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Biomedical subjects

R Ohno

Publications and source records attributed to R Ohno.

At least 289 records · Page 16Linked to original sources
PubMed1989

Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group.

Japanese patients with leukemia who received bone marrow from human leukocyte antigen (HLA)-compatible siblings had a low incidence of acute graft-versus-host disease (GVHD). Twenty-five (21%) of 120 patients developed moderate (grade II) to severe (grades III to IV) acute GVHD. Severe GVHD was only seen in patients older than 20 years of age. It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD. Thirteen (30%) of 44 patients receiving MTX alone and 10 (27%) of 37 patients receiving CSP alone developed grades II to IV acute GVHD. Multivariate life-table analysis indicated that the prophylaxis by MTX/CSP was the risk factor for the low incidence of grades II to IV acute GVHD. Compared with the reported incidence of acute GVHD in the patients of the United States, lower incidence of acute GVHD in Japanese BMT patients might be attributable to a lesser degree of genetic diversity in histocompatibility antigens among Japanese.

Acute Disease↗
PubMed1989

Increased P-glycoprotein expression and multidrug-resistant gene (mdr1) amplification are infrequently found in fresh acute leukemia cells. Sequential analysis of 15 cases at initial presentation and relapsed stage.

Using a DNA probe of mdr1 and an anti-P-glycoprotein monoclonal antibody (MRK16), the authors investigated 19 cases of adult acute leukemia patients (one M1, six M2, three M3, one M4, three M5, two L1, and three L2), comparing leukemia cells at the initial presentation (I) with those at the relapsed stage (R). By Southern hybridization analysis mdr1 DNA levels were not amplified in 32 samples from 19 patients (I: 14, R: 18). By Northern hybridization analysis mdr1 mRNA levels were not expressed in ten samples from seven patients (I: 4, R: 6). By indirect immunofluorescent assay with MRK16 antibody P-glycoprotein was not detected in 30 samples from 18 patients (I: 13, R: 17). Thus, P-glycoprotein expression and mdr1 gene amplification occurred infrequently not only in leukemia cells at the initial presentation but also in those at the relapsed cases and may not be a major cause of refractoriness to antileukemia drugs in adult acute leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Recent progress in the treatment of adult acute leukemia.

In 3 studies for adult acute myelogenous leukemia (AML) treated with BHAC-DMP, BHAC-DMP(II) and M-85 from 1979 to 1987, intensive induction resulted in a higher cure rate, since reduction of the blasts in bone marrow at 2 weeks after the initiation of therapy to less than 20% was the most significant prognostic factor to predict the long complete remission (CR), followed by initial WBC counts (less than 60,000/cmm) and achievement of CR within 50 days or by one course of induction therapy. However, it seemed impractical to give very intensive chemotherapy during the induction because of the high frequency of complications due to prolonged myelosuppression. Consolidation should be as intensive as possible. Non-cross resistant drugs will theoretically produce better results. In M-85 protocol, 71% of 41 adult AML achieved CR. The predicted 3.5-year survival and CR length of CR cases are 74 and 56%; respectively. The preliminary results of JALSG-AML87 and -ALL87 were also reviewed.

Acute Disease↗
PubMed1989

[A case of chronic neutrophilic leukemia with abnormal karyotype].

A 75-year-old man was admitted to our hospital because of leukocytosis and thrombocytosis. The peripheral blood showed RBC 403 x 10(4)/microliters, Hb 14.1 g/dl, PLT 91 x 10(4)/microliters, and WBC 48,000/microliters with a differential count of 24% band forms, 65% segmented forms and 11% others. The bone marrow aspiration revealed myeloid hyperplasia (94.4% myeloid series, 4.8% erythroid series and 0.8% others), and NAP score was consistently high. The serum level of lysozyme and vitamin B12 were elevated. There were no signs of infection or other malignancy. Cytogenetic study of bone marrow cells showed mosaic karyotypes of 46,XY/46,XY,t(7;16) (q22;q24). The Ph1 chromosome was not found. A diagnosis of chronic neutrophilic leukemia was made. Serial chromosomal analysis showed the coexistence of a clone with 46,XY,t(7;16) (q22;q24) and that with 46, XY.

Aged↗
PubMed1989

Recent trends in the treatment and prognosis of adult leukemia with characteristics of patients in Japan: transition during the fifteen years from 1971 to 1985.

Patients with acute (2,569) and chronic (957) leukemia diagnosed at 19 institutes took part in the study on the "Multidisciplinary Treatment of Leukemia" between 1971 and 1985 and were investigated retrospectively. By dividing the 15 years into three five-year periods, we were able to compare patient ratios in the different periods. The proportions of acute to chronic leukemia cases showed no obvious change; however, the proportions of cases diagnosed as acute lymphocytic leukemia in acute leukemia showed a significant increase. The main chemotherapeutic drugs used during the three time periods were cytarabine or its analogues, the anthracyclines, 6-mercaputopurine and prednisolone, against acute myelogenous leukemia, and the vinca alkaloids, prednisolone and the anthracyclines against acute lymphocytic leukemia. The rate of complete remission from acute myelogenous leukemia made marked progress, from 45.1% during 1971-1975 to 62.3% during 1981-1985, but that of acute lymphocytic leukemia showed no significant progress, being 65% during 1971-1975 and 69.7% during 1981-1985. The durations of remission, however, and the survival times for patients with acute lymphocytic leukemia, as well as for those with acute myelogenous leukemia, became significantly longer over the three periods. Median survival times from chronic myelocytic leukemia were 37-40 mo in all three periods, showing no progress. There was a better prognosis in cases of chronic myelocytic leukemia with, than without, Philadelphia chromosome. Except for a low incidence of chronic lymphocytic leukemia in Japan, adult leukemia patients' characteristics and prognoses seem to be almost the same in Japan as in the U.S.A. and Europe.

Adolescent↗
PubMed1989

[Phase I study and early phase II of SM-108 (4-carbamoylimidazolium-5-olate) in lung cancer. SM-108 Study Group].

Phase I study with a new oral purine antagonist, SM-108, was conducted in a total of 73 cases in a 5-day consecutive schedule with the dosage ranging from 20-2,500 mg/m2 at II institutes. The incidences of subjective and objective side effects were 20.5% (15/73) and 31.5% (23/73), respectively, however the correlation between these effects and their dosages was unclear. MTD and DLF values were not determined. SM-108 levels in serum reached maximum in 2-4 hours after oral administration of SM-108, and exhibited a dose-response relationship up to the dosage of 2,000 mg/m2/day. Forty to 60% of the administered drug was excreted into urine in 24 hrs; thus, the main excretory pathway was considered to be renal. An early phase II study was undertaken in patients with lung cancer in 5 cancer centers and university hospitals. Each patient had received 400 mg/m2/day (in two divided doses) or 600 mg/m2/day (in three divided doses) for more than 2 weeks. Only one case (adenocarcinoma) showed a minor response out of 27 cases but not reached partial response according to our criteria. In the 400 mg/m2/day group and the 600 m/m2/day group the incidences of subjective side effects (mainly GI tract disturbance) were 33.3% (4/12) and 40.0% (6/15), while objective side effects (hematological changes) were 16.7% (2/12) and 26.7% (4/15) respectively. In conclusion, we could not determine the dose limiting factor and maximum tolerated dose from our phase I clinical study and early phase II study for lung cancer.

Adenocarcinoma↗
PubMed1989

[Phase II study of SM-108 (4-carbamoylimidazolium-5-olate) in hematological malignancies].

A total of 165 patients were entered into this study and 140 were evaluate for effects and 165 for toxicities. Of 39 patients with chronic myelogenous leukemia (CML) 21 achieved complete remission (CR), 6 achieved partial remission (PR) with a response rate of 69.2%. In MDS, of 11 patients with chronic myelomonocytic leukemia (CMMoL), one good partial response and 4 partial response were observed (CR + PR:45.5%); of 14 patients with RAEB, one complete response, 4 partial response (CR + PR: 35.7%); of 11 patients with RAEB in T, 3 partial response were observed (response rate: 27.3%). Of 13 patients with polycythemia vera, 4 excellent effect and 7 moderate effect (84.6%) were observed. Seven of 30 patients with acute myelocytic leukemia achieved partial response (23.3%). Mean dosages of SM-108 until remission were 400-500 mg/m2/day on CMMoL, RAEB in MDS, polycythemia vera and CML, and 600-800 mg/m2/day on RAEB in T and AML. In the analysis of adverse effects of SM-108, a subjective side effects including mainly gastrointestinal toxicities were observed in 38 cases (23.0%) of the patients : 26 patients (15.8%) showed objective side effects including liver dysfunction, but these symptoms were transient and not serious. Our study indicates that SM-108 is useful agent against MDS, especially CMMoL, RAEB, RAEB in T, polycythemia vera and CML.

Administration, Oral↗
PubMed1989

[Cancer curable by chemotherapy: acute myelogenous leukemia].

Acute myelogenous leukemia (ALM) can be cured by chemotherapy. We have treated 121 adult AML cases for the past 9 years. With BHAC-DMP therapy starting in 1979, CR was obtained in 82% of 51 consecutive AML and the predicted 8-year continuing CR (CCR). Survival of CR cases was, 15 and 21%, respectively. Multivariate analysis of the prognostic factors revealed that % of blasts in the bone marrow at 2 weeks after the start of induction therapy was the most significant factor for CCR. Thus, we started BHAC-DMP (II) therapy with highly intensive induction therapy in 1983, but were forced to cancel this because of an intolerably high incidence of severe infections during the induction therapy. The CR rate was 76% in 29 consecutive patients, and the predicted 5-year CCR and survival of CR cases are 27 and 47%, respectively. Then we started M-85 protocol with intermediately intensive induction followed by 3 courses of highly intensive consolidation therapy using non-cross resistant drugs in 1985. The CR rate was 71% in 41 consecutive patients. Although 4 patients died of infections or myocardial infarction during the consolidation therapies, the predicted 2.5-year CCR and survival of CR cases are 76 and 74%, respectively, with a median follow-up of 28 months.

Adult↗
PubMed1989

[Treatment with sulbactam/cefoperazone of severe infections in patients with hematological disorders].

Infectious episodes in 90 patients with hematological disorders were treated with sulbactam/cefoperazone (SBT/CPZ), a new combination drug of a potent beta-lactamase inhibitor, sodium sulbactam, and a third generation cephalosporin, sodium cefoperazone. Clinical responses to the SBT/CPZ regimen were excellent in 23 cases, good in 30 cases, fair in 11 cases, and poor in 26 cases. The overall efficacy rate (percentage of cases showing excellent or good responses) was 58.9%. Efficacy rates classified according to different infections were: 80% in documented sepsis, 57.6% in suspected sepsis, 61.1% in pneumonia and 50% in other infections. One episode of side effect was encountered with redness and itching of skin. Hepatic disorders were observed in 3 cases. These adverse reactions, however, were not serious. These results indicate that SBT/CPZ has a high therapeutic efficacy to severe infections in patients with hematological disorders.

Adolescent↗
PubMed1989

[Clinical trial of a combination of human lymphoblastoid interferon (HLBI) and methyl-prednisolone (HLBI-mP) in multiple myeloma].

Two previously treated patients with multiple myeloma were given combination therapy of daily HLBI (3-6 x 10(6) I.U/day) and methyl-prednisolone pulse (250 mg/day). A 77-year-old patient with IgG-kappa myeloma achieved a complete remission, although the initial general condition was poor. The other 59-year-old patient with IgA-lambda myeloma, which had become resistant to previous chemotherapy including VAD, achieved partial remission. Mild myelosuppression and hepatotoxicity were the only side effects observed, and they disappeared upon discontinuation of the drug.

Aged↗
PubMed1988

Generation and characterization of lymphokine-activated killer cells against fresh human leukemia cells.

Lymphokine-activated killer (LAK) cells generated from 15 acute leukemia patients in remission showed significant levels of cytotoxicity against Daudi 1A4, a natural killer-resistant cell line. This indicates that lymphocytes of leukemia patients in remission could respond to interleukin-2 to generate conventional LAK cells. However, LAK cells caused lysis of autologous leukemia cells at considerably lower levels in seven out of the 15 patients, with the exception of one case (48.6% cytolysis). None of the remaining eight patients exhibited LAK activity against autologous leukemia cells. On the other hand, patients' LAK could lyse allogeneic leukemia cells including those resistant to autologous LAK. Thus, patients' LAK seem not to be defective in lysis of leukemia cells. In the cold target competition analysis, the binding of patients' LAK to leukemia cells could be inhibited by autologous and allogeneic leukemia cell competitors, implying that almost all leukemia cells could be recognized by patients' LAK. Most LAK cells from normal donors showed significant lysis of allogeneic leukemia cells, but some leukemia cells were found to be resistant to lysis. LAK cells against both leukemia cells and Daudi 1A4 were phenotypically heterogenous, and were predominantly observed in the T3- fraction in the precursor phase. In the effector phase, whereas LAK activity against leukemia cells was also predominantly shown in the T cell-depleted fraction, similar levels of LAK activity against Daudi 1A4 were found in both the T cell-depleted and -enriched fractions.

Acute Disease↗
PubMed1988

Immune responses in experimental allergic neuritis treated with corticosteroids.

The preventive and suppressive effects of methylprednisolone (MP) were investigated in 22 rabbits immunized with peripheral nerve myelin. Cellular reactivity to bovine P2 protein (P2) and anti-P2 antibody were also examined serially in these animals, using the lymphocyte proliferation test or enzyme-linked immunosorbent assay. Seven animals (preventive group), given 15 mg/day of MP subcutaneously from Days 0-28, showed a significant reduction in maximal severity and a delay in onset in comparison with 8 control animals. The remaining 7 animals (suppressive group), given the same dose of MP from Days 11-28, also showed significantly milder clinical signs than those observed in the controls. However, cellular hypersensitivity to P2 were manifested at Day 14 (just after clinical onset) in the controls, as well as in the preventive or suppressive groups. Furthermore, anti-P2 antibody was detected in each group after Day 14. These results suggested that the interference of inflammatory processes of immune-mediated disease might respond to the preventive and suppressive effects of MP.

Animals↗
PubMed1988

Functional and morphological differentiation induction of a human megakaryoblastic leukemia cell line (MEG-01s) by phorbol diesters.

The effect of differentiation induction by a tumor-promoting phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA) on a clonal human megakaryoblastic cell line, MEG-O1s, was investigated, and a prominent response was demonstrated. The cells became weakly adherent, developed conspicuous cytoplasmic blebs, and displayed mature megakaryocytic characteristics by light microscopy such as the development of azurophilic cytoplasmic granules and a mosaic pattern of oxyphilic patches, multiplication of nuclei, and enhancement of the PAS reaction and alpha-naphthyl acetate esterase staining. Ultrastructural studies demonstrated the development of prominent cytoplasmic blebs, budding of blebs, and multiplication of nuclei. Numerous granules with central nucleoids that are similar to alpha granules had developed as well as granules with high electron density and clearly demarcated zones. Surface marker analysis revealed a moderate increase in IgG Fc receptor levels and a profound decrease in C3 receptor sites. By an immunofluorescent technique using monoclonal and polyclonal antibodies, a dramatic change in the expression of several megakaryocyte-platelet-specific proteins was demonstrated. All the proteins that had been expressed before induction such as platelet glycoprotein (GP) IIb/IIIa, fibrinogen, von Willebrand factor, factor XIIIA, beta-thromboglobulin (beta-TG), and HLA class 1 antigen were profoundly enhanced after induction by TPA. Induction by TPA led to the expression of fibronectin and factor V, which were not detected on nontreated cells. An ultrastructural immunoperoxidase study demonstrated platelet GPIb and GPIIb/IIIa in both plasma membranes and protein synthesis areas such as perinuclear cisternae and endoplasmic reticulum after TPA induction. beta-TG was also observed in some cytoplasmic granules of TPA-treated cells. TPA remarkably increased the secretion of beta-TG into the culture medium of MEG-01s. Ploidy was also increased from 2C to 4C to 4C to 8C. Similar maturation of MEG-01s was induced by other phorbol diester analogues such as phorbol-12,13-dibutyrate, but not by phorbol itself. These results indicate that phorbol diester, TPA, can bring about differentiation and maturation of a human megakaryoblastic cell line (MEG-01s) and that MEG-01s cells will provide a useful model for studying megakaryocytic differentiation and numerous megakaryocyte-platelet-specific proteins.

Antibodies, Monoclonal↗
PubMed1988

Administration of human urinary colony stimulating factor after bone marrow transplantation.

A phase II study of the use of colony stimulating factor derived from human urine (CSF-HU) was performed after bone marrow transplantation (BMT). Steady and rapid recovery of leukocyte and granulocyte numbers was observed. In most patients who received CSF-HU from day 1, leukocyte numbers started to increase on day 6 and monocytes and granulocytes on day 11. Significant differences in the days to recovery of leukocytes over 1 x 10(9)/l and of granulocytes over 0.5 x 10(9)/l were observed in comparison with non-randomized control patients. In some patients in whom recovery of leukocytes was delayed, CSF also seemed to be effective in increasing leukocyte numbers from 8 days after the start of administration. There was no significant difference in the rate of relapse of leukemia between the two groups. CSF-HU seems very promising as a treatment of patients after BMT by shortening the period of leukopenia or granulocytopenia.

Adolescent↗