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Kazuhito Totsune

Publications and source records attributed to Kazuhito Totsune.

49 records · Page 3Linked to original sources
PubMed2004

Control of blood pressure as measured at home and office, and comparison with physicians' assessment of control among treated hypertensive patients in Japan: First Report of the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

The Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study was conducted to measure the control of blood pressure (BP) as evaluated by home BP measurement among 3,400 patients with essential hypertension (mean age: 66 years; females: 55%) receiving antihypertensive treatment in primary care settings in Japan. The purpose of this first report was to compare characteristics of BP control as measured at home and in the clinic (office) and define their association with BP control as evaluated by physicians. Mean systolic/diastolic BP (SBP/DBP) values were 140/82 mmHg for home BP and 143/81 mmHg for office BP. BP levels were not adequately controlled among approximately 60% of the patients, according to reference values described in the national guidelines (office BP: <140/90 mmHg; home BP: <135/85 mmHg). Even among patients evaluated by physicians as having excellent or fairly good BP control, office and home SBP values were insufficiently controlled in approximately 50%. Although the tendency was more remarkable among older patients, whose recommended target BP levels are higher than those of middle-aged patients in the Japanese Hypertension Society 2000 criteria, office and home BP values were not adequately controlled in approximately 50% of the middle-aged patients whose BP control was evaluated as good. Our findings suggest that an important reason why home and office BP values are not adequately controlled is that physicians approve relatively higher BP levels under treatment, even among middle-aged patients.

Aged↗
PubMed2003

Orexin-A expression in human peripheral tissues.

Orexin-A is a neuropeptide present in the brain and is known to regulate feeding and sleeping. In this study, we examined the systemic distribution of orexin-A in human tissues. Immunoreactivity for orexin-A was detected in ganglion cells of the thoracic sympathetic trunk, myenteric plexuses and endocrine cells of the gastrointestinal tract, islet cells of the pancreas and syncytiotrophoblasts and decidual cells of the placenta. In the gastrointestinal tract, orexin-A immunoreactivity was detected in the myenteric plexuses from 26 gestational weeks to birth. In double immunostaining in the pancreas, a great majority of insulin-positive cells was simultaneously positive for orexin-A. mRNA expression for prepro-orexin was also detected in the kidney, adrenal gland, pancreas, placenta, stomach, ileum, colon and colorectal epithelial cells. These results suggest the production of orexin-A in various human peripheral tissues and orexin-A may also play important roles in some peripheral organs.

Adolescent↗
PubMed2003

Adrenomedullin in the eye.

Adrenomedullin (AM) is a multifunctional regulatory peptide that is produced and secreted by various types of cells. We showed the presence of high concentrations of adrenomedullin-immunoreactivity in the vitreous fluid, and the levels were elevated in patients with proliferative vitreoretinopathy. Furthermore, adrenomedullin mRNA expression levels were elevated in the tissues of intraocular tumors and orbital tumors. Adrenomedullin is produced and secreted by cultured human retinal pigment epithelial (RPE) cells. Inflammatory cytokines and hypoxia are strong stimulators for the adrenomedullin expression in retinal pigment epithelial cells. Adrenomedullin stimulated the proliferation of retinal pigment epithelial cells both under normoxia and hypoxia. Dexamethasone (DEX) increased the adrenomedullin expression in two cultured cell lines of human retinal pigment epithelial cells; ARPE-19 cells and D407 cells, while it had no noticeable effects on the cytokine-induced adrenomedullin expression. These findings suggest that adrenomedullin is involved in the pathophysiology of inflammatory and neoplastic eye diseases as an autocrine or paracrine growth stimulator. The findings on glucocorticoid-induced AM expression raise the possibility that it may be related to the pathogenesis of some eye diseases, such as central serous chorioretinopathy and multifocal posterior pigment epitheliopathy, which are frequently seen in patients treated with high doses of glucocorticoids.

Adrenomedullin↗
PubMed2003

Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II.

Urotensin II is a potent vasoactive peptide, which was originally isolated from fish urophysis. We studied expression of urotensin II and its receptor mRNAs in the tumor tissues of adrenocortical tumors, pheochromocytomas and neuroblastomas. Effects of exogenously added urotensin II on cell proliferation were studied in a human adrenocortical carcinoma cell line, SW-13 and a human renal cell carcinoma cell line, VMRC-RCW. The reverse transcriptase polymerase chain reaction (RT-PCR) showed expression of urotensin II and its receptor mRNAs in all the samples examined; seven pheochromocytomas, nine adrenocortical adenomas (four with primary aldosteronism, four with Cushing syndrome and one with non-functioning adenoma), four adrenocortical carcinomas, one ganglioneuroblastoma and five neuroblastomas, as well as four normal portions of adrenal glands (cortex and medulla). Urotensin II-like immunoreactivity was detected in one of eight adrenocortical adenomas, two of four adrenocortical carcinomas, one of six pheochromocytomas, and one of five neuroblastomas by radioimmunoassay, but not in normal portions of adrenal glands (detection limit; 0.2pmol/g wet weight). Treatment with urotensin II for 24h significantly increased number of SW-13 cells (at 10(-8) and 10(-7)mol/l) and VMRC-RCW cells (at 10(-8)mol/l). These findings raise the possibility that urotensin II may act as an autocrine/paracrine growth stimulating factor in adrenal tumors.

Adrenal Cortex Neoplasms↗
PubMed2003

Suppression of cytokine-induced expression of adrenomedullin and endothelin-1 by dexamethasone in T98G human glioblastoma cells.

There is accumulating evidence showing that glial cells and gliomas secrete some neuropeptides and vasoactive peptides, such as adrenomedullin and endothelin-1. We have previously shown that expression of these two peptides is induced by inflammatory cytokines in T98G human glioblastoma cells. Glucocorticoids are frequently used for the treatment of inflammatory diseases and glioblastomas. We therefore studied effects of dexamethasone on expression of adrenomedullin and endothelin-1 in T98G human glioblastoma cells. Dexamethasone dose-dependently increased adrenomedullin mRNA levels and immunoreactive-adrenomedullin levels in the medium in T98G cells, whereas it decreased immunoreactive-endothelin levels in the medium. A combination of three cytokines, interferon-gamma (100 U/ml), tumor necrosis factor-alpha (20 ng/ml) and interleukin-1beta (10 ng/ml) induced expression of adrenomedullin and endothelin-1 in T98G cells. Dexamethasone (10(-8) mol/l) suppressed increases in expression of both adrenomedullin and endothelin-1 induced by these three cytokines. Thus, dexamethasone alone increased adrenomedullin expression whereas it suppressed the cytokine-induced expression of adrenomedullin in T98G cells. These findings raised the possibility that effects of dexamethasone on brain inflammation and glioblastomas may be partly mediated or modulated by its effects on expression of adrenomedullin and endothelin-1.

Adrenomedullin↗
PubMed2003

Decreased expression of adrenomedullin during adipocyte-differentiation of 3T3-L1 cells.

Adrenomedullin (AM) is a potent vasodilator peptide which has an inhibitory action on insulin secretion. Resistin is a novel peptide specifically secreted from adipocytes, and implicated in insulin resistance. We studied the expression of AM and resistin in 3T3-L1 adipocytes and preadipocytes by Northern blot analysis and radioimmunoassay. Immunoreactive-AM was detected in the culture media of 3T3-L1 preadipocytes and adipocytes, with higher concentrations found in preadipocytes. Northern blot analysis showed that AM mRNA was expressed in 3T3-L1 preadipocytes but was undetectable in adipocytes. In contrast, resistin mRNA was expressed in 3T3-L1 adipocytes, whereas it was not detected in 3T3-L1 preadipocytes. The present study thus showed that AM expression was decreased, and resistin expression increased, during adipocyte-differentiation of 3T3-L1 cells.

3T3 Cells↗
PubMed2003

Differential expression of adrenomedullin and resistin in 3T3-L1 adipocytes treated with tumor necrosis factor-alpha.

DESIGN: It has recently been shown that deficiency of adrenomedullin (AM), a potent vasodilator peptide, leads to insulin resistance. We studied expression of AM in NIH 3T3-L1 adipocytes and compared it with expression of resistin, an adipocyte-derived peptide hormone that is proposed to cause insulin resistance. Moreover, we studied the effects of tumor necrosis factor-alpha (TNF-alpha), a known mediator of insulin resistance, on the expression of AM and resistin in 3T3-L1 adipocytes. METHODS: 3T3-L1 cells were induced to differentiate to adipocytes by insulin, dexamethasone and 3-isobutyl-1-methylxanthine. Expression of AM mRNA and resistin mRNA was examined by Northern blot analysis. Immunoreactive AM in the medium was measured by RIA. RESULTS: AM mRNA was expressed in preadipocytes, but barely detectable in adipocytes. Immunoreactive AM was detected in the medium of both preadipocytes and adipocytes, with about 2.5 times higher levels found in preadipocytes. In contrast, resistin mRNA was expressed in adipocytes, whereas it was not detected in preadipocytes. Treatment with TNF-alpha increased AM expression in both adipocytes and preadipocytes, whereas it decreased resistin mRNA levels in adipocytes. CONCLUSIONS: The present study has shown that AM expression was down-regulated and resistin expression was up-regulated during adipocyte differentiation of 3T3-L1 cells. TNF-alpha acted as a potent negative regulator of resistin expression and a potent positive regulator of AM expression in adipocytes, raising the possibility that in addition to its known actions in causing insulin resistance, TNF-alpha may also have actions against insulin resistance through AM and resistin.

1-Methyl-3-isobutylxanthine↗
PubMed2002

Expression of prolactin-releasing peptide and its receptor in the human adrenal glands and tumor tissues of adrenocortical tumors, pheochromocytomas and neuroblastomas.

Adrenal tumors, such as pheochromocytomas, are known to express various peptides and their receptors. Prolactin-releasing peptide (PrRP) is a novel neuropeptide isolated from bovine hypothalamic tissues. In the present study, expression of PrRP receptor was studied in the human brain, pituitaries, adrenal glands and tumor tissues of adrenocortical tumors, pheochromocytomas, a ganglioneuroblastoma and neuroblastomas by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis. The presence of immunoreactive-PrRP in the adrenal glands and in these tumor tissues was studied by radioimmunoassay. Human brain tissues and pituitaries were obtained at autopsy. Normal portions of adrenal glands and tumor tissues were obtained at surgery. RT-PCR analysis showed expression of PrRP receptor in the human brain, pituitaries, normal portions of adrenal glands and various tumor tissues. Northern blot analysis showed high expression of PrRP receptor only in tumor tissues of pheochromocytomas, indicating that PrRP receptor expression is high in pheochromocytomas. Immunoreactive-PrRP was detected in normal portions of adrenal glands (0.162+/-0.024 pmol/g wet weight, n=4, mean+/-S.E.M.), four out of six cases of pheochromocytomas (0.050-7.9 pmol/g wet weight), one neuroblastoma and some adrenocortical tumors. The present study has shown that PrRP receptor mRNA was widely expressed in the brain tissues, pituitaries, adrenal glands and various tumors. The high expression of PrRP receptor in pheochromocytomas suggests potential pathophysiological roles of PrRP in these tumors.

Adrenal Cortex Neoplasms↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2002

Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin: expression and effects on proliferation.

Evidence has accumulated showing that vasoactive peptides, such as endothelin-1, adrenomedullin and urotensin-II, are expressed in various kinds of tumour cells. In the present study, the expression of endothelin-1 and endothelin receptors was studied in eight human tumour cell lines: T98G (glioblastoma), IMR-32 and NB69 (neuroblastoma), BeWo (choriocarcinoma), SW-13 (adrenocortical carcinoma), DLD-1 (colonic carcinoma), HeLa (cervical carcinoma) and VMRC-RCW (renal carcinoma). Reverse transcriptase-PCR showed expression of endothelin-1 mRNA in seven out of the eight cell lines, the exception being BeWo cells. ET(A) receptor mRNA was expressed in T98G, IMR-32 and NB69 cells, but weakly in the other cells. ET(B) receptor mRNA was expressed in IMR-32, NB69 and BeWo cells, but only weakly in T98G and HeLa cells. Immunoreactive endothelin was detected in the culture media of six out of the eight cell lines, but not in that of IMR-32 or BeWo cells. Treatment of T98G cells with an anti-endothelin-1 antibody or an anti-adrenomedullin antibody for 24 h decreased cell numbers to approx. 84% and 90% of control respectively. Treatment with the ET(A) receptor antagonist BQ-610 (1 microM) significantly decreased cell number to about 90% of control, whereas the ET(B) receptor antagonist BQ-788 had no significant effect. On the other hand, exogenously added endothelin-1, adrenomedullin or urotensin-II (0.1 microM) had no significant effects on cell number. These results suggest that endothelin-1 acts as a paracrine or autocrine growth stimulator in tumours. The effect of endothelin-1 on tumour growth appears to be mediated by the ET(A) receptor.

Adrenal Cortex Neoplasms↗
PubMed2002

Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart.

Urocortin (Ucn) is a new member of the corticotropin-releasing factor (CRF) neuropeptide family and has positive inotropic actions and protective effects against ischemia in the rat heart. Ucn binds with very high affinity to both CRF receptor type 1 (CRF-R1) and CRF receptor type 2 (CRF-R2). However, to date, endogenous ligand(s) for CRF receptors expressed in the human heart have yet to be elucidated. In this study, we therefore examined the expression of Ucn and CRF receptors in human heart obtained at autopsy by RT-PCR, immunohistochemistry, and RIA. RT-PCR analysis demonstrated that Ucn and CRF-R2alpha mRNAs were detected in all four chambers. CRF-R1 mRNA was weakly present in some left atria, left ventricles, and in one right ventricle. CRF-R2beta mRNA was detected predominantly in the left atrium. CRF mRNA was not detected in any of the four chambers. Immunostaining for both Ucn and CRF receptors was detected in cardiac myocytes in all four chambers. Ucn-like immunoreactivity was detected in all four chambers by RIA, with the highest concentrations in the left ventricle (1.90 +/- 0.5 pmol/g wet weight, mean +/- SEM; n = 4). On the other hand, CRF-like immunoreactivity was very low or undetectable in the human heart. Sephadex G-50 column chromatography demonstrated that most of the Ucn-like immunoreactivity in the human heart was eluting earlier than the standard Ucn, with one minor peak in the position for Ucn. Ucn immunoreactivity was not detected in skeletal muscle by immunohistochemistry or RIA. These results suggest that Ucn is produced in the human heart and stored there mainly in the larger molecular weight forms. Endogenously produced Ucn may therefore exert its effects mostly through CRF-R2 in an autocrine and/or paracrine manner in the human heart.

Adult↗