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A Togawa

Publications and source records attributed to A Togawa.

At least 73 records · Page 4Linked to original sources
PubMed1995

Species and sex differences of testosterone and nifedipine oxidation in liver microsomes of rat, dog and monkey.

1. Species and sex differences in testosterone hydroxylation and nifedipine oxidation in liver microsomes from rat, dog and monkey have been investigated. 2. The formation of 2 alpha-, 2 beta-, 6 beta-, and 16 alpha-hydroxytestosterone and androstenedione in the male rat was higher than that in the female rat. Microsomes prepared from the male rat oxidized nifedipine about eight times faster than did those from the female rat. In contrast, marked sex-related differences were not seen in the dog and monkey. 3. Nifedipine oxidase activity in rat, dog and monkey correlated significantly with the activities for both testosterone 2 beta-hydroxylation and 6 beta-hydroxylation, suggesting the involvement of P4503A isozymes in these reactions. The ratios of formation of the 2 beta- to 6 beta-hydroxytestosterone in male rat and monkey were 0.17 and 0.18 respectively, whereas that in dog was 0.46. The corresponding activity ratios catalysed by P450DPB-1, a P4503A isoform purified from dog liver microsomes, was 0.36. 4. The formation of 16 beta-hydroxytestosterone was higher than that of the 16 alpha-hydrolated metabolite in liver microsomes from monkey, whereas 16 alpha-hydroxytestosterone was the predominant metabolite in the rat and dog, indicating species differences in stereoselectivity at the 16-position.

Animals↗
PubMed1995

Stimulation and priming of human neutrophils by IL-1 alpha and IL-1 beta: complete inhibition by IL-1 receptor antagonist and no interaction with other cytokines.

Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and triggering effect was obtained by high concentrations (50 to 500 ng/mL) of IL-1 alpha or IL-1 beta, though IL-1 beta was more effective than IL-1 alpha at suboptimal concentrations. Priming effect of IL-1 was very rapid and maximal within 10 minutes, whereas O2- release triggered by IL-1 was gradual and continued for 90 to 120 minutes. Combined stimulation of human neutrophils with IL-1 plus granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) resulted in additive priming effect, and combined stimulation of neutrophils with IL-1 plus G-CSF, GM-CSF, or tumor necrosis factor (TNF) resulted in additive triggering effect, even when the maximal concentration of each cytokine was used. These priming and triggering effects of IL-1 alpha and IL-1 beta on the respiratory burst in human neutrophils were completely inhibited by IL-1 receptor antagonist (IL-1ra). Furthermore, only the net effect of IL-1 was inhibited by IL-1ra, even when human neutrophil was stimulated with IL-1 plus other cytokines to release O2-. Present results indicate that IL-1 does stimulate the respiratory burst activity in human neutrophils via receptor-mediated mechanism and suggest that the post-IL-1-receptor signaling pathways linked to the activation system of the respiratory burst are independent from those utilized by other cytokines in human neutrophils.

Adult↗
PubMed1995

[The general management of multiple myeloma--risk factor].

The introduction of melphalan therapy produced improvement in either response rates or survival of patients with myeloma. Since then, many attempts have been carried out to improve the results achievable with MP therapy by the use of combination chemotherapy, but no difference in survival was found. Recent efforts have evaluated dose intensification for patients with good risk factor to from the viewpoint of bone marrow ablation requiring hematopoietic stem cell support, though these approaches may be ineffective for patients with refractory myeloma.

Humans↗
PubMed1995

[Chemotherapy for multiple myeloma].

Since the introduction of melphalan for the treatment of myeloma, remission rate and survival have been apparently improved. To improve upon the results achievable with MP therapy by the use of combination chemotherapy, many attempts have been done, suggesting that there is no difference in efficacy between them. Results of bone marrow ablative therapy with stem cell support the hypothesis that further intensification of therapy effects further tumor-mass reduction and extends survival times.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Ten-year survival and prognostic factors in multiple myeloma. Japan Myeloma Study Group.

Among 1119 Japanese patients with symptomatic multiple myeloma diagnosed between 1965 and 1981, 38 (3.4%) survived more than 10 years. Younger age, low tumour mass (absence of severe anaemia, hypercalcaemia, renal failure, and multiple bone lesions), low plasma cell percentage in bone marrow, mature and intermediate myeloma according to Greipp's criteria, and a positive response to subsequent treatment, were related to long-term survival according to univariate analysis. Multivariate logistic regression analysis indicated younger age and low tumour mass as pretreatment characteristics to be related to long-term survival. Prognostic factors proposed applicable to myeloma were also related to 10-year survival.

Aged↗
PubMed1994

[CD7 positive undifferenciated leukemia/lymphoma associated with leukemic pericarditis].

We report here a CD7 positive undifferenciated leukemia/lymphoma which showed a rapid clinical course. A 27-year-old female was complained of palpitation and edema. She had a mediastinal tumor and pericardial effusion. Lymphoblastic cells were found in the effusion, but in the peripheral blood initially. After admission the blast cells appeared in the peripheral blood, and they were revealed negative for peroxidase and had phenotype of CD7 and CD33 positive. The patient suffered from cardiac tamponade and died 15 days after admission. The Southern blotting of mediastinal tumor cells disclosed the germline configuration for TCR-beta a chain and the rearrangement of immunoglobulin heavy chain genes.

Adult↗
PubMed1994

[Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all-trans-retinoic acid].

This paper describes the treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all-trans-retinoic acid (ATRA). The patient, a 22-year-old male, was diagnosed to have APL and had been treated with busulfan and then with three and half years interferon (IFN) alpha in the chronic phase. A cytogenetic study of blast cells showed the t(1;17) (p11;q11) translocation as the second chromosomal abnormality without morphological abnormality of chromosome 15. Molecular analysis showed cells to have a chimera gene consisted of PML and retinoic acid receptor alpha genes. Though maturation and differentiation of leukemic cells were seen after ATRA therapy, hematological complete remission did not occur. The ineffectiveness of ATRA may be dut to different pathological conditions from de novo APL, or progressive reduction in plasma ATRA concentration as reported by Muindi et al. When our case was compared with a similar case reported by Wiernick et al., both cases were treated with IFN alpha in the chronic phases, had no t(15;17) translocation involving No.1 chromosome abnormality and did not develop complete remission after ATRA therapy.

Adult↗
PubMed1993

Tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor.

Tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) primed human neutrophils for enhanced release of superoxide in time- and dose-dependent manners. The priming effects of these cytokines were detected at 3 min and maximal at 10 min of preincubation. The potency of the maximal effect was TNF > GM-CSF > G-CSF. Exposure of human neutrophils to TNF, GM-CSF and G-CSF resulted in tyrosine phosphorylation of a 42-kDa protein and intracellular alkalinization in a dose-dependent manner. The dose-response curves for triggering of tyrosine phosphorylation and intracellular alkalinization by each cytokine were similar to those for priming the cells. The potency of the maximal effect on tyrosine phosphorylation was TNF > GM-CSF > G-CSF, whereas that on intracellular alkalinization was GM-CSF > TNF > G-CSF. Tyrosine phosphorylation was detected at 3 min and maximal at 5-10 min after stimulation with each cytokine. Tyrosine phosphorylation induced by TNF declined at 20-40 min, whereas that induced by GM-CSF or G-CSF was maintained for at least 40 min. Intracellular alkalinization induced by each cytokine required a lag time of 3-5 min and was sustained for at least 40 min. Tyrosine phosphorylation preceded or occurred concomitantly with intracellular alkalinization and priming of the cells. These findings indicate that tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by TNF, GM-CSF and G-CSF, and that these early events may, at least in part, mediate activation or priming of human neutrophils by these cytokines.

Dose-Response Relationship, Drug↗
PubMed1993

[Clinical study of fluconazole for systemic fungal infections with hematological disorders].

Fluconazole (FLCZ) was administered orally or intravenously to 161 patients with systemic fungal infections complicated with hematological disorders and it was possible to evaluate clinical efficacies in 109 patients. Systemic fungal infections were documented in 48 patients and suspected in 61 patients. The overall clinical efficiency rates were 43.8% (21/48) in patients with documented fungal infections, and 55.7% (34/61) in patients with suspected fungal infections. Therefore, the overall clinical efficacy rate was 50.5% (55/109). Side effects were observed in 5 patients with an incident rate of 3.1% (5/161), but there was none of them was serious. These results indicate that FLCZ is an agent with good potential in treatment of systemic fungal infections in patients with hematological disorders.

Adolescent↗
PubMed1993

[Recent therapy for refractory myeloma].

There are only 3.3% of patients with multiple myeloma in Japan Myeloma Study Group who have lived longer than ten years. Features associated with long survival include responded well to simple treatment such as melphalan or cyclophosphamide and prednisone, short duration of treated time with long activity and prolonged unmaintained remissions. High-dose melphalan therapy, VAD chemotherapy and MCNU-VP16-melphalan combination were tried for patients relapsed with alkylating agents and the result were reported. Bone marrow transplantation and cytokine therapy for myeloma will be discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Direct injection analysis of melphalan in plasma using column-switching high-performance liquid chromatography.

An automated column-switching high-performance liquid chromatographic (HPLC) method with ultraviolet detection is described for a simple and rapid determination of melphalan, an alkylating agent, in human plasma following direct sample injection. The system consists of a pretreatment column and an analytical column connected in series via a switching valve. Plasma samples are loaded onto a pretreatment column with an aqueous mobile phase, with which the sample to be analyzed is retained and the solubilized plasma proteins are flushed to be discarded. The retained compound is eluted from the pretreatment column onto the analytical column by using the chromatographic mobile phase with a higher elution capacity. The column-switching technique can be used to achieve an automated assay. Analytical recovery of the compound was 99.1%, and the coefficients of both intra- and interday variations did not exceed 3.5%. The detection limit was 10 ng/ml for the compound. Recovery of melphalan in plasma was only 2.1% after 4 weeks at 25 degrees C, as compared to 24.5% at 5 degrees C and 100.1% at -20 degrees C.

Adolescent↗
PubMed1992

[Plasma beta-glucan levels in deep fungal infections accompanying hematological diseases and clinical efficacy of miconazole--a multi-institutional study].

Miconazole (400-1200 mg/day) was administered to patients with deep mycosis and suspected deep mycosis, and the efficacy evaluated. beta-Glucan was determined as the early diagnostic parameter of deep mycosis, and the relationships between the clinical efficacy of miconazole and the titers of beta-glucan were also evaluated. Forty-nine cases were evaluated, including 2 cases of deep mycosis and 47 cases of suspected deep mycosis. Most of the patients had hematological malignancies. The rate of efficacy was 100% (2/2) in deep mycosis, 66.0% (31/47) in suspected deep mycosis, and 67.3% (33/49) in total. beta-Glucan was determined in 39 cases before the administration of miconazole. The rate of beta-glucan positivity was 100% (1/1) in deep mycosis and 44.7% (17/38) in suspected deep mycosis. beta-Glucan was also determined before and after the administration of miconazole in 11 cases. The titers of beta-glucan became negative in 6 cases, decreased in 2 cases and increased in 3 cases. Thus, the beta-glucan titers became negative or decreased in 72.7% (8/11) of the cases. Efficacy of miconazole was 83.3% (5/6) in the cases in which beta-glucan became negative, 50.0% (1/2) in the cases in which the titers of beta-glucan decreased, and 33.3% (1/3) in the cases in which the titers of beta-glucan increased. Miconazole was effective in the treatment of deep mycosis, and the titers of beta-glucan correlated well with the clinical efficacy of miconazole. The determination of beta-glucan appears to be useful for the diagnosis of deep mycosis.

Adolescent↗
PubMed1992

Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group.

Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2'-deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon-alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL.

Adult↗
PubMed1990

[VAD chemotherapy of multiple myeloma].

Twelve patients with resistant or recurrent multiple myeloma were treated with VAD regimen (vincristine, adriamycin, dexamethasone), first reported by Barlogie B et al 1984. Of 11 evaluable patients, 7 responded (partial response [PR] 3, minor response [MR] 4), and the overall response rate was 63.7%. The median interval to achieve remission was 27 days, and the median duration of remission was 125 days. One course seemed sufficient for the assessment of effectiveness of the VAD chemotherapy, because in all responders, over 50% reduction of monoclonal protein was obtained in the first course of chemotherapy. We also administered verapamil or trifluoperazine in addition to VAD in two patients who had acquired resistance to VAD. Both had MR. Side effects included infections, gastro-intestinal bleeding, congestive heart failure or severe malaise. In conclusion, the VAD chemotherapy is effective but the duration of remission is short and side effects cannot be disregarded. Perspective of VAD and improvement of the management of refractory multiple myeloma is discussed.

Adult↗
PubMed1990

[NK- and T-cell granular lymphocyte-proliferative disorders].

For the disease of the granular lymphocytes (GL) that contain azurophilic granules to proliferate in the peripheral blood, which is often complicated by anemia or neutropenia and which generally develop into chronic disease, the new designation of granular lymphocyte-proliferative disorders (GLPD) is being proposed. This disease include T-GL having CD3 antigen which forms a complex with T cell Ag receptor (TCR-alpha beta), and NK-GL which is CD3-negative but CD16- or NKH-1-positive, having non-MHC-restricted cytotoxicity. The two cases presented here demonstrate the characteristics of T-GL or NK-GL, however, while one case with NK-GL showed spontaneous decrease of GL, improvement of neutropenia and anemia without any treatment, the other case with T-GL became intractable and required repeated blood transfusion. On such differences in the clinical development of the disease, we have conducted investigations including a review of the literature to see whether there is any correlation between the characteristics of the proliferating cells and pathologic conditions of the disease, and whether this disease is indeed tumorous.

Aged↗