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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 91 records · Page 5Linked to original sources
PubMed1992

Superoxide dismutase enhances ischemia-induced reactive hyperemic flow and adenosine release in dogs. A role of 5'-nucleotidase activity.

To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n = 62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307 +/- 5 versus 92 +/- 1 ml.100 g-1.min-1 at baseline) with increased release of adenosine (14.4 +/- 1.4 versus 0.4 +/- 0.1 nmol.100 g-1.min-1 at baseline). Superoxide dismutase augmented (p less than 0.001) both peak coronary blood flow (333 +/- 6 ml.100 g-1.min-1) and repayment (436 +/- 12 versus 320 +/- 7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5'-nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia.

5'-Nucleotidase↗
PubMed1992

Heparin adheres to the damaged arterial wall and inhibits its thrombogenicity.

Heparin binds to thrombogenic extracellular matrices as well as to smooth muscle cells of the vascular wall in vitro. The inhibitory effects of heparin on thrombogenicity of the damaged arterial wall were examined in vivo using small mesenteric arteries of rats and a video recording system attached to a microscope. To induce thrombosis, we damaged the vessel wall over a short segment by compression and exposed the media to the blood stream. A platelet-rich thrombus enlarged gradually at the damaged site, occluded the vascular lumen for a short period, and then flowed away. Compression damage induced such thrombus formation several times. Heparin (500 units/ml) was given in three different ways: intravenous and intra-arterial administration (both 300 units/kg) and intraluminal application under stopped-flow conditions (less than 0.01 ml) for 1-2 minutes with subsequent draining out. Intravenous heparin significantly decreased both the total duration and the number of thrombotic occlusions, whereas intra-arterial heparin abolished thrombotic occlusion. Both routes of heparin administration similarly prolonged the blood coagulation time. Intraluminal application of heparin significantly inhibited subsequent thrombus formation after restoring the flow without changes in the blood coagulation time. After an intra-arterial administration or intraluminal application of fluorescein isothiocyanate-bound heparin, strong fluorescence was observed only at the damaged vascular segment. A heparin fraction with low affinity to antithrombin III or chondroitin sulfate A did not inhibit thrombosis. To clarify anticoagulant activity of vascular wall-bound heparin, damaged carotid arterial segments of rats were incubated (inside out) in platelet-poor plasma with thrombin, and fibrin clot formation around the segments with or without heparin binding was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Assessment of valvular regurgitation using cine magnetic resonance imaging coupled with phase compensation technique: comparison with Doppler color flow mapping.

To elucidate whether or not a newly developed technique in cinematic-displayed (cine) magnetic resonance imaging (MRI) can improve the semiquantitative evaluation of valvular regurgitant flow, 20 patients with valvular lesions were studied. Three pulse sequences of cine MRI, ie, standard, short echo time (TE), and rephasing scans, were compared with reference obtained by Doppler color flow mapping. Short TE technique and rephasing scan technique improved image quality remarkably as compared with standard technique. Each of the three cine MRI techniques showed good correlation with the Doppler method (p < 0.001). However, short TE and rephasing scan techniques gave a faithful estimation of the extent as compared with the Doppler method, whereas standard technique overestimated the regurgitation. Thus, cine magnetic resonance imaging with phase compensation technique can be utilized for the semiquantitative assessment of valvular regurgitation in a manner similar to that of Doppler color flow mapping.

Aged↗
PubMed1992

Serum propeptide and intact molecular osteocalcin in normal children and children with growth hormone (GH) deficiency: a potential marker of bone growth and response to GH therapy.

To establish a sensitive marker for bone formation we have developed a sandwich enzyme-linked immunosorbent assay for intact osteocalcin (OC) and its propeptide. Serum levels of these peptides were studied in 185 normal children, aged 4-15 yr, and in 23 GH-deficient children treated with GH. The serum levels of the propeptide in normal prepubescent children were 1.43 +/- 0.23 (mean +/- SE) micrograms/L in boys and 1.53 +/- 0.23 micrograms/L in girls. The peak value occurred at the age of 13 yr in boys (2.91 +/- 0.42 micrograms/L) and 11 yr in girls (2.34 +/- 0.34 micrograms/L). The serum intact OC levels in prepubescent boys and girls were 18.8 +/- 2.1 and 20.7 +/- 2.1 micrograms/L, respectively, and these levels increased to 41.0 +/- 3.7 micrograms/L in boys aged 13 yr and to 27.0 +/- 2.5 micrograms/L in girls aged 11 yr. In the GH-deficient patients, a 2.3-fold increase in the propeptide level and a 1.7-fold increase in the intact OC level was observed after 1 month of GH therapy. Serum propeptide and intact OC levels after 1 month of GH therapy correlated with the growth response after 12 months of GH therapy (r = 0.660 and P < 0.01, for propeptide; r = 0.537 and P < 0.01 for intact OC). These results show that since both propeptide and intact OC in serum were increased when the growth rate was elevated, these peptides are sensitive markers of bone formation. Serum levels of these peptides, particularly propeptide, after 1 month of GH therapy might be a helpful predictor of the growth response to long term GH therapy.

Adolescent↗
PubMed1992

Effects of Shosaikoto (kampo medicine) on lipid metabolism in macrophages.

We investigated effects of Shosaikoto treatment on cholesterol metabolism in macrophages. Although macrophages, harvested from mice treated with Shosaikoto, took up a small amount of control low density lipoprotein (LDL) (thiobarbituric acid-reactive substance (TBA-RS) value was 0.27 pmol/mg of protein) as control macrophages, they took up more LDL modified with CuSO4 (TBA-RS value was 6.12 pmol/mg of protein) than control macrophages. Degradation of both control LDL and oxidized LDL was enhanced in Shosaikoto treated macrophages. In the presence of control LDL or in the absence of LDL, incorporation of [3H]oleic acid into chlesteryl oleate was significantly reduced in Shosaikoto treated macrophages. This suggests that acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in macrophages was partly inhibited by Shosaikoto treatment. On the other hand, in the present of oxidized LDL, cholesteryl ester accumulated in Shosaikoto treated macrophages as much as in controls. However, cholesteryl oleate efflux from macrophages in the presence of high density lipoprotein (HDL) was enhanced in Shosaikoto treated macrophages. These result indicate that Shosaikoto facilitates oxidized LDL catabolism in macrophages, resulting in the augmentation of oxidized LDL uptake and the elimination of cholesterol from macrophages by HDL. These Shosaikoto effects may prevent foam cell formation and the progression of atherosclerotic lesions.

Animals↗
PubMed1992

Relation between monocytes in peripheral blood and development of atherosclerosis in hypercholesterolemic rabbits.

The relation among circulating monocytes, serum cholesterol and LDL cholesterol in manifestation of atherosclerosis was investigated in hypercholesterolemic rabbits. Serum cholesterol increased sharply and reached a plateau at 12 weeks after the start of cholesterol diet feeding; LDL cholesterol gradually increased until 24 weeks, and the number of monocytes in blood started to decrease abruptly around 12 weeks and resulted in less than 1% total white blood cells at 24 weeks, as reflected by a severe progression of atheroma formation. This result indicated that the decrement of monocyte number in blood was predictive of the presence of severe atherosclerotic plaques.

Animals↗
PubMed1992

Molecular design of potent inhibitor specific for cathepsin B based on the tertiary structure prediction.

To design a potent inhibitor specific for cathepsin B (rat liver), the tertiary structure was predicted based on the crystal structure of the papain complexed with (+)-(2S,3S)-3-(1-[N-(3-methylbutyl)amino]leucylcarbonyl)oxirane-2- carbolylic acid (E-64-c), a thiol protease inhibitor. Taking advantage of the structural characteristics of the predicted active site, seventeen inhibitors were chemically synthesized by molecular modeling, and one of them, N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-p rol ine (CA-074) was shown to be the first potent inhibitor specific for cathepsin B. The relationship between the structure and inhibitory activity is discussed based on the model structure of the cathepsin B-inhibitor complex.

Amino Acid Sequence↗
PubMed1992

Blunted cardiac responses to exercise-induced sympathetic stimulation in non-failing aortic regurgitation: insight into role of cardiac dilation in hyporesponse of failing hearts.

Although blunted cardiac response to sympathetic stimulation in patients with heart failure is usually attributed to myocardial beta 1-adrenoceptor downregulation secondary to elevated circulating catecholamines, cardiomegaly per se may also play a role through presynaptic mechanisms such as reduction in cardiac norepinephrine (NE) concentration. To evaluate effects of cardiac dilatation on cardiac response to sympathetic stimulation, we studied left ventricular contractile and heart rate responses to plasma NE levels increased by exercise in 10 asymptomatic patients with a dilated left ventricle due to aortic regurgitation (AR), but with normal resting plasma NE levels, using 10 normal subjects and 10 patients with heart failure due to dilated cardiomyopathy (DCM) as controls. Plasma NE levels, systemic blood pressure, echocardiographic left ventricular dimensions, and heart rate were measured at rest, and at 3 submaximal levels of supine bicycle exercise. The ratio of peak systolic blood pressure to end-systolic dimension (P/D ratio), heart rate, and plasma NE increased with the intensity of exercise. In each subject, both P/D ratio and heart rate increased in a logarithmic manner against plasma NE levels. The slope of the regression line for log (plasma NE)--P/D ratio relation, and that for log (plasma NE)--heart rate relation, were significantly less in patients with AR than in normal subjects (p less than 0.001 and p less than 0.05, respectively), and were less in patients with DCM than in patients with AR (p less than 0.005 and p = 0.051, respectively). Thus, the left ventricular contractile and heart rate responses to sympathetic stimulation are blunted in patients with dilated hearts due to AR, even in the absence of overt heart failure and elevated plasma NE levels. These responses were further decreased in patients with heart failure due to DCM. Cardiac responses to sympathetic stimulation appear to be blunted by cardiac dilatation per se, independently of myocardial beta 1-receptor downregulation secondary to high circulating catecholamines. The decrease in mechanical response to sympathetic stimulation in failing hearts is likely to be combined result of cardiac dilatation and beta 1-receptor downregulation.

Adult↗
PubMed1992

Effects of reduction of contractile work on mechanical function in post-hypoxic guinea pig papillary muscles and on myocardial energy metabolism in post-ischemic rat hearts.

This study was designed to investigate effects of quiescence by cessation of electrical stimulation during the first stage of reoxygenation on recovery of mechanical function from hypoxia-induced contractile dysfunction in papillary muscles and effects of the absence of cardiac output on myocardial energetic metabolism of post-ischemic hearts. (1) Regular contractions and postextrasystolic contraction were evoked. After 120 min hypoxia, muscles were reoxygenated. In muscles of quiescence during the first 30 min reoxygenation, the recovery of regular contractions was better than that in muscles in which programmed stimulation was continued. However, the quiescence had no effect on the recovery of post-extrasystolic contractions from hypoxia-induced contractile dysfunction. (2) Isolated hearts were perfused either according to Langendorff technique or as working heart preparations. After 40 min ischemia, hearts were reperfused for 25 min. Although there was no difference in energy charge of myocardium between 2 modes of reperfusion, % incidence of sustained ventricular fibrillation in muscles in which non-working mode was maintained for the first step of reperfusion was lower than that in which working mode was continued. We presume that the reduction of contractile work during the initial step of reperfusion is of value for cardio-protection.

Animals↗
PubMed1992

Norepinephrine disrupts cytoskeletal framework of microtubules in rat hearts.

Sympathetic activations may deteriorate myocardial failure due to progression of myocardial cell injury. In the present study, to test whether microtubules, calcium ion (Ca2+) sensitive cytoskeletons, are disrupted by norepinephrine (NE) and whether beta-adrenoceptor antagonist could attenuate the disruption of microtubules, structures of microtubules are studied in rat hearts with continuous subcutaneous infusions of norepinephrine. In the sham operated rats the microtubules stained by immunohistochemical technique showed normal network structures. A low dose of NE infusion (2 micrograms/kg/h) for 6 h resulted in a minimal change in microtubule structures. However, infusion for 24 h of NE (2 micrograms/kg/h) and a large dose of NE infusion (20 micrograms/kg/h) for 6h caused disruptions of microtubules in small patchy lesions (8 +/- 3%, 12 +/- 4% of area, respectively). A large dose of NE infusion for 24 h increased systolic blood pressure from 116 +/- 6 to 152 +/- 4 mmHg and increased plasma NE concentration from 430 +/- 40 to 17100 +/- 3700 pg/ml and further disrupted the network of microtubules in 40 +/- 6% of the total area. Propranolol (500 micrograms/kg/h) markedly attenuated NE-induced disruptions of microtubules. Disruptions of microtubules may be one of the underlying mechanism of deterioration of myocardial failure in chronic heart failure in which sympathetic activity is markedly activated.

Animals↗
PubMed1992

Disruption of microtubules in cultured neonatal rat cardiomyocytes during rapid contractions: protective effects of beta-adrenoceptor antagonist.

Tachycardia may play a key role in the progression of heart failure probably through Ca2+ overload. In the present study, to test whether microtubules, Ca(2+)-sensitive cytoskeletons, are disrupted by rapid contractions and whether the beta-adrenoceptor antagonist, propranolol could attenuate the disruption of microtubules, cultured neonatal rat cardiomyocytes with various contraction rates were studied. The microtubules were stained by immunohistochemical technique and the extent of microtubule disruption was quantified by disruption scores (grade 0-intact; grade 3-severe disruption). In 97% of the non-contracting cells, intact microtubules (grade 0) were observed, whereas in the cells that contract at the rate of 100-120/min, intact microtubules were observed only in 25% of the cells. The disruption scores were significantly correlated with contraction rates of the cells. Treatment with propranolol (10(-6)M) decreased the extent of microtubule disruption associated with a decrease in the contraction rate. However, this treatment did not alter the relationship between the contraction rate and the disruption score of microtubules. These results indicate that rapid contractions may induce disruption of microtubules which can be attenuated by beta-blocker mainly by its negative chronotropic effect. This may be one of the underlying mechanisms of the long-term effect of beta-blockers for chronic heart failure.

Animals↗
PubMed1992

Sequential appearance of fibronectin, collagen and elastin during fatty streak initiation and maturation in hypercholesterolemic fat-fed rabbits.

To elucidate whether tissue fibronectin increases in the early stages of atherogenesis induced by hypercholesterolemia without mechanical trauma, we investigated sequential changes in the distribution of tissue fibronectin during fatty streak initiation and maturation in the aortas of hypercholesterolemic fat-fed rabbits. The presence of fibronectin was examined on immunoperoxidase stained tissue specimens with the aid of a microscope-photometric technique. Twenty male albino rabbits were used. Cholesterol supplemented chow (1%) was given for 4 weeks (n = 6), 8 (n = 5) or 14 weeks (n = 5). A membrane-like layer positive for fibronectin was observed along the endothelium in the normal aorta. After 4 weeks of the cholesterol-feeding, fatty streaks were initiated in the intima, where fibronectin was more densely accumulated than the normal intima. After 8 weeks of the cholesterol-feeding, fatty streaks were expanding, associated with the dense staining for fibronectin. After 14 weeks, fibronectin was still concentrated in the endothelial layer and also in the superficial areas of the thickened intima, but decreased in the deep areas of the thickened intima where collagen and elastin appeared as bundles. The photometric data of fibronectin supported these visual observations. Thus, fibronectin appeared early and disappeared later in the intima during the process of fatty streak initiation and maturation. These findings suggest that in hypercholesterolemia without mechanical endothelial injury, fibronectin may play an important role in an early process of atherogenesis.

Animals↗
PubMed1992

[Neuronal intracellular chloride ion concentrations and their regulatory mechanisms].

Intracellular chloride ion concentration ([Cl-]i) plays an important role in cellular functions including the control of membrane potential and excitability. In neurons, Cl- equilibrium potential (ECl) is lower or higher than the membrane potential (Em), suggesting that [Cl-]i is lower or higher than that expected from passive distribution. As the mechanisms to control [Cl-]i, active outwardly or inwardly directed Cl- transport systems have been reported. The former includes Na(+)-dependent Cl-/HCO3- exchanger, K+/Cl- cotransporter and ATP-dependent Cl- pump; and the latter includes Na+/K+/2Cl- cotransporter and amino acid-dependent Na+/Cl- cotransporter. In hippocampal pyramidal cells, recent studies using a Cl(-)-sensitive fluorescent probe to monitor [Cl-]i revealed the presence of an ATP-dependent Cl- pump and a Na+/K+2Cl- cotransporter, and an uneven distribution of [Cl-]i (cell body less than dendrite) and these Cl- transport systems. Intracerebroventricular administration of an inhibitor of the ATP-dependent Cl- pump, ethacrynic acid, induces status epilepticus in mice. Thus, it appears to be necessary to elucidate cellular and molecular mechanisms of Cl- transporters and their control systems for a better understanding of Cl(-)-related functions in neurons.

Animals↗
PubMed1992

Subluxation of the patella: evaluation of patellar articular cartilage with MR imaging.

In patients with subluxation of the patella, injury of the patellar articular cartilage is frequently observed, and correct evaluation of this cartilage injury is extremely important for the management of these patients. Magnetic Resonance (MR) studies were performed on 102 patellofemoral (PF) joints of 51 patients with subluxation of the patella and 20 PF joints of 10 healthy volunteers. In 77 of the 102 PF joints with subluxation, arthroscopy and/or operation were performed. MR images were obtained with spin-echo and FLASH sequences, and para-axial images were obtained. We retrospectively analysed the MR findings of the 77 joints with special attention to the surface and thickness of the cartilage, and classified them into four grades. These MR grades were compared with the grades on arthroscopy, and the following results were obtained: MR grade 0, normal cartilage (n = 27, sensitivity 90.9%, specificity 74.2%); MR grade 1, thickening of the cartilage (n = 24, sensitivity 50%, specificity 89.1%); MR grade 2, surface irregularity of the cartilage (n = 20, sensitivity 85%, specificity 94.7%); MR grade 3, loss of the cartilage (n = 6, sensitivity 100%, specificity 100%). Although the early changes observed by arthroscopy were underestimated from the MR images, MR imaging proved to be extremely useful for evaluating moderately or advanced patellar cartilage injury.

Adolescent↗
PubMed1992

Impaired water diuresis in a patient with pseudo-Bartter syndrome.

A 32-year-old man was diagnosed as having pseudo-Bartter syndrome due to surreptitious habitual vomiting and to maldigestion related to decayed teeth. His chief complaints were muscle pain and weakness. In this case, metabolic alkalosis, hypokalemia, hypochloremia, increased plasma renin activity and aldosterone levels were noticed with marked decreases in urinary chloride excretion. Creatinine clearance (GFR) and renal plasma flow (RPF) were also decreased. Blood pressure was normal, but the pressor response to angiotensin II was attenuated. Before treatment with 0.9% saline infusion, plasma vasopressin (AVP) was not suppressed sufficiently by lowering the plasma osmolality (Posm) with an oral water load (WL), but it normally responded to a rise in Posm due to hypertonic saline infusion. Moreover, plasma AVP was normally suppressed by WL after the replenishment of saline. Plasma atrial natriuretic peptide (ANP) was low before WL, but increased normally in response to WL. However, inconsistent with the normal response in this case, decreases in plasma AVP failed to dilute urinary osmolality and to increase urine flow, irrespective of the levels of plasma ANP. These results indicate that chronic inanition due to surreptitious vomiting causes impaired renal diluting ability through decreases in GFR and RPF, irrespective of the levels of plasma AVP and ANP.

Adult↗
PubMed1992

Plasma vasopressin and atrial natriuretic hormone levels in hypopituitarism with and without hydrocortisone treatments: responses to an acute water load.

To assess whether arginine vasopressin and atrial natriuretic hormone participate in impaired urinary dilution and excretion in glucocorticoid deficiency secondary to hypopituitarism, an acute oral water load of 20 ml.kg-1 BW was undertaken in the absence and presence of an oral hydrocortisone (60 mg) treatment in patients with ACTH deficiency (N = 7) and panhypopituitarism (N = 2). Plasma arginine vasopressin and atrial natriuretic hormone and renal water handling were simultaneously determined and compared with those in similarly water-loaded normal subjects. Plasma arginine vasopressin did not fall in response to decreased blood osmolality after an acute water load in the absence of hydrocortisone; plasma atrial natriuretic hormone did not change despite blood volume expansion; and impairment in urinary dilution and excretion remained. On the other hand, in the presence of hydrocortisone, plasma arginine vasopressin fell in response to a decrease in plasma osmolality and plasma atrial natriuretic hormone increased, thereby restoring urinary dilution and excretion. These results demonstrate that the impaired arginine vasopressin response to acute water loading play an essential role in deranged renal water and electrolyte handling in the state of glucocorticoid deficiency; the impaired release of atrial natriuretic hormone also may affect these disorders.

Adult↗