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Biomedical subjects

J Takayama

Publications and source records attributed to J Takayama.

At least 37 records · Page 2Linked to original sources
PubMed1998

Peripheral blood stem cell autografts for the treatment of children over 1 year old with stage IV neuroblastoma: a long-term follow-up.

This is the first report of the long-term therapeutic results in 22 children more than 1 year old with stage IV neuroblastoma who were treated with autologous peripheral blood stem cell transplantation (PBSCT). The median age of the patients at PBSCT was 4 years (1 to 10 years) and seven of the 17 patients who were evaluated for N-myc amplification were positive. PBSC were collected by a median of four aphereses per patient. The patients underwent PBSCT from 6 to 21 months after the start of therapy (median 10.5 months) at which time 13 patients were in CR, seven were in PR, and two had refractory disease. Multi-drug therapy using the 'high-MEC' regimen consisting of carboplatinum (400 mg/m2) and VP-16 (200 mg/m2) on days -7 to -4, and melphalan (90 mg/m2) on days -3 and -2, was the primary cytoreductive regimen. The median number of infused MNC and CFU-GM was, respectively, 4.3 x 10(8)/kg and 2.4 x 10(5)/kg. After PBSCT, three patients died of regimen-related toxicities and one patient who was transplanted with refractory disease died of disease progression without any benefit from transplantation. Hematological recovery was evaluated in 21 patients, excluding one early death. The median number of days required to achieve an AGC of >0.5 x 10(9)/l and platelet count of >50 x 10(9)/l were, respectively, 11 and 46. Eleven patients relapsed 3 to 50 months after PBSCT, and currently seven patients (5/13 who were transplanted in CR and 2/7 in PR) are surviving disease-free at 52 to 84 months. Although the retrospective nature of this study and several variables prevent a meaningful analysis, the overall results still support the feasibility of developing a prospective study of PBSCT with a larger number of children with high-risk neuroblastoma.

Child↗
PubMed1998

Second primary rhabdomyosarcomas in patients with bilateral retinoblastoma: a clinicopathologic and immunohistochemical study.

We reviewed six cases of rhabdomyosarcoma as a rare second primary malignancy in children with bilateral retinoblastoma after irradiation treatment. The patients comprised four females and two males (age range 1 year 4 months-7 years 11 months). Second tumors arose in the temporal muscle inside or close to the previously irradiated fields. All the children were alive and well 24-72 months after diagnosis. Microscopic examination showed proliferation of closely packed, small round cells with scanty cytoplasm, coarse nuclear chromatin, and increased mitotic activity without a myxoid background nor obvious alveolar architecture. The most characteristic feature was the presence of rosette-like structures in four tumors. Immunoreactivity for many skeletal muscle markers was evident, including desmin (six of six), muscle-specific actin (HHF35) (six of six), sarcomeric actin (six of six), myogenin (six of six), vimentin (six of six), and myoglobin (three of six). On reverse transcriptase-polymerase chain reaction examination, three second tumors lacked specific chimeric transcripts for alveolar rhabdomyosarcoma and Ewing's sarcoma. Unexpectedly, variable reactivity for neurofilament (150 kd) was identified in six of six second tumors as well as 15 of 20 sporadic primary rhabdomyosarcomas (75%) examined as controls, the result being confirmed by Western blot analysis. In addition, staining for retinoblastoma-susceptibility gene protein was negative in all second tumors, in contrast to positivity in 14 of 17 sporadic primary tumors (82%). This finding suggests that retinoblastoma-susceptibility gene abnormalities could be associated with the development of second primary rhabdomyosarcoma. We consider that knowledge of the occurrence of rhabdomyosarcoma and appropriate immunohistochemical study are helpful for avoiding a misdiagnosis of recurrent retinoblastoma or Ewing's sarcoma when encountering patients with a history of bilateral retinoblastoma who developed second small round cell neoplasms.

Antigens, Neoplasm↗
PubMed1997

[Improvement in function-preservation in radiotherapy for pediatric malignancies].

In radiotherapeutic management for pediatric tumors, we have to pay more attention to confinement of higher dose to the target volume than for adult tumors, in order that the risk of untoward normal tissue complications dose not increase, such as growth retardation. Two current approaches performing in our department to match this purpose are presented, namely, perioperative brachytherapy and fractionated stereotactic radiotherapy (F-SRT). In perioperative brachytherapy for bone and soft tissue sarcoma, plastic guide tubes for introducing radioactive sources are placed in the residual tumor bed or at the margins during the surgery, and patients are treated by high-dose-rate brachytherapy after surgery. Patients are not restricted in radioprotective area, and the overall treatment period is short enough. F-SRT is used either as the boost of conventional brain radiotherapy in primary brain neoplasms, or as hypofractionated F-SRT for control of metastatic brain tumors, with nearly perfect local control and maintenance of good quality of life. F-SRT is planned in 3-dimensional fashion from computed tomography images. Easily detachable, relocatable cast made for F-SRT is useful in pediatric patients.

Brachytherapy↗
PubMed1996

Herpes zoster infection after bone marrow transplantation in children.

OBJECTIVE: To determine the frequency of, risk factors for, and clinical course of herpes zoster (HZ) after bone marrow transplantation (BMT) in children. STUDY DESIGN: A total of 107 children with hematologic malignancy or solid tumor who underwent allogeneic or autologous BMT were studied retrospectively. RESULTS: Of the 107 patients, HZ developed in 35 (33%) after BMT; 31 (89%) of these 35 patients had localized HZ. The median onset of infection was day 96 after BMT, and 89% of cases of HZ occurred before day 365 after BMT. HZ developed in 26 (58%) of 45 patients (13/21 (62%) allogeneic and 13/24 (54%) autologous patients) with hematologic malignancy; most of these patients had undergone total body irradiation. Of 33 patients with solid tumor, HZ developed in 9 (27%). All patients with HZ were treated with acyclovir, and no patients died of complications directly resulting from HZ. CONCLUSION: Herpes zoster occurred earlier after BMT than in adults, and it occurred frequently in children who had hematologic malignancy and/or had undergone total body irradiation. Prompt antiviral therapy reduced the mortality rate and significant morbidity associated with HZ.

Acyclovir↗
PubMed1996

A novel human leukaemic cell line, CTS, has a t(6;11) chromosomal translocation and characteristics of pluripotent stem cells.

A novel human leukaemic cell line, designated CTS, was established from the peripheral blood of a 13-year-old girl suffering from acute myeloblastic leukaemia (AML) in relapse. CTS cells expressed CD7, CD13, CD33, CD34 and HLA-DR antigens, and showed ultrastructural myeloperoxidase activity. In addition, CTS cells showed DNA rearrangements of the immunoglobulin heavy chain gene and the light kappa chain gene, and deletions of the T-cell receptor delta 1 gene. Cytogenetic analysis revealed a human female diploid karyotype with a t(6;11)(q27;q23) chromosomal translocation. Molecular studies demonstrated a DNA rearrangement of the MLL gene, the expression of a truncated 11.0 kb MLL mRNA and the detection of the MLL/AF-6 fusion transcript in CTS cells. To our knowledge, this cell line is the first report of a human leukaemic cell line with a t(6;11) chromosomal translocation. CTS cells showed no significant proliferative response to the cytokines, IL-2, IL-3, IL-6, IL-11, GM-CSF, G-CSF, EPO, SCF, but were induced to differentiate to the T-cell, B-cell, erythroid or megakaryocytic lineage in the presence of particular cytokines. This CTS cell line may provide a useful tool in the study of the oncogenesis of mixed lineage leukaemia with 11q23 abnormalities and for the analysis of growth and differentiation of pluripotent stem cells.

Adolescent↗
PubMed1996

Osteochondroma after total body irradiation in bone marrow transplant recipients: report of two cases.

We present two cases of osteochondroma after total body irradiation in bone marrow recipients, the first in a 6-year-old boy with juvenile chronic myelogenous leukemia and the second in a 13-year-old boy with acute myelogenous leukemia. The patients developed multiple osteochondromas three years and seven years, respectively, after 12 Gy of total body irradiation. Neither had a family history of hereditary multiple osteochondromatosis. A review of the English literature revealed only one report describing five cases of osteochondroma after 12 Gy of total body irradiation in bone marrow transplant recipients. Osteochondroma should be considered as an additional adverse effect of total body irradiation.

Adolescent↗
PubMed1995

Prognostic value of proliferating cell nuclear antigen (PCNA) immunostaining in neuroblastoma.

Immunostaining for proliferating cell nuclear antigen (PCNA), a marker of cell proliferation, is being increasingly used to study the proliferative activity of tumors, and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms. Formalin-fixed, paraffin-embedded tissue specimens of 24 primary neuroblastomas were immunostained using an anti-PCNA monoclonal antibody and the PCNA index was calculated. Then the relationship between the PCNA index, prognosis, and various other factors was assessed, retrospectively. The mean PCNA index was 11.0%. Patients having tumors with a high PCNA index (> or = 11.0%) showed a significantly lower survival rate than those possessing tumors with a low PCNA index (P < 0.001). Moreover, the tumors showing N-myc amplification had a high mean PCNA index of 15.6%, while those without N-myc amplification had a low mean index of 1.7% (P < 0.01). The PCNA index was closely related to the prognosis of neuroblastoma and to N-myc amplification. It has the potential to be a useful prognostic indicator of the patients with neuroblastoma.

Child↗
PubMed1994

Mutations in the retinoblastoma gene and their expression in somatic and tumor cells of patients with hereditary retinoblastoma.

Two intragenic deletions (exon 18-19 and exon 24) and two point mutations (one missense mutation in exon 21 and one mutation at splice-donor site for exon 13) were detected in the retinoblastoma gene in somatic and tumor cells of patients with hereditary retinoblastoma. Three mutations were located in a domain essential for binding to oncoproteins encoded by DNA tumor viruses (Hu et al., 1990; Huang et al., 1990). One mutation (deletion of exon 24) was outside this domain but it is in the region essential for binding to transcriptional factor E2F, and for suppression of malignant phenotypes (Qian et al., 1992; Qin et al., 1992). A minisatellite-like sequence and short repeated sequences were located at the breakpoint of the deletion of exon 24, suggesting that two deletions on both sides of the minisatellite-like sequence may be generated by a "DNA slippage and misalignment" mechanism. Upon amplification of cDNA by the polymerase chain reaction, no transcript of gene with frameshift mutation (deletion of exon 24) was detected in skin fibroblasts, while transcripts of genes with missense mutations were detected. The results, in combination with previous reports (Dunn et al., 1989; Hashimoto et al., 1991), suggest the instability of transcripts with a premature stop codon or the suppressed expression of alleles with a premature stop codon in the retinoblastoma gene in somatic cells of hereditary patients.

Amino Acid Sequence↗
PubMed1994

Parental origin of germ-line and somatic mutations in the retinoblastoma gene.

Segregation analysis of polymorphic sites within the retinoblastoma (RB) gene and on chromosome 13, as well as the parental origin of the lost allele in the tumor, were analyzed in 24 families with RB patients. Four mutant alleles transmitted through the germ-line and seven de novo germ-line mutant alleles were identified in 11 patients with hereditary RB. Segregation analysis within the RB gene and on chromosome 13 was useful for DNA diagnosis of susceptibility to RB in relatives of hereditary patients, even if mutations were not identified. All seven de novo germ-line mutant alleles were paternally derived. The bias toward the paternal allele for de novo germ-line mutations of the RB gene was statistically significant. Seven paternal alleles and six maternal alleles were lost in 13 non-hereditary RB tumors with no bias in the parental origin of the somatic allele loss. These results suggest that the physical environment or a deficiency in DNA repair during spermatogenesis may be associated with significant risk factors for de novo germ-line mutations.

Alleles↗
PubMed1993

Extramedullary plasmacytoma producing biclonal gammopathy.

A case of extramedullary plasmacytoma presenting with biclonal gammopathy is reported. The patient was an 82-year-old man in whom monoclonal-protein (M-protein) was not noted during his first hospitalization. On his second hospitalization generalized lymph node swelling and biclonal gammopathy (IgG-kappa, IgA-kappa) were observed. Histological findings were compatible with those of extramedullary plasmacytoma. In the terminal stages, the patient became cachexic. The autopsy disclosed dissemination of the plasmacytoma. Only two other cases have been reported in the literature, and a review of these previous reports is included.

Aged↗