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Y Takata

Publications and source records attributed to Y Takata.

At least 73 records · Page 4Linked to original sources
PubMed1999

Postprandial hypotension is associated with asymptomatic cerebrovascular damage in essential hypertensive patients.

offelucidate the relationship between postprandial hypotension (PPH) and asymptomatic cerebrovascular damage, we evaluated changes in blood pressure after a meal by 24-hour blood pressure monitoring in 70 hospitalized essential hypertensive patients aged >/=50 years. They received a diet containing standard nutritional ingredients with 120 mmol (7 g) NaCl and were free from medication for at least 1 week. PPH was defined as the mean reduction of systolic blood pressure during 2 hours after a meal. Patients were divided into three groups according to mean values of PPH after 3 meals: PPH-1 (n=16, 5 mm Hg</=PPH<10 mm Hg), PPH-2 (n=18, PPH>/=10 mm Hg), and normal (n=36, PPH<5 mm Hg). As asymptomatic cerebrovascular damage, lacunae and leukoaraiosis were evaluated by magnetic resonance imaging. PPH did not correlate with daytime or nighttime blood pressure or the nondipper phenomenon; however, PPH was significantly related to asymptomatic cerebrovascular damage. The prevalence of lacunae in the normal, PPH-1, and PPH-2 groups was 44%, 69%, and 83%, respectively (chi2=8.22, P<0.05). The number of lacunae in the normal, PPH-1, and PPH-2 groups was 1.0+/-1.3, 1.3+/-1.2, and 1. 9+/-1.4, respectively (F[2,67]=3.2, P<0.05). The prevalence of advanced leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 44%, 50%, and 83%, respectively (chi2=7.63, P<0.05). Severity score of leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 1.5+/-0. 7, 1.7+/-0.8, and 2.1+/-0.7, respectively (F[2,67]=4.3, P<0.05). These findings indicate that elderly hypertensive patients with marked PPH should be considered to have advanced cerebrovascular damage even in the absence of abnormal neurological findings.

Aged↗
PubMed1999

Giant unruptured aneurysm of the thoracic aorta--a case report.

An asymptomatic 88-year-old woman underwent a screening medical examination. The chest x-ray film showed a large mediastinal mass with calcification. Both chest computed tomography and nuclear magnetic resonance imaging revealed an unruptured aortic aneurysm, predominantly affecting the ascending aorta and the proximal part of the aortic arch. Its maximum diameter was 10.5 cm. An ascending aortic aneurysm more than 10 cm in diameter is very rare. She died of acute pulmonary embolism unrelated to the aneurysm, and autopsy indicated that the etiology of the aneurysm was atherosclerotic degeneration. Retrospectively, the natural progression of the aneurysm was able to be followed on a series of chest x-ray films obtained over 18 years.

Aged↗
PubMed1999

Synergistic role of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase cascade in the regulation of insulin receptor trafficking.

To examine the molecular mechanism of insulin receptor trafficking, we investigated the intracellular signaling molecules that regulate this process in Rat1 fibroblasts overexpressing insulin receptors. Cellular localization of insulin receptors was assessed by confocal laser microscopy with indirect immunofluorescence staining. Insulin receptors were visualized diffusely in the basal state. Insulin treatment induced the change of insulin receptor localization to perinuclear compartment. This insulin-induced insulin receptor trafficking was not affected by treatment of the cells with PI3-kinase inhibitor (wortmannin), whereas treatment with MEK [mitogen-activated protein (MAP) kinase-Erk kinase] inhibitor (PD98059) partly inhibited the process in a dose-dependent manner. Interestingly, treatment with both wortmannin and PD98059 almost completely inhibited insulin receptor trafficking. The functional importance of PI3-kinase and MAP kinase in the trafficking process was directly assessed by using single cell microinjection analysis. Microinjection of p85-SH2 and/or catalytically inactive MAP kinase ([K71A]Erk1) GST fusion protein gave the same results as treatment with wortmannin and PD98059. Furthermore, to determine the crucial step for the requirement of PI3-kinase and MAP kinase pathways, the effect of wortmannin and PD98059 on insulin receptor endocytosis was studied. Insulin internalization from the plasma membrane and subsequent insulin degradation were not affected by treatment with wortmannin and PD98059. In contrast, insulin receptor down-regulation from the cell surface and insulin receptor degradation, after prolonged incubation with insulin, were markedly impaired by the treatment. These results suggest that PI3-kinase and MAP kinase pathways synergistically regulate insulin receptor trafficking at a step subsequent to the receptor internalization.

Androstadienes↗
PubMed1999

A rabbit model for evaluation of chlorpromazine-induced orthostatic hypotension.

The present study was conducted to develop an experimental model for evaluation of chlorpromazine-induced orthostatic hypotension in rabbits. In addition, the alpha-adrenoceptor blocking effect of chlorpromazine was investigated in isolated rabbit aorta and saphenous vein in comparison with prazosin. Chlorpromazine (0.1 and 1 mg/kg, i.v.) potentiated significantly a decrease in mean blood pressure at 1 min after the onset of head-up tilt in rabbits anesthetized with urethane alone, urethane+alpha-chloralose or nitrous oxide alone, but not in conscious and morphine+urethane+alpha-chloralose-anesthetized rabbits. There was a negative correlation (r=-0.986, p<0.01) between the extent of chlorpromazine-induced orthostatic hypotension and the amplitude of tilt-induced reflex tachycardia before chlorpromazine treatment. Both prazosin and pentolinium elicited orthostatic hypotension under all four anesthetic conditions. The pA2 value for chlorpromazine to antagonize norepinephrine-induced contraction in aorta was significantly larger than that in saphenous vein, whereas prazosin blocked aortic and venous contractions to a similar extent. These results suggest that a rabbit under an anesthesia which impairs tilt-induced reflex tachycardia may be useful for evaluation of orthostatic hypotension by chlorpromazine. The relatively low potential of chlorpromazine to produce orthostatic hypotension may be partly due to its weak venodilating action.

Adrenergic alpha-Antagonists↗
PubMed1999

Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats.

The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation.

Allylglycine↗
PubMed1998

Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice.

Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4-mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.

Animals↗
PubMed1998

Involvement of heat shock protein 90 in the degradation of mutant insulin receptors by the proteasome.

We previously reported three families with type A insulin-resistant syndrome who had mutations, either Asp1179 or Leu1193, in the kinase domain of the insulin receptor. The extreme insulin resistance of these patients was found to be caused by the decreased number of insulin receptors on the cell surface, due to the intracellular rapid degradation (Imamura, T., Takata, Y., Sasaoka, T., Takada, Y., Morioka, H., Haruta, T., Sawa, T., Iwanishi, M., Yang, G. H., Suzuki, Y., Hamada, J., and Kobayashi, M. (1994) J. Biol. Chem. 269, 31019-31027). In the present study, we first examined whether these mutations caused rapid degradation of unprocessed proreceptors, using the exon 13 deleted mutant insulin receptors (DeltaEx13-IR), which were accumulated in the endoplasmic reticulum as unprocessed proreceptors. The addition of Asp1179 or Leu1193 mutation to DeltaEx13-IR caused accelerated degradation of the unprocessed DeltaEx13-IR in the transfected COS-7 cells. Next, we tested whether these mutant receptors were degraded by the proteasome. Treatment with proteasome inhibitors Z-Leu-Leu-Nva-H (MG-115) or Z-Leu-Leu-Leu-H (MG-132) prevented the accelerated degradation of these mutant receptors, resulting in increased amounts of the mutant receptors in the COS-7 cells. Essentially the same results were obtained in the patient's transformed lymphocytes. Finally, we found that these mutant receptors bound to heat shock protein 90 (Hsp90). To determine whether Hsp90 played an important role in the accelerated receptor degradation, we examined the effect of anti-Hsp90 antibody on the mutant receptor degradation. The microinjection of anti-Hsp90 antibody into cells prevented the accelerated degradation of both Asp1179 and Leu1193 mutant insulin receptors. Taken together, these results suggest that Hsp90 is involved in dislocation of the mutant insulin receptors out of the endoplasmic reticulum into the cytosol, where the mutant receptors are degraded by the proteasome.

Animals↗
PubMed1998

Performance of the YB(66) soft X-ray monochromator crystal at the wiggler beamline of the UVSOR facility.

Soft X-ray spectra have been measured using a pair of YB(66)(400) monochromator crystals at the double-crystal monochromator beamline BL7A of the UVSOR facility, where the wiggler radiation has a magnetic field of 4 T. Deformation of the YB(66) crystal due to heat load from the synchrotron radiation is almost negligible. The photon flux is about 10(8) photons s(-1) (100 mA)(-1) in the energy region 1.2-2 keV and the energy resolution is 0.7 +/- 0.1 eV around hnu = 1.5 keV. These results show that the YB(66) crystal is suitable for use as a monochromator crystal. Its application to soft X-ray spectroscopy is discussed.

Journal Article↗
PubMed1998

Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) enhance lipopolysaccharide binding to neutrophils via CD14.

OBJECTIVE: Lipopolysaccharide (LPS), a potent and pleiotropic stimulator of immune cells, binds to neutrophils via CD14, but less densely than to monocytes. The present study was designed to investigate whether cytokines modulate LPS binding to neutrophils via CD14. METHODS: Neutrophils were cultured with LPS after pretreatment with cytokines, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), or granulocyte-colony stimulating factor (G-CSF). Binding of LPS and CD14 expression on neutrophils were analyzed by flow cytometry, using anti-LPS and anti-CD14 monoclonal antibodies (mAb). RESULTS: LPS alone showed only slight binding to neutrophils, but pretreatment with IFN-gamma or TNF-alpha before LPS exposure markedly increased LPS binding and CD14 expression on the surfaces of neutrophils. The dramatic increase in LPS binding was not seen with IL-1alpha or G-CSF. Anti-CD14 blocking mAb completely inhibited the binding effect. CONCLUSIONS: These results demonstrate that IFN-gamma and TNF-alpha enhance LPS binding to neutrophils via CD14, suggesting that the priming effect of cytokines on neutrophils is important for LPS binding.

Antibodies, Monoclonal↗
PubMed1998

Changes in blood pressure and heart rate variability during dental surgery.

The objective of the present study was to determine the changes in blood pressure, pulse rate, and heart rate variability during dental surgery. The study included 40 patients, 19 to 74 years of age (mean age: 42.7+/-3.0 years), who underwent tooth extraction at our hospital. Holter electrocardiographic monitoring was used to determine the power spectrum of R-R variability before and during dental surgery. The low frequency (LF: 0.041 to 0.140 Hz), high frequency (HF: 0.140 to 0.500 Hz), and total spectral powers (TF; 0.000 to 4.000 Hz) were calculated, and the ratio of LF to HF and percentage of HF relative to TF (%HF: HF/TF x 100) were used as indices of sympathetic and parasympathetic activities, respectively. The baseline blood pressure and pulse rate were 121+/-3/70+/-2 mm Hg and 70+/-1 beats/min, respectively. After the administration of local anesthetic (2% lidocaine) containing 1:80,000 epinephrine, both the blood pressure and pulse rate increased. During dental surgery, blood pressure increased further to 132+/-3/73+/-2 mm Hg. The increase in blood pressure was greater in middle-aged and older patients (> or =40 years old). In young patients (<40 years old), the %HF decreased and the LF/HF increased during local anesthesia. In contrast, in middle-aged and older patients, the LF/HF decreased during local anesthesia. These results suggest 1) that middle-aged and older patients have a greater increase in blood pressure during dental surgery than younger patients, and 2) that the regulation of the autonomic nervous system during dental surgery differs between younger and older patients.

Adult↗
PubMed1998

Postprandial hypotension: evaluation by ambulatory blood pressure monitoring.

To elucidate whether postprandial hypotension (PPH) is associated with any diurnal change of blood pressure, ambulatory blood pressure monitoring was performed on 121 hospitalized essential hypertensive patients who received standardized meals. Postprandial change in blood pressure was defined as the difference between mean systolic blood pressure (SBP) 1 h before and 2 h after each meal. The postprandial decline of SBP showed age-dependent augmentation. The degree of PPH was significantly related to the level of preprandial blood pressure for each meal. Patients were divided into the following three groups according to the mean PPH of three meals: Normal group (n = 79); mean postprandial decline of SBP <5 mm Hg, PPH-1 group (n = 24); 5 mm Hg ' mean PPH < 10 mm Hg, and PPH-2 group (n = 18); PPH 2 > or = 10 mm Hg. There was no difference in 24-h, nighttime, or daytime blood pressure among the three groups. The prevalence of dipper and nondipper patients was not different among the three groups. However, patients in PPH-2 showed significantly greater daytime and 24-h blood pressure variability. Furthermore, there was a significant positive relationship between the morning surge of SBP and PPH after breakfast (r = 0.36, P < .001). These findings indicate that PPH increases blood pressure variability independently of nocturnal change in blood pressure.

Adult↗
PubMed1998

Inhibition of IL-12 synthesis of peripheral blood mononuclear cells (PBMC) stimulated with a bacterial superantigen by pooled human immunoglobulin: implications for its effect on Kawasaki disease (KD).

The aim of this study was to further assess the role of pooled human immunoglobulin (PHIG) on cytokine production from PBMC stimulated with a bacterial superantigen. Human PBMC were cultured with Streptococcus pyrogenic exotoxin A (SPE-A) with or without PHIG and several proinflammatory cytokine levels of culture supernatants were measured. Serum cytokine levels of KD patients before and after PHIG therapy were also examined. PHIG greatly reduced the production of IL-12, interferon-gamma (IFN-gamma) and other cytokines from SPE-A-stimulated PBMC, while exogenous IL-12, but neither IL-1 nor tumour necrosis factor-alpha (TNF-alpha), restored IFN-gamma production inhibited by PHIG. Although PHIG partially adsorbed SPE-A, its inhibitory effect on cytokine production was not played by anti-SPE-A antibody. Although purified CD4+ T cells cultured with human HLA-DR-transfected mouse L cells and SPE-A could not effectively produce IFN-gamma, they produced large amounts of IFN-gamma if exogenous IL-12 was introduced. KD patients in the acute phase had higher levels of serum IFN-gamma than did controls and patients with bacterial infection. Although IL-12 levels of children with or without KD were not significantly different, IL-12 levels of children were much higher than those of adults. However, serum levels of IL-12 of KD patients were transiently but significantly decreased by PHIG therapy and IFN-gamma amounts subsequently reverted to basal levels thereafter. These findings indicate that PHIG inhibits IL-12 production of SPE-A-activated monocytes and thereby decreases IFN-gamma synthesis by T cells and suggest that inhibition of IL-12 and IFN-gamma production is an important part of the mechanisms underlying PHIG therapy on KD.

Adsorption↗
PubMed1998

Isolation and characterization of a putative keratin-associated protein gene expressed in embryonic skin of mice.

Embryonic mouse skin undergoes substantial morphologic changes from 13 days post-coitus (dpc) to 16 dpc, i.e., from simple layers of epithelial cells and periderm at 13.5 dpc to almost fully differentiated stratified epithelium with the rudiments of hair follicles at 16.5 dpc. Using RNA differential display, we isolated a gene involved in the development of mouse epidermis. This gene, tentatively designated as 4C32, encodes 197 amino acids containing six direct repeats of 10 amino acids with the CQ motif. The repetitive structure with the CQ motif is seen in most keratin-associated protein families, which are known to be specifically expressed in hair follicles. 4C32 is expressed in the outermost layer of the embryonic epidermis at 15.5 and 16.5 dpc, and abruptly disappears at 17.5 dpc, suggesting that 4C32 is expressed in the periderm. The periderm is a superficial layer of embryonic epidermis, and is known to disappear at 17 dpc in mouse embryos. The 4C32 transcripts were also detected in the developing and matured tongue tissues and in the tail scale, but not at any stage in hair follicles.

Amino Acid Sequence↗
PubMed1998

Molecular structure and function of rat platelet-derived growth factor beta-receptor gene promoter.

OBJECTIVE: To understand the regulatory mechanism of platelet-derived growth factor beta-receptor gene expression. METHODS: A 1.7 kb genomic fragment was obtained from a rat genomic library. After we had determined an entire sequence of this fragment, transcription start sites were determined both by primer extension analysis and by riboprobe mapping. We performed a functional promoter assay by using a dual-luciferase reporter system. Progressive 5'-deletions of the fragment and site-directed mutagenesis for the CCAAT motif located at -67 or -94 were used for the assay, and their promoter activities in vascular smooth muscle cells were assessed. Gel-mobility shift analysis was also performed for the CCAAT motif at -67. Effects of the upstream sequence spanning -310 through -120 on heterologous gene promoters were also investigated. RESULTS: Multiple transcription start sites were observed in the 5'-flanking region, and the 1.7 kb sequence was actually active as a functional promoter in vascular smooth muscle cells. Two important sequences responsible for the basal transcriptional activity were identified by the functional promoter assay. One was the CCAAT motif at -67 which acts as a promoter itself, and the other was the upstream region spanning -310 through -210 which positively regulates the basal promoter activity. CONCLUSION: The basal promoter activity of the rat platelet-derived growth factor beta-receptor gene is mainly regulated by the interaction or coordination of two sequences, the CCAAT motif and the upstream control element.

Animals↗
PubMed1998

Endothelin-1 expression in hearts of transgenic hypertensive mice overexpressing angiotensin II.

Cardiac myocytes and vascular endothelial cells produce endothelin (ET)-1, which has potent hypertrophic effects on cardiac myocytes. Although in cultured cardiomyocytes, angiotensin II (Ang II) was reported to enhance ET-1 production in vitro, it is not known whether ET-1 production is enhanced by Ang II in vivo. We investigated the production and pathophysiologic roles of ET-1 in 20-week-old male transgenic hypertensive mice (THM), in which the renin-angiotensin system (RAS) was markedly activated because of the presence of both human renin and angiotensinogen genes. Systolic blood pressure and the ratio of left ventricular weight to body weight were significantly higher in the THM than in control mice, indicating that THM developed cardiac hypertrophy. ET-1 production was significantly increased in the heart of THM because both ET-1 mRNA expression and peptide levels were significantly higher than in controls. However, circulating plasma ET-1 levels did not differ between the groups, and blood pressure did not change after i.v. injection with a high dose (3 mg/kg) of the ETA/B-nonselective receptor antagonist SB209670. These findings suggest that increased cardiac ET-1 production may contribute to the progression of cardiac hypertrophy and that endogenous ET-1 may not be involved in the short-term modulation of blood pressure in THM of this age.

Angiotensin II↗
PubMed1998

Antihypertensive activity and pharmacokinetics of KD3-671, a nonpeptide AT1-receptor antagonist, in renal hypertensive dogs.

The antihypertensive activity and pharmacokinetics of KD3-671 (previously named KT3-671), a nonpeptide AT1-receptor antagonist, were investigated in renal hypertensive dogs with normal or high plasma renin activity (PRA). A single administration of KD3-671 at 3 and 10 mg/kg, p.o., to the hypertensive dogs with high PRA dose-dependently reduced mean blood pressure (MBP), which was not correlated with plasma KD3-671 concentration. Significant increases in PRA and plasma angiotensin (Ang) II occurred 2 h after KD3-671 dosing. Enalapril at 3 mg/kg, p.o., also reduced MBP. Neither KD3-671 nor enalapril affected heart rate. When given orally once a day for 29 days to the hypertensive dogs with normal PRA, KD3-671 at 3 and 10 mg/kg/day dose-dependently reduced MBP, which was smaller than that in the dogs with high PRA. This was the case for enalapril. The hypotension induced by the first dose of KD3-671 or enalapril was consistently observed after doses 8, 15, 22, and 29. After cessation of repeated dosing, no rebound phenomenon in MBP was observed. Pharmacokinetic parameters of KD3-671 were not influenced by repeated dosing. KD3-671 markedly increased both PRA and plasma Ang II concentration at 2 h after dosing. These results suggest that KD3-671 may be useful for the treatment of hypertension.

Aldosterone↗
PubMed1998

A disrupted cholecystokinin A receptor gene induces diabetes in obese rats synergistically with ODB1 gene.

Otsuka Long-Evans Tokushima fatty (OLETF) rats develop hyperglycemia, hyperinsulinemia, and mild obesity, which are characteristic of human non-insulin-dependent diabetes mellitus. We have shown that two recessive genes, ODB1 mapped on the X chromosome and ODB2 mapped on chromosome 14, are involved in the induction of the diabetes in OLETF rats. Recently we found that OLETF rats are the naturally occurring cholecystokinin type A receptor (CCKAR) gene knockout rats. In this study, we focused on the genotype of CCKAR gene and the ODB1 gene in regulation of glucose homeostasis in the F2 cross of the OLETF rats. Relatively high plasma glucose levels were observed in the F2 offspring with the homozygously disrupted CCKAR gene. A synergistic effect for increasing plasma glucose levels in F2 rats between disrupted CCKAR gene and the ODB1 gene was shown. The CCKAR gene was found to map very close to ODB2 by a linkage analysis using microsatellite markers. These results suggest that CCKAR gene maintains normoglycemia in rats.

Animals↗