-5 monoclonal antibody directed for common ALL antigen (CALLA; CD10). J-5 did not block the reactivity of ALL-specific serum, and vice versa, when CD10-positive ALL cell lines were used as targets. These findings suggest the possibility that there exists an ALL-specific antigen(s) which is different from CALLA and that this antigen(s) elicits a tumor-specific antibody response.

Antibodies, Monoclonal↗

Autologous tumor-specific cytotoxic T-lymphocytes in a child with neuroblastoma.

Activation of peripheral blood lymphocytes from a neuroblastoma patient by co-cultivation with autologous neuroblastoma cells in a mixed lymphocyte-tumor cell culture (A-MLTC) resulted in the generation of cytotoxic activity against the autologous neuroblastoma cell line HNB-MS. A-MLTC was set up in the presence of recombinant human interleukin-2 (IL-2). HNB-MS stimulator was treated with recombinant human interferon-gamma (IFN-gamma) prior to A-MLTC. CTL generated in short-term culture effectively lysed HNB-MS, while they had no effect on an Epstein-Barr virus transformed autologous B-cell line EB-MS. Moreover, CTL lysed 3 different allogeneic neuroblastoma cell lines, but not a rhabdomyosarcoma cell line RBB. Recombinant human tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) enhanced and suppressed CTL generation, respectively, when added to the A-MLTC from the beginning of culture. CD3+ CD4- CD8+ T cells were the major anti-tumor effectors. Furthermore, 111indium-labeled CTL clearly accumulated in metastatic sites. These results indicate that CTL can be used for adoptive immunotherapy in neuroblastoma.

Abdominal Neoplasms↗

A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis.

We report a novel chromosome translocation--t(2;5)(p23;q35) or its variant, t(2;5;13)(p23;q35;q12)--in 3 patients with peripheral T-cell lymphoma. All 3 were female children who had peripheral lymphadenopathy without organomegaly and underwent complete remission with or without chemotherapy. Their tumors were characterized histologically by predominant large cells, at times showing phagocytosis, and immunologically by peripheral T-cell phenotype and expression of Ki-1 antigen and epithelial membrane antigen (EMA). Since the same translocation has been reported in the literature in 4 patients with malignant histiocytosis (MH), and our patients had histologic features suggestive of that disease, it is likely that many tumors previously interpreted as MH are actually phagocytic large T-cell lymphoma carrying this translocation.

Antigens, Differentiation↗

Discontinuing therapy in childhood acute lymphoblastic leukemia treated with a chemoimmunotherapy protocol.

We examined the results of discontinuing therapy in Japanese children with acute lymphoblastic leukemia. Of the 209 patients in the chemoimmunotherapy study, 120 (57.4%) had all chemotherapy stopped after 3 years of complete remission, and 72 (34.4%) reached the point of discontinuing immunotherapy after 5 years of complete remission. Of the 120 children removed from chemotherapy, 14 (11.7%) have relapsed, mainly in the extramedullary sites (5: testis, 5: bone marrow, 3: central nervous system, 1: bone); relapses occurred 1-23 months after cessation of chemotherapy (median 11 months). Boys had higher post-chemotherapy relapse rate than girls (0.21 versus 0.08, P less than 0.05). None of the 72 children removed from immunotherapy have yet relapsed. Long-term remission and possibly cure can be expected in approximately one-half of newly diagnosed Japanese patients. Although the active immunotherapy had no beneficial effect on the overall outcome for leukemic children, it could be of benefit to the elimination of bone marrow relapses after cessation of chemotherapy.

Antineoplastic Agents↗

[Lymphoblastic lymphoma associated with subcutaneous nodules, intramuscular mass, pericardial effusion and peripheral lymphadenopathy].

A 14-year-old boy was admitted to Department of Pediatrics at Mie University Hospital with a 12-day history of facial cervical edema associated with venous dilatation on the upper chest wall. On admission anterior mediastinal mass was found on chest X-ray film and computed tomography. A needle biopsy revealed non-Hodgkin's lymphoma, diffuse lymphoblastic type and he was staged as III. He was treated with High-risk lymphoma protocol and achieved complete remission. At relapse he developed various manifestations unusual for lymphoblastic lymphoma including peripheral lymphadenopathy, an intramuscular mass of the lt-lower leg, multiple subcutaneous nodules at anterior chest wall and upper abdomen, and pericardial effusion. No lymphomatous infiltration into bone marrow or central nervous system was observed throughout his clinical course. Immunological phenotype of lymphoma cells from pericardial effusion was quite compatible with that of common thymocytes. However cytogenetic analysis showed unique translocation: (2; 5) (q 33; q 35). Translocations with a break at 5 q 35 have been reported in peripheral T-cell lymphoma and malignant histiocytosis.

Adolescent↗

[Laboratory and clinical investigations of cefodizime in infectious diseases in childhood].

In this study, cefodizime (CDZM, THR-221) was administered to 34 children with infections and the efficacy was evaluated in 30 patients. The efficacy rate was 90.0% and CDZM was proved to be a highly effective antibiotic for infectious diseases in childhood. We also demonstrated that CDZM had strong antibacterial activities against both Gram-positive and Gram-negative bacteria. No severe toxicity related to intravenous injection of CDZM was observed in our 34 cases.

Age Factors↗

The non immunogenicity of CALLA in leukemic children.

The sera from 55 children with acute lymphoblastic leukemia (ALL) treated with active immunotherapy were examined for the presence of antibodies against common ALL antigen (CALLA). A solid phase indirect radioimmunometric assay (IRA) was developed which enabled the detection of anti-CALLA antibody in patients' sera, utilizing the ability of affinity-purified CALLA to bind Ricinus communis agglutinin and anti-CALLA antibody simultaneously. Using IRA, anti-CALLA antibody activity could not be detected in a majority of patients. We concluded that the patients did not raise comparable antibodies against CALLA, indicating this antigen is not immunogenic for ALL patients.

Antibodies, Neoplasm↗

A novel translocation, t(9;17)(q34;q23), in aggressive childhood lymphoblastic lymphoma.

In a chromosome study of childhood lymphoblastic lymphoma, we found a novel translocation, t(9;17)(q34;q23), in three patients. They presented with mediastinal mass and no bone marrow involvement. Despite intensive chemotherapy, one patient had no response, the other two relapsed after a brief remission, and all progressed to death. The 9;17 translocation may have a clinical implication for lymphoblastic lymphoma patients in predicting a poor prognosis. Since, in addition to our cases, involvement of the 9q34 breakpoint, together with 2q33, 14q11, or 7q34, has been reported in the literature in four lymphoblastic lymphoma patients, a gene located in 9q34 and referred to as tcl-3 may participate in the genesis of the T cell malignancies carrying these translocations. Furthermore, as is the case in other lymphomas, the reciprocal breakpoint, 17q23, might be the site of a yet unidentified T cell function gene.

Adolescent↗

Discontinuing chemoimmunotherapy in childhood acute lymphoblastic leukemia.

We examined the results of discontinuing therapy in Japanese children with acute lymphoblastic leukemia. Of the 209 patients in chemoimmunotherapy study, 120 (57.4%) had all chemotherapy stopped after 3 years of complete remission, and 72 (34.4%) reached the point of discontinuing immunotherapy after 5 years of complete remission. Of the 120 children removed from chemotherapy, 14 (11.7%) have relapsed, mainly in the extramedullary sites (5 testis, 5 bone marrow, 3 central nervous system, 1 bone); relapses occurred 1-23 months after cessation of chemotherapy (median 11 months). Boys had a higher post-chemotherapy relapse rate than girls (0.21 vs. 0.08, P less than 0.05). None of the 72 children removed from immunotherapy have yet relapsed. Long-term remission and possibly cure can be expected in approximately one half of newly-diagnosed Japanese patients. Moreover, the active immunotherapy could be of benefit to elimination of bone marrow relapses after cessation of chemotherapy in children with acute lymphoblastic leukemia.

Adolescent↗

Shedding of leukemia-associated P24 antigen by lymphoblastoid cell lines.

We report the development of a unique enzyme-linked immunosorbent assay (ELISA) which makes possible the detection of leukemia-associated P24 antigen, utilizing its ability to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4 simultaneously. Using the RCA1/SJ-9A4-ELISA, P24 antigen, as few as 50 X 10(3) cells from a common acute lymphoblastic leukemia (C-ALL) cell line could be detected. The presence of D-galactose gave complete and specific inhibition of P24 antigen binding to RCA1. Matched concentrations of D-glucose and D-sucrose had no effect on binding. The release of the P24 antigen into the culture medium by a C-ALL cell line maintained at 37 degrees C could be detected; however, no P24 antigen was present in the culture medium when the cells were maintained at 4 degrees C. Sequential analysis of the culture medium for soluble P24 antigen revealed that release of the P24 antigen associated with cell growth. Molecular sieve chromatography of concentrated culture medium indicated that shed P24 antigen was eluted in the macromolecule fraction. P24 antigen was detected in the cerebrospinal fluid (CSF) of four patients with P24 positive ALL at the time of relapse of the central nervous system (CNS) and was undetectable while in complete remission. The CSF from three patients with P24 negative ALL and three patients with aseptic meningitis had no detectable activity.

Antibodies, Monoclonal↗

Predictable risk factors in children with acute lymphoblastic leukemia.

The predictable prognostic factors were analysed among 174 children with acute lymphoblastic leukemia who were treated during the last ten years under different protocols in one institute. It was confirmed that the children under 1 year of age, or with T-cell marker, had poor prognosis. The initial WBC of more than 50,000/mm3 was less significant as a predictable risk factor with chemotherapy of the newer protocols. Cell kinetic study was found to be of no more help than the initial WBC, but a more accurate prediction could be obtained by measuring glucocorticoid receptor of leukemic cells. The prognosis was poor among children with initial WBC of more than 50,000/mm3 and receptors of less than 20,000 sites per cell.

Child↗

Shedding of the common acute lymphoblastic leukemia antigen (CALLA) by lymphoblastoid cell lines.

The release of common acute lymphoblastic leukemia antigen (CALLA) into culture medium by lymphoblastoid cell lines was studied. CALLA release was detected using a solid phase indirect radioimmunometric assay which combines the specificity of lectins and monoclonal antibodies and using immunoadsorption of labeled CALLA in spent medium from cells incubated with 35S-methionine. No CALLA was present in the medium of cells pulse-labeled at 37 degrees C, when they were placed at 4 degrees C, thus this is an active process. Sequential analysis of soluble CALLA revealed shedding of CALLA to be associated with cell growth.

Antibodies, Monoclonal↗

Immunological subclassification of non-T, non-B acute lymphoblastic leukaemia in childhood.

41 cases of non-T, non-B acute lymphoblastic leukaemia (ALL) were classified by immunological criteria using a panel of monoclonal antibodies against common ALL antigen (cALLa), p24, p20 and HLA-DR antigens. Out of 41 cases, cALLa, p24, p20 and HLA-DR antigens were positive in 31 cases, 34 cases, 35 cases and 41 cases, respectively. 4 cases expressing cytoplasmic mu heavy chains were included in the group of common ALL. We demonstrated that a majority of non-T, non-B ALL would be derived from B-lineage cells. The expression of p24 and p20 was followed by the expression of cALLa and the synthesis of cytoplasmic immunoglobulin. These items of evidence support the idea that the expression of cALLa, p24, p20 and HLA-DR antigens on ALL cells would be universal in the USA, Europe and Japan. Although morphologically identical, non-T, non-B ALL cases could be subdivided into phenotypically-defined subgroups on the basis of cALLa, p24, p20 and HLA-DR antigens.

Antibodies, Monoclonal↗

A monoclonal antibody (SJ-9A4) to P24 present on common alls, neuroblastomas and platelets - I. Characterization and development of a unique radioimmunometric assay.

We report the development and characterization of SJ-9A4, a monoclonal antibody (MoAb) produced against common acute lymphoblastic leukemia (C-ALL) cell lines. SJ-9A4 reacted with C-ALL, B-cell chronic lymphocytic leukemia (B-CLL), platelets and C-ALL neuroblastoma (NB) and the K562 cell lines. It had no significant reactivity with erythrocytes, granulocytes, circulating T or B lymphocytes, monocytes, granulocytic cell lines or a Ewing's sarcoma cell line. SJ-9A4 was shown to recognize the same region as two other MoAb to the p24 antigen, BA-2 and DU-ALL-1, as demonstrated by their ability to inhibit the binding of labeled SJ-9A4 to NALM-1 and NB cells. Other MoAb: J5, PI 153/3 and monoclonal anti-HLA-DR antibodies gave no inhibition. A solid phase indirect radioimmunometric assay (IRA) was developed which enabled the detection of P24 from C-ALL cells, utilizing its ability to bind the Ricinus communis agglutinin (RCA1) or wheat germ agglutinin (WGA) and SJ-9A4 simultaneously. When BA-2 and DU-ALL-1 were used in place of SJ-9A4, similar IRA results were obtained. Using the RCA1/SJ-9A4-IRA, P24 from as few as 1.6 X 10(4) cells of a C-ALL cell line could be detected; however, similar extracts of NB cell lines were negative despite high levels of SJ-9A4 binding to intact cells. The presence of P24 in NB extracts was demonstrated by (1) preincubation of NB extracts with SJ-9A4 which blocked MoAb binding to P24 and (2) immunoadsorption of P24 from solubilized membranes of 35S-methionine (met) labeled NB cells. Treatment of NB cells with neuraminidase did not result in IRA binding when either RCA1 or WGA were used as the solid phase lectin indicating that the differences in lectin affinity are not due to over sialation of NB membrane glycoproteins. These findings demonstrate a difference in the glycosylation of P24 from C-ALL and NB cells.

Antibodies, Monoclonal↗

A monoclonal antibody (SJ-9A4) to P24 present on common alls, neuroblastomas and platelets - II. Characterization of P24 and shedding in vitro and in vivo.

The release of soluble P24 antigen into culture medium by common acute lymphoblastic leukemia (C-ALL) and neuroblastoma (NB) cell lines was studied. P24 release by C-ALL cells was detected using a solid phase indirect radioimmunometric assay (IRA) which combines the specificity of lectins and monoclonal antibodies (MoAb) and using immunoadsorption of labeled P24 in spent medium from cells incubated with 35S-methionine (met). No P24 was present in the medium of cells pulse labeled at 37 degrees C when they were placed at 4 degrees C, thus this is an active process. P24 release by NB cells could not be detected by IRA, but could be detected by immunoadsorption of spent medium of metabolically-labeled cells. The absence of IRA activity of P24 from NB spent medium was due to decreased glycosylation and thus no binding to the lectins employed in the IRA was observed. This was confirmed by lectin affinity chromatography which showed that P24 in the spent medium from C-ALL cells bound Ricinus communis agglutinin (RCA1), wheat germ agglutinin (WGA), concanavalin A (Con A), and lentil lectin (LcH), but not peanut agglutinin (PNA). P24 from NB cell spent medium did not bind to any of these lectins. The lectin affinity of P24 derived from lymphoblasts is consistent with the presence of N-linked oligosaccharide chains having N-acetyl glucosamine residues, a mannose core, and a terminal D-galactose. P24 from C-ALL cell spent medium was present in the 35-45% fraction of a saturated ammonium sulfate (SAS) partition of spent medium. The P24 antigen was detected in the fractionated plasma of five patients with C-ALL at the time of diagnosis and was undetectable when the patients had achieved a complete remission. Plasma from 2 patients with P24 negative ALL, normal human plasma, and normal human serum had no detectable activity.

Antibodies, Monoclonal↗