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Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 127 records · Page 7Linked to original sources

Comparative studies of patients with Takayasu arteritis in Japan, Korea and India--comparison of clinical manifestations, angiography and HLA-B antigen.

Comparative study of Takayasu arteritis in 3 Asian countries (India, Korea and Japan) has revealed some significant differences. In angiographic findings, Japanese patients more frequently have lesions at the aortic arch and/or its branches (99% of 96 cases), while most lesions in Korean (76% of 109 cases) and Indian patients (92% of 50 cases) are at the abdominal aorta. The presence of HLA-Bw52 or B5 is closely associated with Takayasu arteritis in all 3 Asian countries. The complications in 108 Japanese, 101 Korean and 50 Indian patients were also compared. The most frequent complications were aortic regurgitation in Japan and hypertension in the other 2 countries. Death occurred most frequently due to congestive heart failure or sudden death resulting from aortic regurgitation in Japan, but resulting from hypertension in Korea and India.

Adolescent↗

Bidirectional regulation of smooth muscle cell proliferation by IFN-gamma.

We studied the effects of interferon gamma (IFN-gamma), a T-cell lymphokine, on the proliferation and chemotaxis of vascular smooth muscle cells (SMC). Recombinant human IFN-gamma dose-dependently inhibited the proliferation of SMC cultured in the presence of 20% fetal calf-serum. It also inhibited PDGF-induced chemotaxis of SMC. Similar concentrations of IFN-gamma induced DNA-synthesis of SMC cultured in mitogen-depleted medium for 5 days. The inhibition and the stimulation of SMC proliferation were accompanied by concomitant decrease and increase in the number of PDGF receptors. Our study indicated that IFN-gamma is a bidirectional regulator of SMC proliferation.

Cell Division↗

Ventricular arrhythmias in Takayasu arteritis.

We studied the prevalence, severity and clinical significance of ventricular arrhythmias in 78 female patients with Takayasu arteritis by 24-h ambulatory electrocardiography monitoring. Fifty (64%) of 78 patients had no or less than 30 beats/h premature ventricular contractions (Group A). The remaining 28 (36%) patients exhibited frequent or complex premature ventricular contractions (Group B). The frequency of HLA Bw52 which is closely associated with this morbid condition, echocardiographic and thallium-201 stress myocardial scintigraphic findings were then compared between these two groups. The frequency of positive HLA Bw52 was not significantly different between these two groups. Echocardiographically determined left ventricular mass (309 +/- 94 vs. 166 +/- 64 g; P < 0.01), frequency of complicated aortic regurgitation (77% vs. 24%; P < 0.01) and abnormal thallium-201 scintigraphic findings (76% vs. 38%; P < 0.05) were found higher in Group B as compared with those in Group A. These data indicate that frequent or complex ventricular arrhythmias in patients with Takayasu arteritis were associated with the presence of left ventricular hypertrophy, aortic regurgitation and decreased coronary reserve.

Adult↗

DNA typing of HLA-B gene in Takayasu's arteritis.

Sixty-four patients with Takayasu's arteritis and 156 healthy individuals in the Japanese population were examined for HLA-B specificity at the DNA level by DNA typing using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe (SSOP) analysis and by subsequent sequencing analysis. The frequency of epitope combination group-B52 (EC-B52) corresponding precisely to HLA-B52 specificity and that of EC-B39.2 which is a newly-identified subtype of HLA-B39 specificity were increased in the patient group. These two disease-associated HLA-B alleles share an epitope composed of 63Glu and 67Ser. Because two HLA-B alleles, HLA-B51 and B39.1, which are similar but different at the epitope from HLA-B52 and B39.2, respectively, are not associated with Takayasu arteritis, 63Glu and 67Ser are supposed to be involved in the pathogenesis.

Alleles↗

Takayasu arteritis: evaluation with MR imaging.

The authors evaluate the usefulness of magnetic resonance (MR) imaging in the diagnosis of Takayasu arteritis (TA). MR images of 77 patients with TA (74 women, three men) were obtained with a 1.5-T system, and the resulting images were compared with those obtained at conventional angiography. Aortic lesions--including stenosis, dilatation, aneurysms, wall thickening, and mural thrombi--were clearly visualized at MR imaging, particularly in aortic long-axis images. Further, aortic regurgitation, which occurs frequently in patients with TA, was clearly seen in cine MR images. Also, aortic branch vessel lesions adjacent to the aortic arch were well visualized, although distal lesions were often not as clear. Pulmonary arterial lesions, including occlusion and dilatation, were seen as well. The authors conclude that MR imaging can clearly depict various vascular lesions in both the systemic and pulmonary arteries of patients with TA, thus enabling a definitive diagnosis of the disease.

Adolescent↗

Ethanol modulates cyclic GMP metabolism in cultured coronary smooth muscle cells.

The authors tested the hypothesis that ethanol or its metabolite acetaldehyde might interfere in cyclic guanosine monophosphate (GMP) metabolism in coronary smooth muscle cells. Ethanol at the physiologically relevant concentration of 4.0 mg/mL or more significantly decreased basal guanylate cyclase activity and inhibited activation of the enzyme by sodium nitroprusside (SNP) in cultured porcine coronary smooth muscle cells. Two isoforms of phosphodiesterase (PDE), cyclic GMP-specific form and calmodulin-stimulated form, were both inhibited by 12.0 mg/mL or more ethanol. Intact cell study revealed that although 12.0 mg/mL or more ethanol was needed to significantly decrease cyclic GMP accumulation in control cells, 4.0 mg/mL or more ethanol significantly inhibited the increase of cyclic GMP accumulation induced by 1 microns SNP. Acetaldehyde showed similar effects, but the concentrations involved were more than physiological. Thus, ethanol may decrease cellular cyclic GMP levels and attenuate cyclic GMP accumulation in response to SNP in coronary smooth muscle cells by inhibiting soluble guanylate cyclase activity at physiologically relevant concentrations.

Acetaldehyde↗

Concentric left ventricular hypertrophy in patients with Takayasu arteritis.

Although aortic regurgitation (AR) in patients with Takayasu arteritis (TA) is believed to be caused by dilatation of the aortic ring or thickening of the aortic cusps, the pattern of left ventricular hypertrophy (LVH) in these patients has not been described. To clarify the geometry of the LV in patients with TA that had been documented both echocardiographically and hemodynamically, the authors evaluated 22 patients with TA and severe AR (group 1), 10 with TA and systemic hypertension (group 2), and 17 with isolated severe AR of other etiologies (group 3). M-mode echocardiography showed that LV dimensions were smaller in groups 1 and 2 than in group 3 and that wall thickness was greater in group 1 than in group 3. The concentric hypertrophic ratio (CHR = wall thickness/LV end-diastolic dimension+wall thickness) was larger than group 1 (p < 0.001) and group 2 (p < 0.01) than in group 3. CHR was similar in groups 1 and 2. Systolic blood pressure was significantly increased in group 2 and showed a tendency to increase in group 1 as compared with group 3. The results confirmed the presence of concentric LVH related to a pressure overload in patients with TA, even when TA was complicated by severe AR.

Adult↗

Enhanced flow velocity increase through the left ventricular inflow tract of patients with isolated aortic regurgitation.

Twenty-five patients with chronic aortic regurgitation (AR), and 12 control subjects were studied using Doppler echocardiography to investigate the effects of AR on transmitral flow. Peak early filling velocities at the levels of the mitral valve tips (E1) and annulus (E2) were measured, and the transmitral flow restriction index (delta E = (E1-E2)/E2) was obtained. Patients with AR were classified into 2 groups according to the ratio of the cross-sectional area of the regurgitant jet to that of the left ventricular outflow tract. Group I had the ratio less than 0.20, and group II had greater than or equal to 0.20. E2 in group II was lower than in control subjects, whereas E1 was not significantly different in any groups. delta E in group II was higher than in group I or in control subjects (p less than 0.05 and 0.01, respectively). delta E showed a significant correlation with the cross-sectional area ratio in all patients with AR (r = 0.70, p less than 0.01) and in group II (r = 0.82; p less than 0.01). Our data suggest that AR restricts early transmitral filling, and that delta E may indicate the increased driving pressure caused by flow restriction and is a useful hemodynamic index of AR.

Adult↗

Alteration of adenine nucleotide metabolism in coronary smooth muscle cells by activated platelets.

Cultured porcine coronary smooth muscle cells were preloaded with [3H]adenine and the inside and outside radioactive metabolites of the cells were analyzed following exposure to activated platelets. Incubation of the cells with human platelets activated by collagen enhanced intracellular conversion of ATP to ADP and caused dose- and time-dependent increase in radioisotopic release, mainly adenosine. Isolation of cyclic AMP revealed decreased cyclic AMP levels in the treated cells, both intra- and extracellularly. Of the substances released by the activated platelets, thromboxane A2 and serotonin enhanced radioisotopic release. The modulation of adenine metabolism by the activated platelets was preceded by increase in accumulation of inositol phosphates in the cells and was prevented by Iloprost (1 microM), a prostacyclin analog, cilostamide (10 microM), a cyclic AMP-specific phosphodiesterase inhibitor, or dibutyryl cyclic AMP (1 mM). Nifedipine showed only minor preventive effect. The agents which elevate cyclic AMP accumulation also attenuated phosphoinositide hydrolysis, whereas nifedipine had no effect. These results suggest that activated platelets may stimulate adenine metabolism in coronary smooth muscle cells, presumably due to activation of phosphoinositide turnover resulting in increased intracellular calcium. Enhanced adenosine release from the cells exposed to activated platelets may be a compensatory mechanism to prevent further platelet aggregation and contraction of coronary smooth muscle.

Adenine↗

Pathological features of the pulmonary artery in Takayasu arteritis.

Little attention has been paid to the pathological features of the pulmonary artery in Takayasu arteritis. Autopsy specimens of 6 cases of this disease were studied. Lesions were found in the aortic arch and its brachiocephalic branches in all cases and in both the aortic arch and thoracoabdominal aorta in 5 cases. The pathohistologic characters of the pulmonary artery were very similar to those of the systemic artery. Stenosis-recanalization, so-called blood vessels-in-blood vessels, of the pulmonary elastic arteries were found in four cases. These lesions were not observed in the systemic arteries, and most of the newly formed channels in them seemed to be branches of bronchial arteries. Luminal obstruction of pulmonary muscular arteries was observed in 4 cases, cellular arteritis of muscular arteries in 2 cases, and angiomatoid dilatation of small blood vessels in 2 cases. Thus in this study we found peculiar stenosis-recanalization lesions of the pulmonary elastic arteries, and also showed that the pulmonary elastic and muscular arteries are frequently involved in Takayasu arteritis. These findings suggest that pulmonary hypertension could influence morbidity and long-term mortality in this disease.

Adult↗

Coronary artery lesions in Takayasu arteritis: pathological considerations.

This communication reviews the clinical and pathological features of coronary artery lesions in Takayasu arteritis. The incidence of coronary artery involvement has been reported to be 9% to 10%, and is observed mainly in autopsy cases because coronary artery disease is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. On the basis of pathological features, the following three types of coronary artery lesions can be distinguished: type 1, stenosis or occlusion of the coronary ostia and the proximal segments of the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysm. Most of the coronary artery lesions in Takayasu arteritis are of type 1. Narrowing of the coronary arteries is mainly due to the extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia from the ascending aorta. In some cases, coronary stenosis may be caused by coronary arteritis as skip lesions in Takayasu arteritis, but even in these cases the lesions have been reported to affect mainly the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysm seem to be very rare in Takayasu arteritis. Other causes of coronary ostial stenosis, coronary arteritis and coronary artery aneurysm are also discussed.

Adult↗

Hereditary factors of Takayasu arteritis.

Takayasu arteritis is a chronic vasculitis characterized by a clinical pulseless condition and is predominant in young female patients. Its loci is found mainly in Asian countries, and its etiology is still unknown. Our experiences of cases of twin sisters with Takayasu arteritis led us to suppose that hereditary factors participate in the pathophysiology of this disease. Population and family-incidence studies employing HLA analysis in Japan have focused on an complotype Aw24-DW52-C4A2-C4BQ0-Dw12 which was in disequilibrium with Takayasu arteritis. Clinical features and clinical courses were found to be intimately related to this complotype. Recent studies on HLA typing in other countries have also suggested the important roles of hereditary factors in this morbid condition and international collaborative studies on these hereditary factors are now under way.

Adolescent↗

HLA-linked susceptibility and resistance to Takayasu arteritis.

To investigate genetic factors involved in the pathogenesis of Takayasu arteritis, patients in the Japanese population were examined for HLA-A, -B, and -C alleles by serological typing and for HLA-DR, DQ, and DP alleles by DNA typing using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe (SSOP) analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601, and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, and DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the haplotype of HLA-B252-DRB1*1502-DRB5*0102-DQA1*0103-DQB1++ +*0601-DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. These observations clearly indicate that HLA-linked gene(s) are involved in the development of Takayasu arteritis.

Genetic Linkage↗

Comparative studies between Japanese and Korean patients: comparison of the findings of angiography, HLA-Bw52, and clinical manifestations.

A Japan-Korea cooperative survey on Takayasu arteritis has shown some differences in the features between Japanese and Korean patients with this disease. In angiographic findings, Japanese patients more frequently had lesions at the aortic arch and/or its branches (58% of 75 cases), while, in Korean patients, the abdominal aorta is the site of relatively frequent lesions (30% of 112 cases). Higher occurrence of HLA-Bw52 was found in Japanese patients in comparison with Korean patients (46% vs 15%). The presence of HLA-Bw52, however, might have a close association with Takayasu arteritis in Korea as well as in Japan. The complications in 126 Japanese and 88 Korean patients were also compared. The complications occurring with higher frequency in Japanese patients were aortic regurgitation, ischemic heart disease, and visual disturbances, while, in Korean patients, the more frequent complications were renovascular hypertension as well as hypertension of some other etiology.

Adolescent↗

Aortic regurgitation in patients with Takayasu arteritis: assessment by color Doppler echocardiography.

To characterize aortic regurgitation in patients with Takayasu arteritis, we studied 48 females with arteritis (mean age 47 +/- 12 years) by means of color Doppler echocardiography. Aortic regurgitation was confirmed in 32 out of 48 patients (67%) by color-flow mapping. Twenty-four patients had mild or no aortic regurgitation (group A), 9 had moderate (group B), and 15 had severe (group C) aortic regurgitation. We compared the echocardiographic data obtained from patients with Takayasu arteritis with those of 14 normal controls and 9 patients with severe aortic regurgitation of valvular origins (group V). The aortic root diameter (AOD) in group B (23 +/- 4 mm/M2) and group C (22 +/- 3 mm/M2) revealed a statistically significant large value as compared with that in group A (18 +/- 2 mm/M2) and normal controls (17 +/- 3 mm/M2). However, the differences, between groups B and C and groups C and V, were not significant. The AOD was not obviously dilated in a considerable number of group C patients. Aortic valve involvement was seen in several group C patients and moderate concentric left ventricular hypertrophy was present in all group C patients. Group C patients therefore, have concentric left ventricular hypertrophy but may or may not have dilatation of the aortic root which can be detected on echocardiography. We conclude that aortic valve involvement may cause aortic regurgitation in some patients with Takayasu arteritis and that aortic regurgitation is more common than previously believed.

Adult↗