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Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 199 records · Page 11Linked to original sources

[Coordination of unrelated bone marrow donors in the Tokai Bone Marrow Bank--psychological reactions of donors to donation].

The Tokai Bone Marrow Bank was established in 1989 and coordinated 1,415 patients with 3,000 HLA-A, B-typed donors. Of the 1,415 patients, 757 patients had HLA-A, B-identical donors, 206 patients had HLA-DR-identical donors, and 80 patients had MLC-compatible donors. Finally, 55 unrelated donor bone marrow transplantations were done. The most frequent reason of interruption in coordination was disagreement of donor's family. We sent several questions by mail around 1 month after the donation to 55 donors to analyze the psychological reactions of unrelated bone marrow donors to donation. Donors were generally quite positive about the donation. 92% of the donors felt it was worthwhile and no one felt it was not at all worthwhile. 73% of the donors would be willing to donate again in the future. 79% of donors would like to know the clinical course of the patient after the bone marrow transplantation. We hope that these results may be helpful in the development of the Japan Marrow Donor Program.

Bone Marrow↗

Minimal residual disease after bone marrow transplantation for chronic myelogenous leukemia and implications for graft-versus-leukemia effect: a review of recent results.

Cure of leukemia by allogeneic BMT is achieved by the combined effect of the myeloablative preparative regimen and an allo-immune response of donor cells to residual leukemia termed the graft-versus-leukemia (GVL) effect. In the first year following BMT for CML, PCR used to detect the leukemia-specific BCR/ABL message frequently reveals subclinical levels of persisting leukemia. In a meta-analysis of reports on qualitative PCR findings after BMT for CML in 12 recently published series, we found that for unmanipulated BMT in chronic phase, PCR detection was not associated with a higher relapse risk and that most patients became PCR negative within 2 years post-BMT. In contrast, PCR detection of BCR/ABL transcripts was a more reliable predictor in recipients of T cell-depleted BMT and in those transplanted in accelerated or blastic phase of their disease. For accurate prediction of relapse, serial quantitative PCR is necessary. It could also be used to monitor efficacy of experimental treatments of relapse with interferon or donor lymphocyte transfusions. Furthermore, studies of the association of GVHD with PCR detection of BCR/ABL message may shed light on the relationship of GVL with minimal residual disease in CML.

Bone Marrow Transplantation↗

Recombinant human non-glycosylated granulocyte-macrophage colony-stimulating factor in allogeneic bone marrow transplantation: double-blind placebo-controlled phase III clinical trial.

In a randomized double-blind placebo-controlled phase III clinical trial, the effects of a non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (CSF 39-300) were investigated in patients who had received allogeneic bone marrow transplantation. CSF 39-300 was administered at a daily dose of 10 micrograms/kg (maximum dose, 300 micrograms/body) via three-hour intravenous infusions from days 1 to 21 following reinfusion of the marrow. Twenty-eight patients received CSF 39-300 and 25, placebo. The median number of days to recovery for leucocytes (> or = 1000/mm3), neutrophils (> or = 500/mm3), lymphocytes (> or = 300/mm3) and reticulocytes (> or = 20/1000) were significantly shortened (16 vs 20, 17 vs 21 and 22 vs 28, respectively) with CSF 39-300. The duration of stay in laminar-air-flow room after transplantation was also significantly shortened in the CSF 39-300 group (21 vs 30 days). There was no significant difference in the incidence of acute or chronic graft-versus-host disease between the two groups. A follow-up during the year after transplantation revealed there to be no significant difference in either survival rate or leukemia relapse rate between the two groups. CSF 39-300 is therefore considered useful after allogeneic bone marrow transplantation, especially in the early period.

Adolescent↗

[Secondary leukemia after etoposide treatment involved MLL gene rearrangement].

The 11q23 chromosomal abnormality is frequently observed in infantile leukemia and secondary leukemia, and the translocation associated gene in infantile leukemia is called mixed-lineage leukemia (MLL) gene. A 50-year-old man was admitted because of left axillary lymphadenopathy and IBL like T cell lymphoma was diagnosed by lymph node biopsy. The patient responded to the LSG-9 protocol with complete remission. After 10 months he was readmitted because of fever and was diagnosed acute myeloblastic leukemia by bone marrow aspiration. Chromosome analysis revealed 11q23 abnormality, suggesting that the leukemia was induced by etoposide treatment. Southern blot analysis demonstrated DNA rearrangement in the MLL gene at 11q23. It was suggested that the breakpoint region of the MLL gene in secondary leukemia is the same as that of infantile leukemia.

Chromosomes, Human, Pair 11↗

[Allogeneic cryopreserved marrow transplantation in a patient with chronic myelogenous leukemia].

A 45-year-old male with chronic myelogenous leukemia received cryopreserved allogeneic bone marrow from his HLA-identical sister. Bone marrow was harvested and cryopreserved prior to chemoradiotherapy since the donor had neurotic tendencies. The preconditioning regimen consisted of standard dosage of busulfan plus cyclophosphamide and total lymphoid irradiation (5Gy). A total of 3.1 x 10(7)/kg marrow mononuclear cells, containing 4.7 x 10(5) CD34+ cells/kg, and 8.0 x 10(6)/kg buffy coat cells collected from the donor at day 0 was infused. Marrow engraftment occurred by day 38 although hematological recovery was delayed and subsequent administration of GM-CSF, methylprednisolone and donor buffy coat cells were required. Mononuclear cells obtained from the patient's blood at day 28 had an inhibitory effect on CFU-GM formation of the donor's bone marrow mononuclear cells. We considered that this case suffered from a transient myelosuppression due to residual host cells after bone marrow transplantation.

Bone Marrow↗

[The clinical effect of chemotherapy with 5-FU and low-dose CDDP in patients with advanced gastric cancer].

A trial of FP therapy, a novel systemic chemotherapy consisting of 5-FU and low-dose CDDP, was carried out in patients with advanced gastric cancer and the clinical effects were evaluated. Five hundred mg/body/day of 5-FU was continuously administered via the central venous catheter for 7 consecutive days and 10mg/day of CDDP was rapidly administered with 500ml saline on days 1-5. The regimen was repeated for at least 4 weeks. The FP therapy was carried out in 22 cases, including several patients who underwent FP as an adjuvant therapy; 1 CR, 2PR's 1MR and 2NC's were obtained among the 6 patients with clinically evaluable lesions, resulting in a response rate of 50%. In four cases, the FP therapy was given as a neoadjuvant therapy, and histopathological examination of the resected specimen revealed histological effects exceeding Grade 2 in all 4 cases. Bone marrow suppression was the most commonly observed side effect, but renal dysfunction and nausea were not found. FP therapy is considered an effective therapy against advanced gastric cancer, from the viewpoint of both the clinical and adverse effects, in comparison with conventional regimen consisting of 5-FU and a single and large dose of CDDP.

Adenocarcinoma↗

Reduction of immunoreactivity of bovine serum albumin conjugated with comb-shaped polyethylene glycol derivatives.

Bovine serum albumin (BSA) was chemically modified with two types of comb-shaped copolymers of polyethylene glycol derivative and maleic anhydride, one with the molecular weight of 13,000 (activated PM13) and the other with 100,000 (activated PM100), to form PM13- and PM100-BSA. The immunoreactivity of BSA was markedly reduced by coupling with each modifier and was completely lost when 30% or 20% of amino groups in BSA were modified with activated PM13 or PM100, respectively. The esterase activity of PM13- and PM100-BSA without immunoreactivity were retained 63% and 93% of non-modified one, respectively. These results were discussed with those of modified-asparaginases(1).

Asparaginase↗

Randomized study of individualized induction therapy with or without vincristine, and of maintenance-intensification therapy between 4 or 12 courses in adult acute myeloid leukemia. AML-87 Study of the Japan Adult Leukemia Study Group.

BACKGROUND: It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance-intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML). METHODS: A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6-mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance-intensification therapy was randomized to 4 or 12 courses given every 6 weeks. RESULTS: Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4-year survival, continuing CR, and disease-free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance-intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French-American-British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course. CONCLUSIONS: Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML.

Acute Disease↗

Long persistent bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia without clinical relapse: a study of 64 patients.

We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had > or = 1 negative PCR result < or = 1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had > or = 1 positive PCR result > or = 1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the t-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P < .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.

Adolescent↗

Growth inhibition of human gastrointestinal cancer xenograft lines by treatment with CPT-11 and VP-16.

A water-soluble and stable camptothecin derivative, CPT-11, was found to possess a strong antitumor activity against various murine tumors. In the present study, CPT-11 was tested against ten human gastrointestinal cancer xenograft lines carried by nude mice. CPT-11 was very effective against nine xenograft lines, with the exception of one xenograft. On the other hand, VP-16 was ineffective against all these xenograft lines. Therefore, CPT-11 is expected to be clinically more effective against gastrointestinal cancer than the topo II targeting agent.

Adult↗

Expression of carcinoembryonic antigen (CEA) and nonspecific crossreacting antigen (NCA) in gastrointestinal cancer; the correlation with degree of differentiation.

In spite of its reputation as a tumour marker, little is known about the function of carcinoembryonic antigen (CEA). We examined the mRNA expression of CEA and NCA in 26 gastric and 14 colorectal cancers together with adjacent morphologically normal mucosae. There was no significant difference between the CEA mRNA levels of colorectal cancer and adjacent mucosa, whereas the CEA mRNA levels were significantly elevated in gastric cancer compared with normal gastric mucosa. The expression of NCA, on the other hand, was more cancer-specific and was significantly up-regulated in both gastric and colorectal cancers compared with the corresponding normal mucosae. No correlation was found between the mRNA level and plasma CEA value. No significant up-regulation was recognised in the node positive cancer, cancer with distant metastasis, or the metastatic tissues themselves. Marked diversity in the degree of differentiation in gastric cancer tissues, however, resulted in varied expression of the CEA gene family, compared with the constantly high expression found in colorectal cancer. Further analysis revealed significant up-regulation of NCA in well and moderately differentiated gastric cancers over poorly differentiated cancers, suggesting that NCA might have roles in differentiation.

Antigens, Neoplasm↗

Acute renal failure and degenerative tubular lesions associated with in situ formation of adenovirus immune complexes in a patient with allogeneic bone marrow transplantation.

We describe the development of acute renal failure and degenerative tubular lesions associated with local immune deposits in a patient with allogeneic bone marrow transplantation. A 21-year-old man with an acute myelocytic leukemia received a bone marrow graft from a cousin mismatched for a single HLA-DR locus antigen. Hemorrhagic cystitis due to adenovirus type 11 infection occurred 26 days after transplantation, and 17 days later the patients developed acute renal failure. A study of renal tissue obtained by needle biopsy showed degenerative and necrotic lesions, especially in the distal part of the nephron. By electron microscopy adenovirus type 11 particles were found in the nuclei of tubular cells and in cellular debris in tubular lumina. By immunofluorescence technique, granular immune deposits containing adenovirus type 11 related antigen(s), immunoglobulins, C3, and membrane attack complex (MAC) C5b-9 of the complement system were detected along the tubular basement membranes but not in glomeruli. The patient's IgG did not bind to normal human kidneys. These findings suggest that adenovirus type 11 directly induced acute tubular damage, and that the tubular immune deposits were formed "in situ" by viral antigens and circulating viral antibody.

Acute Kidney Injury↗