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Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 181 records · Page 10Linked to original sources
PubMed1986

Antiaggregative aspirin dosage at the affected vessel wall.

The present study, using patients with Takayasu's disease (pulseless disease), characterized by segmentally affected arterial lesions and stenotic conditions with a nonspecific inflammatory morbid condition, was designed to assess whether or not a low dose of aspirin can practically exert its preventive effect against the aggregation of platelets that have just passed along a rough-surfaced arterial wall. Twenty Japanese women with Takayasu's disease were selected under the following criteria: A unilateral upper extremity was angiographically confirmed to be affected with the disease, while the contralateral limb was almost normal. Systolic blood pressure on the affected side was almost half that on the nonaffected side. The patients showed neither a positive CRP nor an accentuated ESR. In these patients, mean plasma levels of TXB2 and 3 microM ADP-induced platelet aggregation in blood obtained from the affected side were 156.5 +/- 17.7 pg/ml, and 59.5 +/- 6.0%, respectively, which were significantly high as compared with 104.5 +/- 17.6 and 41.7 +/- 8.8%, respectively, in samples from the nonaffected side. Forty and eighty mg of aspirin per day administered to two randomly composed groups, respectively, showed an improvement in platelet aggregability and TXB2 levels on the nonaffected side. In the affected limbs, though 80 mg/day led to significant decreases in TXB2 levels (108.0 +/- 7.8 pg/ml, p less than 0.05) and platelet aggregability (21.3 +/- 7.6%), the 40-mg regimen showed no significant reductions (134.6 +/- 9.4 pg/ml, 35.6 +/- 17.1%). Plasma levels of 6-keto PGF1 alpha revealed no differences between 40- and 80-mg regimens, or between before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Arch Syndromes↗
PubMed1986

Involvement of cyclic AMP in vasodilatation by amrinone: a comparative study with 3-isobutyl-methyl-xanthine (IBMX).

We investigated the effect of amrinone, a non-glycosidic, non-adrenergic cardiotonic drug, on rabbit aortic strips and vascular smooth muscle cells cultured from rabbit aorta. Amrinone relaxed the strips precontracted by KCl, norepinephrine, serotonin or STA2 in a dose-dependent manner, and it shifted the dose-response curves downward. A similar mode of relaxation was noted with IBMX, an inhibitor of cyclic AMP phosphodiesterase (cAMPPDE). Although propranolol did not affect the relaxation induced by amrinone, W-7, a calmodulin antagonist, slightly potentiated and IBMX attenuated the response. In intact smooth muscle cells in culture, amrinone increased basal levels of cAMP and markedly potentiated cAMP accumulation in response to 10(-6) M isoproterenol. The effect on cAMP accumulation mimicked that of IBMX but the effects were not additive. Inhibition of cAMPPDE was also demonstrated in a cell-free system, IC50 values for amrinone and IBMX being 2.1 X 10(-5) M and 1.2 X 10(-6) M, respectively, using a preparation of cAMPPDE partially purified from the cells by DEAE cellulose chromatography. Amrinone seems to exert a direct effect on vascular smooth muscle cells by potently inhibiting cAMPPDE. This inhibition would to some extent explain the vasodilatory property.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Hereditary factors in Takayasu disease. II. Various blood types.

As HLA studies suggest that the genetic factors contributing to the pathogenesis of Takayasu disease may be polygene, various red blood types, allotypes of serum protein and red blood cell enzyme polymorphisms in eighty-four patients with Takayasu disease were studied and their phenotypes and gene frequencies were compared with those in healthy Japanese. Statistically significant high frequencies of phenotypes and/or gene frequencies were confirmed in MNSs, Rh-Hr, Tf, Gc and Pi in Takayasu disease, as compared with those in controls. These characteristics of gene frequencies were more remarkable in patients who do not carry HLA Bw52. These data suggest that the genetic factors contributing to the pathogenesis of Takayasu disease are polygene and may be located in chromosome No. 1, 4 and 14.

Adult↗
PubMed1986

HLA in Buerger's disease.

Recent studies have focused on the possible genetic factor(s) in the pathogenesis of Buerger's disease as well as in Takayasu's disease. We investigated HLA-A, B, C, DR, and DQ antigens in 59 patients with Buerger's disease to confirm statistically significant high frequencies of Aw24, Bw40, Bw54, Cw1, and DR2 antigens and a low frequency of DR9 and DRw52 as compared with those in 152 normal Japanese individuals. As the haplotpye Aw24-Bw54-Cw1-DR4 is known to be common among Japanese, a significantly high frequency of haplotype Bw54-DR2 found in cases of Buerger's disease, instead of that of Bw54-DR4, may suggest a possible cross-linkage occurrence in chromosome 6, which could prove to be an important causative phenomenon in the pathophysiology of Buerger's disease.

Disease Susceptibility↗
PubMed1985

Cyclic AMP accumulation in rabbit aorta smooth muscle cells altered in the presence of hyperlipidemic serum.

We investigated the effect of hyperlipidemic serum on cAMP accumulation in cultured smooth muscle cells from the rabbit aorta. The cells were grown to confluence, then cultured for 24 h in hyperlipidemic medium (total cholesterol: 2.2 mmol/l). cAMP accumulation was enhanced in response to isoproterenol 10(-6) M, as compared to control cells, and this enhancement was still detectable in the presence of IBMX 10(-3) M, a potent inhibitor of phosphodiesterase. Application of propranolol 10(-4) M at 5 min after isoproterenol showed a similar time course for cAMP disappearance. The phosphodiesterase activity in the 40 000 g supernatant of the Triton X-100 solubilized homogenates of the cells in hyperlipidemic medium remained unchanged. Beta-receptor assays showed an increased Bmax with a similar Kd, and such may contribute, at least in part, to the increased adenylate cyclase activity. An extended incubation in the presence of hyperlipidemic medium attenuated the cAMP accumulation, possibly due to excessive increases in the total cholesterol content.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Prostacyclin and variant angina.

Plasma levels of thromboxane B2 (TXB2) and 6-keto PGF1 alpha in the blood samples taken at the coronary sinus and ascending aorta from twenty-one Japanese patients with variant angina and twenty with effort angina were measured by radioimmunoassay, the objective being to search for the contribution of prostanoids in coronary spasm. The data were compared with data on thirteen subjects free from coronary artery diseases. In coronary sinus blood, plasma TXB2 in patients with effort angina exhibited statistically significant high levels, as compared with data in the controls. These with variant angina also had high levels, albeit without a statistically significant difference. Eight patients with variant angina and for whom the coronary angiogram showed more than 50% of narrowing had statistically significant high levels of TXB2, and the other thirteen with variant angina and normal coronaries or less than 50% of narrowing had the same plasma levels of TXB2 as the controls. In contrast to TXB2, the plasma levels of 6-keto PGF1 alpha in both coronary sinus and aortic blood of patients with variant angina were very low, as compared with normal controls. Statistically significant low levels of 6-keto PGF1 alpha were noted in the coronary sinus blood of patients with variant angina with normal coronaries and in the aortic blood of those with variant angina, as compared with data on the normal controls. Neither ergonovine test nor spontaneous attacks in patients with variant angina revealed characteristic changes in levels of TXB2 and 6-keto PGF1 alpha in the coronary sinus. These data suggest that high levels of TXB2 in patients with atherosclerotic coronaries may be one factor leading to spasm, while low levels of PGI2 may be a contributing factor.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Coronary spasm, prostaglandin and HLA factors.

To elucidate the contribution of prostanoids in coronary spasm, plasma levels of thromboxane B2 (TXB2) and 6-keto PGF1 alpha at the coronary sinus and ascending aorta in 21 patients with variant angina were measured, as compared with findings in 20 with effort angina and 13 subjects with normal coronaries. In the coronary sinus blood, plasma TXB2 in patients with effort angina exhibited statistically significant high levels, as compared with data in the controls. On the contrary, the data obtained from patients with variant angina were not statistically significant. However, eight patients whose coronary angiogram revealed more than 50% of coronary stenoses had statistically significant high levels of TXB2 and other patients with normal coronaries or less than 50% of narrowing showed almost the same levels of TXB2 as the controls. In contrast to TXB2, the plasma levels of 6-keto PGF1 alpha in patients with variant angina were very low in both groups with variant angina. These data suggest that high levels of TXB2 observed in patients with atherosclerotic coronaries may be an accelerating factor while low levels of prostacyclin may be an essential factor leading to spasm. HLA analysis of 23 patients with variant angina was performed to search for genetic factors, under the hypothesis that such may contribute to the low levels in prostacyclin. This preliminary study revealed statistically significant high frequencies of Bw52 and B-40 in the patients, as compared with frequencies among 152 normal Japanese. Genetic studies are ongoing in our clinic.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Plasma thromboxane B2, 6-keto PGF1 alpha and cyclic nucleotides levels as related to treadmill exercise test in patients with ischemic heart disease.

Plasma prostanoids and levels of cyclic nucleotides were studied in forty-nine outpatients with precordial pains and subjected to the treadmill exercise test. Blood samples were drawn before, immediately after and 30 minutes after exercise, from antecubital veins. Plasma TXB2, 6-keto PGF1 alpha, cyclic AMP and cyclic GMP levels were measured by radioimmunoassay. The results of exercise tests were evaluated according to the treadmill exercise score (TES) of Hollenberg et al. Patients were divided into two groups; those with TES (-) with ischemic findings in exercise and those with TES (+) with normal exercise response. There were no differences in TXB2 levels between the two groups before exercise. Immediately after exercise statistically significant differences in TXB2 levels were present between the two groups. There were increased levels in the TES (-) group and decreased levels in the TES (+) group (p less than 0.01). Although the 6-keto PGF1 alpha levels were the same between the two groups before exercise, 6-keto PGF1 alpha levels in the TES (+) group increased significantly immediately after exercise. Similar changes were noted in the case of cyclic nucleotides, and the differences increased immediately after exercise. We conclude that high responses of cyclic nucleotides and PGI2 are required to counteract increases in levels of TXA2 and diminution of these responses may be an important phenomenon involved in the physiological status of ischemic heart disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Contractions in normal and atherosclerotic rabbit aortas.

Length-tension relationships and contractile responses to agonists associated with cyclic nucleotide levels in aortas from atherosclerotic rabbits were studied. The same number of tissues from healthy rabbits was also studied. Diffuse lesions were produced by denudation of the vascular endothelium of rabbit aorta using a balloon catheter and then feeding these rabbits a high cholesterol diet for two months. Stretch-passive tension curves and length-active tension curves which developed in the presence of 60 mM KCl significantly shifted to the left. The altered length-tension relationships indicate a decreased distensibility in these strips and this is attributed to an enhanced accumulation of collagen. Dose-response curve analysis revealed a marked hypersensitivity to serotonin as indicated by greater pD2 values (negative logarithm of half maximum dose) than seen in the controls. In addition, the mean absolute values of the maximum contraction induced by serotonin and KCl were significantly higher than in the controls. Although cyclic AMP levels in the strips with a pathology were lower and cyclic GMP/cyclic AMP ratios were higher than the controls in the basal state, serotonin induced no marked alterations in the cyclic nucleotides levels in the strips from either the diseased or control rabbits. These mechanical and pharmacological alterations of atherosclerotic vessels may relate to clinical events such as coronary spasm.

Animals↗
PubMed1983

HLA-DR MT and MB antigens in Takayasu disease.

Recent studies on the pathogenesis of Takayasu disease have focussed on the participation of genetic factors, and HLA analysis has confirmed the close relationship between Takayasu disease and HLA Bw52. In an attempt to investigate the association of immune response gene with the disease, HLA-DR (DR-1, -2, -3, -4, -5, -w6, -7, -w8, -w9, -w10), MT (-1, -2, -3), MB (-1, -3) antigens were studied in 52 patients with Takayasu disease and the data compared with findings in healthy Japanese. As there were no statistical differences between the two groups in the frequencies of all these antigens, genetic factors in Takayasu disease may be much more closely associated with B than with D loci.

Aortic Arch Syndromes↗