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Biomedical subjects

M Ohira

Publications and source records attributed to M Ohira.

At least 109 records · Page 6Linked to original sources
PubMed1993

Dosing rate-dependent relationship between propranolol plasma concentration and beta-blockade.

The effect of propranolol dosing rate on beta-blockade was studied in human volunteers after administration of a conventional tablet and a sustained release capsule. The slope of the plot of the percentage of reduction in the heart rate against log plasma propranolol concentration was significantly greater after administration of a sustained release capsule than after administration of a conventional tablet. A marked leftward shift of the plasma concentration-response curve was also observed in rabbits as the infusion rate was decreased over the same infusion period. This shift was not altered by pretreatment with 6-hydroxydopamine and plasma catecholamine levels were not affected by the rate of infusion, indicating that the contribution of sympathetic activation to the effect was minimal. By contrast to the anticlockwise hysteresis of the temporal response after propranolol, no such hysteresis was found with the more hydrophilic beta-adrenoceptor antagonist atenolol, or was there any leftward shift in the plasma concentration- response relationship. Data from the isolated guinea pig atrial preparation also showed anticlockwise hysteresis and a leftward shift of the concentration-response curve at a low propranolol input rate, whereas no shift was observed with more hydrophilic beta-blockers such as atenolol, pindolol and metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Comparative hematology in marine fish.

1. A comparative study involving 80 species (14 ray, 14 shark and 52 teleost species) of marine fish found at the southeastern Brazilian coast is presented. 2. Active species displayed higher values for all hematological parameters studied when compared to the less active forms. 3. Mean values of hematocrit, hemoglobin concentration and red blood cell counts increased according to the sequence: rays, sharks, teleosts. 4. As a group, cartilaginous fish blood displayed larger and fewer erythrocytes containing more hemoglobin than teleosts; mean cell hemoglobin concentration was significantly higher in rays and sharks than in teleosts. 5. For all but the hemoglobin concentration, the hematological values studied revealed a marked contrast between bony and cartilaginous fishes which suggests distinct ways to accomplish their oxygen demands.

Animals↗
PubMed1991

A shuttle vector for analysis of illegitimate recombination in mammalian cells: effects of DNA topoisomerase inhibitors on deletion frequency.

To study the mechanism of illegitimate recombination in mammalian cells, we have developed a shuttle vector, pNK1, that contains three bacterial markers, amp (ApR), galK, and neo (KmR). The frequency of deletions occurring in autonomously replicating pNK1 DNA during the growth of monkey COS1 cells was measured by transfecting the plasmid into Escherichia coli cells and counting the number of galK- ApS double mutants among total KmR cells. This method allowed us to test the effects of topoisomerase inhibitors on deletion formation in mammalian cells. The DNA topoisomerase II (TopII) inhibitor, 4'-dimethylepipodophyllotoxin thenylidene-beta-D-glucoside (VM26), stimulated deletions in pNK1 DNA in monkey cells. Since VM26 does not inhibit the strand-break activity of TopII, but rather stabilizes an enzyme-DNA complex in which DNA is cleaved upon treatment with sodium dodecyl sulfate, it is implicated that TopII participates in the deletion process in mammalian cells.

Amsacrine↗
PubMed1991

A new type of insertion mutation in monkey cells: insertion accompanied by long target site duplication.

We have developed a system for the detection of a new type of insertion mutation in mammalian cells. We have used a shuttle vector, plasmid pNK1, which contains the SV40 and pBR322 replication origins, and ApR, galK, and neoR genes. This plasmid was introduced into monkey COS1 cells, allowed to replicate, and then recovered plasmids were reintroduced into Escherichia coli HB101 to detect insertion mutations in the galK gene. We selected galK- KmR ApR mutants in order to eliminate galK- KmS deletion mutants. Insertion mutations in the plasmids recovered were then screened by agarose gel electrophoresis. Finally, insertion mutants that had the following characteristics were selected. First, they had the ability to produce gal+ revertants caused by the precise excision of inserted DNA in E. coli, implying that they had a target site duplication on both sides of the insertion. Second, they contained some repetitive sequence(s) as judged by hybridization with a bulk monkey DNA probe. Nucleotide sequence analysis of one of the mutants, 15K-1, showed that it contained alpha-satellite sequences within the coding region of the galK gene. It contained 13 1/2 tandem repeat units of alpha-satellite sequence and was flanked by a 64 bp target site duplication, indicating that the alpha-satellite sequence had been translocated from the monkey genome into the plasmid by illegitimate recombination. Another insertion mutant, N11-1, contained an 11 kb insert which included an unknown repetitive sequence that was also flanked by a target site duplication of 353 bp.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Familial aggregation of cancer from proband cases with childhood adrenal cortical carcinoma.

Family pedigree of Li-Fraumeni syndrome was investigated from probands with childhood adrenocortical carcinoma in Japan. From 47 probands, 7 families had 3 or more cancer cases at ages less than 45 years within the first generation; one satisfied Li's original criteria, two were acceptable because of multiple primary cancer in the probands, and others showed an aggregation of cancers with onsets at early ages, though no sarcoma of mesenchymal origin was found. A significantly higher occurrence of cancer in the mothers of the probands, especially of the breast, was consistent with reports from the USA, and liver cancer, osteosarcoma and lung cancer among family members under the age of 45 also showed a higher frequency than in the general population. Similarities and differences between Japanese and Caucasian cases are discussed.

Adolescent↗
PubMed1991

Comparison of autologous and allogeneic bone marrow transplantation in children with acute leukemia.

Thirty-one patients with acute non-lymphocytic leukemia (18 patients) or with high-risk refractory acute lymphocytic leukemia (13 patients) underwent bone marrow transplantation between March 1980 and March 1990. The high-dose conditioning regimen employed included cyclophosphamide followed by fractionated total body irradiation (12 GY). Fourteen patients who had an HLA-identical sibling donor received allogeneic bone marrow transplantation (allo-BMT); the other 17 patients received autologous bone marrow transplantation (auto-BMT) purged with 4-hydroperoxycyclophosphamide (4HC). Four of the 14 allo-graft recipients died of leukemic relapse and 2 others died of graft-versus-host disease. Three of the 17 auto-graft recipients died of relapse and 1 suffered relapse in the testes. The actuarial risk of relapse was 29% for the allo-BMT patients and 24% for the auto-BMT patients (P less than 0.05). The event-free survival rate at five years was 57% and 74% respectively (P less than 0.05). Although there was no difference between them, a trend toward a higher survival rate and a lower mortality and morbidity was observed in the auto-BMT group. These results suggest that autologous bone marrow transplantation purged with 4HC is an effective and useful treatment for children with acute non-lymphocytic and lymphocytic leukemia who have no HLA-identical donor.

Adolescent↗
PubMed1991

[The effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on childhood neutropenias].

The clinical effect of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was studied in 27 patients with childhood neutropenias. The sample consisted of 8 patients with congenital neutropenia (Kostmann type), 9 with neutropenia with miscellaneous causes (5 chronic benign, 2 associated with hypogammaglobulinemia, 1 drug-induced, and 1 hypoplastic type), 3 with cyclic neutropenia, and 7 with severe aplastic anemia. The rG-CSF was given subcutaneously (or in a few cases intravenously) at a dose of 2 micrograms/kg/day for 7 days and 5 micrograms/kg/day for additional 7 to 28 days in cases with poor response. The rG-CSF was effective in 18 of 27 cases (67%). Patients with congenital neutropenia and aplastic anemia responded less frequently and poorly. The mean level of absolute neutrophil counts of 8 congenital neutropenia cases increased from 88/microliters to 2,718/microliters. That of 9 miscellaneous cases changed from 189/microliters to 7,224/microliters at a dose of 2 micrograms/kg/day. In 7 aplastic anemia cases pretreatment level of 220/microliters rose to 851/microliters, usually after increasing the dose up to 5 micrograms/kg/day. The rG-CSF was apparently effective in 3 cases of cyclic neutropenia. In any type of neutropenia, the effect was largely transient; after the discontinuation of rG-CSF, the absolute neutrophil counts tended to decrease to pretreatment levels within 1 to 2 weeks. The G-CSF was well tolerated, and only one case with mild lumbago and another with minimal elevation of transaminases were observed. We conclude that the rG-CSF can be effective for treating various types of childhood neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Tumor markers--personal experience. A case of advanced extragonadal germ-cell tumor showing complete remission by high-dose combination chemotherapy with autologous bone marrow transplantation].

A twenty-four-year-old male patient with stage III advanced extragonadal germ-cell tumor obtained complete remission after comprehensive treatment including high-dose combination chemotherapy with autologous bone marrow transplantation. He had massive tumors in cervical, mediastinal, abdominal and inguinal lymph nodes, bilateral lungs and liver. Ascites, plural effusion and pericardial effusion were also noted. Cancer cells were demonstrated from his bloody sputum, pericardial drainage and an aspirate from supraclavicular tumor. His tumor produced hCG, AFP, placental ALP and LDH, and hCG was the best marker for the diagnosis and monitoring. The initial serum hCG level was high at 460,000 mIU/ml, but fell to 13 mIU/ml after 3 courses of PVP therapy. However, it rose ten-fold in a week. After ultra-high dose combination chemotherapy with autologous BMT, the patient's hCG fell to 1.8 mIU/ml and remained at that level thereafter. He has remained well with no sign of recurrence after 25 months.

Adult↗
PubMed1991

Non-Hodgkin's lymphoma in patients under twenty years of age. A clinicopathological study.

A retrospective clinicopathological study was performed on 149 patients who developed malignant lymphoma at under 20 years of age and were diagnosed and treated at the National Cancer Center Hospital between 1962-1986. Using the Japanese Lymphoma Study Group classification (and Working Formulation), we reclassified the 84 evaluable tissue specimens as follows: follicular large and mixed lymphoma (two cases), diffuse lymphoblastic lymphoma (40 cases), Burkitt's lymphoma (small noncleaved, SNC) (12 cases), diffuse large and mixed cell lymphoma (25 cases), and unclassified (five cases). The age of the patients ranged from 6 months to 20 years, with a median of 11 years. The clinical characteristics were found to depend upon the histological diagnosis, as reported previously. To evaluate the influence of various clinical and morphological parameters on survival, univariate analysis was performed for each histological subtype. In lymphoblastic lymphoma, patients with a mediastinal mass had significantly earlier development of leukemic conversion and a shorter survival than patients without a mass. Because of the small number of patients and their short survival, no significant prognostic factors were found in Burkitt's lymphoma (SNC). In large and mixed cell lymphoma, response to therapy was the most significant prognostic factor. As therapy became more intense and systematic throughout the study period, the complete remission rate and survival improved steadily. Autopsy findings confirmed that lymphoblastic lymphoma and Burkitt's lymphoma (SNC) spread systemically earlier than large and mixed cell lymphoma.

Adolescent↗
PubMed1991

Severe herpes simplex virus hepatitis following autologous bone marrow transplantation: successful treatment with high dose intravenous acyclovir.

A 17-year-old male patient with T-cell type lymphoblastic lymphoma in complete remission underwent high dose chemotherapy (busulfan 16 mg/kg and cyclophosphamide 120 mg/kg) followed by autologous bone marrow transplantation (ABMT). The patient had been taking oral acyclovir (200 mg x 5) daily from seven days prior to the ABMT (day -7). On day +24, he complained of epigastralgia and general malaise, and the next day his GOT and GPT rose to 570 U/l and 397 U/l, respectively. Although he had no mucocutaneous lesions, hepatitis caused by a herpes virus was suspected, and high dose intravenous acyclovir (10 mg/kg x 3/day) was immediately started. His GOT, GPT and total bilirubin reached peaks of 2,870 U/l on day +26, 1,830 U/l on day +27 and 10.3 mg/dl on day +39, respectively, and rapidly improved thereafter. Serological analyses on IgG antibody titers to herpes simplex virus type 1 using an enzyme-linked immunosorbent assay revealed specific increases (454-fold before transplantation to 3,830-fold on day +46). Antiviral antibody titers to cytomegalovirus, varicella-zoster virus and Epstein-Barr virus showed no significant changes. The serologic markers of hepatitis B virus, hepatitis A virus and hepatitis C virus were all negative. The results indicate the patient's severe icteric hepatitis to have been caused by a reactivation of herpes simplex virus type 1 due to immunosuppression after high dose chemotherapy with ABMT. It is suggested that prompt commencement of high dose intravenous acyclovir is required to treat severe herpes simplex virus hepatitis affecting immunocompromised patients.

Acyclovir↗
PubMed1990

Decreased absorption as a possible cause for the lower bioavailability of a sustained-release propranolol.

The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg x 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration-time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CL) for P and its metabolites that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

Adult↗
PubMed1990

[Clinical evaluation of recombinant human G-CSF in children with cancer].

Recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was administered in 69 chemotherapy-induced neutropenic pediatric patients (pts) with malignant tumors. Each pt received two cycles of the same chemotherapy and had neutropenia with absolute neutrophil counts (ANC) less than 500/microliter in the first cycle. Initiating 72 hours after termination of chemotherapy in the second cycle, rG-CSF (2 micrograms/kg/day) was given subcutaneously or intravenously to each pt for 10 days. rG-CSF significantly increased ANC at nadir; 72 +/- 14 vs. 206 +/- 40/microliter (data in the first cycle vs. data in the second cycle, respectively), and reduced the period of neutropenia with ANC less than 500/microliter; 9.7 +/- 0.6 vs. 5.1 +/- 0.6 days, and the period for restoration to ANC greater than or equal to 1,000/microliter after initiation of chemotherapy; 25.5 +/- 0.6 vs 17.5 +/- 0.9 days. rG-CSF did not affect other components of peripheral blood. The number of days with fever greater than or equal to 38 degrees C was significantly reduced by rG-CSF treatment. Neck pain and lumbago were observed in one pt, pollakisuria in one pt, and elevation of the serum levels of LDH and uric acid in one pt, however these were mild to moderate, transient, and resolved without any specific treatment. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for malignant tumors without any serious side effects.

Adolescent↗
PubMed1990

[Clinical evaluation of aztreonam for infections accompanying febrile neutropenic children with hematologic disorders and solid tumors. A cooperative study].

One hundred four children with infection accompanying hematologic disorders and solid tumors were treated with aztreonam (AZT) (120-150 mg/kg), either alone or in combination with one of the following drugs; cefmetazole (CMZ) (120-150 mg/kg), piperacillin (PIPC) (120-150 mg/kg), or amikacin (AMK) (5-10 mg/kg). The overall efficacy rate was 69.2%. Efficacy rates by regimen were as follows: AZT alone was 63.2%, AZT plus CMZ was 73.6%, AZT plus PIPC was 74.1% and AZT plus AMK was 20.0%. Efficacy rates in different types of infections were 53.2% for sepsis and suspected sepsis, 78.9% for pneumonia and respiratory tract infection, 93.1% for fever of undetermined origin and 55.6% for other infections. The efficacy rate was 71.3% in 94 patients in whom causative organisms were not identified and 50.0% in 10 patients in whom causative organisms were identified. Most of infections in which causative organisms were identified were caused by Gram-negative pathogens. The response rate among infections caused by Gram-negative bacilli was 50.0%. A combination of AZT and CMZ or PIPC was effective in 3 (100.0%) out of 3 patients in whom Escherichia coli was the causative organism. Efficacies classified according to different neutrophil counts were 59.3% for less than or equal to 100/microliters, 78.6% for 101-500/microliters and 82.4% for greater than or equal to 501/microliters. No significant adverse reactions were observed. These results indicated that combination of AZT and 2nd generation cephalosporins or penicillins were well tolerated and effective for infections complicated with accompanying hematologic disorders and solid tumors.

Adolescent↗
PubMed1990

[Autologous bone marrow transplantation in pediatric cancer].

Since May 1979, 47 patients with pediatric malignancy aged 1 to 18 years (median: 7) were treated with cryopreserved autologous bone marrow transplantation (ABMT) in the department of pediatrics, National Cancer Center Hospital. The malignancies were acute non-lymphocytic leukemia (n = 8), acute lymphocytic leukemia (n = 5), osteosarcoma (n = 7), neuroblastoma (n = 6), brain tumor (n = 5), rhabdomyosarcoma (n = 4), retinoblastoma (n = 3), Ewing's sarcoma (n = 3), non-Hodgkin's lymphoma (n = 2), malignant histiocytosis (n = 1), hepatoblastoma (n = 1), malignant melanoma (n = 1) and malignant neuroepithelioma (n = 1). Conditioning regimens for solid tumors were multi-agent high-dose chemotherapy, mainly consisted of cyclophosphamide (CY) 120 mg/kg or melphalan 180mg/m2 and that for hematological malignancies were CY with fractionated total body irradiation (12 Gy). In vitro purging by 4-hydroperoxycyclophosphamide was performed in 12 leukemia patients and 5 solid tumor patients. Of the 13 patients with acute leukemia, 1 died from relapse 1 year after the unpurged marrow transplantation and 1 relapsed in the testis. Remaining 11 patients are alive in continuous complete remission with a median follow up of 30 months (range, 2 to 65 months) after transplantation. The disease-free survival rate of them was 78%. Of the 34 patients with solid tumor, 21 patients died, their cause of death were relapse in 18 and each one of infection, graft failure and brain hemorrhage. Thirteen patients are alive without disease with a median follow up of 28 months (range, 2 to 107 months) posttransplant. The longest survivor is a brain tumor girl, and there are 5 other long survivors; 2 of them are osteosarcoma and each one of rhabdomyosarcoma, Ewing's sarcoma and malignant histiocytosis. The disease-free survival rate of total 34 solid tumor patients is 29%, but that of 17 patients who received ABMT in responsive and minimum tumor residue (MTR) period was 69%. These results suggest that autologous bone marrow transplantation is an effective and tolerable treatment for poor prognostic pediatric malignancies, especially for acute leukemia and such solid tumor as that in MTR state.

Adolescent↗