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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 883 records · Page 49Linked to original sources

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↗

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↗

HLA study of Japanese patients with Creutzfeldt-Jakob disease: significant association with HLA-DQw3.

To demonstrate genetic susceptibility to Creutzfeldt-Jakob disease (CJD), 10 Japanese patients with pathologically proved CJD and 6 patients with clinically definite CJD were tissue typed for 48 class I and 14 class II human leukocyte antigen (HLA) specificities. The patients were scattered throughout Japan and there were no consanguineous relationships. Among 62 HLA specificities, HLA-DRw53 and DQw3 were found in all pathologically proved CJD cases. When the frequencies of the HLA antigens in the 16 CJD cases were compared to those of normal Japanese, a highly significant (p less than 0.005) increase was found for HLA-DQw3 in the CJD group. The present findings provide evidence for genetic control of susceptibility to CJD in humans.

Aged↗

Studies on drug metabolism by use of isotopes. XXVIII--Biological isotope effect for deuterated ephedrine.

The stability of the deuterium label and the occurrence of an isotope effect for deuterated (-)-ephedrine during metabolic processes were investigated. Determination of the deuterium content in deuterated (-)-ephedrine and its metabolites excreted into urine showed that little, if any, deuterium exchange had occurred. In rats, a slight isotope effect was observed for p-hydroxylation (about 15%) and glucuronide formation of p-hydroxyephedrine and/or its enzymatic hydrolysis (about 20%). In human subjects, there was about 15% difference in the excretion of norephedrine between deuterated and non-deuterated species.

Animals↗

Studies on drug metabolism by use of isotopes. XXIX--Studies of the differences in biological fates of ephedrine isomers by use of a pseudo-racemic mixture.

The differences in metabolic fates of the optical isomers of ephedrine were investigated by use of a pseudo-racemic mixture technique. In rats, the (-)-isomer was more easily p-hydroxylated than the (+)-isomer. A stereoselective reaction in the formation of the glucuronides of ephedrine, norephedrine and p-hydroxyephedrine was observed. The (-)-isomers were more easily subjected to glucuronide formation than the (+)-isomers. In human subjects, N-demethylation proved to be a stereoselective reaction. It is also suspected that oxidative dealkylation of norephedrine is a stereoselective reaction.

Animals↗

Genetic and chemical factors affecting chemical mutagenesis in cultured mammalian cells.

The genetic and chemical factors affecting chemical mutagenesis in cultured Chinese hamster V79 cells are described. The frequency of mutations induced by the same chemicals at the same concentrations was markedly affected by the genetic markers used. Some chemicals that were positive in the Ames tests induced 8AGr and 6TGr mutations at higher frequencies than OUAr mutations. Carcinogens that were negative in the Ames tests induced only 8AGr mutations, but did not induce OUAr mutations. As a compound affecting mutations induced by EMS, vitamin C showed marked effects in reducing the cytotoxicity and frequency of 6TGr mutations induced by EMS when cells were treated simultaneously with vitamin C at a concentration of 100 micrograms/ml.

Animals↗

Effects of anti-insulin antibody on insulin binding to liver membranes: evidence against antibody-induced enhancement of insulin binding to the insulin receptor.

In the presence of anti-insulin antibody, 2-to 3-fold enhancement of 125I-insulin binding to liver membranes was observed when binding was estimated by the radioactivity of 125I-insulin bound to the membrane pellets. However, after 125I-insulin was covalently cross-linked to liver membranes using disuccinimidyl suberate in the presence of anti-insulin antibody, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed that 125I-insulin bound to the alpha-subunit of the insulin receptor was inhibited by anti-insulin insulin antibody in an dose-dependent manner. More importantly, at an anti-insulin antibody dilution range between 1:50 and 1:5,000, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two 125I-labelled bands of mol wt 62,000 and 27,000, while only one band of mol wt 130,000 was revealed in the absence of anti-insulin antibody. These Mr = 62,000 and Mr = 27,000 bands were found to be the heavy and the light chain of anti-insulin IgG molecules respectively. Pepsin digested anti-insulin serum had only an inhibitory effect on 125I-insulin binding to liver membranes. Non-immunized guinea pig serum or IgG completely abolished the enhanced effect of anti-insulin antibody. Further, this enhanced effect was inhibited by Fc fragment-specific anti-IgG serum or H&L-chain-specific anti-IgG serum in a dose-dependent manner. Protein A also inhibited the effect of anti-insulin antibody. In IM-9 lymphocytes and human red blood cell ghosts, which have no Fc gamma receptors, enhancement of insulin binding was not observed in the presence of anti-insulin antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗

Chronic polymyositis: presence of coxsackievirus A9 antigen in muscle.

We report a case of chronic recurrent polymyositis associated with increasing antibody titers of coxsackievirus A9 in serum during clinical exacerbations. Muscle biopsy specimens showed pathologic changes consistent with chronic myositis, including perivascular mononuclear cell infiltration and hyalinization of muscle fibers with cytoplasmic vacuolations. The specific fluorescence was observed in the muscle fibers stained with antiserum for coxsackievirus A9. These findings indicate that this viral subtype as the etiologic agent in this case and virus plays a pathogenic role in some cases of chronic polymyositis.

Antigens, Viral↗

[Clinical investigation of neuron-specific enolase, squamous cell carcinoma-related antigen and carcinoembryonic antigen in carcinoma of the lung].

Serum levels of neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC antigen) and carcinoembryonic antigen (CEA) were measured in 53 untreated patients with carcinoma of the lung. The positive rates of serum NSE were 17.0% in all patients with lung cancer, 53.8% in small cell carcinoma, 6.7% in adenocarcinoma, 5.0% in squamous cell carcinoma and 0% in large cell carcinoma; 0% in stage I, 14.3% in stage III and 26.7% in stage IV. The positive rates of serum SCC antigen were 45.3% overall, 70.0% in squamous cell carcinoma, 40.0% in adenocarcinoma, 23.1% in small cell carcinoma and 0% in large cell carcinoma; 42.9% in stage I, 57.1% in stage III and 46.7% in stage IV. In comparison with serum CEA, serum NSE and SCC antigen were much more specific in small cell carcinoma and squamous cell carcinoma, respectively. Moreover, serum levels of NSE and SCC antigen changed in parallel with the clinical course during the treatments. In conclusion, serum NSE and SCC antigen were considered to be very useful markers of lung cancer, especially of small cell carcinoma and squamous cell carcinoma, respectively.

Adenocarcinoma↗