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Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hmg-CoA reductase inhibitor modulates monocyte-endothelial cell interaction under physiological flow conditions in vitro: involvement of Rho GTPase-dependent mechanism.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been reported to exert actions independent of their lipid-lowering effects. To critically assess the effects of statins on monocyte-endothelial cell interactions, we used an in vitro model that mimicked physiological flow conditions. Monocytic U937 cells were incubated in the presence of cerivastatin for 48 hours. Adhesive interactions of statin-treated U937 cells were then analyzed by use of activated (interleukin-1beta 10 U/mL, 4 hours) human umbilical vein endothelial cells in an in vitro flow apparatus. Flow cytometric analysis of adhesion molecules and measurement of F-actin content in U937 cells were performed before and after statin treatment. Preincubation with cerivastatin significantly decreased U937 firm adhesion to activated human umbilical vein endothelial cells, whereas U937 rolling was not decreased. Fluorescence-activated cell sorter analysis revealed downregulation of U937 surface expression of CD11a, CD18, and VLA4 after statin treatment. Cerivastatin significantly reduced F-actin content in U937 cells and inhibited RhoA translocation, whereas preincubation with C3 exoenzyme reduced U937 adhesion under flow. Cerivastatin reduces monocyte adhesion to vascular endothelium under physiological flow conditions via downregulation of integrin adhesion molecules and inhibition of actin polymerization via RhoA inactivation. Our findings have important implications for the lipid-independent effects of statins.

ADP Ribose Transferases↗
PubMed2001

Polymorphic ventricular tachycardia in patients with vasospastic angina--clinical and electrocardiographic characteristics and long-term outcome.

There have been few clinical studies exploring the characteristics of spontaneous polymorphic ventricular tachycardia (VT) during a vasospastic angina attack. During a 4-year recruitment period, Holter ECG recordings were monitored for 42+/-24 h during a drug-free period in 60 consecutive patients with vasospastic angina (VSA) and of these, 8 patients had at least one episode of polymorphic VT during monitoring. Ischemic ST segment elevation was immediately preceded the spontaneous polymorphic VT in all 8 patients, 4 of whom had silent coronary vasospasm. Immediately before the onset of polymorphic VT, both R-on-T and long-short sequences were observed in 4 of the 8 patients and ST wave alternans were recorded in 2 patients. VT exhibited a pattern of torsade de pointes in 4 of the 8 patients. Five patients underwent electrophysiologic testing during a drug-free asymptomatic phase, and polymorphic VT was induced in 2 of the 5 patients, with one developing ventricular fibrillation. During a follow-up period of 73+/-17 months, there was a significant difference in the incidence of sudden death between patients with and without VT (2/8 cases [25%] vs 0/52 [0%]; p<0.01). Thus, vasospastic attacks, even if asymptomatic, that immediately precede the development of polymorphic VT may be associated with a repolarization abnormality and an increased risk of sudden death.

Acetylcholine↗
PubMed2001

Left ventricular apical aneurysm in cardiac sarcoidosis.

A 53-year-old woman was hospitalized for general fatigue and palpitations. An electrocardiogram showed ST elevation and T wave inversion in leads II, III, aVF, and V4-6. Cardiac catheterization was performed since the echocardiogram demonstrated the existence of a left ventricular apical aneurysm. Left ventriculography showed an aneurysm of the apex. An endomyocardial biopsy specimen from the left ventricular apical wall demonstrated typical noncaseating granulomas with giant cells. The patient was diagnosed as having cardiac sarcoidosis. There was no evidence suggesting involvement of other systemic organs. Cardiac sarcoidosis should be considered within a spectrum of diseases that cause left ventricular aneurysm.

Cardiomyopathies↗
PubMed2001

Fluid shear stress suppresses interleukin 8 production by vascular endothelial cells.

The effects of shear stress on interleukin 8 (IL-8) production by human umbilical vein endothelial cells (HUVEC) were studied by subjecting the HUVEC to a steady flow laminar shear stress of up to 0.7 N/m(2) in a parallel plate flow chamber. Shear stress decreased IL-8 mRNA expression in a dose and time-dependent fashion. High glucose concentrations increased IL-8 mRNA levels in a MAPK-p38-dependent manner, which was suppressed by shear stress. Measurement of IL-8 protein in HUVEC culture media by ELISA demonstrated that IL-8 secretion was also increased by high glucose and suppressed by shear stress. These results suggest that the anti-atherogenic effect of shear stress arises partly from the suppression of the production of IL-8 which has been shown to trigger the adhesion of monocytes to a vascular endothelium and also acts as a mitogen and chemoattractant for vascular smooth muscle cells.

Arteriosclerosis↗
PubMed2001

Regional wall motion abnormalities during early diastole in patients with hypertensive left ventricular hypertrophy: a Doppler tissue echocardiographic study.

To investigate left ventricular wall motion asynchrony in patients with hypertensive heart disease, we measured regional myocardial velocity in hypertensive patients with left ventricular hypertrophy and in normotensive individuals using tissue Doppler imaging. The endocardial velocity and the myocardial velocity gradient were measured in the basal and mid segments of the septal and posterior walls. The dilating velocity of the left ventricular cavity were determined for the basal and mid ventricular segments of left ventricle. The peak myocardial velocity gradient was significantly lower in the hypertensive group than in the control group for all regions. The peak endocardial velocity during early diastole in the mid ventricular septum was significantly lower in the hypertensive group (Hypertensive vs Controls; 3.8 +/- 1.3 vs 5.1 +/1.6 cm/s, P < 0.05), whereas the peak endocardial velocity at the other three sites were similar in the two groups. The peak dilating velocity was significantly lower in the hypertensive group only in the mid portion of the left ventricle (Hypertensive vs Controls; 7.2 +/- 2.4 vs 9.8 +/- 1.3 s(-1), P < 0.005). These results suggest that there were regional wall motion abnormalities and nonuniformity during the early diastolic phase in the hypertensive hearts with left ventricular hypertrophy.

Blood Flow Velocity↗
PubMed2000

Mapping of the HLA-linked genes controlling the susceptibility to Takayasu's arteritis.

To further define the HLA-linked genes controlling the susceptibility to Takayasu's arteritis, polymorphisms in five microsatellites around the HLA-B and MICA genes, C1-2-A, MIB, C1-4-1, C1-2-5, and C1-3-1, were investigated in 91 Japanese patients with Takayasu's arteritis and 248 healthy Japanese controls. It was found that allele 238 of C1-2-A [60.4% in patients vs. 29.8% in controls, odds ratio (OR)=3.59, P(c)<0.000004], allele 332 of MIB (22.0% vs. 6. 1%, OR=4.32, P(c)<0.0003), allele 208 of C1-2-5 (47.3% vs. 24.6%, OR=2.75, P(c)=0.001), and allele 291 of C1-3-1 (62.6% vs. 44.8%, OR=2.07, P(c)<0.02) were significantly associated with the disease. Combined analyses of polymorphisms in the HLA-B and MICA genes with those in the microsatellites suggest that there are two different disease-susceptible loci for Takayasu's arteritis; one is mapped near the C1-2-A locus and the other is more closely linked to the HLA-B gene than to the MICA gene, because there are at least two different disease-associated HLA-B haplotypes, HLA-B*52 and -B*39.2 haplotypes, in which the disease-associated C1-2-A allele is shared in common.

Alleles↗
PubMed2000

Surgical technique for management of Takayasu's arteritis.

Anastomotic aneurysm may occur after surgical treatment of Takayasu's arteritis. We describe a surgical technique designed to prevent this problem. The technique includes a bypass from a donor artery to a nondiseased distal artery, reinforcement of the suture line to prevent stretching or expansion at the anastomoses, and minimization of inflow perfusion to the brain. The technique was used in two patients, whose grafts were patent 1 and 2 years, respectively, after surgery. Careful differential diagnosis is essential to the success of this method, which may also be used to treat aortic aneurysm resulting from Behcet's disease but which is not appropriate for mid-aortic syndrome or Buerger's disease.

Adult↗
PubMed2000

Vasa vasoritis, vasculitis and atherosclerosis.

Takayasu arteritis, Buerger's diseases, temporal arteritis, vascular Behcet disease and inflammatory abdominal aortic aneurysm are classified in Japan as intractable vasculitides involving mainly large vessels, because their etiologies are not yet elucidated and, therefore, treatments for them were not yet established. Recent experimental and vascular biological studies, however, have focussed on the roles of virus infection in vasa vasorum (vasa vasoritis) and on the subsequent inflammatory vascular changes through HLA and/or other autoimmune mechanisms. Several studies including ours have demonstrated that these vascular inflammatory changes progress from the adventitial side to the intimal side of the vessel, finally complicating atherosclerotic changes in the intima. These vascular inflammatory changes are also recognized during progression of atherosclerosis and these observations strongly suggest that inflammation is a serious risk factor of atherosclerosis.

Arteriosclerosis↗
PubMed2000

Repression of TNF-alpha-induced E-selectin expression by PPAR activators: involvement of transcriptional repressor LRF-1/ATF3.

Peroxisome proliferator-activated receptor (PPAR) activators were shown to inhibit the expression of E-selectin of human vascular endothelial cells in response to tumor necrosis factor-alpha (TNF-alpha). Troglitazone, pioglitazone, alpha-clofibrate, and 15-deoxy-Delta12,14-prostaglandin J2 all inhibited the TNF-alpha-stimulated E-selectin gene transcription in reporter assay. To further clarify the underlying transcriptional regulation, nuclear factor(s) that binds to the nuclear factor-endothelial leukocyte adhesion molecule 1 (NF-ELAM1) site of the E-selectin gene promoter was investigated. The activators caused a significant induction of liver regenerating factor 1 (LRF1)/activating transcription factor 3 (ATF3), which bound to the NF-ELAM1 site and repressed the TNF-alpha-induced E-selectin gene expression. From these data, the effect of PPAR activators was mediated, in part, through the induction of LRF1/ATF3. This might provide a novel molecular mechanism of anti-inflammatory effect of PPAR activators.

Activating Transcription Factor 3↗
PubMed2000

Transforming growth factor-beta(1) restores antiplatelet function of endothelial cells exposed to anoxia-reoxygenation injury.

Transforming growth factor-beta(1) released from platelet alpha-granules may preserve endothelial functions in injured vessels. However, direct evidence is lacking regarding how this cytokine modifies the antithrombotic function of injured endothelial cells. We performed an in vitro study to investigate the effects of transforming growth factor-beta(1) on platelet functions in the presence of cultured endothelial cells exposed to anoxia-reoxygenation injury. Cultured bovine aorta endothelial cells were placed in an anoxic chamber (0.5% O(2), 5% CO(2)) for 60 minutes followed by a 90-minute reoxygenation. Collagen (2 microg/mL)-induced platelet aggregation (10(8) platelets/mL), as determined by impedance aggregometry, was potently inhibited in the presence of control endothelial cells (17.4+/-3.3 Omega) at a concentration of 5x10(4) cells/mL, as compared to their absence (68. 2+/-2.2 Omega). Inhibition of platelet aggregation was attenuated in endothelial cells exposed to anoxia-reoxygenation (54.6+/-2.5 Omega). However, preincubation of endothelial cells with transforming growth factor-beta(1) (1.0 ng/mL) for 16 hours partially recovered the inhibitory capability of platelet aggregation by injured endothelial cells (40.6+/-3.8 Omega). Cell viability, confirmed by a trypan blue dye exclusion test, was similar (93-96%), including control, 1.0 ng/mL transforming growth factor-beta(1)- and/or anoxia-reoxygenation-pretreated cells. The capability of platelet inhibition was restored when the endothelial cells were preincubated for 4 hours or more. Restoration of antiplatelet capacity in endothelial cells by transforming growth factor-beta(1) was suggested to be due to several mechanisms, including an increase in nitric oxide synthase activity, up-regulation of prostacyclin release, and restoration of adenosine triphosphate diphosphohydrolase activity, which was attenuated by anoxia-reoxygenation pretreatment. In summary, transforming growth factor-beta(1) released from activated platelets may play a compensatory role in the preservation of endothelial functions to inhibit platelet activation.

Animals↗
PubMed2000

Takayasu arteritis: diagnosis with breath-hold contrast-enhanced three-dimensional MR angiography.

The purpose of the study was to determine the diagnostic accuracy of breath-hold contrast-enhanced three-dimensional (3D) magnetic resonance (MR) angiography in Takayasu arteritis. Thirty patients suspected of having Takayasu arteritis were examined with MR angiography and conventional angiography. Takayasu arteritis was diagnosed in 20 of these patients. MR angiography was performed using a 1.5-T system after bolus injection of 0.1 mmol/kg of gadodiamide. MR angiography clearly depicted various vascular lesions in the aorta and its major branches in all 20 patients with Takayasu arteritis. It also depicted pulmonary artery lesions in 10 (50%) of the 20 patients. MR angiography accurately depicted 323 (98%) of 330 arteries, but 7 (2%) stenotic arteries were overestimated as occluded. The sensitivity and specificity of MR angiography for the diagnosis of Takayasu arteritis were both 100%. Breath-hold contrast-enhanced 3D MR angiography clearly depicts various vascular lesions in both the systemic and pulmonary arteries in Takayasu arteritis, thus allowing a definitive diagnosis of Takayasu arteritis.

Adult↗
PubMed2000

Influence of stent design on the immediate and long-term outcome after coronary stent implantation: a comparison of sinusoidal-ring and tube stents.

To evaluate the influence of stent design on the immediate and long-term outcome after coronary stent implantation, we retrospectively reviewed 151 patients (170 lesions) who underwent coronary stent implantation. The patients were divided into two groups according to the stent design, namely, the sinusoidal-ring group (GFX stent and AVE S670 stent; 64 patients, 66 lesions) and the tube group (Multi-Link stent and NIR stent; 87 patients, 104 lesions). The indication for coronary stent implantation was only provisional and additional stenting was considered in the presence of suboptimal results (residual stenosis >30%) or of a large dissection after balloon angioplasty. Angiographically confirmed success was achieved in all patients. No major adverse cardiac events were documented in either group during the hospitalization period. There were no cases of death nor of Q-wave myocardial infarction in either group during the follow-up period. The restenosis and target lesion revascularization (TLR) rates were 24.1% and 15.3% in the sinusoidal-ring group, and 20.2% and 12.6% in the tube group. respectively. The restenosis and TLR rates were similar in both groups. In conclusion, an influence of stent design on the immediate and long-term outcome after coronary stent implantation was not observed using sinusoidal-ring and tube stents.

Aged↗
PubMed2000

Effects of acidosis and NO on nicorandil-activated K(ATP) channels in guinea-pig ventricular myocytes.

1. Nicorandil is a hybrid compound of K(+) channel opener and nitrate. We investigated a possible interaction of acidosis and nitric oxide (NO)-donors on the nicorandil-activated ATP-sensitive K(+) channel (K(ATP)) in guinea-pig ventricular myocytes using the patch-clamp technique. 2. In whole-cell recordings, external application of 300 microM nicorandil activated K(ATP) in the presence of 2 mM intracellular ATP concentration ([ATP](i)) at external pH (pH(o)) 7. 4, but the activated current was decreased by reducing pH(o) to 6.5 - 6.0. 3. Single-channel recordings of inside-out patches revealed decreased open-state probability (P(o)) of K(ATP) activated by nicorandil with reducing internal pH (pH(i)) from 7.2 to 6.0, whilst the channel activity increased at low pH(i) in the absence of nicorandil. 4. Application of NO donors, 1 mM-sodium nitroprusside (SNP) or -NOR-3 to the membrane cytoplasmic side at pH(i) 7.2 increased the channel activity but decreased it at pH(i) 6.5 - 6.0. Neither removal of the drugs nor application of NO-scavengers reversed depression of channel activity induced by NO-donors. 5. We conclude that an increase in pH(o) and pH(i) depresses rather than stimulates the nicorandil-activated K(ATP). Since NO-donors at low pH(i) exhibited a similar trend, involvement of H(+) and NO interaction can be considered as a mechanism of decreased K(ATP) activated by nicorandil.

Acidosis↗
PubMed2000

Decreased left ventricular contractility reserve in patients with never-treated essential hypertension.

1. Left ventricular diastolic dysfunction is often present in patients with essential hypertension. To determine whether left ventricular systolic function is normal or subnormal, we evaluated the global left ventricular contractile reserve in patients with untreated essential hypertension. 2. Thirty-one untreated men with essential hypertension and 12 normotensive healthy men were evaluated. Hypertensives were divided into two groups based on the presence (group Hc; n = 21) or absence (group Hn; n = 10) of concentric left ventricular geometric remodelling, which was defined as a relative wall thickness > or = 0.45 on M-mode echocardiography. We compared echocardiographic data of left ventricular function in hypertensive men with those in healthy men under beta-adrenoreceptor activation by up to 10 microg/kg per min dobutamine infusion. 3. At baseline, endocardial (eFS) and midwall fractional shortening of the left ventricle, the early peak filling velocity (E), the peak late filling velocity (A) and the ratio E/A were similar in the three groups. During dobutamine infusion, eFS was significantly lower in groups Hc and Hn (54.1+/-9.2 and 54.1+/-7.9%, respectively) than that observed in group N (61.7+/-7.4%). In addition, eFS was highly correlated with circumferential end-systolic wall stress (ESS) during dobutamine infusion in the three groups. In 11 subjects in group Hc (52%), the eFS-ESS relationship was lower than the 95% confidence limit of the normal regression. Comparing group Hc with groups N and Hn, it was found that E (0.52+/-0.12, 0.71+/-0.16 and 0.63+/-0.15 m/s, respectively) and E/A (0.74+/-0.23, 1.24+/-0.53 and 0.98+/-0.37, respectively) were significantly lower. 4. Our results suggest that, in addition to diastolic dysfunction, the reserve of systolic function decreased under beta-adrenoceptor activation in patients with essential hypertension.

Adrenergic beta-Agonists↗
PubMed2000

Expression of apolipoprotein B-100 in isolated human small intestine epithelium.

Apolipoprotein B-48 (apoB48) is synthesized in the small intestine and becomes a component of chylomicrons (CM). Apolipoprotein B-100 (apoB100) is synthesized in liver and becomes a component of both very low density lipoprotein (VLDL) and low density lipoprotein (LDL). To evaluate whether apoB100 is present in the human small intestine, we performed immunohistochemical staining using anti-apoB100 monoclonal antibody (mAb). Jejunal samples stained positive and the granular staining was noted in the supranuclear region of epithelial cells. We also identified apoB100 expression in the epithelial cells by immunoblotting and dot-blotting of PCR-amplified cDNA. In order to exclude submucosal stroma contaminated with blood, we used isolated epithelium from human small intestine obtained by a crypt isolation technique. The results indicate that not only apoB48, but also apoB100 are expressed in human small intestine epithelium. The expression of apoB100 suggests that the dietary VLDL may be synthesized in human small intestine epithelium and converted into LDL, which might play an important role in atherosclerosis.

Apolipoprotein B-100↗
PubMed2000

Ibudilast modulates platelet-endothelium interaction mainly through cyclic GMP-dependent mechanism.

3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast) has been widely used in Japanese clinics for its antiasthmatic and antithrombotic effects. We investigated the mechanisms involved in the antiplatelet effects of the agent, specifically focusing on platelet-endothelium interaction. Ibudilast inhibits both phosphodiesterase (PDE) 3 and 5, the two major PDE isoforms of human platelets, with an IC50 of 31 and 2.2 microM, respectively. Cyclic guanosine monophosphate (GMP) accumulation in washed human platelets exposed to ibudilast alone increased significantly only at high concentrations of the agent (100 microM), whereas > or = 1 microM ibudilast enhanced cyclic GMP levels in the platelets cocultured with bovine aorta endothelial cells (ECs). In contrast, ibudilast enhanced cyclic AMP accumulation only at 100 microM, either with or without ECs. The synergistic effect of ibudilast and EC on cyclic nucleotide accumulation also was demonstrated by the inhibitory capability of the drug and the cells on platelet aggregation. The synergism between ibudilast and aspirin-pretreated ECs was more pronounced than that between ibudilast and N(omega)-nitro-L-arginine (L-NNA)-pretreated ECs. Ibudilast affected neither ATP diphosphohydrolase activity nor NO release from EC up to a concentration of 10 microM. We conclude that ibudilast exhibits antiplatelet properties mainly by inhibiting PDE5 to potentiate antiplatelet function of endothelium-derived NO.

Animals↗