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Biomedical subjects

T Ohkubo

Publications and source records attributed to T Ohkubo.

At least 181 records · Page 10Linked to original sources
PubMed1996

Carbamazepine augmentation therapy in three patients with trazodone-resistant unipolar depression.

In three patients with trazodone-resistant unipolar depression, carbamazepine 400 mg/day was co-administered for 4 weeks. They all showed favourable responses; two non-delusional patients completely or almost recovered, while one delusional patient showed considerable improvement in depressive symptoms other than delusions of guilt. Plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were decreased, while the m-CPP/trazodone ratio was increased in all cases. The present report suggests that carbamazepine augments antidepressant effects of trazodone by an enhancement of serotonin function.

Aged↗
PubMed1996

Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine.

Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP) were studied in six depressed patients treated with trazodone. The daily dose of trazodone was 150 mg in three cases and 300 mg in three cases. Carbamazepine, 400 mg/day, was coadministered for 4 weeks, and blood samples were taken before carbamazepine addition and at weekly intervals after the addition. Carbamazepine significantly (p < 0.01) decreased plasma concentrations of not only trazodone but also m-CPP at each week. On the average, plasma concentrations of trazodone and m-CPP at 4 weeks were 24 and 40% of the corresponding precarbamazepine values. This study thus suggests that carbamazepine coadministration decreases plasma concentrations of trazodone and m-CPP by inducing the metabolism of these compounds.

Anticonvulsants↗
PubMed1996

Column-switching high-performance liquid chromatography of ofloxacin in human saliva and correlation of ofloxacin level in saliva and serum.

A column-switching high-performance liquid chromatography (HPLC) assay was developed for the determination of ofloxacin in saliva. The saliva samples were directly introduced into a C8 HPLC column using a C18 precolumn. Ofloxacin and lomefloxacin as internal standards were detected spectrophotometrically at 300 nm. Determination of ofloxacin was possible in the concentration range 50-3,000 ng/ml, and the limit of detection was 20 ng/ ml. The recovery of ofloxacin added to saliva was 96.9-101.2% with a coefficient of variation of < 2.9%. These pharmacokinetic studies were made of healthy volunteers after treatment with ofloxacin. The maximum concentration of saliva and serum ofloxacin was 513.3-2,053.0 ng/ml and 768.2-3,089.0 ng/ml for dose of 100 mg or 200 mg, respectively. The AUC0-6 was 1,736.8-6,519.9 ng/h/ml in saliva and 2,875.5-10,086.0 ng/h/ml in serum, respectively. The saliva versus serum concentration ratio was 0.4-0.7 for doses of 100 and 200 mg. A good correlation between saliva and serum level of ofloxacin was obtained by this HPLC method (r = 0.949).

Anti-Infective Agents↗
PubMed1996

Induction of brain prolactin receptor long-form mRNA expression and maternal behavior in pup-contacted male rats: promotion by prolactin administration and suppression by female contact.

Prolactin (PRL) is considered to induce maternal behavior toward foster young in female rats. In the present study, we studied the relationship between pup contact-induced maternal behavior and serum PRL concentrations and brain PRL receptor (PRL-R) mRNA expression in male rats. Both intact and castrated male rats exposed to foster pups gradually developed caretaking behavior such as crouching and licking, but their exhibitions of other maternal behavior components, retrieval/grouping and nest building, were incomplete. However, in the male rats displaying crouching and licking, the concomitant increases in serum PRL concentration and brain mRNA expression for long-form PRL-R were observed. The expression of short-form PRL-R mRNA in the brain was not stimulated by pup contact. Administration of PRL remarkably promoted the onset of those maternal responses in male rats. On the other hand, when an intact male rat was housed in a cage where a lactating female rat and her pups were living, his scores in maternal behavior tests toward pups were lowered. And, concomitantly, increases in serum PRL concentration and brain expression of long-form PRL-R mRNA were reduced. In castrated male rats, however, the ratings of maternal behavior toward foster young, serum PRL concentration increase, or brain long-form PRL-R mRNA expression were not reduced at all by cohabitation with a female and her pups. These findings indicated that maternal behavior was triggered and maintained in pup-contacted male rats through elevated serum PRL levels and induced brain long-form PRL-R.

Animals↗
PubMed1996

Growth hormone-independent expression of insulin-like growth factor I messenger ribonucleic acid in extrahepatic tissues of the chicken.

The sex-linked dwarf (SLD) chicken, which lacks GH receptor (GHR), and its normal littermates provide a useful experimental system to investigate GH-dependent cellular responses. The GH dependence of insulin-like growth factor I (IGF-I) expression in tissues was examined in SLD and normal chickens of the Gifu 20 strain. Four weeks after hatching, the most abundant expression of IGF-I messenger RNA (mRNA) was observed in liver of normal chickens, whereas no IGF-mRNA expression was detected in that organ of dwarf chickens. On the contrary, in extrahepatic tissues such as spleen, lung, brain, kidney, heart, intestine, thymus, and muscle, IGF-I mRNA expression was equally observed in normal and GHR-lacking dwarf chickens. In the testis, expression of IGF-I mRNA was enhanced by about 5-fold in dwarf chickens showing an expression level comparable to that in normal liver. On day 16 in the embryonic stage, IGF-I mRNA was expressed in muscle, brain, eye, heart, and lung in both normal and SLD chick embryos. However, no IGF-I mRNA expression was observed in liver or kidney of normal and dwarf chick embryos. These results suggest that in chicken, IGF-I mRNA is expressed in liver in a GH-dependent manner after hatching, whereas in other tissues, mRNA expression is independent of GH and GHR before and after hatching, except for testis, in which GH seems to inhibit IGF-I mRNA expression.

Animals↗
PubMed1996

Increased deoxycytidine kinase activity by etoposide in L1210 murine leukemic cells.

Deoxycytidine kinase (dCK) is a rate-limiting enzyme for the activation of ara-C. It is responsible for the phosphorylation of ara-C which is widely used in the treatment of leukemia. We examined the effect of etoposide on dCK in L1210 cells and found that incubation with 10 microM etoposide for 1 h increased dCK activity to 170% of the control. This effect of etoposide on dCK activity was concentration-dependent up to at least 100 microM of the substance.

Animals↗
PubMed1996

Ambulatory blood pressure monitoring in evaluating the prevalence of hypertension in adults in Ohasama, a rural Japanese community.

We estimated the prevalence of hypertension and evaluated the degree of blood pressure control on the basis of ambulatory blood pressure monitoring in patients receiving antihypertensive medication. A total of 969 adults (mean age +/- SD, 59.3 +/- 12.1 years old range: 20-79 yr) among 1,575 eligible persons (65.1%) recruited from a total adult population of 2,789 people living in a rural region of northern Japan underwent measurement of initial screening blood pressure; ambulatory blood pressure was measured subsequently. A total of 285 subjects (66.5 +/- 9.2 years old) were taking antihypertensive medication (treated group), while 684 (56.3 +/- 12.0 years old) were not (untreated group). The WHO criteria were used to categorize screening blood pressure. Ambulatory blood pressure levels were classified as follows: hypertension, systolic blood pressure > or = 144 mmHg and/or diastolic blood pressure > or = 85 mmHg; and normotension, systolic blood pressure < or = 133 and diastolic blood pressure < or = 78 mmHg. Of the 285 treated subjects, 49 (17.2%) were classified as hypertensive by screening measurements, while 36 (12.6%) were classified as such by ambulatory blood pressure monitoring. Only 12 (24.5%) of the former 49 subjects were also classified as hypertensive, while 20 (40.8%) were classified as normotensive by ambulatory blood pressure monitoring. Of the 684 untreated subjects, 34 (5.0%) were hypertensive by screening measurements and 43 (6.3%) were hypertensive by ambulatory blood pressure monitoring. Only 14 (41.2%) of the former 34 subjects were classified as hypertensive by ambulatory blood pressure monitoring. Of the 34 untreated subjects classified as hypertensive by screening measurements, ambulatory blood pressure monitoring showed 12 (35.3%) to be normotensive, suggesting that they were cases of "white coat" hypertension. The study first confirmed, based on community-derived data, that there are large discrepancies between screening (casual) blood pressure measurements and ambulatory blood pressure monitoring with respect to the recognition of hypertension and normotension. The determination of blood pressure levels by ambulatory blood pressure monitoring may result in a different prognosis of hypertension from that made on the basis of screening blood pressure measurements. The prognostic value of ambulatory blood pressure has to be further investigated.

Adult↗
PubMed1996

Molecular cloning and characterization of the yellowtail GH gene and its promoter: a consensus sequence for teleost and avian Pit-1/GHF-1 binding sites.

The gene and 5' flanking promoter region for yellowtail (Seriola quinqueradiata) GH (yGH) have been cloned, sequenced and characterized. The yGH gene spans approximately 4.6 kb and consists of six exons and five introns, as has been observed with rainbow trout, Atlantic salmon and tilapia GH genes. This result suggests that the structure of six exons and five introns is a dominant form in fish GH genes. A typical TATA box exists 26 bp upstream from the transcription start site, and Pit-1/GHF-1 (Pit-1) binding site-homologous regions were found in the promoter region of the yGH gene. In a gel shift assay, however, a single shifted band was detected with the fragments containing a region from -128 to -90 of the yGH 5' flanking region when they were incubated with yellowtail pituitary nuclear extracts. The bound fragments contained an octamer base sequence similar, but not identical, to mammalian consensus Pit-1 binding element. A consensus octamer sequence is also proposed in this report for the binding of teleost and avian Pit-1 transcription factors.

Amino Acid Sequence↗
PubMed1996

Heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C cytotoxicity in childhood leukemias which express myeloid markers.

It is uncertain if acute lymphoblastic leukemia (ALL) cells expressing myeloid makers can respond to granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). We investigated the effects of G-CSF (0.01 microgram/ml) and GM-CSF (0.01 microgram/ml) on [3H]thymidine (TdR) uptake, and the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in leukemia cells from 17 pediatric patients. ALL cells without myeloid markers did not respond to G-CSF or GM-CSF. On the other hand, these cytokines enhanced the [3H]TdR uptake and cell growth, not only of AML cells but also of ALL cells expressing myeloid antigens. However, G-CSF and GM-CSF did not always enhance the growth inhibitory effect of the cell cycle specific drug ara-C when the cells were co-cultured with the drug. There was no relationship between cell growth and the amount of [3H]TdR incorporation or the intracellular ara-CTP level. These results indicate the heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C sensitivity in childhood leukemia cells.

Adolescent↗
PubMed1996

Prevalence of hypertension and rate of blood pressure control as assessed by home blood pressure measurements in a rural Japanese community, Ohasama.

A cross-sectional community survey using home blood pressure measurements was performed in northern Japan to estimate the prevalence of definite hypertension, white coat hypertension and the success of blood pressure control in patients receiving antihypertensive drugs. A total of 1334 subjects (mean age +/- SD, 53.8 +/- 17.3 years; 8-91 years) participated in the screening and home blood pressure measurement program. They measured blood pressure at home at least 3 times (mean measurement frequency, 20.8 +/- 8.3 times). Of these 1334 subjects, 314 (65.1 +/- 8.9 years) were taking drugs (treated group) while 1020 (50.3 +/- 17.8 years) were not (untreated group). The WHO criteria were used to categorize screening blood pressure. Criteria for diagnosis of hypertension by home blood pressure measurements were as follows: definitely hypertensive (systolic blood pressure > or = 144 mmHg and/or diastolic blood pressure > or = 89 mmHg) and normotensive (104 < systolic blood pressure < or = 131 mmHg and 60 < diastolic blood pressure < or = 79 mmHg). Of the 1018 subjects identified as normotensive on screening measurements, home measurements indicated that 73 (7.2%) were hypertensive and 765 (74.7%) were normotensive or lower. Of the 112 subjects identified as hypertensive on screening measurements, home measurements showed that 42 (37.5%) were hypertensive and 30 (26.8%) were normotensive or lower. Of the 314 treated subjects, 45 (14.3%) were identified as hypertensive by screening measurements and 88 (28.0%) as hypertensive by home measurements. Only 20 (44.4%) of the former 45 subjects were also defined as definitely hypertensive by home measurements. Of the 1020 untreated subjects, 67 (6.6%) were hypertensive by screening measurements and 84 (8.2%) by home measurements. Only 22 (32.8%) of the former 67 subjects were classified as hypertensive by home measurements. Of the 67 untreated subjects identified as hypertensive by screening measurements, 20 (29.9%) were normotensive or lower by home measurements, suggesting that these subjects were "white coat" hypertensives. The study first confirmed based on the large community data that there are large discrepancies between screening (casual) blood pressure and home blood pressure measurements for recognition of hypertension and normotension. Determination of blood pressure levels by home blood pressure measurements may predict prognosis of hypertension differently from that by screening blood pressure measurements. Further prospectively study is needed to validate the prognostic value of home blood pressure measurements.

Adolescent↗
PubMed1996

Predictive power of screening blood pressure, ambulatory blood pressure and blood pressure measured at home for overall and cardiovascular mortality: a prospective observation in a cohort from Ohasama, northern Japan.

OBJECTIVE: To investigate the risks of high and low blood pressure levels determined by ambulatory blood pressure monitoring and home blood pressure measurements. METHODS: A long-term prospective study of all-cause mortality and cardiovascular mortality has been conducted in Ohasama, Japan since 1987. RESULTS: The Cox proportional hazards model after adjusting for age and sex demonstrated that, during a 5-year follow-up period involving 893 of the subjects aged 50 years or more in this cohort, those with the lowest quintile of ambulatory blood pressure levels exhibited a significantly higher hazard ratio for cardiovascular and for all-cause mortality. During the same follow-up period, of 1226 subjects aged 50 years and more, those with the lowest and highest quintiles of home blood pressure levels demonstrated a significantly higher hazard ratio with respect to cardiovascular and all-cause mortality (i.e., a J-shaped relationship). CONCLUSION: These results suggest that there is a significant risk associated with low blood pressure levels, which can be determined by ambulatory and home blood pressure measurements, but not by casual blood pressure measurements.

Journal Article↗
PubMed1996

[Two cases of breast cancer detected by 99mTc-tetrofosmin myocardial scintigraphy].

Breast cancer ranks the second position among the cancer of women in Japan. We report two cases of breast cancer detected by 99mTc-tetrofosmin. First case was 51 years old female with breast cancer (invasive papillotubular carcinoma) and dextrocardia. She received 99mTc-tetrofosmin myocardial scintigraphy to evaluate dextrocardia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy showed myocardium at the right side, gall bladder at the left lower side and abnormal uptake on the left chest wall. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed myocardium at the right side and abnormal uptake on the left chest wall. Second case was 78 years old female with breast cancer (intracystic papillary carcinoma) and arrhythmia. 99mTc-tetrofosmin myocardial scintigraphy was performed to evaluate arrhythmia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy shows hot nodule at the lateral side of the myocardium. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed abnormal uptake at the left lateral side on the chest wall. Both cases appeared illed foci as abnormal uptake with 99mTc-tetrofosmin scintigraphy, although histological diagnosis was different. We conclude that 99mTc-tetrofosmin scintigraphy is helpful for evaluating breast cancer.

Aged↗
PubMed1995

Sequence of the flounder (Paralichthys olivaceus) growth hormone-encoding gene and its promoter region.

The flounder (Paralichthys olivaceus) growth hormone (GH)-encoding gene (fGH) and its promoter region were cloned and sequenced following amplification of genomic DNA by the polymerase chain reaction. The fGH gene is 2.1-kb long and consists of six exons and five introns. In the 5'-flanking region of the determined transcription start point, a potential TATA box is located at -24, and Pit-1/GHF-1-binding site candidates are located in the -70 to -53 and -133 to -141 regions.

Amino Acid Sequence↗
PubMed1995

A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors.

Cytokines manifest their function through alteration of gene expression. However, target genes for signals from cytokine receptors are largely unknown. We therefore searched for immediate-early cytokine-responsive genes and isolated a novel gene, CIS (cytokine inducible SH2-containing protein) which is induced in hematopoietic cells by a subset of cytokines including interleukin 2 (IL2), IL3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), but not by stem cell factor, granulocyte colony-stimulating factor and IL6. The CIS message encodes a polypeptide of 257 amino acids that contains an SH2 domain of 96 amino acids in the middle. To clarify the function of CIS in cytokine signal transduction, we expressed CIS in IL3-dependent hematopoietic cell lines under the control of a steroid-inducible promoter. The CIS product stably associated with the tyrosine-phosphorylated beta chain of the IL3 receptor as well as the tyrosine-phosphorylated EPO receptor. Forced expression of CIS by steroid reduced the growth rate of these transformants, suggesting a negative role of CIS in signal transduction. CIS induction requires the membrane-proximal region of the cytoplasmic domain of the EPO receptor as well as that of the common beta chain of the IL3, IL5 and GM-CSF receptor, whereas CIS binds to the receptor that is tyrosine phosphorylated by cytokine stimulation. Thus CIS appears to be a unique regulatory molecule for cytokine signal transduction.

Amino Acid Sequence↗
PubMed1995

ATP-sensitive K+ channels mediate regulation of substance P release via the prejunctional histamine H3 receptor.

Perfusion of histamine (10(-3) M) elicited a significant increase of immunoreactive substance P release in the subcutaneous perfusate in the rat hindpaw. The active L-enantiomer of cromakalim, lemakalim (50 micrograms/kg, i.v.), a selective K+ channel activator, significantly inhibited the immunoreactive substance P release. Glibenclamide (10 mg/kg, i.v.), an ATP-sensitive K+ channel blocker, abolished the response to lemakalim on the release of immunoreactive substance P. R(-)-alpha-methylhistamine (1 mg/kg, i.v.), a specific histamine H3 receptor agonist, significantly inhibited the release of immunoreactive substance P. Glibenclamide (10 mg/kg, i.v.) antagonized the inhibitory effect of R(-)-alpha-methylhistamine. Tetraethylammonium (10 mg/kg, i.p.), a K+ channel blocker, also reduced the inhibitory effect significantly. These results suggest that the inhibition of substance P release from sensory nerve endings via prejunctional histamine H3 receptors may be achieved by activating the ATP-sensitive K+ channel coupled to the histamine H3 receptor in the rat skin.

Adenosine Triphosphate↗
PubMed1995

Regulation of substance P release mediated via prejunctional histamine H3 receptors.

The involvement of the histamine H3 receptor in the regulation of substance P release in neurogenic inflammation was studied by using rat hindpaw skin. R-(-)-alpha-Methylhistamine, a specific histamine H3 receptor agonist, significantly inhibited the increased vascular permeability induced by antidromic electrical stimulation of the sciatic nerve in a dose-dependent manner at doses of 0.5-3 mg/kg (i.v.), and thioperamide (2 mg/kg i.p.), a specific histamine H3 receptor antagonist, prevented the inhibitory effect of R-(-)-alpha-methylhistamine. The antidromic stimulation also caused a significant increase in immunoreactive substance P release in the subcutaneous (s.c.) perfusate in the rat hindpaw. R-(-)-alpha-Methylhistamine (0.25-2 mg/kg) dose dependently inhibited the increase in release of immunoreactive substance P, and thioperamide (2 mg/mg i.p.) antagonized it. Perfusion of histamine (10(-3) M) elicited a significant increase of immunoreactive substance P release in the perfusate, which was reduced by R-(-)-alpha-methylhistamine and the antagonism of thioperamide was also observed. Histamine (in the presence of histamine H1 and H2 receptor antagonists) had an inhibitory effect on the electrically evoked release of immunoreactive substance P. These results strongly support the hypothesis that histamine regulates substance P release via prejunctional histamine H3 receptors that are located on peripheral endings of sensory nerves.

Animals↗