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Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 55 records · Page 3Linked to original sources
PubMed2000

Factors determining clockwise and counterclockwise conduction patterns in atrial reentrant tachycardias: a rabbit model of atrial flutter.

INTRODUCTION: In the development of atrial flutter due to reentry, the crista terminalis is supposed to pose a conduction barrier, but the role of its longitudinal conduction in determining the propagation pattern of the reentrant impulse is not known. In rabbit right atrial preparations, we induced reentrant atrial tachycardias and examined the effects of transverse section of the crista terminalis on the development and conduction patterns of arrhythmias. METHODS AND RESULTS: Right atrial preparations from 12 albino rabbits were placed endocardial surface down in a chamber with an array of 48 bipolar electrodes to draw activation maps. A single premature stimulus was delivered to induce tachycardias at the free wall. In the control, five instances of tachycardia per preparation were induced and another five were induced after cutting the crista terminalis. In the control, the mean duration of tachycardia was 127.1+/-25.2 seconds. The tachycardia was counterclockwise in 39 of 60 instances, clockwise in 12, and undetermined in 4 defined as "atypical." After transverse section of the crista terminalis, the duration was prolonged to 372.6+/-30.4 seconds, but the conduction patterns were not changed. In the free wall, counterclockwise reentry had a broader wavefront and faster conduction than clockwise reentry. CONCLUSION: Longitudinal conduction block at the crista terminalis contributed to maintenance of reentrant atrial tachycardias, but had no influence on their propagation patterns. Clockwise and counterclockwise rotation of impulses in reentrant tachycardias had different paths and velocities of the wavefront in the free wall of the right atrium.

Animals↗
PubMed2000

Inflammation and atherosclerosis. Atherosclerotic lesions in Takayasu arteritis.

Takayasu arteritis is a chronic vasculitis, mainly involving the aorta and its main branches as well as the coronary and pulmonary arteries, causing stenosis and/or obstruction due to thrombus formation or dilatation due to aneurysmal formation and/or rupture of the involved arteries. These characteristic anomalies resulted from ischemia of retinal arteries due to the obstruction of cervical vessels. In Western countries this disease is also known as "pulseless disease," because the pulse is frequently absent due to the obstruction of subclavian or branchial arteries. The pathogenesis of this morbid condition is still unknown. Epidemiologically, it is found mostly in female patients and is more prevalent in Asian and Latin American countries. Affected areas consist of a mixture of both active, productive inflammatory lesions, and old fibrous lesions. Autoimmune processes stimulated by viral infection and other unknown causative factors may play an important role under these pathophysiological conditions because HLA analysis revealed a statistically significant high frequency of haplotype A24-B52-DR2 in these patients in Japan. Documentation of atherosclerotic complications in young female patients with Takayasu arteritis who are generally free from traditional atherosclerosis risk factors may be clinical evidence that inflammation is indeed an important risk factor in atherogenesis.

Arteries↗
PubMed2000

Differentiation-induced transmigration of HL60 cells across activated HUVEC monolayer involves E-selectin-dependent mechanism.

The leukocyte-endothelial adhesive interaction is one of the key mechanisms during inflammation. The human promyelocytic cell line HL60 has been used in a number of studies to characterize leukocyte-endothelial interactions, especially selectin-mediated adhesion. HL60 also has been used in studies to characterize the myeloid cell function during differentiation. In this study, we investigated the adhesive interactions of HL60 to vascular endothelium, either in its undifferentiated state or after dimethylsulfoxide-induced granulocytic differentiation. Granulocytic differentiation of HL60 cells significantly enhanced their transmigration across cytokine-activated (IL-1 beta 10 U/ml, 4 h) HUVEC monolayer. Interestingly, this enhanced transmigration of differentiated HL60 cells was inhibited by pretreatment of the monolayers with anti-E-selectin mAb as well as anti-ICAM-1 mAb or anti-VE-cadherin mAb, suggesting a potential role for E-selectin in transendothelial migration. Further study of this enhanced transmigration mechanism may elucidate the regulation of selectin-mediated leukocyte-endothelial interactions.

Antibodies, Monoclonal↗
PubMed2000

Construction of recombinant adenoviral vector of annexin II.

Annexin II is a member of the annexin family of calcium-dependent phospholipid binding proteins expressed in vascular endothelium. Recently this molecule was reported to play a role in control of fibrinolysis on the endothelial surface. To examine the role of annexin II in vascular endothelium critically, we developed a recombinant adenoviral vector containing the annexin II cDNA. A full-length annexin II cDNA was inserted into a shuttle vector, pAdRSV4, and co-transfected into 293 cells with a replication-deficient type 5 adenovirus, pJM17. Resulting plaques were isolated and checked for protein expression. The verified clone (AdRSV-ANII) was further analyzed. Characterization of this vector will facilitate the investigation of the mechanism of fibrinolysis on vascular endothelium.

Adenoviridae↗
PubMed2000

QT dispersion in patients with Takayasu arteritis.

This study was designed to test the hypothesis that myocardial involvement exists in patients with Takayasu arteritis and is associated with increased QT dispersion, which is a marker of repolarization inhomogeneity. Twenty-one consecutive patients with Takayasu arteritis and no significant coronary artery disease were included. Twelve-lead electrocardiogram and exercise-induced thallium-201 myocardial scintigraphy were performed in all patients. Ten of 21 patients (48%) had abnormal findings on scintigraphy. Patients were divided into two groups by the presence (group P, n = 10) or absence (group N, n = 11) of exercise-induced thallium-201 myocardial scintigraphic perfusion abnormalities, including permanent defects in three, reversible defects in four, and slow washout in three. The QT dispersion at rest was significantly greater in group P than that in group N (54 +/- 12 vs 40 +/- 8 msec, p < 0.005). The QTc dispersion at rest was also significantly greater in group P than in group N (59 +/- 15 vs 43 +/- 11 msec, p < 0.01). In patients with Takayasu arteritis, myocardial involvement suggested by exercise-induced thallium-201 myocardial scintigraphic perfusion abnormalities is not rare, even when no significant coronary stenosis is present on angiography. Increased baseline QT dispersion was associated with scintigraphic abnormalities and may be a useful marker of myocardial involvement in patients with Takayasu arteritis.

Adult↗
PubMed2000

Relationship between hyperinsulinemia and remnant lipoprotein concentrations in patients with impaired glucose tolerance.

This study was performed to explore further the association between insulin resistance and plasma remnant lipoprotein (RLP) concentration. For this purpose we used the sum of the plasma insulin concentrations before and 30, 60, 90, 120, and 180 min after a 75-g oral glucose load (sigmaIRI) as a surrogate measure of insulin resistance in 61 subjects with impaired glucose tolerance. SigmaIRI was determined on 2 occasions, before and 16 weeks after initiation of a diet and exercise program. At baseline, sigmaIRI correlated with the sum of the plasma glucose concentrations in response to the 75-g oral glucose load (r = 0.26; P < 0.04) as well as plasma concentrations of triglyceride (r = 0.21; P = 0.09), RLP-cholesterol (r = 0.41; P < 0.001), and RLP-triglyceride (r = 0.46; P < 0.001). In contrast, neither total (r = 0.07) nor high density lipoprotein (HDL) cholesterol (r = 0.04) concentrations correlated with sigmaIRI. SigmaIRI was lower in 42 subjects following life-style intervention, associated with significant (P < 0.005) reductions in sigmaglucose, and fasting glucose, insulin, triglyceride, RLP-cholesterol, and RLP-triglyceride concentrations. However, none of these variables decreased in the 19 subjects whose sigmaIRI did not fall. Finally, the change in sigmaIRI following intervention with diet and exercise was significantly associated with differences in sigmaglucose (r = 0.63; P < 0.001) and fasting glucose (r = 0.26; P < 0.05), insulin (r = 0.79; P < 0.001), triglyceride (r = 0.29; P < 0.03), RLP-cholesterol (r = 0.71; P < 0.001), and RLP-triglyceride (r = 0.49; P < 0.001) concentrations. These results demonstrate that variations in concentrations of RLPs are highly correlated with changes in sigmaIRI, consistent with the possibilities that 1) RLP measurements are useful estimates of insulin resistance; and 2) an increase in RLP concentrations may provide the mechanistic link between insulin resistance and coronary heart disease.

Aged↗
PubMed2000

Usefulness of beta blocker therapy in patients with Takayasu arteritis and moderate or severe aortic regurgitation.

The objective of the present study was to evaluate the benefit of beta-blocker therapy for patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. Clinical and echocardiographic evaluation was performed in 20 Japanese women in a follow-up period of 7.0 +/- 2.0 years. The patients were divided into 2 groups: Group A (n=10) patients who did not receive beta-blockers, and Group B (n=10) patients treated with long-term (5.1 +/- 1.6 years) therapeutic doses of beta-blockers. Left ventricular wall thickness increased significantly in all Takayasu patients who did not receive beta-blockers. Consequently, a remarkable increment in left ventricular mass took place (232 +/- 59 to 361 +/- 79 g; p < 0.005). In the same group, progressive worsening of the symptoms, with no reduction in the percent fractional shortening, was observed in 2 patients, while reduction of this last index was present in 1 asymptomatic patient. On the other hand, among the patients who were treated with beta-blockers, left ventricular mass still increased in 6 cases, while it clearly decreased in the other 4 cases (290 +/- 171 to 284 +/- 61 g; NS). The increment in wall thickness or left ventricular mass observed among patients with beta-blocker therapy was clearly less than the one registered among those who had not received beta-blockers. Furthermore, no worsening of the symptoms and/or left ventricular performance was observed during the follow-up period for patients receiving beta-blockers. We conclude that beta-blocker therapy can slow and even reverse the progression of left ventricular hypertrophy in patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. The mechanism still needs to be elucidated. We believe an effective reduction in the excessive afterload imposed on the left ventricle to be most likely responsible, but cardiac beta-receptor up-regulation might also be involved. Deterioration of the clinical status and/or impairment of left ventricular function were not associated with beta-blocker therapy in our patients. Therefore, these agents can be used safely alone or in addition to standard anti-hypertensive therapy when attempting to reduce excessive afterload, in spite of the presence of severe aortic regurgitation.

Adrenergic beta-Antagonists↗
PubMed2000

Adenoviral transduction of human E-selectin into isolated, perfused, rat aortic segments: an ex vivo model for studying leukocyte-endothelial interactions.

E-selectin, a member of the selectin family of adhesion molecules, is thought to play an important role in leukocyte-endothelial (EC) interactions during inflammation and atherosclerosis. To critically examine the role of E-selectin in leukocyte-EC interactions in the vascular system, we created a recombinant adenoviral vector containing a human E-selectin cDNA (AdRSVE-sel) and examined the effect of AdRSVE-sel in an ex vivo vascular model of a rat aortic segment. A segment of abdominal aorta was isolated from a male Sprague-Dawley rat transduced with AdRSVE-sel ex vivo. After 72 h, surface expression of transduced E-selectin in the segment was confirmed by Western blotting and immunohistochemistry using anti-E-selectin mAb. Aortic segments were connected to a perfusion system and the adhesion of human polymorphonuclear neutrophils (PMN), and a human monocytic cell line (THP-1) to the EC surface was studied in the presence of a physiological level of flow (0.85 ml/min, approximate luminal surface shear stress=1.76 dyn/cm2). Adhesion of PMN was assessed by scanning electron microscopy and quantified using fluorescently labeled PMN. AdRSVE-sel transduced aortic segments mediated significantly more PMN and THP-1 adhesion than control segments transduced with AdRSVLacZ. Pretreatment of AdRSVE-sel transduced aortic segments with anti-E-selectin mAb inhibited PMN adhesion significantly, as well as THP-1. These data indicate that human E-selectin expressed in rat aortic segments can support the adhesion of human PMN as well as THP-1 under physiological flow conditions. This genetically modified, excised, vascular-segment model provides a useful tool for the study of leukocyte recruitment in the vascular system.

Adenoviridae↗
PubMed1999

Effect of dipyridamole on QT dispersion in vasospastic angina pectoris.

Life-threatening ventricular arrhythmias have frequently been documented in patients with vasospastic angina. Moreover, the incidence of ventricular arrhythmias has been closely associated with increased QT dispersion. However, the underlying mechanism responsible for this arrhythmogenesis has not been clarified. The effects of dipyridamole and subsequent aminophylline administration on QT dispersion were examined in 35 patients with vasospastic angina and 30 patients with atypical chest pain. None of the patients enrolled in this study revealed any significant stenosis in coronary angiography. QT dispersion during dipyridamole followed by aminophylline administration was compared between the 2 groups. The baseline QT dispersion was similar in both groups (vasospastic angina: 27 +/- 8 ms; atypical chest pain: 28 +/- 7 ms). No significant changes in QT dispersion were observed in patients with atypical chest pain by dipyridamole (23 +/- 9 ms) and subsequent aminophylline administration (23 +/- 5 ms). However, the QT dispersion in patients with vasospastic angina increased significantly by dipyridamole administration (53 +/- 14 ms, p <0.0001) and returned to baseline by subsequent aminophylline administration (26 +/- 10 ms). Our data suggest that the disparity of ventricular repolarization in vasospastic angina may be mediated by increased endogenous adenosine.

Adult↗
PubMed1999

Long lasting spasticity in controlled vasospastic angina.

OBJECTIVE: To evaluate changes in coronary artery spasticity in patients with vasospastic angina who had been stable for years under continuous drug treatment. METHODS: Follow up coronary angiography was performed under intracoronary ergonovine provocation in 27 well controlled patients with vasospastic angina and no organic stenosis; the tests were done > 24 months after the initial coronary angiography, in which occlusive spasm had been induced by the same regimen of ergonovine provocation. RESULTS: The mean (SD) follow up period was 47.2 (21.6) months. All patients had been free from angina attack for more than 24 months under treatment with antianginal drugs. During this follow up period, organic stenosis developed in only one case. Occlusive spasm was observed during follow up coronary angiography in 23 patients. Spasm with 90% narrowing was observed in three other patients, and diffuse significant narrowing was seen in the final patient. No significant difference was found in spasticity (p = 0.75) between the initial and the follow up tests. CONCLUSIONS: Repeated ergonovine provocation during coronary angiography after a controlled period of several years showed that coronary spasm remains inducible in most patients. Discontinuance of drug treatment during the remission from anginal attacks achieved by medication may put the patient at high risk.

Adult↗
PubMed1999

Skin invasion of Hodgkin's disease mimicking scrofuloderma.

We report a case of direct skin invasion by Hodgkin's disease from a left supraclavicular lymph node. Clinical and pathological presentations mimicked infectious disease such as scrofuloderma. The nodule later developed a fistula following a biopsy that never healed despite numerous antibiotic treatments. Ten months later, other nodules with spontaneous fistula formation appeared on the anterior neck. A diagnosis of Hodgkin's disease was then made. Subsequent COPP cytostatic therapy remarkably improved the skin lesions and lymph nodes achieving complete remission.

Aged↗
PubMed1999

New method of estimating myocardial infarct size using technetium-99m pyrophosphate and thallium-201 dual single photon emission computed tomography imaging.

A new method was devised to estimate infarct size using dual single photon emission computed tomography with thallium-201 and technetium-99m pyrophosphate. Designating the ratio of infarct area to whole myocardial volume as %MI, the correlation of %MI with other markers of left ventricular dysfunction was examined: peak creatine kinase, ejection fraction and left ventricular asynergy. As %MI correlated well with these markers, it is considered that %MI will be useful for estimating infarct size and predicting the severity of left ventricular dysfunction in the early stage of acute myocardial infarction.

Adult↗
PubMed1999

Genetic vulnerability of cortical neurons isolated from stroke-prone spontaneously hypertensive rats in hypoxia and oxygen reperfusion.

Severe hypertension and cerebrovascular diseases develop in stroke-prone spontaneously hypertensive rats (SHRSP). Cortical neurons from SHRSP are more vulnerable than those from Wistar Kyoto rats (WKY) to the effects of nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, idebenone, and nilvadipine (a Ca2+ channel blocker) can reduce neuronal damage caused by hypoxia or neurotoxic agents. This study was designed to determine 1) whether cortical neurons from SHRSP are more vulnerable than those from WKY and 2) whether neuronal damage is minimized by the so-called neuroprotective agents in cells exposed to hypoxia and oxygen reperfusion. We demonstrated that 6 to 24 h of hypoxia did not increase cell death in either WKY or SHRSP, whereas 36 h of hypoxia significantly increased cell death in SHRSP (p < 0.01). Furthermore, 6 to 36 h of hypoxia and 1.5 to 5 h of reperfusion heavily damaged cells from both strains of rats, and most cells became apoptotic or necrotic. We also verified that the ability to protect neurons in hypoxia and oxygen reperfusion was as follows: idebenone > insulin-like growth factor-1 (IGF-1) > nilvadipine. These data indicate that oxygen radical generation occurs and the free radicals heavily damage neurons in hypoxia and oxygen reperfusion. SHRSP neurons are weaker than WKY neurons in these conditions. Furthermore, we surmise that idebenone, an antioxidant, decreases free radicals, and IGF-I attenuates p53-mediated apoptosis and thereby prevents cell death. We conclude that antioxidants are more potent than IGF-1 in protecting cortical neurons from damage caused by hypoxia and oxygen reperfusion, although both are very useful in minimizing damage to cortical neurons.

Animals↗
PubMed1999

Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.

Cerebral ischemia followed by oxygen reperfusion induced apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats. Oxygen radicals were involved in reoxygenation injury after hypoxia in hippocampal slices. Vitamin E inhibited the reoxygenation injury in cultured cortical neurons. In addition, the temporal cortices in Alzheimer's disease have increased sensitivity to oxygen radicals, and Vitamin E slowed the progression of the disease. Thus we fed Wistar Kyoto and SHRSP rats either a normal diet or a high Vitamin E diet for 3 weeks. We measured Vitamin E concentrations of plasma and brain by applying the HPLC method. Vitamin E increased its concentration in plasma, cerebral cortex, and hippocampus (p < 0.01) during a 3-week pretreatment. In addition, we clipped both common carotid arteries in these rats for 30 minutes. After the blocking, the rats were reperfused for 6 and 9 days, respectively, and then killed. We cut the brains coronally, removed the hippocampal CA1 regions, and examined the neurons using an electron microscope. SHRSP rats with normal cerebral circulation had 30.4+/-8.0 apoptotic neurons per 1000 neurons. Cerebral ischemia followed by 6 and 9 days of reperfusion, respectively, increased apoptotic neurons in SHRSP rats fed a normal diet (6 days: 542.5+/-154.1 per 1000 neurons; 9 days: 657.5+/-110.2 per 1000 neurons). In contrast, apoptotic neurons in SHRSP rats fed a high Vitamin E diet were significantly (p < 0.01) small in number (6 days: 41.3+/-27.5 per 1000 neurons; 9 days: 35.5+/-19.7 per 1000 neurons) even though the rats were treated in the same way. These data demonstrate that oxygen radical generation occurs after reperfusion and that free radicals heavily damage the neurons in SHRSP rats. Vitamin E reacts with the radicals and prevents neuronal apoptosis caused by cerebral ischemia and reperfusion. Therefore, Vitamin E seems to be an important agent in lowering radical damage to hippocampal neurons.

Animals↗
PubMed1999

Importance of glycation in the acceleration of low density lipoprotein (LDL) uptake into macrophages in patients with diabetes mellitus.

BACKGROUND: Two studies were conducted to determine the importance of glycation in the acceleration of low density lipoprotein (LDL) uptake by macrophages in patients with diabetes mellitus. METHODS: Healthy individuals (n=6) and non-insulin-dependent diabetic patients (n=6) were studied. LDL was separated by sequential ultracentrifugation. Macrophages were collected from the abdominal cavity of ICR-mice and incubated in a medium containing [14C] oleate. In Study 1, LDL from diabetic patients (DM-LDL) and control LDL were then incubated with this medium. The uptake of DM-LDL by macrophages was compared with that of control LDL by measuring the [14C] content of the synthesized cholesteryl ester. In Study 2, glycated LDL was prepared by glycating LDL from 6 healthy individuals in vitro. The uptake of native LDL by macrophages was compared with that of glycated LDL using the same method as in Study 1. RESULTS: In Study 1, the uptake of DM-LDL (median: 1,405; range: 985-2269 dpm) was significantly higher than that of control LDL (median: 1,095; range: 990-1104 dpm, p<0.05). In Study 2, the uptake of glycated LDL (median: 1,556; range: 889-2837 dpm) was significantly higher than that of native LDL (median: 1,176; range: 789-2098 dpm, p<0.05). CONCLUSIONS: The results indicate that the greater uptake of DM-LDL than that of control LDL may be attributed to glycation of LDL caused by hyperglycemia in diabetic patients. Glycation of LDL by hyperglycemia may be one cause of the accelerated atherogenesis in diabetic patients.

Adult↗
PubMed1999

Effect of glycated low density lipoprotein on smooth muscle cell proliferation.

BACKGROUND: We investigated the effect of glycated low density lipoprotein (LDL) on smooth muscle cell proliferation. METHODS: Blood was drawn from 6 healthy subjects after overnight fasting. Native LDL was obtained by separating LDL from the samples with sequential ultracentrifugation. Glycated LDL was prepared by glycating the native LDL in vitro. Native and glycated LDL were added to a medium containing cultured porcine coronary artery smooth muscle cells, and the change in cell proliferation was examined after 24, 48, 72, and 96 hs. The cells were counted using a cell counting kit (Dojin Chemical Co., Ltd.). RESULTS: There was no significant difference in the cell count between the control group, in which only PBS was added, and the native LDL group. However, cell proliferation was appreciably higher in the glycated LDL group than in the native LDL group. The mean total cell count at 24, 48, 72 and 96 hs was significantly higher (p<0.01) in the glycated LDL group (median: 0.843; range: 0.576-1.060) than in the native LDL group (median: 0.541; range: 0.282-0.683). CONCLUSIONS: These findings suggest that glycated LDL induces significantly greater acceleration of smooth muscle cell proliferation than does native LDL. Therefore, the acceleration of smooth muscle cell proliferation requires modification of LDL.

Animals↗