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Y Sakata

Publications and source records attributed to Y Sakata.

At least 55 records · Page 3Linked to original sources
PubMed2001

cDNA array hybridization reveals cardiac gene expression in acute ischemic murine hearts.

PURPOSE: Although cDNA array technique has recently become available in the cardiovascular field, it has not yet been established what kind of genes in the myocardium are expressed by acute ischemia. Since many substances contribute to the pathophysiology of acute ischemic hearts, we investigated transcription responses of murine hearts to ischemia using cDNA array representing 18,376 genes. METHODS AND RESULTS: In 29 male mice, we ligated the proximal site of the left coronary artery for 60 min. In 14 mice, we performed the sham operation without the ligation of the left coronary artery. After 60 min, the hearts were excised to obtain mRNA, and we performed cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10-fold, 11 known genes were upregulated 5.0- to 9.9-fold, and 32 unknown genes were upregulated over 5.0-fold compared to sham-operated controls. In contrast, 11 known genes and 7 unknown genes were downregulated to levels below 0.2-fold. For 9 of the 13 known genes of which expression was increased as analyzed by cDNA array, subsequent Northern blot analysis also revealed an increase in expression. CONCLUSION: Using cDNA array analysis we found that cardiac expression of 24 known and 39 unknown genes was modulated by acute ischemic stress, and appeared to be related to the pathophysiology of ischemic hearts. These results show that cDNA array analysis may provide a new molecular insight to the pathophysiology of acute ischemic hearts.

Animals↗
PubMed2001

Benidipine, a long-acting Ca channel blocker, limits infarct size via bradykinin- and NO-dependent mechanisms in canine hearts.

Amlodipine increases NO levels in coronary vessels and aorta via bradykinin-dependent mechanisms in vitro. We have previously reported that a long-acting Ca channel blocker, benidipine, increases cardiac NO levels in ischemic canine hearts, suggesting that benidipine may also protect against ischemia and reperfusion injury via bradykinin- and NO-dependent mechanisms. We examined this possibility. In open chest dogs, the left anterior descending coronary artery was perfused with blood through a bypass tube and was occluded for 90 min followed by 6 hours of reperfusion. Infarct size was assessed by TTC staining at 6 hours of reperfusion. When benidipine doses of 50, 100, and 200 ng/kg/min were infused via the bypass tube between 10 min prior to the onset of ischemia and after 60 min of reperfusion, systemic blood pressure did not change significantly. Infarct size decreased with the administration of benidipine (50, 100, and 200 ng/kg/min) when compared to the untreated condition (24.8+/-2.5, 17.3+/-3.1, and 16.5+/-2.0 vs. 43.4+/-5.6%, respectively) associated with the increased release of NO and bradykinin in the coronary venous blood upon reperfusion. Myeloperoxidase activity of the myocardium increased after 6 hours of reperfusion, which was attenuated by benidipine. The limitation of infarct size and the increase in myeloperoxidase activity were completely blunted by either L-NAME or HOE140. There were no significant differences in collateral blood flow assessed by the microsphere method after 45 min of ischemia for any of the groups. Thus, we conclude that the Ca channel blocker, benidipine, limits infarct size via bradykinin- and NO-dependent mechanisms.

Adrenergic beta-Antagonists↗
PubMed2001

Recombinant adeno-associated virus vector-transduced vascular endothelial cells express the thrombomodulin transgene under the regulation of enhanced plasminogen activator inhibitor-1 promoter.

We were able to facilitate plasminogen activator inhibitor 1 (PAI-1) promoter activity approximately by 14-fold using an enhancer element. This enhanced PAI-1 promoter has a strong basal activity, comparable to CAG promoter activity, and has a response similar to the PAI-1 promoter with respect to TGFbeta 1 and TNFalpha stimulation. The characteristics of the enhanced PAI-1 promoter are thought to be suited to timely and tissue-specific expression of anticoagulant molecules in the vascular cells. Thus, we developed recombinant adeno-associated virus (rAAV) vectors using the enhanced PAI-1 promoter and were successful in transducing vascular endothelial cells to express the thrombomodulin transgene under the regulation of the enhanced PAI-1 promoter in vitro. Thromobomodulin transgene expression driven by the enhanced PAI-1 promoter in rAAV vector-transduced cultured endothelial cells was between 600- and 1000-fold higher than constitutive thrombomodulin gene expression in cultured human umbilical vein endothelial cells and was up-regulated by TGFbeta1 and TNFalpha stimulation which may down-regulate endogenous thrombomodulin gene expression in endothelial cells. The brain vascular endothelial cells of Mongolian gerbils could also be transduced by the same rAAV vector in vivo. Transduction of endothelial cells by rAAV vectors to express enhanced PAI-1 promoter-driven transgenes may be a useful gene therapy approach for vascular diseases.

Animals↗
PubMed2001

Influence of natural and synthetic compounds on cell surface expression of cell adhesion molecules, ICAM-1 and VCAM-1.

Various natural and synthetic compounds including alkaloids, terpenoids and phenolics were tested for inhibition of the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which are crucial in the regulation of immune response and inflammation. Of 40 compounds tested, two compounds significantly downregulated the expression of VCAM-1 on murine endothelial cells (F-2) and ten compounds that of ICAM-1 on mouse myeloid leukemia cells (M1). Sanguinarine chloride (5) and isoliquiritigenin (13) were capable of lowering the levels of both ICAM-1 and VCAM-1. The structure-activity relationships study on chalcone and flavone derivatives related to 13 suggested that the inhibitory activity of the chalcone derivatives is attributable to the 4-hydroxy group as well as the possible coplanarity between the phenyl ring and the adjacent conjugated ketone.

Alkaloids↗
PubMed2001

Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green.

Indocyanine green (ICG) is a near-infrared dye that has the potential to be used as a tracer for the minimally invasive measurement of cerebral blood flow (CBF). In order to examine the technique, the arterial and cerebral concentrations of ICG were measured in newborn piglets during the bolus passage of ICG at normocapnia and two levels of mild hypercapnia. The results were analysed by applying the Fick principle in both integral and differential forms using a linear regression technique to improve the precision of calculated values of CBF. It was found that the integral method, which has been used previously, is particularly sensitive to errors in the time registration between the arterial and tissue signals whereas the differential method is less so. In addition, the differential method allows the venous outflow to be calculated which gives further information on the state of the capillary bed. CBF was 39.7 +/- 4.6 ml 100 g(-1) min(-1) at an arterial carbon dioxide tension (PaCO2) of 33.0+/-2.2 mmHg and increased to 53.7+/-9.1 and 75.4+/-15.2 ml 100 g(-1) min(-1) at a PaCO2 of 42.1 +/- 2.6 and 54.2 +/- 3.1 mmHg respectively (mean +/- SD, n = 7). There was no significant change in cerebral metabolic rate for oxygen, validating the value of blood flow to an arbitrary scaling factor. When the inspired CO2 fraction was returned to zero, calculated CBF returned to baseline with a variation of 7% of the mean, indicating that this technique is highly precise.

Animals↗
PubMed2001

Sequence analysis of fibroblast growth factor receptor 2 ( FGFR2 ) in Japanese patients with craniosynostosis.

Recently, mutations of the fibroblast growth factor receptor ( FGFR ) genes have been detected in syndromic craniosynostosis. We examined nucleotide sequences of FGFR2 in Japanese craniosynostosis patients (Crouzon syndrome: 9 cases; Apert syndrome: 6 cases; scaphocephaly: 3 cases as non-syndromic patients) by polymerase chain reaction (PCR) followed by direct sequencing methods. The results demonstrated FGFR2 heterozygous mutations at codons 252, 290 of exon 7, and at codon 342, 354 of exon 9 in Crouzon syndromes. In Apert syndrome patients, Ser252Trp and Pro253Arg were detected in five and one patients, respectively. No mutation was detected in one case of Crouzon, all cases of scaphocephaly and healthy individuals. Thus far sequence analysis of FGFR2 in syndromic craniosynostosis has been reported in many white patients, whereas in Japanese only several cases have been studied. The current study with 18 patients confirmed that a similar series of mutations occur in Japanese patients as in white patients regardless of ethnicity and environment. The frequency of the mutation was 82% (9/11 cases) in Japanese Crouzon patients. The ratio of S252W:P253R was 5 : 1 in Japanese Apert patients. Moreover, in Japanese Apert patients, complication rate of cleft palate was 60% for mutation of Ser252Trp and 0 of 2 patients for Pro253Arg, with their syndactyly score being 4.90 and 5.50, respectively.

Acrocephalosyndactylia↗
PubMed2001

Ventricular production of natriuretic peptides and ventricular structural remodeling in hypertensive heart failure.

OBJECTIVES: Brain natriuretic peptide (BNP) is a strong predictor of left ventricular (LV) hypertrophy (LVH) and dysfunction. However, our recent studies suggested that LVH is not necessarily associated with enhanced production of BNP in hypertension. This study aimed to clarify the relation of the characteristics of hypertrophy with the degree of gene expression of BNP in the developmental process of hypertensive heart failure. METHODS: Serial changes in LV geometry, histology and atrial natriuretic peptide (ANP) and BNP mRNA levels, were assessed in a hypertensive heart failure model using Dahl salt-sensitive rats (n = 24). We further studied effects of alpha1-receptor antagonist (doxazosin: 1 mg/kg per day, n = 5) and angiotensin II type 1 receptor (AT1R) antagonist (candesartan cilexetil: 1 mg/kg per day, n = 5). RESULTS: The BNP mRNA level was not elevated at the compensatory hypertrophic stage when ANP mRNA level was elevated. BNP mRNA level was increased with further progression of hypertrophy and development of fibrosis. AT1R blockade prevented such fibrosis and further progression of hypertrophy with normalization of BNP mRNA levels. Compensatory hypertrophy was not suppressed; therefore, ANP mRNA level, although decreased, was still beyond the normal level. The alpha1-receptor blockade slightly attenuated LV hypertrophy with a slight decrease in ANP mRNA levels. LV fibrosis was not prevented, and the BNP mRNA level was not decreased. CONCLUSIONS: BNP gene expression is not enhanced by initial compensatory hypertrophy, but is enhanced by LV fibrosis and late stage progression of hypertrophy dependent on AT1R-mediated signaling pathway.

Animals↗
PubMed2001

Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.

We tested whether mitochondrial or sarcolemmal ATP-sensitive K(+) (K(ATP)) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific K(ATP) channel openers) markedly limited infarct size (6.3 +/- 1.2, 8.9 +/- 1.9, and 7.2 +/- 1.6%, respectively) compared with the control group (40.9 +/- 4.1%). A selective mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 +/- 3.8, 25.1 +/- 4.6, and 19.8 +/- 5.2%, respectively). A nonspecific K(ATP) channel blocker, glibenclamide, completely abolished the effect of IP (38.5 +/- 6.2%). Intracoronary or intravenous administration of a mitochondria-selective K(ATP) channel opener, diazoxide, at >100 micromol/l could only partially decrease infarct size (19.5 +/- 4.3 and 20.1 +/- 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal K(ATP) channels independently play an important role in the limitation of infarct size by IP in the canine heart.

Adenosine Triphosphate↗
PubMed2001

Effect of heparin on activated partial thromboplastin time in patients undergoing gynecologic or obstetric surgery.

The exaggerated prolongation of the activated partial thromboplastin time (APTT) by heparin prophylaxis for postoperative thromboembolism may cause bleeding complications. We examined the effects of various doses of unfractionated heparin on the APTT in patients who underwent a gynecologic or obstetric operation. A total of 68 patients who underwent a gynecologic operation (n = 47) or a cesarean section (n = 21) with risk factors for thromboembolism received a continuous intravenous infusion of unfractionated heparin (110-285 IU/kg/day) after surgery until the patient was mobilized the next day. A group of 61 postoperative patients who did not receive heparin served as controls. The APTT was measured in these 129 patients preoperatively and on postoperative day 1. A clinical deep vein thrombosis occurred in only 1 patient, who was in the control group. No bleeding complications occurred in any patient. The percent change in the APTT was significantly correlated with the dose of heparin administered (p < 0.001). Compared with the control group, the mean APTT was not prolonged in the patients who received heparin at 110-149 IU/kg/day. It was prolonged significantly in the patients who received heparin at greater than 150 IU/kg/day. An exaggerated prolongation of the APTT, defined as an APTT greater than 150% of the preoperative value, was found in 0 of 32 patients in the 110-149 IU/kg/day group, 1 of 28 patients (3.6%) in the 150-199 IU/kg/day group and 2 of 8 patients (25%) in the 200-285 IU/kg/day group. The continuous postoperative administration of intravenous heparin at less than 200 IU/kg/day does not result in an exaggerated prolongation of the APTT.

Adult↗
PubMed2001

Differential subcellular actions of ACE inhibitors and AT(1) receptor antagonists on cardiac remodeling induced by chronic inhibition of NO synthesis in rats.

Chronic inhibition of NO synthesis induces cardiac hypertrophy independent of systemic blood pressure (SBP) by increasing protein synthesis in vivo. We examined whether ACE inhibitors (ACEIs) enalapril and temocapril and angiotensin II type-I receptor antagonists (angiotensin receptor blockers [ARBs]) losartan and CS-866 can block cardiac hypertrophy and whether changes in activation of 70-kDa S6 kinase (p70S6K) or extracellular signal-regulated protein kinase (ERK) are involved. The following 13 groups were studied: untreated Wistar-Kyoto rats and rats treated with NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), D-NAME (the inactive isomer of L-NAME), L-NAME plus hydralazine, L-NAME plus enalapril (3 mg. kg(-1). d(-1)) or temocapril (1 or 10 mg. kg(-1). d(-1)), L-NAME plus losartan (10 mg. kg(-1). d(-1)) or CS-866 (1 or 10 mg. kg(-1). d(-1)), L-NAME plus temocapril-CS866 in combination (1 or 10 mg. kg(-1). d(-1)), and L-NAME plus rapamycin (0.5 mg. kg(-1). d(-1)). After 8 weeks of each experiment, ratios of coronary wall to lumen (wall/lumen) and left ventricular weight to body weight (LVW/BW) were quantified. L-NAME increased SBP, wall/lumen, and LVW/BW compared with that of control. ACEIs, ARBs, and hydralazine equally canceled the increase in SBP induced by L-NAME. However, ACEIs and ARBs equally (but not hydralazine) attenuated increase in wall/lumen and LVW/BW induced by L-NAME. The L-NAME group showed both p70S6K and ERK activation in myocardium (2.2-fold and 1.8-fold versus control, respectively). ACEIs inactivated p70S6K and ARBs inactivated ERK in myocardium, but hydralazine did not change activation of either kinase. Thus, ACEIs and ARBs modulate different intracellular signaling pathways, inhibiting p70S6K or ERK, respectively, to elicit equal reduction of cardiac hypertrophy induced by chronic inhibition of NO synthesis in vivo.

Angiotensin Receptor Antagonists↗
PubMed2001

Effect of labor on maternal dehydration, starvation, coagulation, and fibrinolysis.

BACKGROUND: Dehydration, starvation, and enhanced blood coagulability may occur during labor. METHODS: We studied 60 women who gave birth vaginally to a healthy singleton infant at term. Sampling of urine and blood specimens was performed on admission to the hospital with labor pains and just after birth. Paired samples were available from 50 women for urine analysis and 29 women for blood analysis. Total fluid intake (oral and intravenous) during labor was recorded. Changes in various parameters in the urine and blood in relation to the total fluid intake were analyzed. RESULTS: Osmolality and creatinine concentration in the urine, red blood cell count, hemoglobin concentration, hematocrit value, thrombin-antithrombin III complex, plasmin-alpha 2-plasmin inhibitor complex and D dimer significantly increased during labor. Ketone bodies were absent in the urine in 84% (42/50) of women on admission to the hospital whereas these were present in 74% (37/50) of women just after delivery (p < 0.01). The degree of these changes appeared to be smaller with an increase in fluid intake. CONCLUSION: Concentrated urine, hemoconcentration, starvation, and activation of the thrombogenic and fibrinolytic system occur in parturient women. Sufficient fluid intake during labor may ameliorate these unfavorable changes.

Adolescent↗
PubMed2001

[Statistical observation of vertigo and dizziness patients].

Subjects visiting the Department of Otolaryngology at Suita Municipal Hospital reporting vertigo or dizziness numbered 664 women and 343 men from April 1999 to December 2000. As a city hospital, we play an important role in the diagnosis and treatment of acute vertigo or dizziness. The frequency of diagnosis of these cases was divided almost equally into 5 groups: (1) benign paroxysmal positional vertigo (BPPV) 23%; (2) suspected BPPV, 18%; (3) peripheral vestibular disorders other than BPPV, 22%; (4) disorders other than peripheral origin, 18%; and (5) undiagnosed, 19%. Based on our results, BPPV, other peripheral vestibular disorders, and disorders of other origins should be differentiated from the first screening. BPPV was most frequent and diagnosed by typical positioning nystagmus. Many other peripheral vestibular disorders were accompanied by nystagmus. It is also important to differentiate serious illnesses such as cerebrovascular disease (7%), space-occupying lesions in the posterior fossa (1.2%), and cardio-circulatory disease (3.6%).

Adult↗
PubMed2001

[Clinical features of benign paroxysmal positional vertigo].

Our understanding of the pathomechanism of benign paroxysmal positional vertigo (BPPV) has improved dramatically. A type of BPPV featuring mixed torsional and vertical nystagmus induced by the Dix-Hallpike maneuver involves the posterior semicircular canal (P-BPPV). The other type of BPPV featuring horizontal nystagmus induced by spine-to-lateral head positioning involves the horizontal canal BPPV (H-BPPV). In complaints of vertigo or dizziness, 619 patients visited our department last year. Of these, 142 (23%) was had positional nystagmus consistent with a diagnosis of BPPV, 118 (19%) had no nystagmus but were suspected of BPPV due to vertigo episodes. BPPV was the most frequent diagnosis. H-BPPV was not rare, but accounted for 30% of BPPV. Of H-BPPV, 73% featured direction changing geotropic nystagmus, and 27% direction changing apogeotropic nystagmus. H-BPPV resolved faster than P-BPPV. Most cases caused by head trauma were P-BPPV. Transition between P- and H-BPPV was found in 6 cases. Women outnumbered men by about 3 to 2 in both P- and H-BPPV. Peak incidence was found in the those in their 60s and 70s, suggesting that the etiologies of both types of BPPV are essentially the same.

Adult↗
PubMed2001

[Standard therapy of CPT-11 for colorectal cancer].

Irinotecan (CPT-11) is a potent inhibitor of topoisomerase I, and has demonstrated antitumor activity against metastatic colorectal cancer. In phase II studies, CPT-11 showed promising activity. Combining irinotecan with 5-fluorouracil (5-FU) and Leucovorin (LV) has shown benefits for patients with metastatic colorectal cancer CPT-11/5-FU/LV therapy is considered as a standard therapy. Weekly or biweekly administration of CPT-11 is most recommended.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Calcineurin inhibitor attenuates left ventricular hypertrophy, leading to prevention of heart failure in hypertensive rats.

BACKGROUND: There is controversy regarding the contribution of calcineurin activation to the development of pressure-overload left ventricular (LV) hypertrophy and heart failure. The aim of this study was to explore whether the inhibition of calcineurin may prevent the transition to heart failure in hypertensive rats and, if so, to clarify in which developmental stage of LV hypertrophy calcineurin plays a key role. METHODS AND RESULTS: Dahl salt-sensitive rats placed on an 8% NaCl diet from the age of 7 weeks (hypertensive rats) were randomized to no treatment (n=6) or treatment with the calcineurin inhibitor FK506 (1 mg x kg(-1) x d(-1)) from 8 weeks (FKE, n=7) or from 17 weeks (FKL, n=7). Rats placed on a 0.3% NaCl diet were defined as control rats (n=6). The administration of FK506 from 8 weeks attenuated, although it did not block, LV hypertrophy observed in the untreated rats and prevented the transition to heart failure. The development of LV fibrosis, however, was not attenuated by the administration of FK506 from 8 weeks. The administration of FK506 from 17 weeks brought no benefit for cardiac remodeling or LV function and failed to prevent heart failure. CONCLUSIONS: Calcineurin inhibition, if started from the initial stage of pressure overload, attenuated the development of LV hypertrophy without any effect on LV fibrosis and prevented the transition to heart failure. The activation of calcineurin is involved in the development of LV hypertrophy but not of LV fibrosis, and this involvement may be crucial at the initial stage.

Animals↗