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Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 19 recordsLinked to original sources

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

Left ventricular dysfunction and HLA Bw52 antigen in Takayasu arteritis.

Heart disease is the main cause of death in patients with Takayasu arteritis. It has been reported that this disease is closely related to the presence of HLA Bw52 antigen. To assess the correlation between this antigen and left ventricular involvement, we studied 40 patients with Takayasu arteritis, 21 with and 19 without Bw52, using Tl-201 stress myocardial scintigraphy and echocardiography. Those with Bw52 had a significantly higher incidence of abnormal electrocardiographic findings (67% vs 26%; P < 0.05) and of aortic regurgitation (52% vs 11%; P < 0.05). The echocardiographically determined interventricular septal wall thickness plus left ventricular posterior wall thickness (25 +/- 8 vs 17 +/- 3 mm; P < 0.01) and the left ventricular mass (257 +/- 132 vs 142 +/- 51 g; P < 0.01) were significantly increased in the patients with Bw52. Scintigraphically determined perfusion abnormalities were significantly more frequent in those with Bw52 (76% vs 32%; P < 0.05). These observations indicate that patients with Takayasu arteritis and Bw52 antigen have a more severe left ventricular involvement than the patients without that antigen. The left ventricular impairment may account for the poor prognosis of Takayasu patients with Bw52.

Adult

Pregnancy in Takayasu arteritis from the view of internal medicine.

To evaluate the influence of pregnancy on the morbid condition of Takayasu arteritis, we summarized the clinical data and pregnant courses of 18 patients with Takayasu arteritis and a total of 22 deliveries. We followed C-reactive protein (CRP) scores in 16 of 18 patients (20 of 22 deliveries) to ascertain the inflammatory condition inherent in Takayasu arteritis 1 year prior to, during, and 1 year after pregnancy. We also evaluated digital plethysmograms (pulse amplitude, pulse wave, crest time) to follow the hemodynamical condition of patients before, during, and after pregnancy. CRP scores improved significantly during pregnancy and 1 year after delivery. In the digital plethysmograms, pulse amplitude and wave also exhibited improvement after delivery, but crest time remained unchanged. This indicated that pregnancy is a state favorable to this disease. Some factors, such as the sex hormone progesterone, may induce this condition, but the details are still unknown. In conclusion, inflammatory activity and the hemodynamic state improve with pregnancy in patients with Takayasu arteritis. The physiologic aspects which cause this improvement should be maintained even after pregnancy.

Adult

Takayasu arteritis: follow-up studies for 20 years.

We reviewed retrospectively 126 (5 male, 121 female) patients suffering from Takayasu arteritis who had been treated in our clinics from 1971 to 1990. The patients' ages ranged from 19 to 80 yrs old (1990) with a mean age of 48.7 +/- 11.8 years. HLA typing analysis in 98 patients revealed that 45 patients (47%) were confirmed as carrying the Bw52 antigen, a high result that is statistically significant as compared with that in healthy Japanese. Arteriograms (performed in 75 patients) revealed that 28 patients (37%) were affected in the aorta and its main branches by this disease (type IV by Nasu's classification) and 23 patients (31%) were affected only in the main branches (type I). The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved significantly from 2.55 +/- 0.28(+) and 57.0 +/- 5.69 mm/hr to 0.53 +/- 0.12(+) and 31.2 +/- 3.45 mm/hr, respectively after treatment including steroid and antiplatelet therapy (P < 0.01). Patients with Bw52 exhibited more severe inflammatory conditions than those without Bw52. Lung scintillations performed in 81 patients showed pulmonary arterial lesions in 50 patients (62%). Echocardiograms revealed aortic regurgitation (AR) in 44 patients (35%), with a significant difference noted between the Bw52 positive group and the Bw52 negative group [29/40 (73%) versus 11/47 (23%), respectively, P < 0.001]. Patients with Bw52 were prescribed higher doses of steroids (P < 0.05) for longer periods (P < 0.01) than those without Bw52.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Inhibition of platelet aggregation by prostacyclin is attenuated after exercise in patients with angina pectoris.

We tested whether alteration of platelet sensitivity to prostacyclin (PGI2) is involved in the activation of platelets induced by exercise in patients with stable angina. Twenty patients and 20 control subjects underwent treadmill testing. Blood samples were obtained before and immediately after exercise for plasma thromboxane B2 (TXB2) and 6-keto-PGF1 alpha (6kP) assays and platelet aggregation studies. Dose-response curves for platelet aggregation to collagen were obtained in the presence and absence of 1 nmol/L PGI2 to quantify the antiaggregation effects of PGI2. At rest, platelet aggregation by collagen was enhanced in the patients. However, platelets were more sensitive to exogenous PGI2, apparently associated with lower plasma 6kP levels in the patients. After exercise, plasma TXB2 levels increased in the patients but not in the control subjects. Plasma 6kP levels remained unchanged and platelet sensitivity to PGI2 decreased in the patients whereas these values increased in the control subjects. The exercise-induced changes in platelet sensitivity to PGI2 correlated with those of platelet adenylate cyclase activity in response to 1 nmol/L PGI2 (r = 0.787, p less than 0.01). Thus impaired sensitivity of platelets to PGI2, in addition to the reduced response of prostanoid secretion, might be relevant to the platelet activation associated with exercise in patients with stable angina.

6-Ketoprostaglandin F1 alpha

Polymerase-chain-reaction-based analysis of polymorphism in the HLA-B gene.

The polymerase chain reaction (PCR) in combination with the sequence-specific oligonucleotide probe (SSOP) was applied to analyze the polymorphism in the exon 2 of the HLA-B gene. In this study, genomic DNAs from 85 B-lymphoblastoid cell lines homozygous for HLA and peripheral blood granulocytes of 156 Japanese individuals were investigated. Two HLA-B-specific 5'-sided primers (CG4 and CG5) and two 3'-sided primers (CG2 and CG3) were designed for specific amplification of the exon. HLA-B alleles were classified into two groups (groups I and II) according to specific amplification with two types of the 3'-sided primers. The amplified DNAs were hybridized with 23 nonradioactively labeled SSOPs. Based on the hybridization patterns with the SSOPs, 34 HLA-B specificities were divided into 26 epitope combination (EC) groups. Fifteen HLA-B specificities were classified into four EC groups and these HLA-B specificities could not be distinguished from one another in the same EC group. Another 16 HLA-B specificities corresponded one by one to 16 distinct EC groups, and two subtypes of HLA-Bw75, B27, and Bw48 were also identified enabling the accurate typing of 22 HLA-B alleles at the DNA level. Single-strand conformation polymorphism (SSCP) of the PCR products from group I HLA-B alleles was also investigated. The HLA-B alleles showed distinct electrophoretic patterns in nondenaturing polyacrylamide gels, depending on the nucleotide sequences of the exon 2, indicating that the SSCP analysis may be an alternative, useful and practical HLA-matching system of HLA-B specificity in tissue transplantation.

Alleles

HLA-DP antigen and Takayasu arteritis.

Sixty-four patients with Takayasu arteritis and 317 healthy individuals 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 PCR/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, 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 combination or haplotype of HLA-Bw52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 -DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another combination or haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. Because this is the first evidence for the association between an HLA-DP allele and Takayasu arteritis, we examined the nucleotide sequences of the DPB1*0901 allele from a patient and her healthy relatives and found no difference. The disease is therefore not caused by a mutated DPB1 gene.

Alleles

Effect of increasing heart rate on Doppler indices of left ventricular performance in healthy men.

OBJECTIVE: To investigate the effects of heart rate on the Doppler measurements of left ventricular function and to determine the normal pattern of rate dependency. SETTING: University hospital specialising in internal medicine. PARTICIPANTS: 14 healthy male volunteers 10 of whom were studied. INTERVENTION: Transoesophageal atrial pacing. MAIN OUTCOME MEASURES: At paced rates of 70, 80, and 90 ppm the ratio of early to late peak transmitral flow velocity (E/A) was 1.97 (0.28), 1.49 (0.21), and 0.95 (0.11) respectively; the ratio of early to late time-velocity integrals of transmitral flow (Ei/Ai) was 3.03 (0.51), 2.11 (0.24), and 1.14 (0.30) respectively; and the atrial filling fraction (AFF) was 0.17 (0.03), 0.21, (0.04), and 0.24 (0.04) (mean (SD)). RESULTS: Heart rate showed a linear correlation with E/A (r2 = 0.806), Ei/Ai (r2 = 0.838), and AFF (r2 = 0.343). Neither the peak aortic flow velocity or the mean aortic flow acceleration showed significant changes during pacing at rates of 70, 80, 90, and 100 ppm. CONCLUSIONS: E/A and Ei/Ai can be expected to decrease by 0.5 and 0.9 for each increase of 10 beats/min in heart rate. Knowledge of this relation may be useful for the development of algorithms to correct for heart rate when diastolic function is assessed.

Adult

Left ventricular geometry in Takayasu arteritis complicated by severe aortic regurgitation.

Although it has been reported that the aortic regurgitation (AR) of patients with Takayasu arteritis is due to dilatation of the aortic ring, the geometry of the left ventricle (LV) has not been described. We compared the cardiac findings in patients with Takayasu arteritis (TA) and severe AR with those of patients having severe AR of other origins. Echocardiographically, wall thickness (WT) and the concentric hypertrophic ratio (WT/WT + left ventricular end-diastolic dimension) were greater in patients with TA. It is concluded that the LV of the TA patients revealed concentric hypertrophy even when AR was severe.

Aortic Valve Insufficiency