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Biomedical subjects

I Yokota

Publications and source records attributed to I Yokota.

At least 73 records · Page 4Linked to original sources

[Serial assessment of denervated but viable myocardium following acute myocardial infarction by using 123I-MIBG and 201TlCl myocardial SPECT].

123I-MIBG is taken up by sympathetic nerve ending and provides a scintigraphic image of myocardial sympathetic innervation. We investigated the scintigraphic detection of denervated but viable myocardium following acute myocardial infarction by serial 123I-MIBG and 201TlCl myocardial SPECT. Fourteen patients were studied at acute (10 +/- 2 days) and chronic stage (86 +/- 10 days). Simultaneous dual SPECT was carried out after IV administration of 111 MBq (3 mCi) of 201TlCl and 123I-MIBG. The defect size of 123I-MIBG and 201TlCl were compared visually by using Bull's eye display generated from each myocardial SPECT. In all patients, 123I-MIBG defect showed larger compared to 201T1Cl defect at acute stage, which suggest the existence of denervated but viable myocardium. Of these patients, seven showed significant improvement of both defects, though 123I-MIBG defect showed slightly larger compared to 201TlCl defect, even at chronic stage. These patients had exercise induced thallium transient defect at infarcted area. The remaining 7 patients had no improvement of both defects at chronic stage, which suggest the complete scar at infarcted area. In addition to above study, 4 patients of old myocardial infarction demonstrated larger 123I-MIBG defect compared to 201TlCl defect even at old stage, which thought to be pathogenesis of ventricular tachycardia. In conclusion, 123I-MIBG could evaluate sympathetic denervation and reinnervation noninvasively in the patients with acute myocardial infarction.

3-Iodobenzylguanidine↗

Two siblings with vitamin-D-dependent rickets type II: no recurrence of rickets for 14 years after cessation of therapy.

Rickets in a 3-year-old boy and his 1-year-old sister, both with alopecia, was cured by treatment with 50,000 IU of vitamin D2 daily for 2 years and did not recur within 14 years after cessation of therapy. A diagnosis of vitamin-D-dependent rickets type II was made in these patients at the ages of 20 and 18 years based on the findings that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] did not inhibit DNA biosynthesis in phytohaemagglutinin-stimulated lymphocytes and that cultured skin fibroblasts showed impaired nuclear uptake and normal cytosol binding of [3H]1,25(OH)2D3. Surprisingly, the serum 1,25(OH)2D levels of these patients were high and their serum 24,25-dihydroxyvitamin D levels were low, although neither patient showed any symptoms except alopecia. The presence of vitamin D metabolite imbalances in the absence of rickets in these patients might be explained by differences in sensitivity to 1,25(OH)2D3 of bone formation and vitamin D metabolism. In addition, changes of sensitivity to treatment with vitamin D derivatives might be a consequence of differentiation of target cells. From the present findings, it is suggested that in this disease treatment with a sufficient dose of vitamin D derivatives should be initiated in the active phase of rickets.

Alopecia↗

Effect of sodium dichloroacetate on human pyruvate metabolism.

Sodium dichloroacetate (DCA) was administered orally at doses of 12.5 to 50 mg/kg body weight twice or three times per day to a patient with mitochondrial encephalomyopathy associated with congenital lactic acidemia. During therapy, the rates of decarboxylation of (1-14C) pyruvate and (3-14C) pyruvate, which represent the activity of the pyruvate dehydrogenase (PDH) complex and the function of the TCA cycle, respectively, were markedly increased in the platelets and increases in the lactate levels in the blood and urine during exercise were markedly reduced. These results suggest that oral administration of DCA causes significant increases in the activities of the PDH complex and TCA cycle not only in the platelets but also in various tissues of humans, which is important as a pathway for production of energy, resulting in decreases in the lactate and pyruvate levels in the blood and cerebrospinal fluid.

Acetates↗

[Clinical experience with cefodizime in bacterial infection of children].

Clinical studies were performed on cefodizime (THR-221, CDZM), a new cephem antibiotic as described below. CDZM was administered to 13 patients in dose levels ranging from 55 to 96 mg/kg/day t.i.d. for 3-7 days (5.5 days on average). These patients included 8 with pneumonia, 2 with tonsillitis, 1 each with bronchitis, phlegmon and urinary tract infection. The overall efficacy rate was 92.3%, i.e., efficacy was excellent in 8, good in 4 and poor in 1. Bacteriological efficacy was 83.3%, i.e., 5 strains of bacteria (Streptococcus pneumoniae 1, Haemophilus influenzae 3, Haemophilus parainfluenzae 1) were eradicated and 1 was unchanged (Enterobacter cloacae, MIC greater than 100 micrograms/ml). Clinical side effect was not observed during the treatment. Laboratory abnormalities were observed in 2 cases, i.e., a slight elevation of GPT and a mild eosinophilia. The above results suggest that CDZM is a useful antibiotic for treating pediatric bacterial infections.

Age Factors↗

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↗

Intracoronary thrombodynamics in the early phase of acute myocardial infarction.

Intracoronary thrombodynamics in the early phase of acute myocardial infarction were studied in an experimental canine model. Intracoronary thrombus was precipitated at the mock ruptured atheromatous plaque consisting of cholesterol and collagen. (1) Myocardial infarction occurred in 10 and sudden death in 2 secondary to intracoronary thrombotic occlusion in 15 control experiments. (2) Pretreatment with an antiplatelet drug, ticlopidine, significantly reduced the incidence of myocardial infarction and sudden death (7/18, 39% vs. 12/15, 80%, p less than 0.05). (3) During the period when intracoronary thrombus was precipitated, a transient reduction in aortic pressure induced by nitroglycerin resulted in rapid progression of intracoronary thrombotic occlusion in 7 of 21 animals and in 5 of 17 animals treated with nitroprusside. The terminated coronary blood flow could be restored by raising coronary perfusion pressure with methoxamine in 5 of 10 cases with coronary thrombotic occlusion. (4) Cigarette smoking appeared to accelerate the completion of coronary thrombotic occlusion. (5) Sudden death occurred in 12 of 43 models without pharmacological intervention during coronary thrombotic occlusion associated with myocardial dysynergy. Six sudden deaths occurred within 10 min and 9 within 30 min following coronary thrombotic occlusion. Postmortem complete autolysis of intracoronary thrombus was observed in 24% and partial thrombolysis in 28%.

Animals↗

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↗

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↗

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)↗

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↗

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↗