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Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 109 records · Page 6Linked to original sources
PubMed1996

Comparison of effects of vasoactive agents on adenylate cyclase activity in endothelial and smooth muscle cells from the same specimen of fetal bovine aorta.

1. Adenylate cyclase activity in vascular endothelial cells (EC) has not been adequately defined. We compared adenylate cyclase activities in EC and smooth muscle cells (SMC) from the same specimen of fetal bovine aorta. 2. The basal adenylate cyclase activities of EC and SMC did not differ significantly (18.9 +/- 0.8 and 21.4 +/- 1.7 pmol/mg protein per min, n = 10, respectively). 3. The adenylate cyclase of EC responded dramatically to catecholamines, with the ED50 value for isoproterenol being 0.036 mu mol/L, and was also more sensitive to calcitonin gene-related peptide than that of SMC. 4. The adenylate cyclase of SMC was more sensitive to prostaglandins (with the ED50 for PGI2 being 0.024 mu mol/L) and glucagon than that of EC, and responded modestly to catecholamines and was almost selectively sensitive to beta1-adrenoceptor agonists. 5. Maximum responses of adenylate cyclase to F-, guanosine 5'-o-(3-thiotriphosphate) and forskolin were greater in SMC than in EC. 6. Based on these findings, it was concluded that EC and SMC differed significantly in adenylate cyclase responsiveness to agonists including hormones, prostaglandins, peptides and substances which may modify the effects of G proteins, although they shared a common developmental origin. Presumably, beta-adrenoceptor agonists in EC and prostaglandins in SMC may appear to play an important role in cellular functions which are mediated by increases in cAMP.

Adenine↗
PubMed1996

Takayasu arteritis: clinical characteristics and the role of genetic factors in its pathogenesis.

Takayasu arteritis is a chronic vasculitis, the aetiology of which is still unknown. Several characteristic clinical manifestations have led scientists to consider the possibility of the genetic factors in the aetiology, conjecture which is supported by HLA analysis. Recent attention has focused on the different clinical manifestations among Asian and South American countries and further progress is likely to stem from international network studies.

Adult↗
PubMed1996

Multiple endocrine neoplasia type 1 associated with spinal ependymoma.

A 51-year-old man was hospitalized with a gait disturbance and hypoesthesia below the level of his chest. These symptoms were due to a spinal tumor which was surgically resected and identified as an ependymoma. Additionally, the patient had hypercalcemia and a family history of insulinoma. An endocrine evaluation revealed parathyroid hyperplasia and a pancreatic islet cell tumor. Magnetic resonance imaging disclosed a pituitary microadenoma. He was diagnosed with spinal ependymoma and multiple endocrine neoplasia type 1 (MEN 1). A review of the literature revealed that chromosome 11q13 abnormalities have been reported in both ependymoma and MEN 1. We discuss the pathogenesis of these diseases.

Chromosome Aberrations↗
PubMed1996

Visceral leishmaniasis misdiagnosed as malignant lymphoma.

Visceral leishmaniasis is a chronic infectious disease caused by a protozoan parasite of the genus Leishmania, characterized by intermittent fever, monocytosis, hepatosplenomegaly and hypergammaglobulinemia. This morbid condition is rather difficult to diagnose correctly, especially at its early stage, because it is rarely encountered in Japan. Recently we treated a case of visceral leishmaniasis in which the patient was misdiagnosed as malignant lymphoma, and went through splenectomy and steroid administration, which made the diagnosis more difficult.

Adult↗
PubMed1996

Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro.

To clarify the mechanisms that cause elevation of plasma fibrinogen levels in diabetes, we first examined the effect of hyperglycemia on the production of interleukin 6 (IL-6) and tumor necrosis factor (TNF) by cultured human peripheral blood monocytes. Monocyte-enriched fractions isolated from 20 healthy volunteers were incubated with 11 mmol/l glucose, 33 mmol/l glucose, or mannitol as an osmolar control for 6 or 24 h. After 6 h of incubation, IL-6 and TNF-alpha mRNA levels were analyzed by reverse transcription and polymerase chain reaction. In addition, after 24 h of incubation, IL-6 and TNF-alpha immunoreactivity in the culture medium was measured by enzyme-linked immunoassay. Both IL-6 and TNF-alpha mRNA levels and immunoreactivity were significantly increased by treatment with 33 mmol/l glucose compared with treatment with 11 mmol/l glucose or 11 mmol/l glucose with 22 mmol/l mannitol. In addition, preincubation of the cells with an anti-TNF monoclonal antibody (mAb) blocked the stimulatory effect of 33 mmol/l glucose on IL-6 synthesis and secretion. Second, we examined the ability of conditioned media from human peripheral blood monocytes to stimulate beta-fibrinogen mRNA synthesis in HepG2 cells. The conditioned medium from monocytes treated with 33 mmol/l glucose increased beta-fibrinogen mRNA levels. The results of this study demonstrate that hyperglycemia stimulated IL-6 and TNF synthesis and secretion by human peripheral monocytes in vitro and that the IL-6 response to hyperglycemia may be mediated by TNF. Furthermore, hyperglycemia may increase fibrinogen levels through stimulation of peripheral monocytes. These results suggest that hyperglycemia may cause hyperfibrinogenemia in diabetic patients through an IL-6-dependent and TNF-dependent mechanism.

Antibodies, Monoclonal↗
PubMed1995

Magnetic resonance imaging of vascular changes in Takayasu arteritis.

We studied the thoracic aorta in 42 female patients with Takayasu arteritis by magnetic resonance imaging (MRI) with a 1.5-T superconducting instrument and compared the findings with those in 10 healthy female controls. Images in the transaxial and oblique sagittal planes were acquired by cardiac gating using a spin-echo pulse sequence. Images in the oblique plane were also obtained with cine MRI. Vascular changes were found in 41 (98%) of the patients. Dilatation of the ascending aorta was observed in 20 patients (48%), while stenotic changes were more characteristic in the descending aorta (16 patients, 38%). Moderate signal-intensity masses on the aortic wall were encountered in 21 patients (50%), suggesting mural thrombi. Turbulent blood flow was observed around all masses by cine MRI. HLA analysis revealed that patients carrying HLA-B52 typing showed these masses more frequently than those without this typing (P < 0.05). Cine MRI demonstrated aortic regurgitation in 20 patients (48%), all of whom showed dilated ascending aorta; furthermore, 14 (70%) of them were confirmed as carrying HLA-B52. Thus, MRI was a useful non-invasive tool not only for the evaluation of the morphological changes in the aorta and its branches, and of the hemodynamic disturbance in Takayasu arteritis, but also for follow-up of the morbid condition.

Adult↗
PubMed1995

Estimation of EDRF and nitric oxide release using [3H]GTP-labeled human platelets.

We have developed a new bioassay for endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) using human [3H]guanosine triphosphate (GTP)-labeled platelets. The labeled platelets were preincubated with isobutyl-methylxanthine and co-cultured with endothelial cells and the [3H]cyclic guanosine monophosphate (cGMP) formed was isolated by ion-exchange chromatography. Endothelial cells, either in monolayer cells or in suspension, increased platelet cGMP accumulation dose-dependently, a significant increase being detected with 5000 endothelial cells or more/assay when suspended cells were used. Co-culturing with the same number of skin fibroblasts failed to elevate platelet cGMP. Preincubation of endothelial cells with bradykinin and superoxide dismutase (SOD) synergistically potentiated the increase in platelet cGMP, but was attenuated by Nomega-nitro-L-arginine, with partial restoration by L-arginine but not by D-arginine. These compounds, however, did not affect cGMP accumulation by sodium nitroprusside. Moreover, preincubation of the labeled platelets with the NO synthase inhibitor prior to EDRF assay had no effect. We conclude that [3H]GTP-labeled platelets could provide a simple, sensitive and specific bioassay for estimating EDRF or NO release.

Animals↗
PubMed1995

What effect does controlling platelets have on atherosclerosis?

Platelets play important roles for hemostasis with activated platelets adhering to the injured vessel wall to initiate platelet aggregation. At the same time, our study revealed the cytotoxic effect on endothelial cells characterized by an increase of intracellular Ca++ and a decrease of EDRF production, which may cause plasmal infiltration including blood cells and lipids. Our clinical survey using a small dose of aspirin as an antiplatelet therapy clearly demonstrated its suppressive effect on platelet aggregation and its favorable effect on fibrinolysis. These data suggest that the therapeutic effect of aspirin in vascular disease could be applied to the prevention of thrombus formation and the protection of endothelial cells from the cytotoxic effect of activated platelets.

Adenylyl Cyclases↗
PubMed1995

The effect of glucose and advanced glycosylation end products on IL-6 production by human monocytes.

To clarify the mechanism that causes elevation of plasma fibrinogen levels in diabetes, we examined the effect of high concentration of glucose and/or advanced glycosylation end products (AGEs) on the production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by human monocytes. Monocytes isolated from nine healthy volunteers were incubated with glucose, glucose with mannitol, or glucose with AGE-BSA for 24 or 48 h, respectively. IL-6 and TNF-alpha levels of culture supernatants were measured by ELISA methods. IL-6 and TNF-alpha levels of culture supernatants incubated with 22 mM or 33 mM glucose showed considerable increase over basal levels incubated with 11 mM glucose, whereas those levels incubated with high concentration of mannitol showed no increase. These two cytokine levels of culture supernatants, especially IL-6 level, showed synergistic elevation with AGE-BSA concentration. Our serial observation with treatment for lowering glucose levels showed that the diabetics with decreasing plasma fibrinogen levels also showed decrease in plasma IL-6 levels. In this study, we revealed the effect of glucose and AGEs on the production of IL-6 or TNF-alpha by human monocytes. These results suggest that hyperglycemia and AGEs will cause disregulated production of IL-6 and hyperfibrinogenemia in diabetics.

Diabetes Mellitus↗
PubMed1995

Effect of nifedipine on cyclic GMP turnover in cultured coronary smooth muscle cells.

We investigated the effects of nifedipine on cyclic GMP turnover and the pertinent enzyme activities in cultured coronary smooth muscle cells (SMC). Nifedipine at high concentrations slightly decreased basal soluble guanylate cyclase activity and inhibited the action of sodium nitroprusside (SNP) but had no effect on the particulate form of the enzyme. In contrast, nifedipine inhibited cyclic GMP hydrolysis by directly inhibiting the partially purified calmodulin-stimulated isoform of phosphodiesterase (type I PDE) with IC50 of 4.2 microM. Nifedipine > or = 1.0 microM enhanced cyclic GMP accumulation in response to 1.0 microM SNP, although nifedipine alone exerted no influence on cyclic GMP levels. Enhancement of cyclic GMP accumulation by nifedipine in response to SNP was not affected by BAY K 8644, a calcium channel agonist. These properties may be shared by other dihydropyridines since nicardipine and nisoldipine also inhibited type I PDE with similar IC50. However, some other structurally unrelated calcium channel blockers, diltiazem and verapamil, had little effect on cyclic nucleotide hydrolysis or on cyclic GMP accumulation in response to SNP. Nifedipine may synergistically enhance cyclic GMP accumulation in response to nitric oxide (NO)-releasing agents by directly inhibiting type I PDE in coronary SMC. Such effects of nifedipine may partly contribute to coronary vasodilation and prevention of coronary spasm in patients with ischemic heart disease.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Long-term follow-up of the reproducibility of carotid sinus hypersensitivity in patients with carotid sinus syndrome.

The reproducibility of carotid sinus hypersensitivity to carotid sinus massage was studied in the long-term follow-up of 8 patients with carotid sinus syndrome. A cardioinhibitory response was induced in 7 patients, while a vasodepressor response was found in the remaining patient. The 7 patients were treated with dual-chamber pacemaker implantation and the remaining patient was treated with propranolol. All of the patients remained asymptomatic during a follow-up period of 48 +/- 11 months. Carotid sinus massage during the follow-up period in patients with a cardioinhibitory response revealed asystolic intervals of 3 s or longer in 4 patients and in 3 patients at the second and third follow-up examinations, respectively, although there were no significant differences in the ventricular asystolic intervals between before, and 34 +/- 11 months and 48 +/- 11 months after treatment. However, each patient showed a wide variation in asystolic intervals. The differences in asystolic intervals between prior to treatment (first) and the third test were significantly greater than those between the first and the second test (2.4 +/- 1.2 s vs 0.7 +/- 0.6 s; p < 0.05). The one patient with a vasodepressor response had a decreased systolic blood pressure greater than 50 mmHg by carotid sinus massage at all three occasions. In conclusion, most patients with carotid sinus syndrome showed abnormal and variable responses to carotid sinus massage during long-term follow-up period although there was no recurrence of symptoms after treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Cytotoxic effect of activated platelets on endothelial cells.

Modern science has made clear the important roles of endothelial cells in both physiological and biochemical functions of vessel wall and their impairment initiate the process of atherosclerotic changes. Activated platelets also injure endothelial cells which were characterized with energy discharge, the decrease of cAMP content, the Ca++ entry, and dysfunction of No production. These data suggest the protection of endothelial cells from the injury could be the important protective factor from atherosclerosis. From this point of view, antiplatelet therapy is not only for antithrombotic but also for endothelial cell protective therapy.

Animals↗
PubMed1995

Detailed examination of vascular lesions triggered by an inhibitor of endothelium-derived relaxing factor.

BACKGROUND: Inhibition of an endothelium-derived relaxing factor (EDRF) may contribute to the pathogenesis of thrombotic arterial occlusions. EXPERIMENTAL DESIGN: We measured the blood pressure and urinary excretion of protein, sodium, and potassium and histologically examined the brains, hearts, and kidneys in normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) fed on a diet containing: (a) EDRF inhibitor (L-N-nitroarginine:L-NNA); (b) L-arginine, which reverses the effect of L-NNA; or (c) both L-NNA and L-arginine for 1 to 8 weeks. In addition, we examined L-NNA-treated SHRSP, the blood pressures of which were lowered using hydralazine. Furthermore, we produced and examined Goldblatt's renal hypertensive rats, which are of a different type from those resulting from the L-NNA treatment. RESULTS: Both WKY and SHRSP rats fed on a diet containing L-NNA suffered from hypertension and cerebral infarctions in a dose-dependent manner. Cerebral infarctions occurred whether or not SHRSP rats were treated with an antihypertensive agent when they were fed a high dosage of L-NNA. In contrast, SHRSP rats, treated simultaneously with both L-NNA and L-arginine, suffered few cerebral infarctions, although they were severely hypertensive. In addition, there were no cerebral infarctions in Goldblatt's renal hypertensive rats, although they suffered from advanced hypertension. CONCLUSIONS: The data indicate that the inhibition of EDRF injures the vessel walls and encourages platelet adhesion to the damaged areas. The adhering platelets narrow the lumen with resultant thrombotic arterial occlusions. Pathophysiologic conditions that decrease EDRF synthesis appear to play an important role in cerebral, renal, and myocardial infarctions.

Animals↗
PubMed1994

Atrial natriuretic peptide reduces cyclic AMP by activating cyclic GMP-stimulated phosphodiesterase in vascular endothelial cells.

Bovine aortic endothelial cells contain cyclic GMP-stimulated phosphodiesterase (PDE) regulating intracellular cyclic AMP and cyclic GMP levels. To investigate the roles of this PDE isoform for cyclic AMP hydrolysis in intact endothelial cells (EC), we used an adenine prelabeling method to determine cyclic AMP accumulation in response to agents that might produce effects that increase cyclic GMP levels. Atrial natriuretic peptide (ANP), which dramatically increased cyclic GMP accumulation, reduced cyclic AMP in cultured EC from bovine aorta with or without addition of L-isoproterenol (L-ISO), whereas sodium nitroprusside (SNP) and 8-bromo cyclic GMP had no effect. The reduction in cyclic AMP by ANP was dose dependent (> or = 1.0 nM) and rapid (significant reduction was induced in < or = 15 s) and was abolished when EC were preincubated with 3-isobutyl-1-methylxanthine (IBMX) and HL-725, both nonselective PDE inhibitors. ANP had no effects on adenylate cyclase activity, nor any direct effects on the activities of partially purified cyclic GMP-stimulated PDE isoform or cyclic AMP-specific isoform. However, cyclic AMP hydrolyzing activities of EC were enhanced when EC were pretreated with 0.1 microM ANP. ANP activates cyclic GMP-stimulated PDE and induces reduction of cyclic AMP accumulation in intact EC, which may modify cyclic GMP-dependent endothelial function involved in ANP.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Alcohol and coronary spasm.

Alcohol is known to sometimes cause coronary spasm, the mechanism of which is still unknown. The authors monitored changes in plasma levels of prostanoids (thromboxane [TX B2], 6-keto prostaglandin F1 alpha [PGF1 alpha]), catecholamines (CA), serotonin (5-HT), cyclic nucleotides (cyclic adenosine monophosphate--cAMP, cyclic guanosine monophosphate--cGMP), and platelet aggregation after alcohol ingestion (Japanese rice wine 400 mL) in 8 patients with alcohol-induced variant angina and 8 healthy men as controls. Coronary spasm was confirmed to have been induced in 4 patients nine hours after alcohol challenge (VA[+]), when their plasma ethanol levels had already returned to a null level. Neither CA nor 5-HT levels showed any change after alcohol ingestion either in patients or controls, though controls showed high levels of CA during alcohol ingestion. TX B2 in VA(+) patients increased gradually after alcohol ingestion to reach up to a statistically significantly high level just before attack, as compared with those of controls and VA(-) patients, who, on the contrary, did not show such changes. The levels of 6-keto PGF1 alpha, however, which were significantly lower in patients than in controls before the test, exhibited a gradual increase in VA(+) patients in parallel with the increase in TX B2. No significant changes in cAMP levels between either controls or patients were present. On the contrary, cGMP levels had a gradual decrease in patients after alcohol ingestion. Especially six hours after alcohol ingestion, cGMP levels in VA(+) patients decreased so much as to make a statistically significant difference, as compared with the level in controls. Platelet aggregability in controls showed a decrease after alcohol ingestion, in spite of no change or even increase in patients. These data suggest that low levels of PGF1 alpha and the decrease of cGMP levels from alcohol ingestion play important roles in the mechanism of coronary spasm induced by alcohol ingestion.

6-Ketoprostaglandin F1 alpha↗