Biomedical subjects

T Ohkubo

Publications and source records attributed to T Ohkubo.

At least 109 records · Page 6Linked to original sources

PubMed1999

Mechanisms mediating the vasorelaxing action of eugenol, a pungent oil, on rabbit arterial tissue.

The inhibitory actions of eugenol on intracellular Ca2+ concentration ([Ca2+]i) and the contractions induced by excess extracellular K+ concentration ([K+]o) in rabbit thoracic aorta were investigated. Application of excess [K+]o solution (30-90 mM) produced contraction and increased the intensity of the Ca2+ fluorescence signal. Pretreatment with eugenol (> or =0.1 mM) reduced both the amplitude of contraction and the intensity of the Ca2+ fluorescence signal, but the contraction was more strongly affected than the [Ca2+]i. Application of eugenol (0.3 mM) to tissue precontracted by 90 mM [K+]o solution (immediately after the removal of the 90 mM [K+]o solution) slowed the decay of the [Ca2+]i signal, but it did not change the rate of relaxation. Carbonyl cyanide m-chlorophenylhydrozone (10 microM), a mitochondrial metabolic inhibitor, produced a reduction in tension despite a slight increase in [Ca2+]i when applied to muscle precontracted by 90 mM [K+]o solution. These results indicate that eugenol relaxes the rabbit thoracic aorta while suppressing the Ca2+-sensitivity and both the uptake and extrusion mechanisms for Ca2+. To judge from the similarities between its actions and those of metabolic inhibitors, eugenol may produce its actions at least partly through metabolic inhibition.

Animals↗

PubMed1999

Relationships among blood pressures obtained using different measurement methods in the general population of Ohasama, Japan.

To examine the relationships between casual, ambulatory and home blood pressure measurements in the general population, these measurements were obtained in 1,695 of 3,744 subjects aged 20 yr or older in Ohasama, Japan. Of these 1,695 subjects, 1,207 measured their home blood pressure more than 14 times in each of the morning and evening (881 untreated subjects including normotensives and untreated hypertensives, 56.4 +/- 11.5 yr of age; 326 treated subjects, 66.0 +/- 9.2 yr of age). We analyzed data in these 1,207 subjects, examining the distribution of each measurement, the relationships among measurements, and the factors affecting the blood pressure differences among the measurements. For systolic pressure, the casual measurement was the highest among the methods examined. The daytime ambulatory measurement was significantly higher than morning and evening home measurements. Morning home measurements were significantly higher than those in the evening. For diastolic pressure, however, the morning home measurement was the highest among the methods examined. Short-term pressure variability (standard deviation and variation coefficient of ambulatory measurements) was greater than long-term pressure variability (standard deviation and variation coefficient of home measurements). The pressure variability in treated subjects was greater than that in untreated subjects. The correlation between casual pressure and the other pressures was not as strong (r<0.567). Among the relationships between ambulatory and home measurements, the strongest correlation was observed between the 24-h ambulatory measurement and the morning home measurement (r=0.738) in untreated subjects. The morning home measurement was highly correlated with the evening home measurement (r>0.814). The differences among the methods examined were affected by blood pressure level and age. It should be noted that in elderly and treated subjects, blood pressure measurement using one method does not necessarily correlate with that obtained using the other methods. This information is useful for the estimation of the value of one type of blood pressure measurement from values obtained with other methods.

Adult↗

PubMed1999

[Surgical analysis for small cell lung cancer of the lung].

Clinical features of small cell lung cancer were studied in 15 cases. The overall 5-year survival rate of the patients with limited small cell lung cancer was 11.4%. Surgery played substantial role for long-term survival in limited SCLC. The 4-year-survival rate of the patients in stage I was 50%, and that of those in stage II and IIIA was 50% and 37.5%, respectively. In the two survivors over four years in stage IIIA, all tumor was categorized as pT3 disease. The 4-year-survival rate of the patients treated with PE was 100%, and that of those treated with another chemotherapy was 10%, and that difference is statistically significant (p < 0.05). There was no significant difference in prognosis of patients in any other factors such as location (central or peripheral), histological subtype, curability or R number, pT factor, pN factor, p stage or with or without thoracic irradiation. Surgical resection for limited SCLC should be recommended in patients with stage I, II and T3N0M0 or T3N1M0 disease. For the patients in stage IIIA, particularly in N2M0 disease, who showed partial response or no change after chemotherapy, surgery should be considered because those patients might have nonsmall cell carcinoma components.

Adult↗

PubMed1999

[A case of Sjögren's syndrome with retrobulbar optic neuritis and cutaneous vasculitis].

A 52-year-old woman, diagnosed as having Sjögren's syndrome by parotid sialography and lip biopsy after a two years history of recurrent purpuric rashes on her lower extremities, was admitted to our hospital because of visual disturbance in March 1998. On presentation at the department of ophthalmology, her right visual acuity was light perception, and laboratory findings showed elevated levels of antinuclear antibody and anti-Ro/SS-A and anti-La/SS-B antibodies. Cerebrospinal fluid analysis showed mild pleocytosis and elevated levels of total protein and Q-albumin. The IgG-index was within normal level and no oligoclonal band was found. Magnetic resonance imaging showed increased signal intensity at the right optic nerve. After treatment with m-PSL pulse therapy, her visual acuity recovered to 0.08. When prednisolone was gradually tapered to the dose of 30 mg per day, she was transferred to our department because of high grade fever and pancytopenia. She also suffered from palpable purpura in her extremities extending the trunk, whose pathological diagnosis was leukocytoclastic vasculitis. The immunohistochemical examination showed depositions of IgG and C1q. After two additional cycles of mPSL pulse therapies, clinical improvement was achieved. The titers of von Willebrand factor and thrombomodulin correlated with her clinical improvement. Patients with Sjögren's syndrome can develop extra-grandular complications, including neurologic and cutaneus diseases, it is important to understand the role of SS-A-B antibodies in the immunopathogenesis of Sjögren's syndrome.

Female↗

PubMed1998

High-performance liquid chromatographic determination of nemonapride and desmethylnemonapride in human plasma using an electrochemical detection.

A high-performance liquid chromatographic method using an electrochemical detector (HPLC-ED) was developed for the determination of nemonapride and its active metabolite, desmethylnemonapride in human plasma. Nemonapride, desmethylnemonapride and moperone chloride, which was used as the internal standard (I.S.) in plasma, were extracted by a rapid and simple procedure based on C18 bonded-phase extraction, and were separated by C8 reversed-phase HPLC column. Nemonapride and desmethylnemonapride were detected by high conversion efficiency amperometric detection at +0.84 V. Determination of both nemonapride and desmethylnemonapride were possible in the concentration range at 0.25-5.0 ng/ml, and the limit of detection for each was 0.1 ng/ml. The recoveries of nemonapride and desmethylnemonapride added to plasma were 97.0-98.2% and 96.7-98.8%, respectively, with coefficients of variation of less than 7.2% and 10.3%, respectively. This method is applicable to drug level monitoring in the plasma of schizophrenia patients treated with nemonapride and to the study of pharmacokinetics.

Antipsychotic Agents↗

PubMed1998

Soft X-ray multilayer beam splitters.

A semitransparent Mo/Si multilayer beam splitter with a completely self-standing active area (10 x 10 mm) and a flatness of 1.1 nm (r.m.s.) was fabricated. The influence of the roughness of the membrane substrate on the reflectivity of a beam splitter was investigated for different materials and deposition schemes. Precise control of multilayer stress to give a slightly tensile state not only enables the fabrication of a large and flat reflection surface, but also makes it possible to etch away the supporting membrane and obtain a completely self-standing structure. The performance evaluation using synchrotron radiation revealed that the fabricated beam splitter works as a one-to-one beam splitter whose reflectivity and transmittance are both 27% (s-polarization, 45 degrees, lambda = 13.4 nm).

Journal Article↗

PubMed1998

Study of amorphous alloy structures with medium range atomic ordering.

Structures with atomic medium range order (MRO) extending as small as approximately 2 nm in amorphous alloys can be observed under suitable defocus conditions as clear lattice fringe images by means of axial-beam high-resolution electron microscopy (HREM). In this article, our studies of local structure observation in some metal-metalloid amorphous alloys with the "selected-defocus method" are introduced. Also introduced are an HREM image simulation study of amorphous alloy structures and a nano-probe (1-1.5 nm) electron diffraction analysis of MRO structure. A multislice image simulation study for suitable structure models (1) with a random atomic distribution, (2) with MRO regions having different sizes, distributions, and specimen thicknesses, is a necessary step to verify the MRO observation in amorphous alloys. It was demonstrated that not only HREM information but also nano-diffraction information are necessary in order to understand local structures of amorphous alloys.

Alloys↗

PubMed1998

cDNA cloning and characterization of neuron-specific enolase from chicken.

Chicken gamma-enolase cDNA was cloned and its sequence and tissue-specific expression were analyzed. The cDNA, consisting of 2273 bp of nucleotides, was composed of 86 bp of the 5'-noncoding region, 1305 bp of an open reading frame encoding a protein of 434 amino acids and 882 bp of the 3'-noncoding region. The deduced amino acid sequence showed higher homology (more than 90%) to those of mammalian gamma-enolases than to those of chicken alpha- or beta-enolases. Northern blot analysis has revealed that the mRNA for gamma-enolase (2.3 kb) is expressed in the brain and, to much less but significant extents, in the pituitary and adrenal gland of the chicken.

Amino Acid Sequence↗

PubMed1998

Prolactin receptor gene expression in the brain and peripheral tissues in broody and nonbroody breeds of domestic hen.

The objective of this study was to establish whether the gene encoding prolactin receptor (PRLR) is expressed in the hypothalamus and peripheral tissues of the domestic chicken and, if so, to determine whether there are breed differences in the structure or expression of the gene which might account for the observation that broodiness does not occur in the White Leghorn hen but does occur in other breeds of domestic hens, including the bantam. A preliminary experiment demonstrated that the absence of broodiness in White Leghorns is not due to a lack of a prolactin response to the avian prolactin-releasing hormone vasoactive intestinal polypeptide. The largest amounts of PRLR mRNA in the brain, which did not differ significantly between laying White Leghorns and bantams, were found in the pituitary gland and basal and preoptic hypothalamus. Small or nondetectable amounts were found in both breeds in the forebrain, cerebellum, and optic lobes. Prolactin receptor mRNA was widely distributed in peripheral tissues in both breeds, in the following descending order of abundance: kidney, leg skin, brood patch, duodenum, intestine > thyroid gland > adrenal gland, liver, ovary >> adipose tissue > thymus, spleen > muscle > blood. Southern blotting analysis using four restriction enzymes and a chicken PRLR cDNA probe demonstrated identical digestion patterns for White Leghorn and bantam genomic DNA. Northern blotting analysis identified two sizes of chicken PRLR mRNA transcripts (7.5 and 3.3 kb) in hypothalami from laying White Leghorn and bantam hens. It is concluded that differences in the expression of broodiness in White Leghorn and bantam hens cannot be explained by differences in the amounts of PRLR mRNA in the hypothalamus or in the transcription or gross structure of the PRLR gene.

Animals↗

PubMed1998

Relationship between prolactin receptor mRNA in the anterior pituitary gland and hypothalamus and reproductive state in male and female bantams (Gallus domesticus).

The aim of this study was to test the hypothesis that prolactin may up- and down-regulate prolactin receptor gene expression in the anterior pituitary gland and hypothalamus respectively. Experiments were carried out in bantams (Gallus domesticus). Comparisons were made of concentrations of PRLR mRNA in the anterior pituitary gland and basal and preoptic hypothalamus in adult males and females held on long days (low vs high plasma prolactin); in 3-week-old juvenile male and females on short days (high vs low plasma prolactin); in 8-week-old juvenile male and females on short days (both low plasma prolactin); in adult laying, incubating, and out-of-lay (high, very high, and low plasma prolactin, respectively); in adult cockerels exposed to long or short days (high vs low prolactin); and in adult hens exposed to long or short days (high vs low prolactin). There was a sex difference in anterior pituitary and basal hypothalamic PRLR mRNA, with lower values in both tissues in females than in males. Compared with laying and out-of-lay hens, anterior pituitary and basal hypothalamic PRLR mRNA concentrations in incubating hens were increased and decreased, respectively. In adult birds of either sex held on long or short days, there was no difference in pituitary PRLR mRNA, while basal hypothalamic PRLR mRNA was lower on short days. PRLR mRNA in the preoptic hypothalamus was not affected by sex, reproductive state, or photoperiod. It is concluded that there is no consistent relationship between plasma prolactin, in the physiological range, and the concentration of PRLR mRNA in the anterior pituitary gland, basal hypothalamus, and preoptic hypothalamus.

Aging↗

PubMed1998

Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam.

To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam, the study was conducted in a double-blind randomized crossover manner with two phases of treatment with itraconazole-placebo or placebo-itraconazole. Ten healthy male subjects receiving itraconazole 200 mg/day or matched placebo orally for 6 days took an oral 0.8 mg dose of alprazolam on day 4 of each treatment phase. Plasma concentration of alprazolam was measured up to 48 h after alprazolam dosing, together with the assessment of psychomotor function by the Digit Symbol Substitution Test, Visual Analog Scale and Udvalg for kliniske undersøgelser side effect rating scale. Itraconazole significantly (P < 0.01) increased the area under the concentration-time curves from 0 h to infinity (252 +/- 47 versus 671 +/- 205 ng h/ml), decreased the apparent oral clearance (0.89 +/- 0.21 versus 0.35+/-0.10 ml/min per kg) and prolonged the elimination half-life (15.7 +/- 4.1 versus 40.3 +/- 13.5 h) of alprazolam. The test performed during itraconazole treatment showed significantly depressed psychomotor function. It is suggested that itraconazole, a potent CYP3A4 inhibitor, increases plasma concentration of alprazolam via its inhibitory effects on alprazolam metabolism. Thus, this study supports previous studies suggesting that CYP3A4 is the major enzyme catalyzing the metabolism of alprazolam. Enhanced side effects of alprazolam by itraconazole coadministration were probably reflected by these pharmacokinetic changes.

Administration, Oral↗

PubMed1998

Correlation between steady-state plasma concentrations of mianserin and trazodone in depressed patients.

OBJECTIVE: The correlations between steady-state plasma concentrations of mianserin and its active metabolite desmethylmianserin and those of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were examined in 19 depressed patients. METHODS: Ten patients received first mianserin (30 mg per day) and second trazodone (150 mg per day), while 9 patients received these treatments in the opposite sequence, with at least 2-week intervals between the two phases. Blood was sampled at steady state, 1-3 weeks after initiation of each treatment. Plasma concentrations of mianserin, the separate enantiomers S(+)- and R(-)-mianserin, desmethylmianserin, trazodone and m-CPP were measured by means of high-performance liquid chromatography. RESULTS: There was a significant correlation between steady-state plasma concentrations of trazodone and total mianserin (r = 0.59) or S(+)-mianserin (r = 0.57), but not R(-)-mianserin (r = 0.33). CONCLUSION: The present study thus suggests that the metabolic capacity of mianserin, especially the more active S(+)-enantiomer, and that of trazodone correlate to each other. This finding supports the previous suggestions that cytochrome P4502D6 is involved in the metabolism of mianserin and trazodone.

Antidepressive Agents, Second-Generation↗

PubMed1998

Cloning and expression of pigeon growth hormone receptor cDNA in COS-7 monkey kidney cells.

Pigeon growth hormone receptor (pGHR) cDNA has been cloned, sequenced, characterized and expressed in COS-7 cells. The predicted pGHR preprotein was composed of 611 amino acids and contained a putative signal peptide, a single transmembrane region and the conserved proline-rich box 1 domain in the cytoplasmic region. A canonical polyadenylation signal was found in the extracellular region, as was observed in chicken growth hormone receptor cDNA. Northern blot analysis identified a single species of pGHR mRNA and its expression was widely observed in tissues in the young male pigeon. A pGHR expression vector was constructed and transfected into COS-7 cells. The transfected cells were specifically bound by 125I-labeled chicken GH and the binding was suppressed by the addition of excess amounts of unlabeled chicken GH.

Amino Acid Sequence↗

PubMed1998

A study of the concentration of orally administered sparfloxacin found in exudates from suture wounds beneath occlusive dressings.

The concentration of orally administered sparfloxacin (SPFX), an antimicrobial agent, in exudates from the suture wounds beneath occlusive dressings has been measured. Twenty-one patients who received oral therapy with 100 mg of SPFX prior to surgery and 200 mg/day of SPFX after surgery were studied. During the operations, the suture wounds were covered by occlusive film. 48h post-operation, wound exudates under the dressings were drawn and measured using high performance liquid chromatography. SPFX values were 0.801+/-0.340 microg/ml (mean+/-SD). The results suggest that wound exudates beneath the occlusive dressing have concentrations of SPFX high enough to prevent infection in most cases when administered orally.

Administration, Oral↗

PubMed1998

Monitoring of phenytoin in human breast milk, maternal plasma and cord blood plasma by solid-phase extraction and liquid chromatography.

A rapid liquid chromatographic method for the quantitation of phenytoin in human breast milk, maternal plasma and cord blood plasma was developed using a Develosil C85 micron reverse phase column and a potassium dihydrogen phosphate buffer/acetonitrile mobile phase. Phenytoin and mephenytoin as an internal standard were detected by ultraviolet absorbance at 240 nm. The sample preparation method involves a rapid and simple procedure based on solid-phase extraction using a C18-bonded phase. Phenytoin could be determined in the concentration range of 0.05-3 micrograms ml-1. The recovery of phenytoin added to human breast milk and plasma were 91.6-94.7 and 91.6-96.0%, respectively, with coefficient of variation less than 4.2 and 8.7%. The method has been used for drug level monitoring in the human breast milk, maternal plasma and cord blood plasma samples that were taken from patients treated with phenytoin. The average ratio between the breast milk concentrations versus the plasma concentration was 0.28 +/- 0.1, with a rather poor correlation (r = 0.3033).

Adult↗

PubMed1998

Effect of carbamazepine on the single oral dose pharmacokinetics of alprazolam.

The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics of alprazolam was examined in a double-blind, randomized crossover study with two phases. Seven healthy male subjects took carbamazepine 300 mg/day or matched placebo orally for 10 days, and on the 8th day they took a single oral 0.8 mg dose of alprazolam. Blood samples were taken and psychomotor function was assessed by the Digit Symbol Substitution Test, Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma alprazolam concentrations during the elimination phase. Carbamazepine significantly (p < .001) increased the apparent oral clearance (0.90 +/- 0.21 vs. 2.13 +/- 0.54 ml/min/kg) and shortened the elimination half-life (17.1 +/- 4.9 vs. 7.7 +/- 1.7 h), with no significant effect on the peak plasma concentration (11.7 +/- 1.5 vs. 13.0 +/- 3.5 ng/ml). The majority of psychomotor function parameters during the carbamazepine treatment were not significantly different from those during the placebo treatment, probably because of the sedative effect of carbamazepine itself. The present study suggests that carbamazepine decreases plasma concentration of alprazolam by inducing its metabolism. It also supports the previous studies, suggesting that alprazolam is metabolized predominantly by CYP3A4.

Adult↗

PubMed1998

Thyroid hormones are involved in insulin-like growth factor-I (IGF-I) production by stimulating hepatic growth hormone receptor (GHR) gene expression in the chicken.

Effect of thyroid status on IGF-I production in growing chickens was studied. Serum concentrations of GH were not affected by propylthiouracil (PTU) or thyroxine (T4) treatments, whereas serum IGF-I levels were significantly decreased in PTU-treated chickens. The lowered serum IGF-I levels in the PTU-treated group were completely restored to the control levels by T4 injections. In the liver, the messenger RNA (mRNA) expressions both for GH receptor (GHR) and IGF-I were significantly repressed by PTU treatment, and were restored again by T4 replacement. In addition, the results of analysis on radiolabelled GH binding to the liver membrane were consistent with the levels of hepatic GHR mRNA expression. Serum concentrations of IGF-I were positively correlated with hepatic IGF-I mRNA and GHR mRNA expressions. The correlation coefficient between serum T3 levels and hepatic IGF-I mRNA expressions was also significant. These results indicate that thyroid hormones regulate IGF-I production in the chicken by affecting hepatic GHR expression.

Animals↗

PubMed1998

Differential effects of antihypertensive drugs with differing pharmacological properties on the basal ambulatory blood pressure. Japanese Ambulatory Pressure-ANtihypertensive Effects SEarching study group.

To investigate how antihypertensive drugs with different pharmacological properties affect ambulatory blood pressure (BP) the JAPANESE Study Group developed a database of clinic and ambulatory BPs before and after antihypertensive treatment of patients throughout Japan. Drugs evaluated were nilvadipine (n = 195; b.i.d, 4-8 mg/day), amlodipine (n = 75; q.d., 2.5-10 mg/day), lisinopril (n = 80; q.d., 10-20 mg/day) and bisoprolol (n = 49; q.d., 5-10 mg/day). The relationship between basal ambulatory BP and the hypotensive effect on ambulatory BP during treatment was examined. All antihypertensive drugs significantly decreased both clinic BP and ambulatory BP. The hypotensive effect determined by measurement of clinic BP was significantly greater than that determined by ambulatory BP. The hypotensive effect was positively correlated with basal ambulatory BP. However, there was a quantitative difference in this characteristic among the drugs. The critical daytime systolic ambulatory BP below which a hypotensive effect was not observed was extrapolated to 128, 127 and 124 mm Hg with nilvadipine, amlodipine and bisoprolol, respectively, while that with lisinopril was 97 mm Hg. The slope of the correlation coefficient between basal daytime ambulatory systolic BP and hypotensive effect with lisinopril was significantly smaller than those with the other drugs (P < 0.0001). The slope for the relationship between night-time ambulatory systolic BP and the hypotensive effect with bisoprolol was the steepest (P < 0.0001). Antihypertensive drugs with different pharmacological properties exhibited differing hypotensive effects on the basal ambulatory BP. Such differences in efficacy of the drugs on the basal ambulatory BP may reflect adverse effects of the drugs and the prognosis of hypertension.

Adult↗