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Biomedical subjects

H Kajiyama

Publications and source records attributed to H Kajiyama.

At least 37 records · Page 2Linked to original sources

Cloning of the gene encoding DNA binding protein HU from Bacillus stearothermophilus and its expression in Escherichia coli.

The gene (hbst) encoding the DNA binding protein HU from Bacillus stearothermophilus was cloned, with the Bacillus subtilis HU gene (hbsu) as a hybridization probe. The nucleotide sequence, which contains a ribosome binding site, a transcriptional termination signal, as well as the coding region, was analyzed by the dideoxy chain-termination method. The deduced amino acid sequence of an open reading frame was perfectly matched with that of B. stearothermophilus HU (BstHU) determined by the protein chemical methods [M. Kimura and K. S. Wilson, J. Biol. Chem., 258, 4007-4011 (1983)]. The gene, hbst, was overexpressed using the expression vector pET-5a in Escherichia coli, and the recombinant HU protein (r-BstHU) was purified to be homogeneity by heparin-agarose column chromatography followed by ion-exchange column chromatography on S-Sepharose. The recombinant protein thus obtained had a circular dichroism spectrum identical to that of the authentic protein and bound to DNA to the same extent as the authentic protein.

Amino Acid Sequence↗

Chronopharmacology of trichlormethiazide in rats; (II). Examination in aged rats.

We have previously demonstrated a time-dependent variability in the diuretic effects of trichlormethiazide, a thiazide diuretic agent, in young rats. The study suggested that the time-dependent variations in urinary trichlormethiazide and susceptibility of renal tissues to the agent might be involved in this phenomenon. The present study was undertaken to test a hypothesis that such a daily variation in the effects of trichlormethiazide is blunted by age. Trichlormethiazide (0.5 and 2.0 mg/kg) was given orally at 1200 hrs (day trial) or at 2400 hrs (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent and urinary excretions of sodium, chloride and trichlormethiazide were determined. Urine volume and urinary excretions of sodium, chloride and trichlormethiazide following the agent were significantly greater at 1200 hrs than at 2400 hrs in the young rats. However these administration time-dependent changes in the effects of trichlormethiazide and its urinary amount diminished in the aged rats. In the day and night trials, there were significant correlations between urinary trichlormethiazide and its effects (urine volume, urinary sodium and chloride) in both groups of rats. The regression lines in each parameter of two trials differed in the young, but not in the aged group of rats. These data indicate that the mode of the time-dependent changes in the effects of trichlormethiazide is altered in aged Wistar rats. Dampening of the time-dependent variations in urinary trichlormethiazide and susceptibility to the agent might be involved in these chronopharmacological alterations in aged rats.

Administration, Oral↗

Diurnal variation in the diuretic effects of nitrendipine in saline loaded rats.

We have previously reported that the responsiveness of blood pressure to nitrendipine, a dihydropyridine calcium antagonist, varies with its time of administration. The present study was undertaken to examine whether the diuretic effects of the agent also show diurnal variation. Nitrendipine was given orally at 12 a.m. or 12 p.m. to rats, and urine was collected for 8 hours after administration. The urine volume and urinary sodium excretion were greater at 12 p.m. than at 12 a.m. These data indicate that the cardiovascular as well as renal effects of nitrendipine vary with its time of administration.

Animals↗

Chronopharmacology of the new uricosuric diuretic S-8666 in rats: (II). Examination in aged rats.

We have previously demonstrated a time-dependent variability in the diuretic effects of S-8666, a new loop diuretic with uricosuric activity, in young rats. The present study was undertaken to determine whether such a daily variation in the effects of the agent exists in aged rats. S-8666 (30 and 90 mg/kg) was orally given at 12:00 a.m. (day trial) or at 12:00 p.m. (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent; and urinary excretions of sodium, S-8666 and its active metabolite S-8680 were determined. Urinary excretions of volume and sodium following S-8666 at 12:00 a.m. were greater than those at 12:00 p.m. in the young and aged animals. Urinary excretions of S-8666 and S-8680 were also greater in the day trial compared to those in the night trial in both groups of rats. In the day and night trials, there were significant correlations between urinary S-8666 + S-8680 and the diuretic effects in both groups of rats. These findings indicate that the diuretic effects of S-8666 also vary with its time of dosing in aged rats. The time-dependent variations in urinary S-8666 and S-8680 might be involved in this phenomenon.

Aging↗

Pharmacokinetics of pranoprofen in the elderly.

The present study was undertaken to examine whether the pharmacokinetic profiles of pranoprofen, a non-steroidal anti-inflammatory drug, are altered in the elderly. Pranoprofen (75 mg) was given orally to six young and seven elderly subjects, and blood sample was obtained 0.5, 1, 2, 3, 5, 8 and 10 h after administration of the drug. The elimination half-life of pranoprofen was significantly longer and its plasma clearance was significantly lower in the elderly than those levels in the young subjects. The area under the plasma concentration-time curve in the elderly group was significantly greater than that in the younger group. No significant difference was observed in the maximum plasma concentration or the time to maximum plasma concentration between the two groups. These data indicate that the pharmacokinetic profiles of pranoprofen are altered in the elderly.

Administration, Oral↗

Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects.

Following a cross-over design propranolol 20 mg p.o. was given to 7 healthy subjects at 09.00 h and 21.00 h at an interval of 1 week. Heart rate (HR) during submaximal ergometer exercise was measured at four intervals during 10 h after treatment. Plasma propranolol concentrations were also determined. The suppressive effect (%R) of propranolol on the rise in HR during exercise after the morning dosage was significantly greater at 1.5 h and tended to be greater 3 h after administration than at comparable times in the evening trial. Mean plasma propranolol concentrations during the early phase were higher after the morning than the evening dose. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve from 0 to 10 h (AUC (0-10] and absorption rate constant (ka) were significantly greater after the morning dose. The time to maximum concentration (tmax) and elimination half-life (t 1/2) of the morning and evening dosages did not differ. A significant correlation was observed between plasma propranolol concentration and %R in HR during exercise in the morning (r = 0.74) and evening (r = 0.63) trials, and the regression lines of the morning and evening treatments did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Circadian rhythm in recognition threshold of salt taste in healthy subjects.

The circadian rhythm in recognition threshold of salt taste was examined in six healthy young subjects. Plasma aldosterone (PA) and cortisol concentrations, plasma renin activity (PRA), salivary sodium concentration, and salt recognition thresholds were measured every 3 h for a 24-h period. The salt recognition threshold and salivary sodium concentration exhibited similar circadian rhythms, with the lowest values recorded in the afternoon. Positive correlations were observed between the recognition threshold and salivary sodium (P less than 0.001) and between cortisol and PA (P less than 0.001). There was no correlation between PRA and PA. A negative correlation was observed between PA and salivary sodium concentration (P less than 0.01). These data indicate that the recognition threshold for salt taste has a circadian rhythm in young healthy subjects. This rhythm appears to be related to daily variations in the plasma aldosterone concentration and its subsequent effects on salivary sodium concentration.

Adult↗

The influence of fever on the pharmacokinetics of pranoprofen in elderly subjects.

Pranoprofen (75 mg) was given orally during febrile (mean body temperature 38.3 degrees C) and afebrile (mean body temperature 36.3 degrees C) periods in nine elderly subjects. Blood samples for plasma drug concentrations were taken for a 10 hour post-drug period. The mean elimination half-life (t1/2 beta) was significantly prolonged and the mean area under the time-concentration curve from 0 to 10 hrs (AUC0-10) was greater, although not significantly, during fever. No significant difference was observed in the time to maximum concentration (tmax), maximum plasma concentration (Cmax) or apparent volume of distribution (Vd/F) between the both dosages. There was a positive correlation (r = 0.448, 0.05 less than P less than 0.10) between the body temperature and t1/2 beta of pranoprofen. These data indicate that the clearance of pranoprofen is reduced during fever in elderly subjects.

Aged↗

Chronopharmacokinetic studies of pranoprofen and procainamide.

There is increasing evidence demonstrating that plasma drug concentrations are affected by their time of administration. In the current study, the chronopharmacokinetic profiles of an antipyretic agent, pranoprofen, and an antiarrhythmic agent, procainamide, were examined. In the first study, 75 mg of pranoprofen was given orally in seven healthy subjects at 10:00 (morning trial) or 22:00 (evening trial). In the second study, 500 mg of procainamide was given orally in eight subjects with premature ventricular contractions at 10:00 or 22:00. Blood samples for plasma drug concentrations were taken for a 10-hour (pranoprofen study) or a 24-hour (procainamide study) post-drug period. In the first (pranoprofen) study, the mean time to maximum concentration was significantly shorter, and the mean maximum plasma concentration as well as absorption rate constant had a tendency to be greater after the morning than after the evening trial. The mean area under the plasma concentration-time curve, elimination half-life or oral clearance of the morning and evening dosages did not differ. In the second (procainamide) study, no significant difference was observed in any pharmacokinetic parameter concerning procainamide or its active metabolite, N-acetyl-procainamide (NAPA) between the morning and evening trials. These data indicate that plasma levels of pranoprofen are affected by its administration time while plasma concentrations of procainamide and NAPA do not vary with the time of dosage.

Acecainide↗

Shape of the myosin head in the rigor complex. Three-dimensional image reconstruction of the actin-tropomyosin-heavy meromyosin complex.

The structure of the actin-tropomyosin-heavy meromyosin rigor complex was studied by image analysis of electron micrographs. The arrowhead of the rigor complex has a whisker-like structure with a dense turning point at the "barb" of the arrowhead. The neck region of the myosin head in the reconstructed three-dimensional image is present in the area corresponding to the dense point. It is concluded that at least one extra-thin area contributes to the neck region, and that the two heads in the heavy meromyosin molecule join a double helical rope beyond the end of the large head (G in this study). (This is different from previous interpretations). It is also concluded that the heavy meromyosin has a short bent part near the head/rod junction in the rigor complex.

Actins↗

The effect of propranolol on urinary prostaglandin E2 after frusemide administration in healthy subjects.

We have evaluated the effect of propranolol on urinary prostaglandin E2 (PGE2) excretion after frusemide administration in 8 healthy subjects. Urine was collected for 60 min after frusemide administration (20 mg intravenously) with or without propranolol pretreatment, and urinary excretion of PGE2, frusemide, and sodium were determined. Plasma renin activity (PRA) was also measured before and 60 min after frusemide administration. Urinary PGE2 excretion after frusemide administration and frusemide-stimulated PRA were reduced after propranolol pretreatment. However, urine volume and the urinary excretion of frusemide and sodium were not influenced by propranolol pretreatment. These results suggest that urinary PGE2 excretion after frusemide administration may be reduced by propranolol and that the mechanism responsible for the effect of propranolol on the frusemide-induced renal PGE2 production may be, at least in part, secondary to inhibition of the renin-angiotensin system.

Adult↗