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Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 1,459 records · Page 81Linked to original sources

Carbonic anhydrase-immobilized precolumn for selective on-line sample pretreatment in high-performance liquid chromatographic determination of certain sulphonamide drugs.

Carbonic anhydrase (CA)-immobilized aminopropyl silica precolumn was developed for direct injection determination of certain sulphonamide drugs in biological fluids by column-switching (CS) high-performance liquid chromatography. Under the optimized conditions, only the sulphonamide drugs with an unsubstituted sulphonamide group were retained on the CA precolumn and separated on a reversed-phase analytical column. Of these, the retention of hydrochlorothiazide (HCT), chlorothiazide, acetazolamide, furosemide (FS) and chlorthalidone was almost quantitative. The peak area of HCT was proportional to the concentration in the range of 1-100 nmol/mL with relative standard deviations of 3.7% (5 nmol/mL) and 0.7% (100 nmol/mL). This CS system was applied to urine and plasma samples spiked with HCT and FS. Endogenous components of these were effectively removed, and HCT and FS were selectively retained on the CA precolumn. Almost quantitative recoveries and reproducibility were obtained.

Acetazolamide↗

Effects of vanillin on sister-chromatid exchanges and chromosome aberrations induced by mitomycin C in cultured Chinese hamster ovary cells.

Effects of vanillin on the induction of sister-chromatid exchanges (SCEs) and structural chromosome aberrations by mitomycin C (MMC) were investigated in cultured Chinese hamster ovary cells. Vanillin induced neither SCEs nor chromosome aberrations by itself. However, an obvious increase in the frequency of SCEs was observed when MMC-treated cells were cultured in the presence of vanillin. The effect of vanillin was S-phase-dependent. On the contrary, the frequency of cells with chromosome aberrations was significantly decreased by the post-treatment with vanillin at G2 phase.

Animals↗

Formation of a diazoquinone-type mutagen from acetaminophen treated with nitrite under acidic conditions.

Acetaminophen (paracetamol) showed mutagenicity to Salmonella typhimurium TA100 and TA98 either with or without S9 mix when treated with excess nitrite in acidic solution. The mutagen was isolated and identified as 4-acetylamino-6-diazo-2,4-cyclohexadienone. Mutation tests and product analysis by high-performance liquid chromatography, however, suggested that this type of mutagen was hardly formed in the digestive tract of normal subjects.

Acetaminophen↗

The SOS-function-inducing activity of chemical mutagens in Escherichia coli.

The SOS-function-inducing activities of 42 chemical mutagens were investigated in Escherichia coli K12. The induction of the SOS function was assayed by monitoring the beta-galactosidase activity in the sulA::lacZ fusion strain PQ37 . To correct for the inhibitory effects of test chemicals on mRNA or protein synthesis, the level of the constitutive alkaline phosphatase was assayed in parallel. Most of the mutagens reported to be mutagenic to the Ames' Salmonella tester strains showed the SOS-function-inducing activity. The inducible SOS repair may be responsible for not only base-change mutations but also frameshift mutations. However, 9-aminoacridine, ethidium bromide and 4-nitro-o-phenylenediamine did not induce the SOS function, suggesting that the mutagenesis induced by these mutagens may occur independently of SOS repair. Present results support the SOS mutagenesis model that error-prone SOS repair plays an important role in mutagenesis induced by most chemical mutagens.

Alkaline Phosphatase↗

Cytotoxic macrolides from a cultured marine dinoflagellate of the genus Amphidinium.

A fourth cytotoxic macrolide, amphidinolide D[1], together with known amphidinolide B[2], has been isolated from a different batch of the cultured dinoflagellate Amphidinium sp., which was symbiotically associated with an Okinawan flatworm Amphiscolops sp. Two-dimensional nmr experiments including 1H-detected heteronuclear multiple-bond correlation (HMBC) resulted in the structure assignment of 1 and structure revision of the diene moiety (C-13-C-15) of amphidinolide B.

Animals↗

Metachromin C, a new cytotoxic sesquiterpenoid from the Okinawan marine sponge Hippospongia metachromia.

A new sesquiterpenoid quinone, metachromin C[1], with potent cytotoxic activity has been isolated together with a known terpenoid metachromin A[2] from the Okinawan marine sponge Hippospongia metachromia and the structure determined by spectroscopic data, especially several types of 2D nmr spectra including 1H-detected heteronuclear multiple-bone correlation (HMBC).

Animals↗

Primary structure of the alpha-subunit of Torpedo californica (Na+ + K+)ATPase deduced from cDNA sequence.

Sodium- and potassium-dependent ATPase [(Na+ + K+)ATPase], which is responsible for the active transport of Na+ and K+, is distributed universally among animal cell membranes and consists of two types of subunits, alpha and beta (refs 1-4). The larger alpha-subunit with a relative molecular mass (Mr) of 84,000-120,000 is thought to have the catalytic role. We have now cloned and sequenced DNA complementary to the Torpedo californica electroplax messenger RNA encoding the alpha-subunit of (Na+ + K+)ATPase and have deduced the complete amino-acid sequence of the polypeptide. Some structural features of the alpha-subunit molecule related to the function of this active-transport protein are discussed.

Amino Acid Sequence↗

Further study on the genetic correlation between members of a multigene family.

The extent of genetic similarity (in terms of identity coefficients) was investigated among members of a multigene family that is evolving under mutation, unequal crossing over and random genetic drift. The method of KIMURA and Ohta (1979) was used, but the possibility was incorporated that the length of the shift (in terms of the number of genes) involved in unequal crossing over can be more than one gene unit. Extensive numerical analyses show that, at equilibrium, the identity coefficients between two gene members are practically independent of their distance apart on the chromosome when the mean length of the shift at unequal crossing over is more than 10% of the total size of the family. In that case, the approximate treatment by OHTA (1980) is shown to be valid, but when the mean length of the shift is less than 10%, the average identity coefficient at equilibrium is underestimated. In order to clarify the effect of natural selection responsible for keeping the family size stable, Monte Carlo simulation studies were performed. The results indicate that the identity coefficients are not greatly influenced by natural selection on gene family size, particularly when the number of genes shifted is small compared to the family size. In addition, with sufficiently strong selection on family size, unequal crossovers with a large shift (such as with maximum shift of 90% of the family size) become ineffective and almost indistinguishable from those with a small shift.

Biological Evolution↗

Enzyme-linked immunosorbent assay for apolipoprotein B on dried blood spot derived from newborn infant: its application to neonatal mass screening for hypercholesterolemia.

Hypercholesterolemia is a risk factor for atherosclerotic cardiovascular disease, and early diagnosis and treatment should be given attention. We developed a simple and sensitive enzyme-linked immunosorbent assay (ELISA) for apolipoprotein B (apoB) on a dried blood spot (DBS). The specificity of this assay was investigated by constructing curves for other proteins. The cross-reactivity was negligible. The mean intra- and intercoefficients of variation were 5.2 and 7.8%, respectively. We used phosphate buffer with Triton X-100 for extracting apoB on DBS. The elution of apoB was stable up to 30 days after bleeding. The correlation between plasma and DBS apoB was r = 0.94, p less than 0.005, n = 55. Using this method, we screened 2,500 babies between 5 and 7 days of age. The mean +/- SD of DBS apoB was 75 +/- 15 U. Seven hypercholesterolemic neonates were detected. Family studies of these neonates disclosed one definite and two suspected heterozygotes for familial hypercholesterolemia. Four other neonates showed no related familial background. This ELISA method for assaying apoB should prove to be a useful tool for large mass screening for hypercholesterolemia, particularly in the newborn.

Apolipoproteins B↗

Oxygen uptake and its relation to physical activity and other coronary risk factors in asymptomatic middle-aged Japanese.

PURPOSE: Low physical activity is considered to be an important risk factor for atherosclerotic coronary artery disease. However, few data are reported on the Japanese general population. The authors have studied whether oxygen uptake in physical fitness evaluation is a quantitative index for physical activity and whether or not it has a relation to coronary risk factors. METHODS: Five hundred thirteen asymptomatic Japanese (40-64 years of age, 282 males and 231 females) were tested on a cycle ergometer for measurement of peak oxygen uptake (peak VO2) and oxygen uptake at anaerobic threshold (VO2AT). Physical activity was estimated by pedometer score. Data for oxygen uptake were adjusted by age or by age and body mass index (BMI), then its relationship to the following risk factors was investigated: physical activity, BMI, blood pressure, total cholesterol, HDL and LDL cholesterol, fasting blood glucose, and triglycerides. RESULTS: Subjects in the highest peak VO2 quartile walked significantly more than those in the lowest quartile in both males and females. Those in the highest quartile showed lower BMI, lower blood pressure, lower triglyceride, and higher HDL cholesterol. The same relationship was observed for VO2AT. CONCLUSIONS: Higher fitness level determined by peak VO2 or VO2AT is related to higher physical activity and lower coronary risk factors in the asymptomatic middle-aged Japanese. These data provide support for exercise prescription in the primary prevention of coronary heart disease in Japan.

Adult↗

Effects of pimobendan, a new cardiotonic agent, on contractile responses in single skeletal muscle fibres of the frog.

Effects of a new cardiotonic agent, pimobendan, on contraction were investigated in single intact skeletal muscle fibres of the frog. Pimobendan increased twitch tension in a concentration-dependent manner regardless of the presence or absence of Ca2+ without any effect on tetanic tension, the resting membrane potential and the shape of the action potential. Pimobendan caused a further increase in twitch tension potentiated by caffeine (1 mM). Adenine, an inhibitor of Ca2+-induced Ca2+ release from the sarcoplasmic reticulum, inhibited twitch tension potentiated by caffeine but not by pimobendan, suggesting that twitch potentiation by pimobendan is not attributed to increases in Ca2+-induced Ca2+ release. Pimobendan failed to increase cAMP levels in the skeletal muscle, though forskolin significantly increased it without any effect on twitch tension. Contractile responses to high concentrations of caffeine and K+ were also potentiated by pimobendan. These results suggest that the potentiating effect of pimobendan on skeletal muscle contraction is mainly due to the increase in Ca2+ sensitivity to the contractile apparatus.

Animals↗

Angelman syndrome in three siblings: characteristic epileptic seizures and EEG abnormalities.

Neurologic findings in 3 siblings with Angelman syndrome (AS) with apparently normal karyotype but DNA deletion of 15q11-q12 deriving from their mother are described. Increased auditory brainstem response (ABR) thresholds were noted in all 3. Interictal EEG findings included periodic 2- to 3-Hz high-voltage slow wave bursts bioccipitally and sporadic slow spike wave complexes mainly bifrontally. EEG findings suggestive of minor epileptic status were apparent in the elder brother and may be a characteristic feature in young AS patients. Seizures suggestive of generalized epilepsy have been reported in 90% of AS patients. AS is considered a good model of symptomatic generalized epilepsy associated with chromosomal DNA deletion of the (GABA)A receptor beta 3-subunit gene.

Angelman Syndrome↗

Polysymptomatic conversion disorder in childhood and adolescence in Japan. Early manifestation or incomplete form of somatization disorder?

BACKGROUND: In conversion disorder in childhood and adolescence, polysymptomatic (PS) presentations are reportedly commoner than monosymptomatic (MS) ones. Somatization disorder is also associated with pseudoneurological symptoms, but is extremely rare in childhood. This occurs despite the age of onset peaking in the teens among adult somatization disorder patients. METHOD: We reviewed the records of 44 children and adolescents with pseudoneurological symptoms. They were categorized as MS cases (19) or PS cases (25), and their psychological backgrounds and clinical courses were compared. RESULTS: PS patients had a poorer prognosis and more past psychiatric and family problems. While none met the DSM-IV criteria for somatization disorder, 2 PS patients met all but the sexual symptoms criteria. CONCLUSION: PS conversion disorder in childhood and adolescence may constitute a different entity from MS conversion disorder and may be an early manifestation or incomplete form of somatization disorder.

Adolescent↗

Alteration in the low-frequency domain in power spectral analysis of fetal heart beat fluctuations.

OBJECTIVE: Spectral analysis was conducted on fetal heart rate fluctuations for the purpose of investigating the change in gestational age and examining the usefulness as a method of estimating fetal blood gas. STUDY DESIGN: Five hundred and twenty-nine pregnant women with a single normal fetus and 26 women with intrauterine growth restriction (IUGR) were studied during the 20th to 38th gestational weeks. In cases of IUGR, fetal blood gas levels were evaluated with percutaneous umbilical blood sampling. A time series of fetal heart rate fluctuation was obtained with a 1. 15-MHz ultrasonic transducer, and power spectral analysis of 200 consecutive stable beats was performed with an autoregression method. Integrated areas of 0.025-0.125 cycles/beat were defined as low-frequency areas (LFAs) and were examined in normal fetuses. In addition, the relation between LFA and fetal blood gas values was studied. RESULTS: As pregnancy progressed, LFA increased with a cubic regression equation (Y = 6.484 - 0.764X + 0.029X2 - 0.00034X3). The correlation coefficient was 0.625 (p < 0.05). In the cases of IUGR, DeltaLFA was highly correlated with DeltapO2 and DeltapH (correlation coefficient, 0.650 and 0.618, respectively). CONCLUSIONS: Measurement of LFA provides insight into the development of fetal autonomic function and also may serve as a quantitative index of fetal well-being in mid-pregnancy.

Adolescent↗

Tacalcitol, an active vitamin D3, induces nerve growth factor production in human epidermal keratinocytes.

The human epidermal keratinocyte cell line K-TL-1, developed from a benign epidermal tumor, was cultured in the presence of the synthetic vitamin D3 analogue tacalcitol [1alpha,24(R)-dihydroxyvitamin D3] to assess the effects on the production of nerve growth factor (NGF). Confluent K-TL-1 cells were cultured with 10(-8) M of tacalcitol. Supernatants and cell homogenates were collected and NGF concentrations were determined by enzyme-linked immunosorbent assay. The concentration of NGF in the supernatants of cultures treated with tacalcitol peaked within 24 h after the start of tacalcitol treatment and remained stable for 96 h. This NGF induction caused by tacalcitol was dose-dependent, showing an ED50 between 10(-10) and 10(-9) M. Induction of NGF mRNA expression by tacalcitol was also observed by RT-PCR, indicating that tacalcitol induced NGF expression through transcriptional activation. These results suggest that active vitamin D3 could treat peripheral neuropathy by inducing NGF production in the skin.

Cells, Cultured↗