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Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 199 records · Page 11Linked to original sources
PubMed1982

A study of the mechanism of estrogen as an antiatherosclerotic: the inhibitory effect of estrogen on A23187-induced contraction of the aortic wall.

Although the antiatherosclerotic effects of estrogen are well known, the mechanisms involved have not been determined. We designed experiments in which strips of thoracic aorta from oophorectomized rabbits were contracted by the calcium ionophore A23187 and the inhibition of the contraction by estrogen and concomitant levels of cyclic nucleotides were determined. A23187 (10(-5) M) increased the tension slowly but progressively, and there was a concomitant decrease in cyclic AMP levels. While a dose-dependent relaxation occurred in strips contracted by A23187 with addition of theophylline (greater than 10(-4) M) or dibutyryl cyclic AMP (greater than 10(-4) M) to the bath, prior addition of these compounds inhibited the contraction. Pretreatment of the strips with estrogen (2 x 1-(-7) M, 2 x 10(-5) M) significantly prevented contraction of the strips, as induced by A23187, and also prevented reduction in cyclic AMP levels, as induced by the ionophore. Cyclic GMP levels remained unchanged throughout. As the contraction of these tissues wall was inhibited by estrogen in an apparent association with a reduction in the levels of cyclic AMP, this might help to explain the antiatherosclerotic effects of estrogen, as reduction in these nucleotide levels has been suggested to induce atherosclerotic lesions in the arterial wall by enhancing vascular permeability.

Animals↗
PubMed1982

Hereditary factors in Takayasu's disease.

In an attempt to provide support for the genetic link theory as related to the etiology of Takayasu's disease, we analyzed simultaneously A, B, and D loci of HLA antigens in 75 Japanese patients with the disease. Serving as control were 128 healthy Japanese. A statistically significant high frequency of BW52 and DHO was confirmed with the levels being 25.6 and 10.4, respectively, in the chi 2 test. A haplotype of A9-BW52-DHO was frequently evident in these patients as compared to the controls, and here also the statistical difference was significant. There appears to be a closer relationship of the gene to BW52 than to DHO. A survey of the homozygote of BW52 revealed 6 of 75 patients with BW52; however, statistically speaking, this rate did not differ from the expected one. Thus, our analysis of HLA illustrates the genetic factors involved in Takayasu's disease. The genes are located between the B and D loci and are closer to BW52 than DHO and these genes have a dominant character.

Aortic Arch Syndromes↗
PubMed1982

Changes in the plasma levels of thromboxane B2 and cyclic nucleotides in patients with Takayasu disease.

Plasma thromboxane B2 (TXB2), cyclic AMP and cyclic GMP levels in 31 women with Takayasu disease were measured and findings were compared with data on 34 age-matched healthy Japanese. Platelet aggregation determined by the screen filtration pressure (SEP) method and pulmonary lesions assessed by scintillation were studied in 21 patients. Plasma TXB2 levels in patients with Takayasu disease were 265.8 +/- 20.4 pg/ml, which were statistically higher than the levels of 196.3 +/- 10.7 in healthy controls. On the contrary, cyclic AMP levels in the patients were 9.6 +/- 0.7 pmols/ml, statistically lower levels than 13.5 +/- 1.0 seen in the healthy controls. A positive correlation among cyclic AMP, cyclic GMP and TXB2 levels was confirmed only in the controls. SEP values in the patients with pulmonary lesions were significantly higher than in those without lesions and also in the controls. A positive correlation was obtained between SEP and TXB2 levels in healthy controls, but not in the patients. Thus, thromboxane A2 may play an important role in the pathology of Takayasu disease.

Adult↗
PubMed1982

HLA and clinical manifestations in Takayasu disease.

In previous studies on HLA antigens in patients with Takayasu disease, we found a statistically high frequency of haplotype Bw52-Dw12. Clinico-pathological conditions of this disease observed for 85 +/- 3 months were compared between 29 patients with (positive group) and 39 patients without this haplotype (negative group), among 82 patients with Takayasu disease. Blood sedimentation rate and C-reactive protein exhibited statistically significant high figures in the positive group as compared with those in negative group, while no difference were seen in rheumatoid arthritis test, antistreptolysin-0 titer, anti-DNA antibody, levels of circulating immune complexes, platelet aggregation, although all revealed high levels in the positive group. Pulmonary disorders were more frequent in positive group. Fourteen patients (48%) in the positive group and 5 (13%) in the negative group had abnormalities in the aortic valve (p less than 0.01). In 14 patients in the positive (38%) and 5 in the negative (13%) groups, the systolic blood pressure was over 140 mmHg (p less than 0.01). Four patients in the positive (17%) and one in the negative groups (3%) were blind (p less than 0.01). These data suggest that in patients with a haplotype of Bw52-Dw12, there is a greater likelihood of an active inflammatory state and a rapid progression of these morbid conditions.

ABO Blood-Group System↗
PubMed1981

Plasma thromboxane B2 levels and atherosclerotic disorders.

In our ongoing studies of the interrelationship between platelets and the vascular wall we found that an accurate estimate could be made of the clinical condition and more effective therapy prescribed when we monitored alterations in the plasma levels of TXB2. For this purpose we devised a radioimmunoassay with I125-TXB2-Tyramide. Patients with ischemic heart disorders, cerebral apoplexy, diabetes mellitus, Buerger's disease, Takayasu disease etc., all had statistically high levels of TXB2 as compared with healthy controls. In particular, patients with myocardial infarction, cerebral thrombosis and/or hemorrhage all revealed increases in levels of TXB2 and these levels increased in parallel with a worsening of the clinical condition, and there was always a re-increase in TXB2 level before a recurrence of an attack. As plasma TXB2 levels clearly reflect thrombogenic disorders, the assessment of these levels on a routine basis, enables a more accurate diagnosis, an indication of possible recurrences, and more effective chemotherapy and rehabilitation.

Adolescent↗
PubMed1980

Chemotherapy of atherosclerosis.

Clinical and experimental studies have provided an increasing amount of evidence that atherosclerosis is preventable and that regression is feasible. Although the elimination of risk factors would be a form of primary prevention such is hardly feasible in our modern industrial age. Thus the combination of elimination or at least decrease in risk factors and a direct treatment of the arterial wall should help to bring about this prevention and regression. Metabolic changes and/or dysfunction of the vessel wall particularly endothelial cells has been given increasing attention. Energy and cyclic nucleotide metabolism in endothelial cells have been studied in the initiation, progression and regression of atherosclerosis. Several compounds were found to exert beneficial effects on metabolism in the endothelial cells and clinical favorable effects have been documented. Chemotherapy for the treatment of "endotheliopathy" and atherosclerosis will not doubt be the object of intensive studies.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

Circulating immune complexes in Takayasu disease.

Circulating immune complexes in Takayasu disease were investigated to assess the involvement of autoimmune mechanisms. Antibody dependent cell-mediated cytotoxicity (ADCC) and Raji cell assay revealed: The 10 percent inhibition of ADCC in 37 patients was 35.6 +/- 5.2, this being a non-statistically significant value as compared with the values of 25.6 +/- 3.0 in 33 apparently healthy controls. Raji cell assay values were 30.4 +/- 11.5 and 3.5 +/- 2.3 for patients and controls, respectively. As 54% of all these patients had a negative reaction and there was no correlation between immune complex levels and BSR, CRP, or ASO, immune complexes, while accelerating or modifying the pathophysiological state, probably are not primary causative factors.

Adult↗
PubMed1980

Effects of phthalazinol (EG 626) and pyridinolcarbamate (Anginin) on lipolytic enzyme activities in rat adipose tissue -in vivo and in vitro-.

Effects of Phthalazinol (EG 626), a cyclic AMP phosphodiesterase inhibitor, a thromboxane A2 antagonist and an antiatherosclerotic agent was examined regarding lipolytic enzyme activities in rat epididymal adipose tissue. The effect of Pyridinolcarbamate (Anginin) was concomitantly examined. There was a significant decrease in serum triacylglycerol levels in rats given EG 626 (100-500 mg/kg), p.o. for 1-3 weeks. In adipose tissue from EG 626 treated rats, the basal and adrenalin induced lipolysis, and cholesterylester hydrolase activity were markedly enhanced, while the phosphodiesterase activity was decreased. Anginin treatment had no effect either on the serum lipid levels or the cholesterylester hydrolase activity. An elevation in cholesterylester hydrolase activity and lipolysis by EG 626 was observed both in vivo and in vitro. Incubation of the adipose tissue with 0.229 mM of EG 626 or 0.603 mM of theophylline induced a lipolysis equivalent to that seen with 2.7 x 10(-2) mM of adrenalin. These results indicate that EG 626 exerted marked effects on lipolysis and cholesterylester hydrolase activity, probably through inhibition of phosphodiesterase. Possible contributions of the enhanced cholesterylester hydrolase activities to the antiatherogenic effect were discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

HL-A antigens in Takayasu's disease.

Takayasu's disease is characterized by a "pulseless" condition which most often occurs in young females from Asian or South American areas. The cause of this disease remains obscure. Recently, we encountered monozygotic, Japanese, identical twin sisters, both of whom were diagnosed as having Takayasu's disease. The parents, two sisters, and one brother are healthy. HL-A typing analyses revealed that one haplotype found in the father had passed only to these twins. Such observations led us to search HL-A typing in Takayasu's disease to determine the possible participation of genetic factors in the pathogenesis of this morbid condition. Ten families, including that of our own patient, have been reported in the literature in Japan, as family cases of Takayasu's disease. HL-A typings in A and B locus analyzed in all family members of six families in attempts to find a common haplotype composed of A9, A10, B5, or BW40 in patients with Takayasu's disease, were confirmed statistically (chi 2 = 7.8, 0.01 less than p less than 0.05). In a population study, HL-A typing analyses of 65 patients with Takayasu's disease also revealed a high frequency of HL-A A10 and HL-A B5 with the level of 15.3 and 17.0 in the chi 2-test (p less than 10(-4)), as compared with the frequency in 128 healthy Japanese. These data strongly suggest that a genetic-related factor has to be given serious consideration.

Adult↗
PubMed1979

Microassay of cyclic nucleotides in vessel wall. IV. Cyclic GMP phosphodiesterase activity.

Following our microassay for cyclic AMP phosphodiesterase (1978, Microvascular Res. 15:229), a new microassay for cyclic GMP phosphodiesterase (c-GMPPDE) activity was devised, combining the quantitative histochemical method of O.H. Lowry and J.V. Passonneau (1971, A Flexible System of Enzymatic Analysis, Academic Press, New York) with the thin-layer chromatography method of W.A. Scott and B. Solomon (1973, Biochem. Biophys. Res. Comm., 53, 1024). Using this method, c-GMPPDE activity can be accurately measured in a 250 microgram dry weight sample of tissue from the aortic wall. The optimal amount of sample and incubation time were studied, and two Km values were obtained. Low Km is 4.00 x 10(-6) and high Km is 1.25 x 10(-5). The activity of this enzyme was measured in the intima and media of the aorta of three rabbits, three cows and three pigs. The cyclic GMPPDE activities in tissue from cows, pigs and rabbits were 26.61 +/- 2.19, 20.40 +/- 1.35, 43.08 +/- 4.11 pmole/mg dry weight/min in the intima; 52.56 +/- 2.73, 16.07 +/- 3.30 and 66.51 +/- 4.60 pmole/mg dry weight/min in the media. With regard to the relationship between levels of cAMP and cGMP, the activities of cGMPPDE were 10-20 times higher than those of cAMPPDE. These assay systems should provide accurate tools for researching biological, physiological and pathological states of arterial tissues, particularly in the case of atherosclerosis.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1979

Effects of phthalazinol (EG 626) on arterial lipolytic enzyme activities in the rat.

Phthalazinol (EG 626), a thromboxane A2 antagonist and cyclic AMP phosphodiesterase inhibitor, has been shown to prevent the atherosclerosis induced in cholesterol fed rabbits. In an attempt to clarify the antiatherosclerotic mechanism, the effects of this compound on the lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) of rat aorta were examined in vivo. Administration of EG 626 (100-200 mg/kg, per os, daily, 1-2 weeks) affected neither the aortic lysosomal cholesterol esterase nor the acid phosphatase activity, whereas the lipoprotein lipase activity was signficantly decreased by the treatment. These results suggest that with an elevation in HDL-cholesterol, a decrease in lipoprotein lipase activity after ingestion of EG 626 might contribute, at least to some extent, to the prevention of arterial lipid accumulation.

3',5'-Cyclic-AMP Phosphodiesterases↗