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Biomedical subjects

E Takeda

Publications and source records attributed to E Takeda.

At least 127 records · Page 7Linked to original sources
PubMed1988

Detection of pyruvate metabolism disorders by culture of skin fibroblasts with dichloroacetate.

For use in screening for disorders of pyruvate metabolism, a sensitive assay method was developed for measuring the rate of decarboxylation of [1-14C]pyruvate during in vitro culture of skin fibroblasts with dichloroacetate (DCA). The rate of decarboxylation of [1-14C]pyruvate by skin fibroblasts from control subjects increased from 59.6 +/- 13.2 to 97.3 +/- 12.0 nmol/h/mg protein during in vitro culture in medium supplemented with 10 mM DCA for 3 days. In contrast, the rate hardly increased in cells from four of 20 patients with congenital lactic acidosis of unknown cause during in vitro culture with DCA. On day 3 of culture, the values for the four patients did not overlap those of control cells and so these four patients could be clearly distinguished from control subjects. Measurements of the original activity and the activity of the pyruvate dehydrogenase (PDH) complex after activation with a broad specificity protein phosphatase and DCA suggested that in three of the patients the aberration was a disorder in the mechanism for activation of PDH, including deficiency of PDH phosphatase or a mutation of PDH itself, whereas that in the fourth patient it might be a disorder of the mitochondrial transport system for pyruvate. Thus, measurement of the rate of decarboxylation of [1-14C]pyruvate by skin fibroblasts cultured in medium supplemented with 10 mM DCA for 3 days is a useful method for screening for disorders of pyruvate metabolism in cultured skin fibroblasts.

Acetates↗
PubMed1988

[Clinical study of sultamicillin fine granules].

Sultamicillin, a mutual prodrug of a beta-lactam antibiotic and beta-lactamase inhibitor, was administered to 19 child patients with infectious diseases. The patients included 9 boys and 10 girls from 11 months to 13 years old and they were given orally a dosage of 15.4-40.8 mg/kg/day for 3 to 12 days. Clinical efficacies were excellent in 2 cases, good in 13 cases, fair in 3 cases, unknown in 1 case, and the total efficacy rate was 83.3%. Loose stool in 1 case and mild diarrhea in another occurred as side effects of the drug, but no abnormal laboratory test values were found upon the treatment.

Administration, Oral↗
PubMed1987

Urinary homocystine levels in a newborn infant with cystathionine synthase deficiency.

A boy with homocystinuria due to cystathionine synthase deficiency was found to have hypermethioninaemia by neonatal blood screening, but was not diagnosed as homocystinuric until 3 months of age because urinary homocystine was not detected by the cyanide-nitroprusside test or on two examinations with a sensitive amino acid autoanalyser. These findings indicate that tests for urinary homocystine should be made repeatedly with an amino acid autoanalyser in newborn infants with hypermethioninaemia until the enzyme defect is identified.

Cystathionine beta-Synthase↗
PubMed1987

Synergistic inhibitory effects of dipyridamole and vincristine on the growth of human leukaemia and lymphoma cell lines.

The effects of combinations of dipyridamole, an effective blocker of the salvage pathway of DNA synthesis, and 8 types of anti-cancer drugs on the growth of human T, B and myeloid leukaemia/lymphoma cell lines in vitro were examined. In combinations, dipyridamole and vincristine (VCR), and dipyridamole and vindesine had synergistic inhibitory effects. Dipyridamole reduced the efflux of VCR from cells and enhanced their VCR accumulation in a dose-dependent manner at concentrations of up to 10 microM in the lymphoid cell lines, MOLT-3 and BL-TH, and of up to at least 20 microM in the myeloid cell line, ML-1. Dipyridamole also enhanced the accumulation of VCR in PHA-stimulated and un-stimulated lymphocytes of normal donors, but efflux of VCR was more rapid from normal lymphocytes than from cultured cell lines. It is proposed that combination therapy with dipyridamole plus VCR should be effective in the treatment of leukaemia and lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Congenital lactic acidosis.

For use in screening for disorders of pyruvate metabolism in cultured skin fibroblasts, we developed a sensitive assay method for measuring the rates of decarboxylation of (1-14C)-pyruvate using dichloroacetate (DCA). By this method, disorders of the mechanism of activation of pyruvate dehydrogenase (PDH) were found in 2 of 10 patients with congenital lactic acidosis of unknown cause. We also found that DCA activated the PDH complex and the tricarboxylic acid cycle, which is an important pathway of energy metabolism, in the brain and other tissues, and lowered the lactate level in the blood and cerebrospinal fluid. Therefore, DCA therapy may be useful in treatment of chronic congenital lactic acidosis if this treatment is started sufficiently early.

Acetates↗
PubMed1987

1 alpha-hydroxyvitamin D3 treatment of three patients with 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia.

Three patients with clinically different severities of vitamin D-dependent rickets, type II, with alopecia, which is 1,25-dihydroxyvitamin D-receptor-defect rickets and is particularly resistant to treatment with calciferol analogues, were treated with large doses of 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) and 2 g of calcium lactate. Except for the alopecia, all of the abnormalities of patients 1 and 2 were reversed by treatment with 3 micrograms/kg/d of 1 alpha-(OH)D3, and those of patient 3, who had the severest manifestations, were reversed by treatment with 6 micrograms/kg/d. The serum 24,25-dihydroxyvitamin D concentrations of the three patients were low before treatment and those of patients 1 and 2 increased during treatment. These findings suggest that in patients 1 and 2, 25-hydroxyvitamin D-24-hydroxylase was stimulated via a 1,25-dihydroxyvitamin D-receptor-mediated system by treatment with 1 alpha-(OH)D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1986

Rapid diagnosis of vitamin D-dependent rickets type II by use of phytohemagglutinin-stimulated lymphocytes.

The interactions of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] with phytohemagglutinin (PHA)-stimulated lymphocytes from normal subjects and three patients with vitamin D-dependent rickets (DDR) type II were investigated. Impaired nuclear uptake and normal cytosol binding of [3H]1,25-(OH)2D3 were observed with PHA-stimulated lymphocytes of these patients as with their cultured skin fibroblasts. Furthermore, the incorporation of [14C]thymidine into PHA-stimulated lymphocytes of the patients was not reduced by 1,25-(OH)2D3, which is known to inhibit proliferation of various cells. These findings suggest that 1,25-(OH)2D3 receptors are reduced or absent in patients with DDR type II. Thus, the capacities of cytosol binding and nuclear uptake of 1,25-(OH)2D3 in PHA-stimulated lymphocytes seem to reflect those of endo-organs such as the intestine and bone. These findings show that a test of the effect of 1,25-(OH)2D3 on thymidine incorporation into PHA-stimulated lymphocytes is useful for rapid diagnosis of DDR type II.

Calcitriol↗
PubMed1986

Involvement of thiol proteases in galactosialidosis.

The activities of Z-Phe-Arg-NMec(ZPA) hydrolase, cathepsin B and cathepsin H and the concentration of endogenous thiol protease inhibitor in fibroblasts from patients with galactosialidosis were found not to be significantly different from those in control fibroblasts. Culture for 5 days with thiol protease inhibitors such as leupeptin, E-64 or Z-Phe-Phe-CHN2 partially restored the beta-galactosidase activity of fibroblasts from patients, but did not affect the beta-galactosidase activity of fibroblasts from control subjects. However, culture with leupeptin, but not other protease inhibitors, increased the ZPA hydrolase and cathepsin B activities of fibroblasts from both patients and controls 2- to 4-fold. Sephadex G-75 chromatography showed that the activity of high molecular weight ZPA hydrolase, which was initially predominant in fibroblasts, decreased markedly during their culture with leupeptin, while the activities of lower molecular weight ZPA hydrolase and cathepsin B increased about 5-fold. These results suggest that high molecular weight ZPA hydrolase, which is presumably cathepsin J, degrades beta-galactosidase, and that the defect in galactosialidosis is impaired protection of beta-galactosidase from degradation.

Cathepsin B↗
PubMed1986

Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate.

Sodium dichloroacetate (DCA) was administered orally at a dose of 50 mg per kg body weight twice or three times per day to a newborn infant with lactic acidosis of unknown cause (patient 1) and to a 15-year-old boy with mitochondrial encephalomyopathy associated with lactic acidosis (patient 2). In patient 1, during treatment with DCA, DCA accumulated in the blood judging from the findings that the urinary excretion of DCA increased cumulatively and the blood lactate level rapidly decreased to the normal range. In patient 2, the blood DCA level gradually increased during treatment to a concentration of 250 micrograms ml-1 and the blood lactate level decreased and was maintained within the normal range. DCA was detected in the brain (25 micrograms g tissue-1) and the liver, kidney and muscle (33.8, 33.8 and 26.3 micrograms g tissue-1, respectively) obtained at autopsy of patient 1, and in the cerebrospinal fluid of patient 2 at a concentration of 125 micrograms ml-1 when the blood concentration was 250 micrograms ml-1. The lactate levels in the cerebrospinal fluid decreased from 7 and 4 mmol l-1 to 2.4 and 2.6 mmol l-1 in patients 1 and 2, respectively. Thus DCA may be useful in clinical treatment of chronic congenital lactic acidosis because it seems to cross the blood-brain barrier. However, it must be given at non-toxic doses, determined by monitoring the concentrations of lactate and DCA in the blood, because orally administered DCA tends to accumulate in tissues.

Acetates↗
PubMed1986

[Radiation-induced secondary cancer in patients with uterine carcinoma].

PURPOSE: Radiation-induced cancer has been epidemiologically investigated in occupational or atomic radiation exposure cases. These is also a need to clarify the risk in the case of radiotherapeutical exposure. In this study, therefore, cases of post-irradiated uterine carcinoma which was well cured and followed up over a long term were selected for statistical analysis of radiation-induced cancer in the medical division. MATERIALS AND METHODS: A total of 19,384 patients with uterine carcinoma at seven institutions in Japan were registered on a computer system at the NIRS and were statistically analyzed. Of these, 6,655 patients were treated by surgical procedure alone, 4,310 were given a combined treatment modality of radiation and surgery, 8,419 were treated by radiation alone between 1960 and 1978. Radiation-induced cancer was defined according to the following categories: Secondary cancer was developed within the irradiated field. Time interval was over 5 years after the initial irradiation (leukemia was over 2 years). The cancer had a different histological type to the original one. A total of 43 patients with induced cancer were observed, namely: 14 with rectal cancer, 8 with leukemia, 6 with uterine corpus cancer, 4 with urinary bladder cancer, 3 with osteosarcoma or uterine sarcoma, 2 with sigmoid colon cancer or malignant fibrous histiocytoma, and 1 with ovarian cancer, respectively. RESULTS: Rectal cancer, leukemia and urinary bladder cancer were initially analyzed, because their expected values were easily estimated from the basic data. A total of 8,333 patients (43,418 person-years) from 7 institutions were considered. Their average follow-up period was 10.2 years after treatment. 1) Rectal cancer: Observed value (O) = 14, expected value (E) = 7.83, O/E = 1.79, 95% confidence interval of O/E ratio (CI) = 0.98-2.99, there was no significant difference. 2) Leukemia: O = 8, E = 3.78, O/E = 2.12, CI = 0.91-4.18, no significant difference. 3) Urinary bladder cancer: O = 4, E = 2.23, O/E = 1.79, CI = 0.49-4.55, no significant difference. In other words, no significant difference was observed in the risk of occurrence of secondary cancer among the total number of irradiated patients from the 7 institutions. Since these results, however, were influenced by the accuracy of patient follow-up, the O/E ratio of double cancer in each institution was observed to check the accuracy of the follow-up and 3 institutions were selected for further analysis comprising 2,686 patients (13,588 person-years) in all. Their average follow-up period was 10.1 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1986

[An analysis of prognostic factors in radiotherapy of carcinoma of the uterine cervix].

An analysis of prognostic factors for stage 3 carcinoma of the uterine cervix was performed using multivariate analysis. Such factors were closely related to prognosis of the patients as follows; 1) risen temperature during the treatment, kidney function before treatment and age which were concerned in local recurrence 2) risen temperature, leucocytosis, hypertension and kidney function which were concerned in distant metastasis. Since the patients have various factors which have correlation between one another, it is important to investigate each factors separately more detail aspect.

Aged↗
PubMed1985

Activation of branched-chain alpha-ketoacid dehydrogenase complex by alpha-chloroisocaproate in normal and enzyme-deficient fibroblasts.

A method has been developed for the activation of the branched-chain alpha-ketoacid dehydrogenase complex by alpha-chloroisocaproate, an inhibitor of branched-chain alpha-ketoacid dehydrogenase kinase in human cultured skin fibroblasts. The enzyme could be activated by pretreating the cells with alpha-chloroisocaproate before they were disrupted for measurement of the activity. After this treatment, the activity was 2- to 3-fold that of untreated cells (24.8-81.4 pmol/min per mg protein). The enzyme activity in fibroblasts from a patient with maple syrup urine disease was measured by this procedure. After activation by alpha-chloroisocaproate, the activity of fibroblasts from the patient was only 10-14 pmol/min per mg protein (10% of that of controls), and was almost the same as that of the untreated cells from this patient. These results show that it is important to consider the activation state of branched-chain alpha-ketoacid dehydrogenase complex when assaying it in disrupted cells.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1985

Hereditary renal hypouricemia in children.

The renal handling of urate was investigated in four children with hereditary renal hypouricemia and in their parents. The urate/creatinine clearance ratios in the four patients were 1.02 +/- 0.28, 0.93 +/- 0.11, 1.03 +/- 0.24, and 1.46 +/- 0.26, markedly higher than those in control subjects. Except for a partial response to pyrazinamide (change in clearance ratio from 1.46 to 1.07) in one patient, pyrazinamide and benzbromarone did not affect the clearance ratios in our patients. In the parents, the urate/creatinine clearance ratios were intermediate between those of the patients and control subjects, but responses to pyrazinamide and benzbromarone were normal. These data indicate that our patients have a combined defect in renal urate reabsorption, and that one of them might be subclassified as having the hypersecretion of defect. Results also show that heterozygotes can be identified by testing their urate/creatinine clearance ratio.

Benzbromarone↗
PubMed1985

Diagnosis of partial deficiency of the pyruvate dehydrogenase complex in biopsied muscle.

We have measured the total activity of pyruvate dehydrogenase (PDH) complex, by in vitro activation with a broad specificity protein phosphatase, and the basal activity, supposed to be present in vivo, in biopsied muscles from three patients with PDH complex deficiency and 11 patients with lactic acidemia. Results showed that the total PDH complex activity must be determined in biopsied muscles for the diagnosis, because the basal activities of two of three patients with PDH complex deficiency overlapped those of two patients with lactic acidemia whose total activities were within normal range.

Adult↗