Biomedical subjects

Y Takata

Publications and source records attributed to Y Takata.

At least 127 records · Page 7Linked to original sources

PubMed1995

Bellidifolin stimulates glucose uptake in rat 1 fibroblasts and ameliorates hyperglycemia in streptozotocin (STZ)-induced diabetic rats.

Bellidifolin, isolated from Swertia japonica, was found to be a potent hypoglycemic agent in STZ-induced diabetic rats by both oral and intraperitoneal administration. Bellidifolin significantly lowered the loaded glucose level in normal as well as diabetic rats. Bellidifolin also lowered blood triglyceride levels significantly. It stimulated glucose uptake activity in Rat 1 fibroblasts expressing human insulin receptors.

Animals↗

PubMed1995

Effect of a cholecystokinin (CCK) antagonist (CR 1505) on gene expressions of CCK and secretin in rat intestine.

The effects of intragastric administration of cholecystokinin (CCK) antagonist (CR 1505; 60-300 mg/kg/day) to rats for 3 days on the gene expressions of CCK and secretin, the plasma CCK immunoreactivity, and the CCK content in the intestinal mucosa were examined. CR 1505 increased the level of CCK mRNA in the intestine dose dependently to up to 1.6 times the level in control rats but did not affect the level of secretin mRNA. It also significantly increased the plasma CCK immunoreactivity and the amount of CCK extracted from intestine with acid dose dependently. CR 1505 tended to decrease the trypsin activity in the intestine. These results suggest that ingested CR 1505 increased the CCK mRNA level in the intestine.

Animals↗

PubMed1995

Possible role of thromboxane A2 in hyperresponsiveness of isolated rat lung tissue in a Sephadex-induced eosinophilia model.

Antigen-stimulated contraction and release of chemical mediators were examined in saline- or Sephadex-treated rat lung parenchymal strips. Sephadex treatment caused eosinophilia in the blood and the lung tissue. Antigen challenge of the isolated parenchymal strips in Sephadex-treated rat was followed by passive sensitization, resulted in an augmented contraction and elevated releases of thromboxane (TX) B2 and peptide-leukotrienes (p-LTs) in bath fluid compared with those of saline-treated control. Although 5-hydroxytryptamine (5-HT) and histamine were significantly released after antigen challenge, the levels were not different between saline- and Sephadex-treated groups. DP-1904, a selective thromboxane synthetase inhibitor, and methysergide but not atropine significantly reduced the augmented contraction and inhibited the elevated TXB2 release in the Sephadex-treated group. Similar increased contraction and the elevated TXB2 release above were observed when Sephadex-treated rat lung strips were stimulated by exogenous 5-HT and LTD4. These augmented contractions were closely correlated with the increase in TXB2 level (r = 0.83; p < 0.01). In addition, contraction to U-46619, a thromboxane mimetic, was significantly greater in Sephadex-treated rat lung strips. Our results indicate that the ability of Sephadex-treated rat lung tissue to synthesize newly generated mediators such as TXA2 and p-LTs is increased, and the spasmogenic susceptibility of the lung tissue to TXA2 itself is modified by Sephadex treatment, suggesting these are due to the augmented contraction in an established hyperresponsiveness state induced by Sephadex.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1995

Effect of administration and withdrawal of doxazosin on ambulatory blood pressure in patients with essential hypertension.

The effect of both administration and withdrawal of doxazosin on patients with essential hypertension was evaluated by twenty-four-hour ambulatory blood pressure (BP) monitoring. Six hypertensive men were treated with doxazosin starting at 1 mg/day, and the dosage was titrated at weekly intervals up to a maximum of 8 mg/day. The twenty-four-hour BP profile was monitored noninvasively before treatment, in the fourth week of treatment, and on days 2 and 7 after the discontinuation of doxazosin. The average twenty-four-hour systolic and diastolic BPs (SBP and DBP) were lowered by doxazosin treatment and returned to the pretreatment levels within two days of doxazosin withdrawal. Doxazosin treatment produced a significant decrease in the daytime SBP and DBP but not in the nighttime BP values. The daytime BP decrease was no longer detected on days 2 and 7 after drug withdrawal. The twenty-four-hour pulse rate was not influenced by either doxazosin administration or discontinuation. The plasma norepinephrine concentration and plasma renin activity were increased by doxazosin treatment and were decreased by drug withdrawal. There was no rebound hypertension following doxazosin withdrawal. Thus, the present study using twenty-four-hour BP monitoring showed that doxazosin treatment reduced the daytime BP in patients with essential hypertension and that this reduction was abolished within two days after doxazosin discontinuation.

Adult↗

PubMed1995

A functional assessment of insulin/insulin-like growth factor-I hybrid receptors.

Insulin/insulin-like growth factor-I (IGF-I) hybrid receptors are composed of an alpha beta-heterodimer from an insulin receptor and an alpha beta-heterodimer from an IGF-I receptor. In this study, we evaluate the effect of insulin receptor overexpression on hybrid formation. The more human insulin receptors expressed in rodent fibroblasts, the greater the percentage of endogenous rat IGF-I receptors that form hybrid receptors. The IGF-I receptor in rodent fibroblasts has two receptor isoforms, one with a 95-kilodalton (kDa) beta-subunit and one with an 105 kDa beta-subunit. A truncated mutant insulin receptor was used to demonstrate that only activated IGF-I receptors with the 105-kDa beta-subunit form hybrid receptors with the insulin receptor. Insulin/IGF-I hybrid receptors with a kinase-defective insulin heterodimer undergo trans and a small amount of cis autophosphorylation, but overall autophosphorylation is markedly decreased from that seen in hybrids with a kinase-competent insulin receptor. The kinase-defective insulin receptor heterodimer functions as a dominant-negative, inhibiting phosphorylation by the kinase-competent IGF-I receptor heterodimer. The kinase-defective hybrid receptors are, however, able to undergo internalization. Despite an increasing percentage of insulin/IGF-I hybrid receptors in the three cell lines studied, the rates of IGF-I internalization and degradation remain similar to those mediated by the IGF-I receptor and distinct from those of insulin receptor heterotetramers. In conclusion, IGF-I-stimulated insulin/IGF-I hybrid receptors function like IGF-I receptors, rather than like insulin receptors.

Animals↗

PubMed1995

Effects of benidipine hydrochloride on contractions induced by some contractile agents in isolated cerebral and mesenteric arteries of dogs.

The effects of benidipine on contractions induced by contractile agents were studied in isolated dog basilar, middle cerebral and mesenteric arteries and compared with those of nicardipine. KCl (20-80 mM), U-46619 (3 x 10(-10)-3 x 10(-6)M) and 5-hydroxytryptamine (5-HT) (10(-9)-3 x 10(-6)M) produced concentration-dependent contractions in the three arteries. Benidipine (10(-11)-8 x 10(-9)M) inhibited non-competitively the KCl-induced contraction in the basilar, middle cerebral and mesenteric arteries with a pD'2 of 9.1, 9.7 and 8.5, respectively. There was a significant difference between the pD'2 values in the cerebral and mesenteric arteries. Benidipine (10(-6)-3 x 10(-5)M) attenuated significantly the contraction produced by both U-46619 and 5-HT in the three arteries, the pD'2 being 4.4-4.9. Nicardipine inhibited the contraction induced by the three contractile agents in the same manner as benidipine. The contraction caused by 70 mM KCl in the cerebral and mesenteric arteries was reduced by 33-38 and 18%, respectively following treatment with 0.25 mM Ca2+ solution. Furthermore, pretreatment with a Ca(2+)-free solution containing 1 mM EGTA inhibited KCl-induced contractions in the basilar, middle cerebral and mesenteric arteries by 98.7, 95.6 and 92.1%, respectively. It also attenuated the contractions produced by both 10(-6) M U-46619 and 3 x 10(-6) M 5-HT in the cerebral and mesenteric arteries by 56-61 and 34-39%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1995

[Antihypertensive effects of repeated oral administration of cilnidipine, a novel calcium antagonist, in 2K1C renal hypertensive dogs].

Antihypertensive effects of repeated oral administration of cilnidipine in 2K1C renal hypertensive dogs were compared with those of nicardipine. On the first day, oral administration of cilnidipine (3 mg/kg) or nicardipine (3 mg/kg) markedly lowered both systolic and diastolic blood pressure 1 hr after administration. The hypotensive effects of cilnidipine were longer compared with those of nicardipine. Both drugs elevated the heart rate and plasma renin activity. On the 8th and 15th days, similar responses were obtained by repeated administrations of cilnidipine and nicardipine. After withdrawal of these drugs, no rebound phenomena in blood pressure were observed. The changes in mean blood pressure were correlated with plasma cilnidipine or nicardipine concentrations that were obtained at each time of blood pressure measurement (r = -0.598; P < 0.001 and r = -0.594; P < 0.001, respectively). These results suggest that stable and long-acting antihypertensive effects of cilnidipine for 15 consecutive days in renal hypertensive dogs are related to the change in plasma drug concentrations.

Administration, Oral↗

PubMed1995

Inhibitory effect of cilnidipine on pressor response to acute cold stress in spontaneously hypertensive rats.

We investigated the effect of cilnidipine on cardiovascular and neuroendocrine responses to acute cold stress in conscious and unrestrained or moderately restrained spontaneously hypertensive rats (SHRs). Acute cold stress significantly increased mean blood pressure without marked change in heart rate. The acute cold stress-induced elevation in blood pressure was almost abolished by 1 mg/kg, p.o. of prazosin. The cold stress also elevated plasma norepinephrine and epinephrine levels. Cilnidipine at 3 mg/kg, p.o. significantly inhibited the pressor response to acute cold stress. Although 3 mg/kg, p.o. of nifedipine, nicardipine or manidipine lowered mean blood pressure to a similar extent as cilnidipine, none of these three drugs affected the pressor response. Cilnidipine also reduced the cold stress-induced increment in plasma norepinephrine but not the epinephrine level. These findings suggest that acute cold stress may induce the elevation in blood pressure due to an enhanced activation of the sympathoadrenal system in SHRs and that cilnidipine may suppress the pressor response by inhibiting the sympathetic nerve activity.

Animals↗

PubMed1995

Inhibitory effect of cilnidipine on vascular sympathetic neurotransmission and subsequent vasoconstriction in spontaneously hypertensive rats.

We reported previously that cilnidipine inhibited increases in blood pressure and plasma norepinephrine (NE) level in response to cold stress in spontaneously hypertensive rats (SHRs). In the present study, we investigated the effect of cilnidipine on sympathetic neurotransmission and subsequent vasoconstriction in SHRs. In pithed SHRs, electrical sympathetic nerve stimulation (ESNS) elevated blood pressure, and this pressor response was abolished by guanethidine. Cilnidipine at 10 micrograms/kg, i.v. and phentolamine at 1 mg/kg, i.v. suppressed the pressor response to ESNS by 28 +/- 6% and 67 +/- 3%, respectively. Neither nifedipine nor nicardipine inhibited it. The pressor response to exogenous NE was not influenced by cilnidipine. alpha, beta-Methylene ATP inhibited the pressor response to ESNS in the presence or absence of phentolamine. Cilnidipine also attenuated the phentolamine-resistant pressor response to ESNS. In SHR mesenteric vasculatures preloaded with [3H]-NE, cilnidipine (10(-7) M) as well as omega-conotoxin significantly inhibited the 3H overflow evoked by periarterial nerve stimulation. In radioligand binding experiments, cilnidipine inhibited [125I]-omega-conotoxin binding to rat synaptosomes, but it did not inhibit [3H]-prazosin binding to rat cortex membranes. These results suggest that cilnidipine may reduce electrically stimulated NE release from the sympathetic nerve endings of SHR vasculatures probably through its N-type Ca channel blocking action and that cilnidipine may also inhibit the vasoconstriction induced by ATP released concomitantly during nerve stimulation.

Animals↗

PubMed1995

Ambulatory blood pressure monitoring in elderly hypertensives treated with the new calcium antagonist, pranidipine (OPC-13340).

Pranidipine (OPC-13340), a new dihydropyridine calcium antagonist, was given to 9 elderly hypertensive inpatients aged 64-79 years. Once-daily administration of pranidipine (1-2 mg) for 1-2 weeks decreased the 24-h average BP significantly from 167/92 mmHg to 150/83 mmHg without any change in pulse rate (PR) or the variabilities of BP and PR. The reduction of BP was observed exclusively during daytime (171/95 mmHg to 153/86 mmHg, p < 0.01 for SBP, p < 0.05 for DBP), while BP reduction during nighttime was significant only for DBP (157/84 mmHg to 146/79 mmHg, p > 0.05 for SBP, p < 0.05 for DBP). The analysis of the circadian rhythm by the cosinor method revealed that the acrophases of BP and PR were not changed significantly by the treatment with pranidipine. No adverse effects such as flushing and headache developed during the treatment. These results suggest that once-daily treatment with pranidipine is safe and exerts a sufficient antihypertensive effect during daytime with mild reduction of nighttime BP in elderly hypertensives. Furthermore, it does not alter the circadian patterns or variabilities of BP and PR. Thus, pranidipine may be useful as a monotherapy for elderly hypertensives.

Aged↗

PubMed1994

[Maximum-intensity-projection CT angiography for evaluating head and neck tumors: usefulness of helical CT and auto bone masking method].

Angiographic images of 10 adult patients with head and neck tumors were obtained by helical computed tomography (CT) using maximum intensity projection (MIP). In all cases, the vasculature of the head and neck region was clearly visualized, and hypervascular lesions were directly demonstrated. In the head and neck, bone masking is a more important problem than in other regions. We developed an effective automatic bone masking method (ABM) using 2D/3D connectivity. Helical CT angiography with MIP and ABM provided accurate anatomic depiction, and was considered to be helpful in preoperative evaluation of head and neck tumors.

Adult↗

PubMed1994

Two naturally occurring mutations in the kinase domain of insulin receptor accelerate degradation of the insulin receptor and impair the kinase activity.

We identified two novel heterozygous missense mutations of the insulin receptor gene: the Asp1179 mutation in one family and the Leu1193 mutation in two unrelated families with extreme insulin resistance. In these patients, the number of insulin receptors on the cell surface was found to be markedly decreased by insulin binding and surface labeling studies in transformed lymphocytes. Insulin binding to the transfected COS 7 cells and Rat-1 cells with both mutant cDNAs was also decreased to 5-31% of normal, and the mutant insulin receptors showed a markedly decreased kinase activity. Although biosynthetic labeling studies revealed that both mutant receptors were synthesized as 190-kDa proreceptors, the degradation of the mutant proreceptors was 2-fold faster than that of the wild type proreceptors. However, the degradation rate of the mutant receptors on the cell surface was comparable to that of wild type insulin receptor. These results suggest that the Asp1179 and Leu1193 mutations in the kinase domain are unique in causing decreased insulin receptor number on the cell surface by accelerated intracellular degradation, and that insulin resistance in these patients is mainly due to the decreased receptor number rather than impaired kinase activity.

Adult↗

PubMed1994

Leu 193 mutation in the cysteine rich region of the insulin receptor inhibits the cleavage of the insulin receptor precursor but not insulin binding.

To characterize the Leu 193 mutant insulin receptor, which was found in a patient with extreme insulin resistance, the mutant insulin receptor was overexpressed in Rat-1 fibroblasts by transfection of mutated insulin receptor cDNA. In the pulse-chase experiment, the cleavage of the proreceptors to the matured receptor subunits was impaired in the cells expressing Leu 193 insulin receptor and therefore, the mutant proreceptors were accumulated in the cell. Insulin bound to the Leu 193 insulin receptor on the cell surface with normal affinity, although the mutation was in the alpha-subunit of the insulin receptor. Therefore, the Leu 193 mutation impaired proreceptor cleavage but not insulin binding.

Animals↗

PubMed1994

Mutation of the two carboxyl-terminal tyrosines in the insulin receptor results in enhanced activation of mitogen-activated protein kinase.

Activation of mitogen-activated protein (MAP) kinase represents an important mechanism in hormonal regulation. To clarify the role of MAP kinase activation in insulin action, we compared the activation of the enzyme in Rat-1 cells transfected with wild-type (Hirc) and mutant insulin receptors in which the 2 carboxyl-terminal tyrosines were substituted with phenylalanine (Y/F2). Expression of the Y/F2 mutant receptor enhanced the responsiveness of MAP kinase to insulin. Moreover, the insulin responsiveness of the activator of this enzyme, MAP kinase kinase, was also increased in these cells. To explore the early signaling events that might account for this increase in responsiveness, we evaluated the tyrosine phosphorylation of the insulin receptor substrate, IRS-1, and its subsequent association with phosphatidylinositol (PI)-3 kinase. In both cell types, insulin led to a dose-dependent increase in the association of tyrosine phosphorylated IRS-1 with the SH2 domain of the p85 regulatory subunit of PI-3 kinase, and also increased the amount of PI kinase activity detected in anti-IRS-1 immunoprecipitates. The effect of insulin was significantly greater in Y/F2 cells, as determined in both assays. In previous studies, cells bearing this receptor mutant exhibited an identical metabolic response but enhanced mitogenic response to insulin when compared with wild-type receptor. These data provide further evidence for divergence of the mitogenic and metabolic signaling pathways at or near the insulin receptor.

Animals↗

PubMed1994

Little or no expression of the cholecystokinin-A receptor gene in the pancreas of diabetic rats (Otsuka Long-Evans Tokushima Fatty = OLETF rats).

Expression of the CCK-A receptor gene in the pancreas and pancreatic exocrine function was examined in diabetic model rats (OLETF) at 5 wks of age. Little or no CCK-A receptor was detected in the pancreas of OLETF rats. Pancreatic exocrine function in response to exogenous CCK and to bile-pancreatic juice diversion (endogenous CCK) was impaired in conscious OLETF rats. The pancreatic insulin and protein contents of OLETF (Otsuka Long-Evans Tokushima Fatty) and control LETO (Long-Evans Tokushima Otsuka) rats were not significantly different. No histological abnormalities or expression of pancreatitis associated protein (PAP) mRNA was detected in the pancreas in either group. These results suggest that OLETF rats are a new experimental model for congenital deficiency of CCK-A receptor in the pancreas.

Animals↗

PubMed1994

Rat guanidinoacetate methyltransferase. Effect of site-directed alteration of an aspartic acid residue that is conserved across most mammalian S-adenosylmethionine-dependent methyltransferases.

Most mammalian S-adenosylmethionine (AdoMet)-dependent methyltransferases have a conserved aspartate residue in a sequence oDso (o denotes a hydrophobic amino acid and s denotes a small neutral amino acid). Rat guanidinoacetate methyltransferase has two aspartate residues (Asp-129 and Asp-134) conforming to the motif in close proximity to Tyr-136 that is photoaffinity-labeled by AdoMet (Takata, Y., and Fujioka, M. (1992) Biochemistry 31, 4369-4374). In order to investigate the role of these residues, we prepared variant forms of the enzyme by oligonucleotide-directed mutagenesis. Conversion of Asp-129 to asparagine or alanine resulted in a functional enzyme. Alteration of Asp-134 to glutamate (D134E) and asparagine (D134N) decreased activity, and replacement with alanine (D134A) led to inactivation. Decreases of 3- and 120-fold were found for kcat values of D134E and D134N, respectively. The Km values of D134E for AdoMet and those for guanidinoacetate were increased about 160- and 80-fold over the respective values of wild type. The corresponding increases in D134N were 800- and 50-fold, respectively. Conservative changes of the residues flanking Asp-134 had little effect on activity. Guanidinoacetate methyltransferase obeys an ordered Bi Bi mechanism in which AdoMet binds first. Thus, the large decreases in kcat/Km values for AdoMet indicate that Asp-134 is crucial for binding AdoMet. Spectroscopic studies indicated that the amino acid substitutions of Asp-134 resulted in no significant changes in the secondary and tertiary structures, and urea denaturation experiments showed that the altered enzymes were not destabilized.

Amino Acid Sequence↗

PubMed1994

Correlative retention time peak identification method for glycated haemoglobin in high-performance liquid chromatography.

A convenient peak identification method in stepwise elution was investigated and correlation among the retention times of peaks in ion-exchange chromatography of glycated haemoglobin was assessed. By using a correlation method, accuracy of peak identification among columns with degradation and product deviations can be maintained. The correlative retention time identification procedure is treated theoretically.

Chromatography, High Pressure Liquid↗

PubMed1994

Molecular cloning and analysis of the yeast flocculation gene FLO1.

The DNA sequence of the flocculation gene FLO1 of Saccharomyces cerevisiae, which is located on chromosome I (Watari et al., 1989) was determined. The sequence contains a large open reading frame (ORF) of 2586 bp and codes for a protein of 862 amino acids. However, further study (genomic Southern and polymerase chain reaction analyses) indicated that the gene we cloned was not the intact FLO1 gene but a form with an approximately 2 kb deletion in the ORF region. The intact FLO1 gene was then cloned and its nucleotide sequence determined. The sequence revealed that the ORF of the intact gene is composed of 4611 bp which code for a protein of 1537 amino acids. A remarkable feature of the putative Flo1 protein is that it contains four families of repeated sequences composed of 18, 2, 3 and 3 repeats and that it has a large number of serines and threonines. In the deleted FLO1 form, a large part of these repeated sequences was missing. The N- and C-terminal regions are hydrophobic and both contain a potential membrane-spanning region, suggesting that the Flo1 protein is an integral membrane protein and a cell wall component.

Amino Acid Sequence↗