Production of interleukin-6 induced by hypoxia linked to peripheral arterial disease.
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Cell Hypoxia↗
Biomedical subjects
F Numano
Publications and source records attributed to F Numano.
Impaired NO release from bovine aortic endothelial cells exposed to activated platelets.
We have previously shown that aggregated human platelets elicited a decrease in intracellular adenosine triphosphate (ATP), enhanced adenosine egress and damage to mitochondria in bovine aortic endothelial cells (ECs). To test whether such metabolic and ultrastructural changes could be associated with functional impairment of ECs, we investigated the effects of activated platelets on nitric oxide (NO) and prostacyclin release, and on the antiaggregation property of ECs. Pretreatment of ECs with aggregated platelets transiently stimulated basal NO release while prolonged (> or = 30 min) exposure dose-dependently inhibited NO release, both basal and in response to ATP or serotonin, with NO synthase activity being attenuated in these cells. Supplementary L-arginine (L-A) restored NO release completely. Prostacyclin release was also stimulated transiently but not affected by prolonged pretreatment. The antiaggregation property of ECs was attenuated by pretreatment with activated platelets but restored with L-A supplement. Although the effects of activated platelets and 0.5 mM acetylsalicylic acid (ASA) to attenuate the antiaggregation property of ECs were additive, activated platelets had no effect on ECs treated with 0.2 mM N omega-nitro-L-arginine (L-NA), suggesting a common mechanism. We conclude that prolonged exposure to aggregated platelets may affect the antiaggregation property of ECs by directly inhibiting NO synthesis, which may be normalized by L-A supplementation.
Adenosine Triphosphate↗
Oxidation of remnant-like particles from serum of diabetic patients, patients with ischemic heart disease and normal subjects.
Remnant-like particles (RLP) are reportedly involved in the pathogenesis of atherosclerosis, as are lipid peroxides. To assess the role of the oxidation of RLP in this disease, we compared the oxidation of RLP with that of total very low density lipoproteins (VLDL) obtained from the serum of 10 patients with ischemic heart disease (IHD), 10 patients with diabetes mellitus (DM) and 10 normal subjects by measuring the levels of thiobarbituric acid reactive substances (TBARS). Our results indicated that RLP were oxidized in vivo to a greater extent than total VLDL in all three groups of subjects. The serum levels of RLP were significantly higher in the patients than in the normal subjects. The oxidation of RLP may therefore be involved in the progression of atherosclerosis in patients with IHD or DM.
Adult↗
Differences in clinical presentation and outcome in different countries for Takayasu's arteritis.
Takayasu's arteritis is a chronic vasculitis, the etiology of which is still unknown. This condition involves primarily the aorta, its main branches, and the coronary and pulmonary arteries. One epidemiologic characteristic of this morbid condition is that almost all patients come from Asian and South American countries, which has led to searches in the role of genetic factors in its pathogenesis. International surveys on HLA analysis have focused on HLA-B52 and B39 disequilibrium with this morbid condition. These comparative studies have made clear the different characteristic clinical manifestations among Asian and South American countries, which will prompt further studies in relation to genetic factors in the future.
Asia↗
Demonstration of Purkinje potential during idiopathic left ventricular tachycardia: a marker for ablation site by transient entrainment.
During VT of QRS morphology with right bundle branch block and left axis deviation in a patient without obvious structural heart disease, entrainment by pacing from the right ventricular outflow tract and high right atrium was demonstrated. During entrainment of VT, a Purkinje potential preceding the QRS and recorded at the left ventricular mid-septum was activated by orthodromic impulses in the reentry circuit. The interval between the Purkinje potential and the earliest left ventricular activation was decrementally prolonged with shortening of pacing cycle length. Radiofrequency energy was applied to this site, resulting in successful elimination of VT. Therefore, the Purkinje potential represented activation by an orthodromic wavefront in the reentry circuit, while the orthodromically distal site to this potential showed an area of slow conduction with decremental property.
Adult↗
Clinical manifestations of Takayasu arteritis in India and Japan--new classification of angiographic findings.
In this retrospective review 102 Indian and 80 Japanese patients with Takayasu arteritis were compared in regard to their clinical manifestations and angiographic findings. Regardless of nationality, most patients were initially affected in their teens or twenties. Japanese patients were female in a larger ratio compared with the ratio in India. Clinically, the two groups exhibited several different features. More Japanese patients were found to be pulseless (P < 0.01) whereas many Indian patients were hypertensive (P < 0.01). Inflammatory conditions in Japanese patients were more severe (P < 0.01) and tended to be more prolonged than those in the Indians. More Japanese patients suffered from aortic regurgitation (P < 0.01), but Indians suffered from hypertension (P < 0.01). Angiographic findings revealed that the aortic arch and its branches were mainly involved in Japanese patients (type I, IIa) whereas the abdominal aorta and its branches were mainly involved in Indian patients (type IV). However, the diffusely involved type (type V) was the one most commonly found in both countries. From the analyses of vascular lesions in both Indian and Japanese patients, 510 and 396, respectively, different progressions of vasculitis are speculated. In Japanese patients, vasculitis generally occurs in the ascending aorta, the aortic arch, and/or its branches and extends into the thoracic and abdominal aorta, subsequently forming various complicated lesions with prolonged inflammatory activity. On the other hand, in Indian patients, vasculitis generally occurs in the abdominal aorta involving renal arteries, subsequently extending into the thoracic aorta within one or two decades, simple vascular lesions being formed. Data analysis suggests that this morbid condition progresses differently in India and Japan, in spite of some common etiologic factor(s).
Adult↗
A case of scurvy rarely encountered in Japan.
We report a case of scurvy, which is rarely encountered in Japan. A 75-year-old male was hospitalized with diffuse subcutaneous hemorrhaging of both feet, pain on walking, and shortness of breath. A remarkably low serum level of vitamin C was confirmed. Administration of ascorbic acid dramatically improved his clinical symptoms. Improvement paralleled the increase of serum vitamin C level. This case underscores the important role of vitamin C on the integrity function of the vessel wall.
Aged↗
Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.
Cerebral ischemia induces a massive efflux of glutamate causing delayed neuronal death in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). It is obvious that L-N-nitroarginine (L-NNA; NO synthase (NOS) inhibitor), benzamide (poly(ADP-ribose) synthetase inhibitor), and growth factors are involved in reducing neuronal cell death due to toxic conditions, especially phosphatidylinositol 3 (PI3)-kinase activity; however, no studies have clarified whether genetic vulnerability to neurotoxic states is present in cortical neurons isolated from SHRSP. For this purpose, we prepared cortical neurons from WKY and SHRSP (15 weeks of gestation) to test the genetic vulnerability involved in the pathogenesis of stroke as well as apoptosis of cortical neurons isolated from SHRSP. We also examined the mechanisms necessary to reduce apoptosis under neurotoxic states using ultrastructural and biochemical techniques. Cortical neurons from SHRSP were in fact found to be more vulnerable than neurons from WKY and resulted in apoptosis when treated with nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, especially insulin-like growth factor (IGF), rescued neurons from NO- and NMDA-mediated neurotoxicity, particularly those from SHRSP. Conversely, benzamide and L-NNA reduced NMDA-mediated neurotoxicity but not NO-mediated toxicity. The ability to protect neurons from neurotoxicity was as follows: IGF-->nerve growth factor epidermal growth factor-->L-NNA-->benzamide. In addition, it was demonstrated that wortmannin, a PI3-kinase inhibitor, lessened the protective effects of these growth factors against NO-mediated toxicity. The data thus indicate that genetic factors related to neuronal vulnerability to apoptosis are involved in the pathogenesis of stroke lesions in SHRSP. PI3-kinase activity, which is stimulated by growth factors, is closely related to protective effects against NO- and NMDA-mediated toxicity in cortical neurons, especially those isolated from SHRSP. Moreover, the genetic vulnerability observed in SHRSP neurons is possibly linked to the inadequate activation of signaling pathways in the downstream of protein tyrosine kinases.
Animals↗
Insulin-like growth factor-1 attenuates apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.
Cerebral ischemia followed by reperfusion induced apoptosis in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). Our in vitro studies revealed that IGF-1 prevented apoptosis caused by nitric oxide- and N-methyl-D-aspartate-mediated toxic agents in cortical neurons isolated from SHRSP. In addition, it was reported that IGF-1 given 1 hour before ischemia significantly attenuated the incidence of myocyte apoptosis after myocardial ischemia and reperfusion. IGF-1 (20 micrograms/rat) was administered ip 1 hour before the clipping of both common carotid arteries in WKY and SHRSP. Rats underwent cerebral ischemia for 20 minutes and reperfusion for 6 days before they were killed. We cut the brain coronally, removed sections from the hippocampal CA1 region, and examined the neurons in these samples using an electron microscope. We tried to clarify whether pretreatment using IGF-1 decreases the number of apoptotic neurons in SHRSP with cerebral ischemia followed by reperfusion. SHRSP with normal cerebral circulation had 30.4 +/- 8.0 apoptotic neurons per 1000 neurons. Cerebral ischemia followed by reperfusion significantly (p < 0.01) increased the number of apoptotic neurons (235.2 +/- 25.2/1000 neurons) in SHRSP. In contrast, pretreatment with IGF-1 reduced the number of apoptotic neurons in SHRSP (82.8 +/- 11.2/1000 neurons; p < 0.01) under otherwise identical conditions. We concluded that the genetic vulnerability to apoptosis in SHRSP neurons was involved in the pathogenesis of stroke lesions and that this vulnerability was attenuated by the IGF-1 pretreatment.
Animals↗
Effects of dobutamine on left ventricular diastolic performance are attenuated in patients with systemic hypertension.
We measured Doppler echocardiographic diastolic parameter during infusion of low-dose dobutamine in 14 untreated hypertensive subjects and in 14 normal controls. Low-dose dobutamine accelerated left ventricular relaxation in normal controls but not in hypertensive subjects.
Adult↗
Ultrastructural analysis of survival in cultured smooth muscle cells isolated from stroke-prone spontaneously hypertensive rats: effect of growth factors.
Our previous study in vivo suggested that vascular smooth muscle cells (VSMCs) in stroke-prone spontaneously hypertensive rats (SHRSP) were vulnerable when plasma components were deficient. Therefore, we cultured VSMCs isolated from normotensive and hypertensive rats to clarify the weakness of VSMCs isolated from hypertensive rats and maintained in plasma-deficient conditions by employing ultrastructural and biochemical analyses. VSMCs, obtained from normotensive rats and cultured without fetal bovine serum (FBS) for 1 week, were intact and well differentiated; without FBS for 2 weeks retained their original structures except for several degenerative changes. VSMCs, obtained from hypertensive rats and cultured without FBS for 2 weeks, were extensively damaged and lost their cell organelles. Apoptotic bodies were frequently observed. We also cultured VSMCs in medium containing a variety of growth factors. VSMCs obtained from normotensive rats and cultured with epidermal growth factor or insulin-like growth factor-1 for 2 weeks were almost intact, as were VSMCs from hypertensive rats, although some degenerative changes of cell organelles were observed. VSMCs from hypertensive rats, maintained with platelet-derived growth factor-BB or basic fibroblast growth factor, were generally in poor condition. Thus VSMCs from hypertensive rats have hereditary weaknesses in cell survival including apoptosis and require specific growth factors for their maintenance.
Animals↗
Takayasu arteritis--five doctors in the history of Takayasu arteritis.
Takayasu arteritis is a chronic vasculitis mainly involving the aorta, its main branches, pulmonary and coronary arteries. Recent international survey has made clear different sex ratio, different involvement and different clinical manifestations among countries. At the same time, ethnic distribution of this morbid condition has focused on the role of genetic factors and the mechanisms inducing vasculitis. In this paper, five doctors who contributed in history to the elucidation of Takayasu arteritis were introduced as an aid in understanding recent studies on this morbid condition.
Eponyms↗
Impaired glucose tolerance with late hypersecretion of insulin during oral glucose tolerance test in patients with vasospastic angina.
OBJECTIVES: This study tested whether patients with vasospastic angina have impaired glucose tolerance or impaired insulin response. BACKGROUND: Hyperinsulinemia has been demonstrated in patients with coronary artery disease and syndrome X. METHODS: We performed an oral glucose tolerance test (75 g) in 30 patients with vasospastic angina in whom severe coronary vasospasm was induced by acetylcholine and in a matched group of 30 patients with atypical chest pain in whom no significant vasospasm was induced. The responses of insulin and glucose were compared between the two groups. No subjects had overt diabetes mellitus, hypertension, dyslipidemia, obesity or angiographically detected significant baseline coronary stenosis. Venous blood samples were taken during fasting and at 30, 60, 120 and 180 min after glucose load to obtain plasma glucose and immunoreactive insulin levels. RESULTS: Impaired glucose tolerance was detected in the 19 (63%) of 30 patients with vasospastic angina and in none of 30 patients with atypical chest pain (p < 0.001). The immunoreactive insulin levels at 60 and 120 min as well as the interval to peak insulin level were significantly greater in patients with vasospastic angina (p < 0.001). Among patients with vasospastic angina, those with acetylcholine-induced multivessel coronary vasospasm showed a significantly higher sum of insulin concentrations than those with single-vessel spasm (p < 0.01). During induction of coronary spasm, 10 patients with vasospastic angina presented ventricular arrhythmias. The sum of insulin concentrations was significantly greater in patients with than in those without ventricular arrhythmias. CONCLUSIONS: Patients with vasospastic angina exhibited a high incidence of impaired glucose tolerance and delayed and significantly higher insulin responses. These findings suggest that impaired glucose tolerance with late hypersecretion of insulin may contribute to the pathogenesis of severe coronary vasospasm.
Adult↗
Angiographic findings of Takayasu arteritis: new classification.
Having proposed a new classification on angiographic findings of patients with Takayasu arteritis, we evaluated the angiographic findings of 80 Japanese patients and 102 Indian patients according to this classification. Japanese patients showed a higher frequency of involvement of the ascending aorta, aortic arch and its branches than did the Indians (P < 0.01). On the other hand, the frequency of involvement of the abdominal aorta and/or renal arteries was higher in Indian patients (P < 0.01). Type III cases of the new classification which involves the thoracic descending aorta, abdominal aorta and/or renal arteries were observed in 3% of the Indian patients, but not at all in the Japanese. In conclusion, in Japanese patients, vascular lesions tend to occur primarily in the ascending aorta, aortic arch and/or its branches and extend into the abdominal aorta. On the other hand, in Indian patients, the tendency is primarily in the abdominal aorta including renal arteries and extending into the thoracic aorta.
Adolescent↗
Comprehensive analysis of HLA genes in Takayasu arteritis in Japan.
To identify an HLA-linked susceptibility gene to Takayasu's arteritis, comprehensive analysis of HLA genes was performed. By serologic HLA typing, positive associations of Takayasu's arteritis with HLA-B52 and B39 were observed. The DNA typing of HLA-B gene and class II genes (DRB1, DQA1, DPB1) showed positive associations of the disease with HLA-B52, B39.2, DRB1 * 1502 and DPB1 * 0901, confirming in part the serologic observations. Comparison of odds ratio for the risk of disease revealed that HLA-B52 and B39.2 were primarily involved in the susceptibility, while the associations with DRB1 * 1502 and DPB1 * 0901 were suggested to reflect a strong linkage disequilibrium of these class II alleles with HLA-B52 in the Japanese population. Sequencing analyses of HLA-B52 and B39.2 from patients confirmed that they were B 5201 and B 3902, respectively. Comparison of amino acid sequences of these disease-associated HLA-B alleles identified critical amino acid residues of the HLA-B molecule, Glu and Ser at 63rd and 67th positions, respectively, which may determine the susceptibility to Takayasu's arteritis via binding and presenting a yet unknown disease-related antigen.
Alleles↗
Diagnostic criteria for Takayasu arteritis.
Diagnosis of Takayasu arteritis (TA) is often delayed because of a non-specific clinical presentation. Ishikawa's criteria (1988) has been widely used for the diagnosis of this disease. Few modifications have been proposed in Ishikawa's criteria for the diagnosis of TA. The proposed modifications include: (a) removal of the obligatory criteria of age less than 40 years; (b) inclusion of characteristic signs and symptoms as a major criteria; (c) removal of age in defining hypertension; (d) deletion of the absence of aorto-iliac lesion, in defining abdominal aortic lesion; and (e) an addition of coronary artery lesion in absence of risk factors. The criteria proposed consists of three major criteria including left and right mid subclavian artery lesions and characteristic signs and symptoms of at least one month duration and ten minor criteria-a high erythrocyte sedimentation rate, carotid artery tenderness, hypertension, aortic regurgitation or annuloaortic ectasia, pulmonary artery lesion, left mid common carotid lesion, distal brachiocephalic trunk lesion, descending thoracic aorta lesion, abdominal aorta lesion and coronary artery lesion. Presence of two major or one major and two minor criteria or four minor criteria suggests a high probability of TA. When applied to 106 Indian patients of angiographically proven TA and 20 control subjects, it had a sensitivity of 92.5% and specificity of 95% that was higher than that of Ishikawa's criteria (sensitivity 60.4%, specificity 95%) and American college of Rheumatology criteria (sensitivity 77.4%, specificity 95%). Similarly, this criteria had a 96% sensitivity and 96% specificity in 79 Japanese patients of TA and 79 control subjects. Adoption of these criteria is expected to prevent the possibility of an under diagnosis of TA.
Adult↗
Four years follow-up study in patients with Takayasu arteritis and severe aortic regurgitation; assessment by echocardiography.
We prospectively performed the follow-up study in 11 female patients with Takayasu arteritis and severe aortic regurgitation by echocardiography. A mean follow-up period was 4 years. The inflammatory state was controlled in all patients. Antihypertensive agents including beta-blocker were administered in nine patients. Heart failure did not progress in all patients except one. No candidate for cardiac surgery appeared during the follow-up period. Aortic root diameter, left atrial, left ventricular end-diastolic and end-systolic dimensions, wall thickness, left ventricular mass, and percent fractional shortening of the left ventricle showed no significant change in echocardiography. These data indicate that left ventricular disturbance might be slowly progressive in patients with Takayasu arteritis and severe aortic regurgitation. Systemic hypertension and the inflammatory state should be well controlled in managing the patients. beta-blocker might be useful in some patients with Takayasu arteritis and severe aortic regurgitation. Further follow-up is necessary for the decision of the cardiac surgical indication.
Adrenergic beta-Antagonists↗
HLA class II DNA typing in Buerger's disease.
To analyze the genetic factors involved in the pathogenesis of Buerger's disease, the polymorphisms of HLA class II genes (HLA-DP, -DQ and -DRB) were investigated in 36 patients using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. HLA class I (B54 and B52) and HLA class II (DQ alleles) genes were also typed by polymerase chain reaction-sequence-specific oligonucleotide probe (PCR SSOP) method to confirm alleles. PCR-RFLP typing revealed that the frequencies of HLA class II genes, DRB1*0405, DQB1*0401, DQA1*03 and DPB1*0501, were significantly increased in the patients with Buerger's disease compared with the healthy controls. Further, DNA typing confirmed that HLA-B54 was associated with Buerger's disease. These results suggested that the haplotype of HLA-B54-DRB1*0405-DQB1*0401- DQA1*03-DPB1*0501 was associated with Buerger's disease in Japanese population.
Adult↗