Biomedical subjects

Koichi Sato

Publications and source records attributed to Koichi Sato.

At least 19 recordsLinked to original sources

PubMed2007

Increased oxidative stress impairs endothelial modulation of contractions in arteries from spontaneously hypertensive rats.

OBJECTIVES: The endothelium modulates vascular contractions. We investigated the effects of oxidative stress on endothelial modulation of contractions in hypertension. METHODS: Changes in isometric tension of femoral arterial rings from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were recorded. RESULTS: The contractile response to norepinephrine of arteries with endothelium was greater in SHR than in WKY rats (P < 0.0001). Endothelium removal augmented the norepinephrine-induced contraction (P < 0.05). The augmentation was more pronounced in WKY than in SHR, which resulted in comparable contraction of arteries without endothelium in both strains. Nomega-nitro-L-arginine methyl ester (100 micromol/l) mimicked the effect of endothelium removal. Production of nitric oxide (NO, assessed by measuring nitrite/nitrate concentrations) during the contraction was not different between SHR and WKY. Vitamin C suppressed the contraction of arteries with endothelium from SHR but not from WKY (P < 0.05). Diphenyleneiodonium and apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, attenuated the contraction of arteries with endothelium from SHR (P < 0.001) but not WKY, but did not affect contractions induced by serotonin. Superoxide generated by xanthine oxidase/hypoxanthine enhanced the norepinephrine-induced contraction of arteries with endothelium from WKY (P < 0.0001), and this effect was reversed by vitamin C. CONCLUSIONS: In rat femoral arteries, NO released from the endothelium modulates vascular contraction. In SHR, production of superoxide by NADH/NADPH oxidase, which may be activated by norepinephrine, is enhanced, resulting in the inactivation of NO and impairment of endothelial modulation of vascular contractions. Vascular oxidative stress may contribute to the altered circulation in hypertension by impairing endothelial modulation of vascular contractions.

Animals↗

PubMed2006

Bleeding Meckel diverticulum associated with a vitellointestinal artery aneurysm found on preoperative angiography: report of a case.

An 18-year-old man was admitted to a local hospital with abdominal pain and bloody stool. Upper and lower gastrointestinal endoscopy failed to show any bleeding sites; however, an angiography of the superior mesenteric artery done on hospital day 4 showed an abnormal artery with an aneurysm, branching from the ileal artery. This artery was thought to be the vitellointestinal artery, a feeding artery of Meckel diverticulum. After embolization, he was transferred to our hospital, where we performed emergency laparotomy with partial resection of the ileum, including a bleeding Meckel diverticulum. Pathological examination revealed ectopic gastric mucosa and peptic ulceration, which we assumed was the origin of the bleeding. The patient had an uneventful postoperative course. Visceral artery aneurysms are rare but important vascular lesions because of their potential for fatal rupture. Although a minimally invasive procedure can be performed for a vitellointestinal artery aneurysm in patients with asymptomatic Meckel diverticulum, we treated our patient surgically because he presented with hemorrhagic shock and had been unresponsive to an H(2)-receptor antagonist.

Adolescent↗

PubMed2006

Ca2+-independent, inhibitory effects of cyclic adenosine 5'-monophosphate on Ca2+ regulation of phosphoinositide 3-kinase C2alpha, Rho, and myosin phosphatase in vascular smooth muscle.

We have recently demonstrated in vascular smooth muscle (VSM) that membrane depolarization by high KCl induces Ca(2+)-dependent Rho activation and myosin phosphatase (MLCP) inhibition (Ca(2+)-induced Ca(2+)-sensitization) through the mechanisms involving phosphorylation of myosin-targeting protein 1 (MYPT1) and 17-kDa protein kinase C (PKC)-potentiated inhibitory protein of PP1 (CPI-17). In the present study, we investigated whether and how cAMP affected Ca(2+)-dependent MLCP inhibition by examining the effects of forskolin, cell-permeable dibutyryl cAMP (dbcAMP), and isoproterenol. Forskolin, but not its inactive analog 1,9-dideoxyforskolin, inhibited KCl-induced contraction and the 20-kDa myosin light chain (MLC) phosphorylation without inhibiting Ca(2+) mobilization in rabbit aortic VSM. dbcAMP mimicked these forskolin effects. We recently suggested that Ca(2+)-mediated Rho activation is dependent on class II alpha-isoform of phosphoinositide 3-kinase (PI3K-C2alpha). Forskolin inhibited KCl-induced stimulation of PI3K-C2alpha activity. KCl-induced membrane depolarization stimulated Rho in a manner dependent on a PI3K but not PKC and stimulated phosphorylation of MYPT1 at Thr(850) and CPI-17 at Thr(38) in manners dependent on both PI3K and Rho kinase, but not PKC. Forskolin, dbcAMP, and isoproterenol inhibited KCl-induced Rho activation and phosphorylation of MYPT1 and CPI-17. Consistent with these data, forskolin, isoproterenol, a PI3K inhibitor, or a Rho kinase inhibitor, but not a PKC inhibitor, abolished KCl-induced diphosphorylation of MLC. These observations indicate that cAMP inhibits Ca(2+)-mediated activation of the MLCP-regulating signaling pathway comprising PI3K-C2alpha, Rho, and Rho kinase in a manner independent of Ca(2+) and point to the novel mechanism of the cAMP actions in the regulation of vascular smooth muscle contraction.

Animals↗

PubMed2006

Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells.

We characterized the molecular mechanisms by which high density lipoprotein (HDL) inhibits the expression of adhesion molecules, including vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, induced by sphingosine 1-phosphate (S1P) and tumor necrosis factor (TNF) alpha in endothelial cells. HDL inhibited S1P-induced nuclear factor kappaB activation and adhesion molecule expression in human umbilical vein endothelial cells. The inhibitory HDL actions were associated with nitric-oxide synthase (NOS) activation and were reversed by inhibitors for phosphatidylinositol 3-kinase and NOS. The HDL-induced inhibitory actions were also attenuated by the down-regulation of scavenger receptor class B type I (SR-BI) and its associated protein PDZK1. When TNFalpha was used as a stimulant, the HDL-induced NOS activation and the inhibitory action on adhesion molecule expression were, in part, attenuated by the down-regulation of the expression of S1P receptors, especially S1P(1), in addition to SR-BI. Reconstituted HDL composed mainly of apolipoprotein A-I and phosphatidylcholine mimicked the SR-BI-sensitive part of HDL-induced actions. Down-regulation of S1P(3) receptors severely suppressed the stimulatory actions of S1P. Although G(i/o) proteins may play roles in either stimulatory or inhibitory S1P actions, as judged from pertussis toxin sensitivity, the coupling of S1P(3) receptors to G(12/13) proteins may be critical to distinguish the stimulatory pathways from the inhibitory ones. In conclusion, even though S1P alone stimulates adhesion molecule expression, HDL overcomes S1P(3) receptor-mediated stimulatory actions through SR-BI/PDZK1-mediated signaling pathways involving phosphatidylinositol 3-kinase and NOS. In addition, the S1P component of HDL plays a role in the inhibition of TNFalpha-induced actions through S1P receptors, especially S1P(1).

Cell Adhesion Molecules↗

PubMed2006

LC/ESI-tandem mass spectrometric determination of bile acid 3-sulfates in human urine 3beta-Sulfooxy-12alpha-hydroxy-5beta-cholanoic acid is an abundant nonamidated sulfate.

We developed a highly sensitive and quantitative method to detect bile acid 3-sulfates in human urine employing liquid chromatography/electrospray ionization-tandem mass spectrometry. This method allows simultaneous analysis of bile acid 3-sulfates, including nonamidated, glycine-, and taurine-conjugated bile acids, cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), ursodeoxycholic acid (UDCA), and lithocholic acid (LCA), using selected reaction monitoring (SRM) analysis. The method was applied to analyze bile acid 3-sulfates in human urine from healthy volunteers. The results indicated an unknown compound with the nonamidated common bile acid 3-sulfates on the chromatogram obtained by the selected reaction monitoring analysis. By comparison of the retention behavior and MS/MS spectrum of the unknown peak with the authentic specimen, the unknown compound was identified as 3beta,12alpha-dihydroxy-5beta-cholanoic acid 3-sulfate.

Adult↗

PubMed2006

Protein misfolding cyclic amplification as a rapid test for assessment of prion inactivation.

Abnormal isoform of prion proteins (PrP(Sc)), which are infectious agents associated with prion diseases, retain infectivity after undergoing routine sterilization processes. A sensitive method to detect the infectivity is a bioassay, and it has been used for assessing prion inactivation. However, the result is obtained after several hundred days. Here, protein misfolding cyclic amplification (PMCA) in which PrP(Sc) can be amplified in vitro was applied for assessing prion inactivation by dry heating and autoclaving. Scrapie-infected hamster brains were inactivated under various conditions, and residual infectivity and PrP(Sc) were detected by the bioassay and PMCA, respectively. The PMCA results were in good agreement with those of the bioassay. In samples autoclaved at temperatures below 150 degrees C, while infected mice died in the bioassay, protease-resistant PrP (PrP(res)) signals were detected in the second or third round of PMCA. Three rounds of PMCA require only 6 days, which means that the PMCA method is much faster than the bioassay.

Animals↗

PubMed2006

Specific affinity extraction method for small molecule-binding proteins.

Validation of the targets of candidate drugs is critical for rapid and efficient drug discovery and development and for understanding the pharmacological action and potential toxicities of the prospective therapeutic agent. Due to the nonspecific binding of abundant proteins to small molecule-immobilized gels, it is difficult to identify the protein targets of small molecules from crude biological samples by affinity extraction. To address this problem, we have developed an affinity gel for the specific extraction of small molecule-binding proteins. We immobilized small molecules on the agarose gel through a disulfide linker that is cleavable by mild reduction. This system has allowed specific and noncovalent complex formation between the small molecule and the target protein, keeping the effect of the nonspecific abundant proteins adsorbed on both the linker and gel surface to minimum. By preparing this affinity matrix with deoxycholate as a model small molecule, we captured two independent deoxycholate-binding proteins of different affinities from mouse ascites, anti-deoxycholate antibody, and serum albumin. As other proteins were not captured, this affinity extraction method should contribute significantly to the accurate and rapid drug discovery and development.

Amino Acid Sequence↗

PubMed2006

Association among C-reactive protein, oxidative stress, and traditional risk factors in healthy Japanese subjects.

BACKGROUND: Inflammation and oxidative stress play a key role in the pathogenesis of atherosclerosis. This study was designed to examine the interrelationships among C-reactive protein (CRP), oxidative stress, and traditional cardiovascular risk factors. METHODS: We conducted a cross-sectional analysis among 551 apparently healthy Japanese subjects not receiving medication (mean age, 53+/-11 years; males/females, 400/151). Subject underwent laboratory assessment of cardiovascular disease risk factors, and CRP and 8-isoprostane, a marker of oxidative stress, were measured. RESULTS: In unadjusted analyses, CRP was positively correlated with age, male gender, body mass index, blood pressure, smoking habit, creatinine, uric acid, triglycerides, an index of insulin resistance, and 8-isoprostane, and inversely correlated with high-density lipoprotein-cholesterol. 8-Isoprostane was positively correlated with age, pulse pressure, smoking habit, brain natriuretic peptide, and CRP. In multiple regression analyses, body mass index (r=0.177), high-density lipoprotein-cholesterol (r=-0.162), uric acid (r=0.141), and 8-isoprostane (r=0.097) were independently correlated with CRP (P<0.001), whereas smoking (r=0.341), age (r=0.217), and pulse pressure (r=0.091) remained independently correlated with 8-isoprostane (P<0.001). CONCLUSIONS: CRP levels are associated not only with clinical cardiovascular risk factors but also with oxidative stress. There are significant interrelationships among inflammation, oxidative stress, and traditional cardiovascular risk factors.

Adult↗

PubMed2006

Temocapril, an Angiotensin converting enzyme inhibitor, ameliorates age-related increase in carotid arterial stiffness in normotensive subjects.

BACKGROUND/AIMS: Oxidative stress plays an important role in vascular ageing. The close relationship of the renin-angiotensin system with mechanisms of oxidative stress suggests its possible involvement in the deleterious effects of ageing. The present study was designed to investigate whether inhibition of the renin-angiotensin system improves the age-related increase in arterial stiffness. METHODS: Normotensive elderly subjects in a geriatric nursing home (n = 24; male/female = 7/17; 86 +/- 9 years, mean +/- SD) were randomly assigned to receive either an angiotensin converting enzyme inhibitor, temocapril (n = 12, 1 mg daily) or nothing (n = 12). Carot id arterial stiffness parameter beta and circulating levels of malondialdehyde-modified low-density lipoprotein were measured before and 6 months after randomization. RESULTS: Temocapril decreased beta (from 7.0 +/- 1.0 to 4.9 +/- 0.9, p < 0.05) and malondialdehyde-modified low-density lipoprotein levels (from 73.2 +/- 19.9 to 61.3 +/- 18.4 U/l, p < 0.05) without changing the blood pressure. The changes in beta and malondialdehyde-modified low-density lipoprotein levels were significantly correlated (rho = 0.600, p < 0.05). CONCLUSION: These results suggest that temocapril ameliorates the age-related increase in carotid arterial stiffness in healthy, normotensive elderly subjects.

Aged↗

PubMed2006

Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation.

Protease-activated receptor (PAR)-2 plays important roles in intestinal inflammatory responses. Changes in PAR-2-mediated smooth muscle function may contribute pathophysiologically to the intestinal motility disorders often observed in inflammatory bowel disease (IBD). Stimulation of PAR-2 by trypsin-induced relaxation of carbachol- and KCl-induced contractions in normal rat colonic smooth muscle was completely resolved by tissue pretreatment with apamin, but not by pretreatment with l-NMMA or a cocktail of neuronal blockers (tetrodotoxin, hexamethonium and propranolol). In colon inflamed by dextran sodium sulphate (DSS), trypsin-induced inhibitory effects were significantly reduced. Relaxation induced by SLIGRL-NH(2), a selective PAR-2-activating peptide, was also reduced in DSS-treated rat colon. However, inhibitory effects of 1-ethylbenzimidazolin-2-one, an activator of small conductance Ca(2+)-activated K(+) channel, were unaffected. Expression of PAR-2 mRNA in colonic muscularis externa was significantly lower in DSS-treated rats than in control rats. These results suggest that the PAR-2 mediated relaxation system in colonic smooth muscle is suppressed in this experimental colitis rat model, and may contribute to motility disorders in IBD.

Animals↗

PubMed2006

Effects of ascorbic acid on ambulatory blood pressure in elderly patients with refractory hypertension.

The increased production of reactive oxygen species plays a role in the etiology of hypertension, but the effects of antioxidants on blood pressure are controversial. However, antioxidants possibly lower blood pressure in elderly patients with hypertension, because vascular aging is also closely related to oxidative stress. Effects of chronic treatment with ascorbic acid (CAS 50-81-7; 600 mg/day for 6 months) on blood pressure and levels of C-reactive protein, 8-isoprostane, and malondialdehyde-modified low-density lipoproteins were examined in elderly patients (n = 12, six males/six females, age 78.3 +/- 5.0 years, mean +/- SD [range, 67 to 84 years]; elderly group) and adult patients (n = 12, five males/seven females, age 54.6 +/- 6.7 years [range, 39 to 621; adult group) with refractory hypertension. Chronic treatment with ascorbic acid markedly reduced systolic blood pressure and pulse pressure in ambulatory blood pressure monitoring in the elderly group (from 154.9 +/- 21.6 to 134.8 +/- 19.7 mmHg, p < 0.001; and from 79.1 +/- 22.1 to 63.4 +/- 18.7, p < 0.05; respectively), which was accompanied by an increase in the serum levels of ascorbic acid and decreases in the levels of C-reactive protein, 8-isoprostane, and malondialdehyde-modified low-density lipoproteins. In contrast, ascorbic acid did not affect blood pressure in the adult group. These results suggest that ascorbic acid is useful for controlling blood pressure in elderly patients with refractory hypertension.

Adult↗

PubMed2006

Pulmonary sarcoidosis and antiphospholipid syndrome.

Various autoimmune diseases have been reported to occur in patients with sarcoidosis. However, coexistence of sarcoidosis and antiphospholipid syndrome (APS) is extremely rare. We describe a 59-year-old female patient with pulmonary sarcoidosis who had preceding APS. Her previous medical history consisted of a miscarriage and ischemic colitis. She was diagnosed as APS during the onset of a brainstem infarction with positive reaction to beta2-glycoprotein I-dependent anticardiolipin antibody. Two years later, chest CT revealed enlargement of the hilar and mediastinal lymph nodes and small nodules in the lung fields. Transbronchial lung biopsy demonstrated non-caseating epithelioid cell granuloma leading to the diagnosis of definite pulmonary sarcoidosis. This is the first APS case where pulmonary involvement with sarcoidosis has been confirmed through lung biopsy. Our case report suggests that APS should be recognized as an accompanying disorder of sarcoidosis.

Ambulatory Care Facilities↗

PubMed2006

Vasoconstrictor administration during cardiopulmonary bypass affects acid-base balance in infants and children.

BACKGROUND: In experimental reports, blood flow redistribution occurred during cardiopulmonary bypass (CPB) and perfusion pressure was restored by vasoconstrictor administration without improving splanchnic perfusion. The influence of vasoconstrictor administration during CPB was clinically examined. MATERIALS AND METHODS: Twenty-two consecutive pediatric CPB cases of ventricular septal defect without blood transfusion were divided into two groups, depending upon whether a vasoconstrictor was administered during CPB or not (n = 7 vs. 15). Bypass flow and systemic perfusion pressure during CPB were maintained at 2.5 L/m(2)/min and not lower than 30 mm Hg by vasoconstrictor administration, respectively. RESULTS: Although preoperative state and CPB conditions were comparable between the two groups, more sodium bicarbonate was administered (P < 0.05); duration from the operation to extubation was longer (P < 0.05); and bowel movement occurred later in the vasoconstrictor-administered group than in the control group. CONCLUSIONS: Vasoconstrictor administration during CPB may deteriorate the acid-base balance and the postoperative state in infants and children.

Acid-Base Equilibrium↗

PubMed2006

A reduced priming system.

Cardiopulmonary bypass (CPB), an integral part of valve surgery, is known to cause hemodilution, which can lead to a need for blood transfusion as well as a systemic inflammatory reaction. Our aim was to evaluate a reduced priming (RP) system for CPB with regard to clinical outcomes in patients undergoing valve surgery. Eleven patients were assigned to the new system with an RP volume. The RP system allowed for reduced hemodilution and a possible reduction in the necessity for blood transfusions.

Adult↗

PubMed2006

Effects of audience awareness on procedural text writing.

Effects of audience awareness were examined. Some participants acted as writers and the others acted as readers. Writers wrote a text describing a geometrical figure. Readers read the text and tried to draw the figure according to the description. In Exp. 1, audience awareness was manipulated among undergraduate students, 11 men and 34 women. Writers in the high audience-awareness condition spent more time planning and writing texts than writers in the low audience-awareness condition. Texts in the high audience-awareness condition consisted of more letters and sentences with descriptions elaborating the texts. In Exp. 2, prototype texts were constructed based on the results of Exp. 1. Undergraduate students, 11 men and 47 women, who read the prototype text in the high audience-awareness condition could draw the figure more accurately. In Exp. 3, effects of feedback from readers were examined. Ninth-grade students, 22 boys and 34 girls, participated as writers and 7th-grade students, 22 boys and 34 girls, participated as readers. Merely being told to attend to an audience did not improve the quality of texts written by 9th-grade students. However, feedback from the readers who were 7th-grade students was effective. Writers could revise the texts appropriately according to feedback and improve the quality of texts. In addition, the experience of revising the text according to feedback transferred to later writing. Educational implications of the results are discussed.

Adult↗

PubMed2006

[Childhood Graves' disease].

Because of the low frequency of childhood Graves' disease, detailed evidence-based clinical studies have not been reported. Practical clinical work has been performed on the basis of adult clinical references. Therapeutic management includes antithyroid drugs, surgical thyroidectomy and radiologic therapy. Recently in the U.S.A. radiotherapy has become the recommended course of action, even for childhood Graves' disease, whereas in Japan, antithyroid drug therapy is the primary course of action for childhood Graves' disease. In some cases, thyroidectomy is performed following drug therapy. Methimazole (MMI) and propylthiouracil (PTU) have been used, however, MMI is the preferred drug treatment. Compared to PTU, MMI is administered once a day and the frequency of side effects is lower than that of PTU. Evaluation of the TSH receptor antibody value before administration of antithyroid drugs is very useful in estimating the duration of the treatment. No appropriate index has been established guiding when to quit antithyroid drug therapy.

Antithyroid Agents↗

PubMed2005

Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells.

A potential role for 1-oleoyl-sn-glycero-3-phosphate or lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) in the regulation of malignant diseases has been widely considered. In this study, we found that in transformed astroglial cells, the expression profile of lysophospholipid receptor mRNA and the action modes of LPA and S1P on cell motility were changed: there was a change in the acquisition of the ability of LPA to stimulate cell migration and a change in the migratory response to S1P from stimulation through S1P(1) to inhibition through S1P(2). LPA-induced cell migration was almost completely inhibited by either pertussis toxin, LPA(1) receptor antagonists including Ki16425 (3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfonyl)propanoic acid) or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin. The LPA-induced action was also suppressed, although incompletely, by several specific inhibitors for intracellular signaling pathways including Rac1, Cdc42, p38 mitogen-activated protein kinase (p38MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase. Nearly complete inhibition of migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Rac1 suppressed JNK but not p38MAPK, while the activity of p38MAPK was abolished by a dominant-negative form of Cdc42. These findings suggest that, in glioma cells, the PI3K/Cdc42/p38MAPK and PI3K/Rac1/JNK pathways are equally important for LPA(1) receptor-mediated migration.

Animals↗

PubMed2005

Sphingosylphosphorylcholine antagonizes proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1)-mediated inositol phosphate production and cAMP accumulation.

Ovarian cancer G-protein-coupled receptor 1 (OGR1), previously proposed as a receptor for sphingosylphosphorylcholine (SPC), has recently been identified as a proton-sensing or extracellular pH-responsive G-protein-coupled receptor stimulating inositol phosphate production, reflecting the activation of phospholipase C. In the present study, we found that acidic pH stimulated cAMP accumulation, reflecting the activation of adenylyl cyclase, in addition to inositol phosphate production in OGR1-expressing cells. The cAMP response was hardly affected by the inhibition of phospholipase C. SPC inhibited the acidification-induced actions in a pH-dependent manner, while no OGR1-dependent agonistic action of SPC was observed. Thus, the dose-response curves of the proton-induced actions were shifted to the right in the presence of SPC regardless of stereoisoform. The antagonistic property was also observed for psychosine and glucosylsphingosine. In conclusion, OGR1 stimulation may lead to the activation of adenylyl cyclase in addition to phospholipase C in response to extracellular acidification but not to SPC. However, SPC and related lysolipids antagonize the proton-induced and OGR1-mediated actions.

Adenylyl Cyclases↗