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Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 181 records · Page 10Linked to original sources

[Indication of allogeneic bone marrow transplantation (BMT) from HLA identical sibling in adult acute myeloblastic leukemia--comparative study of BMT and chemotherapy in patients with the first remission state. Nagoya BMT Group. Japan Adult Leukemia Study Group].

The indication of allogeneic bone marrow transplantation (BMT) from HLA identical siblings during the first remission of acute myeloblastic leukemia was discussed according to the results of BMT and chemotherapy study groups. The comparison of disease free survival between both groups was done, after selection biases such as risk factors and time of BMT were adjusted by multivariate analysis or matched-pair analysis. In conclusion, patients with more than one high risk factors for leukemia relapse, that is, high peripheral white blood cell count (PBC) (> 20,000/cmm) at diagnosis or more than two remission induction courses should be considered for BMT, and the indication of treatments for patients with no high risk factors should be determined depending on situations of the disease and patient's intention.

Adult↗

Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese.

To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.

Adolescent↗

Detection of minimal residual disease in patients with childhood common acute lymphoblastic leukemia after autologous bone marrow transplantation with ex vivo purging and systemic IL-2 infusion: unsuccessful prediction of subsequent relapse.

We sequentially analyzed minimal residual disease (MRD) in 7 children with common acute lymphoblastic leukemia (cALL) after autologous bone marrow transplantation (ABMT) with ex vivo purging followed by systemic interleukin-2 infusion. After ABMT, 3 of the 7 patients remained in complete remission (CR) for more than 1 year, and 4 subsequently relapsed. MRD was estimated by polymerase chain reaction amplification to detect the leukemia clone-specific immunoglobulin heavy chain third complementarity determining region (IgH CDR-III). The IgH CDR-III sequences from the relapsed patients were identical with those determined at each respective initial diagnosis. In 2 patients, the levels of MRD were 10(-2) and 10(-5) in the harvested bone marrow (BM) cells, and even after purging the levels were 10(-4) and 10(-5) cells, respectively. One of the 2 patients relapsed 3 months after ABMT, while the other remained in CR for 33 months after ABMT. Among the 4 patients who subsequently relapsed after ABMT, MRD was not detected in the BM samples even 1 month before relapse. Our results suggest that PCR-negativity does not necessarily indicate a lower risk of subsequent relapse. Detection of MRD tends to favor the assessment of the therapeutic effects rather than prediction of relapse.

Base Sequence↗

Inhibition of Df-protease--induced kinin release by synthetic inhibitors.

A protease (Df-protease) from house dust mite (D. farinae) is closely associated with mite-induced allergy: Df-protease has a similar substrate specificity to blood coagulation factor XIIa and catalyzes the activation of kallikrein-kinin system in human plasma. With the purpose of prevention of kinin-formation in plasma by Df-protease, inhibition of Df-protease with synthetic inhibitors was tested in vivo and in vitro. Among the inhibitors, including amidine and guanidine derivatives, N-allyl-N-[4-(4-amidinophenoxycarbonyl)-alpha-methylcinnamoyl++ +]glycine ethyl ester mesylate was the most effective to inhibit Df-protease with Ki = 9 x 10(-9) M and also to prevent kinin-release from Df-protease in human plasma. Enhancement of vascular permeability in guinea pigs caused by kinin-release was stoichiometrically suppressed by the inhibitor.

Amidines↗

A reverse transcriptase-polymerase chain reaction detects heterogeneous chimeric mRNAs in leukemias with 11q23 abnormalities.

The MLL gene involved in 11q23 translocations found in the majority of infantile leukemias and some secondary leukemias makes fusion transcripts with genes such as LTG4 (chromosome 4), LTG9 (chromosome 9), and LTG19 (chromosome 19) as a result of reciprocal translocation. We have examined 25 cases of leukemias with 11q23 abnormalities by Southern blot analysis and the reverse transcriptase-polymerase chain reaction (RT-PCR). Using various primer pairs, chimeric mRNAs could be amplified in 6 of 7 leukemias with t(4;11), 6 of 8 leukemias with t(9;11) including secondary leukemia, 8 of 9 leukemias with t(11;19), and 1 with a deletion at 11q23. The chimeric mRNAs were heterogeneous and differential usage of the MLL exons was found, irrespective of the partner chromosomes. Sensitivity studies showed that a single clone with chimeric mRNA in 10(4) to 10(5) cells could be detected. These findings show that the present RT-PCR settings provide a rapid, accurate, and sensitive tool for diagnosing leukemias with 11q23 translocations and for monitoring response to therapy in these patients.

Adult↗

Alcoholysis of epsilon-decalactone with polyethylene glycol-modified lipase in 1,1,1-trichloroethane.

Lipase from Pseudomonas cepacia was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine, activated PEG2, to form PEG-lipase. The PEG-lipase is soluble and active in organic solvents. It catalyzes alcoholysis of racemic epsilon-decalactone with ethanol in 1,1,1-trichloroethane to form (R)-hydroxydecanoic acid ethyl ester. No alcoholysis of (S)-decalactone takes place. These results were discussed in relation to carbon number of n-alcohol, optimum temperature and comparison with modified and non-modified lipases.

Ethylene Glycols↗

Expression of nm23 H-1 RNA levels in human gastric cancer tissues. A negative correlation with nodal metastasis.

BACKGROUND: Gene expression of nm23 has been investigated in number of tumors, including breast cancer, colon cancer, malignant melanoma, and hepatocellular carcinoma. Its down-regulation has been shown to be associated with metastasis or disease progression in some of the tumors. METHODS: nm23 H-1 mRNA levels were investigated in 31 surgically resected specimens of gastric cancer by Northern blot analysis, and association with clinical stages was determined. RESULTS: There was no significant difference in nm23 expression between tumor and matching normal mucosa. There was a significant down-regulation of the nm23 gene in gastric cancer with serosal invasion (T3 and T4 by the TNM classification) and nodal metastasis (pN1 and pN2), although the association of the down-regulation with clinically manifest hepatic or peritoneal metastasis was not significant. The tumors with low nm23 expression were associated with a poor prognosis. CONCLUSIONS: It was suggested that the down-regulation of nm23 gene might have a role in metastasis and invasion in gastric cancer, possibly leading to a poor prognosis.

Cell Line↗

Expression of glutathione-S-transferases alpha and pi in gastric cancer: a correlation with cisplatin resistance.

Glutathione-S-transferase (GST) in one of several factors that are proposed to affect tumor sensitivity to anticancer drugs, including cisplatin (CDDP). Attempts are made herein to evaluate the significance of the enzymes in resistance to CDDP in clinical samples of gastric cancer. A total of 22 gastric cancer specimens, 16 of which were obtained with matching normal mucosae, underwent immunoblotting with polyclonal antibodies against GST-alpha and GST-pi. At the same time, the chemosensitivity of 15 gastric cancer specimens to CDDP was evaluated by the succinic dehydrogenase inhibition (SDI) test. The expression of GST-pi was detected in all the specimens, and its content in the neoplasms exhibited a significant positive correlation with that in the matched normal mucosae. The expression of GST-alpha was detected in 18 of 22 cancer specimens (82%), but its content in the neoplasms did not correlate with that in the matched mucosae. A comparison of the drug-sensitivity findings with the results of immunoblotting revealed a weak but interesting correlation between the protein levels of GST-alpha and CDDP resistance. The cellular content of GST-alpha correlated weakly with CDDP resistance in gastric cancer, and its quantification could contribute to prediction of the clinical effects of CDDP in patients with gastric cancer.

Cisplatin↗

Experimental study on chemotherapy using adsorbent charcoal with CDDP administered directly into the mediastinum following esophagectomy.

In this study, 1500AA, an activated charcoal with a strong affinity for the lymphatic system, was examined for its ability to deliver chemotherapy to metastatic lymph nodes. First, the anticancer effect on metastatic lymph nodes was assessed in an experiment using the mouse mammary tumor, MM48. Pathological examination of the inguinal lymph nodes revealed a metastatic rate of 50% in the group given cisplatin (CDDP)-saline, but 20% in the group given CDDP-charcoal. Next, in a canine model, CDDP dissolved in normal saline was administered directly into the mediastinum, and CDDP was given with fine particles of activated charcoal in the same manner in the other group. The concentration of CDDP in the lymph nodes and the plasma rapidly increased to peak in 10 min in the CDDP-saline group, whereas it increased slowly to peak in 20-30 min in the CDDP-charcoal group. Moreover, the CDDP-charcoal group was found to have a much higher concentration of CDDP in the lymph nodes than the CDDP-saline group.

Adenocarcinoma↗

Expression of pi-glutathione S-transferase gene (GSTP1) in gastric cancer: lack of correlation with resistance against cis-diamminedichloroplatinum (II).

Class pi-glutathione S-transferase (GSTP-1) is one of several factors proposed to affect drug sensitivity to cisdiamminedichloroplatinum (II) (CDDP). It has also been investigated as a potential marker for the serodiagnosis of various types of cancers. In this study, attempts were made to quantify mRNA levels of the enzyme in healthy and cancerous gastric mucosa specimens, and to evaluate their significance in inherent drug resistance to CDDP. Thirty gastric cancer specimens were analysed by northern blotting with radiolabelled GSTP1 cDNA. Of these, the chemosensitivities of 22 specimens were evaluated by the succinic dehydrogenase inhibition (SDI) test. GSTP-1 mRNA was detected in all the specimens, with slightly increased, but non-significant expression in the neoplasms. Comparison of these drug sensitivities with results of northern blotting analysis showed no inverse correlation, as was expected from the widely investigated role of the enzyme in drug resistance.

Blotting, Northern↗

In vitro granulocyte-macrophage colony-stimulating factor production by peripheral blood mononuclear cells in aplastic anemia.

We studied the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by peripheral blood mononuclear cells from 48 patients with aplastic anemia by using an enzyme-linked immunosorbent assay. Detectable concentrations of spontaneous GM-CSF production, ranging from 1.0 to 480 pg/ml (mean +/- SD, 51 +/- 100 pg/ml), were observed in 45 of 48 patients. These concentrations were not significantly different from those observed in normal controls. Phytohemagglutinin-stimulated production of GM-CSF in patients with aplastic anemia, ranged from 1.0 to 2,610 pg/ml (mean +/- SD, 754 +/- 550 pg/ml), which was significantly higher than in normal controls (p < 0.01). The spontaneous production of GM-CSF increased following antilymphocyte globulin (ALG) treatment in 7 of the 11 ALG responders and in 4 of the 14 nonresponders (p = 0.08). The present observations support the hypothesis that ALG functions as an inducer of hematopoietic growth factor in order to restore hematopoiesis.

Adolescent↗

[A comparative clinical study on flucytosine alone and in combination with fluconazole in hematological malignancies: a multicenter study using the envelope method].

Two different flucytosine (5-FC) treatment regimens, one by itself and the other in combination with fluconazole (FLCZ) were compared in chemotherapy against mycotic infections in 60 patients with hematological diseases. The patients in a randomized fashion were assigned to the two treatments. In the combination regimen, the two drugs were used in half doses. beta-D-Glucan and D-arabinitol in the sera of patients were measured to document mycotic infections, and bacterial examinations were also performed. The efficacy of the combination therapy was 60.0% (18/30) and that of 5-FC alone was 65.5% (19/29). The stratified evaluation indicated that no factor was found to contribute to the efficacy in the two treatments with statistical significance. The side effects occurred in few cases and none of those was serious; including, one case of subjective symptom in each groups and two episodes of liver dysfunction in combination treatment. Changes in beta-D-glucan concentrations in the sera reflected well the pathophysiology of mycotic infections and clinical improvement. These results suggested that a combination of 5-FC and FLCZ at half doses provided a clinical benefit comparable to 5-FC alone at the ordinary dose, and the safety was considered satisfactory.

Adult↗

Allogeneic bone marrow transplantation in Japan.

Allogeneic bone marrow transplantation (BMT) is being used increasingly to treat diverse diseases in Japan. The distinctive aspects of allogeneic BMT in Japan include the lower incidence of acute graft-versus-host disease, which may be attributable to less disparity in histocompatibility antigens in Japanese. Research in the field of allogeneic BMT in Japan has covered the use of recombinant hemopoietic growth factors, especially granulocyte colony-stimulating factor, and novel immunosuppressive agents.

Bone Marrow Transplantation↗