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Biomedical subjects

M Naka

Publications and source records attributed to M Naka.

At least 55 records · Page 3Linked to original sources
PubMed1994

Progressive decreases in coronary vein flow during reperfusion in acute myocardial infarction: clinical documentation of the no reflow phenomenon after successful thrombolysis.

OBJECTIVES: This study was undertaken to examine the effects of coronary flow dynamics after thrombolysis on infarct size limitation. BACKGROUND: It has been commonly accepted that early thrombolysis does not necessarily salvage infarcted myocardium. Plausible causes for myocardial necrosis include such factors as elapsed time to reperfusion, residual stenosis, collateral vessels, hemodynamic loads, preconditioning and reperfusion injury. Recently, the no reflow phenomenon has been elucidated to be associated with infarct extension in clinical studies employing contrast echocardiography or thallium scintigraphy. METHODS: Nineteen patients with early reperfusion in acute anterior myocardial infarction and comparable clinical background were studied. The patients were classified into two groups on the basis of pattern of thermodilution measurements of great cardiac vein flow after reperfusion: group A, 9 patients with a progressive decrease in great cardiac vein flow during the 1st 24 h of the onset of infarction; and group B, 10 patients without this observation. Left ventricular ejection fraction and thallium perfusion defect were compared between the two groups at follow-up. RESULTS: There were no significant differences in systemic hemodynamic variables between groups A and B, and neither group had recurrent ischemic events suggesting reocclusion or restenosis during the study. In group A, both great cardiac vein flow (mean +/- SD 44 +/- 17% reduction) and oxygen extraction (38 +/- 15% reduction) were progressively decreased after the onset of reperfusion. Compared with group B, this group showed a lower left ventricular ejection fraction (36 +/- 7% vs. 63 +/- 15%, p < 0.01) and a larger thallium-201 defect severity index (1,091 +/- 366 U vs. 247 +/- 261 U, p < 0.01) at follow-up. Although other patient characteristics were comparable between the two groups, antecedent angina occurred in 90% of group B patients in contrast to only 33% of group A patients. CONCLUSIONS: Salvage of myocardium from infarction by successful thrombolysis was not observed in the patients demonstrating progressive decreases in great cardiac vein flow (group A). In those patients, inadequate myocardial reperfusion on a microvascular basis might be associated with a much larger myocardial infarction. Antecedent angina may protect against a progressive decrease in coronary flow and may have beneficial effects on infarct size limitation.

Adult↗
PubMed1994

Separation and characterization of a novel isoenzyme of cyclic nucleotide phosphodiesterase from rat cerebrum.

Anion-exchange chromatography on a Mono-Q column of the supernatant fraction, after ultracentrifugation, from a homogenate of rat cerebrum, prepared under isotonic conditions in the presence of protease inhibitors, yielded a novel isoenzyme of cyclic nucleotide phosphodiesterase (PDE) with properties unlike those of known PDEs. The isoenzyme was insensitive to stimulation by Ca2+/calmodulin and cyclic GMP, and it hydrolyzed both cyclic AMP and cyclic GMP with KM values of 0.109 +/- 0.008 microM and 1.78 +/- 0.04 microM, respectively. The ratio of Vmax of hydrolysis of cyclic GMP to that of cyclic AMP was 1.90 +/- 0.07. Nicardipine (PDE I inhibitor), SK&F 94120 (PDE III inhibitor), rolipram (PDE IV inhibitor) and zaprinast (PDE V inhibitor) had very weak inhibitory effects on the PDE activity of the isoenzyme. These results suggest that the isoenzyme is a novel and previously unreported species of PDE, which we tentatively designate PDE VIII.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Calponin phosphatase from smooth muscle: a possible role of type 1 protein phosphatase in smooth muscle relaxation.

Smooth muscle myosin bound phosphatase (MBP) purified from chicken gizzard, which is a holoenzyme of type 1 delta protein phosphatase and dephosphorylated intact myosin, catalyzed the dephosphorylation of calponin phosphorylated by protein kinase C (PK-C). The Km of MBP for calponin was 0.6 microM and the Vmax was 350 nmol/min/mg. All of the multiple sites of phosphorylation by PK-C of calponin were completely dephosphorylated by MBP. Functionally, calponin dephosphorylated by MBP recovered its inhibitory effect on the actin-activated Mg(2+)-ATPase activity of myosin. Therefore, these results suggest that a type 1 delta protein phosphatase causes relaxation of smooth muscle by the dephosphorylation not only of myosin but also of calponin.

Animals↗
PubMed1993

Identification of the regulatory site in smooth muscle calponin that is phosphorylated by protein kinase C.

F-actin and tropomyosin inhibited the phosphorylation of calponin by protein kinase C, and the phosphorylation reduced the binding of calponin to F-actin and tropomyosin. Labeled phosphate from [gamma-32P]ATP was retained both on the chymotryptic NH2-terminal 22-kDa fragment, which contains the actin-, tropomyosin-, and calmodulin-binding regions, and on the COOH-terminal 12-kDa fragment. Fractionation of tryptic 32P-labeled peptides by high performance liquid chromatography allowed isolation of three phosphopeptides (designated T1, T2, and T3), each of which was located in three repeating amino acid motifs of calponin. Both the relative initial rates and extent of phosphorylation decreased in the order T2 > T3 > T1. Both serine and threonine residues were phosphorylated in T1 (GASQAGMTAPGTK), and only a threonine residue was phosphorylated in T2 (FASQQGMTAYGTR) and in T3 (GASQQGMTVYGLPR). As the 22-kDa fragment contained only T2, the phosphorylation site in T2 appeared to regulate the binding of calponin to F-actin and tropomyosin. The amino acid sequence of T2 indicates that protein kinase C phosphorylates Thr184. Thus Thr184 is the preferred site of phosphorylation and is functionally the most important of the sites phosphorylated by protein kinase C in smooth muscle calponin.

Actins↗
PubMed1993

Myocardial hibernation in the infarcted region cannot be assessed from the presence of stress-induced ischemia: usefulness of delayed image of exercise thallium-201 scintigraphy.

To examine the relationship between the improvement of wall motion in infarcted regions after percutaneous transluminal coronary angioplasty (PTCA) and thallium-201 uptake in the delayed image of exercise thallium-201 scintigraphy before PTCA, 14 patients with anterior old myocardial infarction were studied. Exercise thallium-201 scintigraphy was performed before PTCA of left anterior descending artery, and mean percent thallium-201 uptake of abnormal segments was calculated in the initial and 4-hour delayed images. Left ventricular angiography was performed during catheterization, before, and 4 to 13 months after PTCA; and regional ejection fraction of anterior wall was calculated. Atrial pacing stress test with the measurement of lactate concentration of aorta and great cardiac vein was performed during catheterization before PTCA. In five patients with mean percent thallium-201 uptake in the delayed image < or = 50% (group I), regional ejection fraction did not increase after PTCA (23% +/- 9% to 24% +/- 12%). In the other nine patients with mean percent thallium-201 uptake > 50% (group II), regional ejection fraction increased significantly after PTCA (39% +/- 18% to 47% +/- 14%; p < 0.05). There was no significant difference in regional ejection fraction, lactate extraction ratio during maximal pacing, and the redistribution of exercise thallium-201 scintigraphy between the two groups before PTCA. Thus the delayed image before PTCA is useful to detect reversible nonfunctioning viable myocardium (hibernating myocardium) in the infarcted region. However, the wall-motion abnormality and the degree of stress-induced ischemia in the infarcted region before PTCA may not be necessarily useful for the detection of hibernating myocardium.

Aged↗
PubMed1993

Effect of OP-41483.alpha-CD, a prostacyclin analog, on a clamp-induced endothelial injury in rats.

We studied the effect of OP-41483.alpha-CD, a stable prostacyclin analog, on clamp-induced endothelial injury in rats. The injury was assessed by vascular Evans blue leakage and using a scanning electron microscope. OP-41483.alpha-CD significantly reduced the Evans blue leakage at doses of 30 and 100 ng/kg/min. PGE1.CD was also found to show an equipotent inhibitory action on the dye leakage. From scanning electron microscopic observations, a moderate degree of intimal defects, microvillous projections and platelet adhesions at the luminal surface were seen in the specimens from OP-41483.alpha-CD (30 and 100 ng/kg/min) treated rats. Furthermore, OP-41483.alpha-CD, PGE1.CD and Dibutyryl cyclic AMP (DbcAMP) were found to accelerate a proliferation of cultured bovine endothelial cells in a dose-dependent manner in vitro. Taken together, these data indicate that the endothelial regenerative effect of OP-41483.alpha-CD could contribute to healing of clamp-induced endothelial injury and it may be an important therapeutic drug to protect vascular intimal injury.

Animals↗
PubMed1993

Thromboxane A2/prostaglandin H2 receptors in streptozotocin-induced diabetes: effects of insulin therapy in the rat.

Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) are potent vasoactive and proaggregatory agents whose synthesis has been shown to be elevated in diabetes mellitus. In the present study the effects of streptozotocin (STZ)-induced uncontrolled diabetes (Severe) and insulin-treated STZ diabetes (Moderate) on TXA2/PGH2 receptor density and affinity in platelets, glomerular membranes and aortic membranes were determined using [125I]-BOP, a TXA2/PGH2 receptor agonist. The affinity and density of platelet TXA2/PGH2 receptors in Control, Moderate and Severe groups and glomerular membranes were not significantly different. However, daily insulin therapy caused significant changes in both TXA2/PGH2 receptor affinity and density of aortic membranes: Kd (nM) = 0.67 +/- 0.09, (n = 5), for Control; 0.27 +/- 0.05*, (n = 6), Moderate; and 0.74 +/- 0.16, (n = 5), Severe; Bmax (fmoles/mg protein) = 38.6 +/- 3.1, Control; 20.2 +/- 4.2*, Moderate; and 37.1 +/- 4.1, Severe: (*p < 0.05 compared to Control and Severe). Contractile responses of aortic segments to the TXA2/PGH2 receptor agonist U46619 were determined. Untreated diabetes mellitus (Severe) was associated with a decreased responsiveness of aortic segments without affecting maximum contractile responses (EC50 = 24.6 +/- 5.9* nM, (n = 10); *p < 0.05) compared to Control rats (EC50 = 11.8 +/- 1.6 nM, (n = 13)). Insulin therapy reversed the decrease seen in the Severe group to a value not different from Control (EC50 = 11.4 +/- 1.2* nM, (n = 10); *p < 0.05 compared to Severe). These results suggest that insulin therapy in the diabetic state significantly influences aortic TXA2/PGH2 receptors, as well as vascular responsiveness to TXA2/PGH2 mimetics.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Response to octreotide of intestinal pseudoobstruction and pneumatosis cystoides intestinalis associated with progressive systemic sclerosis.

Intestinal pseudoobstruction and pneumatosis cystoides intestinalis are uncommon complications of progressive systemic sclerosis. We report a 26-year-old woman with this disorder who responded poorly to conventional treatment. Subcutaneous administration of octreotide, a long-acting somatostatin analogue, at a dose of 50 micrograms/day for 3 weeks, relieved symptoms such as nausea and bloating. There was also a marked decrease of intestinal gas accumulation, as documented on X-ray films.

Adult↗
PubMed1993

Effects of OP-41483.alpha-CD, a stable prostacyclin analog, on cultured endothelial cell dysfunction caused by 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) in vitro.

We studied the effect of OP-41483.alpha-CD, a stable prostacyclin analog, on, 15-HPETE induced bovine endothelial cell dysfunction, which was assessed by measuring a number of endothelial cells attached to plastic plates. 15-HPETE decreased the number of attached endothelial cells in a concentration- and time-dependent manner. OP-41483.alpha-CD and PGI2 significantly inhibited 15-HPETE induced dysfunction of the cells at a concentration of more than 10(-9)M. Besides, DDA (10(-6) - 10(-4)M) an adenylate cyclase inhibitor, diminished the inhibitory effect of OP-41483.alpha-CD on 15-HPETE induced cell dysfunction in a concentration-dependent manner. Furthermore, OP-41483.alpha-CD increased cAMP levels in the endothelial cells in the range of 10(-10) to 10(-8)M in a dose-dependent manner. These data suggest that OP-41483.alpha-CD could exert an inhibitory action on 15-HPETE induced endothelial cell dysfunction via partly increasing its effect on the intracellular cAMP level.

Alprostadil↗
PubMed1992

Inhibition of actin-activated myosin Mg(2+)-ATPase in smooth muscle by ruthenium red.

Ruthenium red was found to inhibit actin-activated myosin Mg(2+)-ATPase in smooth muscle and to bind to myosin heavy chain, but not to F-actin. The inhibition by Ruthenium red of actin-activated Mg(2+)-ATPase was of the competitive type with respect to actin (Ki 4.4 microM) and of the non-competitive type with respect to ATP (Ki 6.6 microM). However, Ruthenium red scarcely dissociated the acto-heavy meromyosin complex during the ATPase reaction. These results suggest that Ruthenium red interacts directly with the binding site for F-actin on the myosin heavy chain. This site is considered to be necessary not for maintaining the binding affinity of myosin for F-actin, but for activation of the Mg(2+)-ATPase.

Actins↗
PubMed1992

Left ventricular filling abnormalities in non-insulin-dependent diabetes mellitus and improvement by a short-term glycemic control.

To determine whether left ventricular (LV) filling abnormalities in diabetes are associated with diabetic microangiopathy, and to evaluate the effect of a short-term glycemic control on the filling abnormalities, diastolic filling dynamics were assessed by pulsed Doppler echocardiography in 246 patients with non-insulin-dependent diabetics. Isovolumic relaxation time and the ratio of peak flow velocity of atrial filling wave to peak flow velocity of early filling wave (A/E) were significantly greater in diabetic patients than in age- and sex-matched control subjects. Diabetic patients with retinopathy had significantly greater isovolumic relaxation time and A/E values than those without retinopathy. A/E was significantly decreased 1 month after insulin treatment in those without, but not with retinopathy. It is concluded that LV diastolic filling is impaired in mildly hyperglycemic patients with non-insulin-dependent diabetes mellitus without severe complications, the abnormality being more intense in patients with retinopathy. A short-term glycemic control results in a marked decrease in abnormalities in patients without, but not with retinopathy.

Adult↗
PubMed1992

Ruthenium red inhibits the binding of calcium to calmodulin required for enzyme activation.

The Ca(2+)-calmodulin (CaM)-dependent activation of myosin light chain kinase is inhibited by ruthenium red competitively with respect to Ca2+, with a Ki value of 8.6 microM. The binding of Ca2+ to CaM is inhibited by micromolar concentrations of ruthenium red. In the absence of Ca2+, CaM has two binding sites for ruthenium red with the dissociation constants of 0.36 and 8.7 microM, respectively. Ca2+ antagonizes the binding of ruthenium red to the low-affinity site on CaM. Binding of ruthenium red to the high-affinity site is not affected by Ca2+. The low- and high-affinity sites for ruthenium red are shown to be located in the NH2-terminal half and the COOH-terminal half of CaM, respectively. Lower concentrations of ruthenium red are needed for enzyme inactivation than for the dissociation of enzyme-CaM-Sepharose complex, suggesting these events have different Ca2+ requirements. Moreover, ruthenium red inhibits Ca(2+)-induced contraction of depolarized vascular smooth muscle in a competitive manner with respect to Ca2+. These results suggest that ruthenium red may be a new type of CaM antagonist that inhibits the binding of Ca2+ to CaM and thereby inhibits Ca(2+)-CaM-dependent enzymes and smooth muscle contraction competitively with respect to Ca2+.

Animals↗
PubMed1992

Effect of flosequinan on exercise capacity and cardiac function in patients with chronic mild heart failure: a double-blind placebo-controlled study.

Although beneficial effects of a new vasodilating agent, flosequinan, have been demonstrated in patients with severe heart failure, its efficacy has not been studied in patients with a less severe form of chronic heart failure. In this study, the effects of 4 weeks' administration of flosequinan, 50 mg daily, and placebo on exercise capacity, cardiac function, and symptoms of heart failure were investigated in 24 patients with chronic mild heart failure (New York Heart Association functional class, mainly class II) in a double-blind clinical trial. When the parameter changes during the treatment period of the flosequinan and placebo groups were compared, no significant difference was found in any of the measurements except for left ventricular fractional shortening determined from M-mode echocardiograms; it was increased by 2.9 +/- 1.3% in the flosequinan group whereas it was decreased by 1.3 +/- 0.9% in the placebo group (P less than 0.05 vs flosequinan treatment). However, when compared to baseline values, flosequinan significantly increased exercise time in the symptom-limited maximal exercise test (704 +/- 103 to 763 +/- 107 s, P less than 0.05) and the oxygen uptake at the anaerobic threshold (13.8 +/- 1.3 to 16.7 +/- 1.4 ml/min kg, P less than 0.05), and improved symptoms assessed with a new heart failure severity classification (a median value of 2.0-1.5, P less than 0.05). These improvements were not observed in the placebo group. Serious adverse effects were not observed in either group. These results suggest that flosequinan is useful for the treatment of chronic mild heart failure as well as severe heart failure.

Adult↗
PubMed1992

Silent myocardial ischemia in patients with non-insulin-dependent diabetes mellitus as judged by treadmill exercise testing and coronary angiography.

Patients with diabetes were compared with nondiabetic control subjects, with respect to the prevalence of silent myocardial ischemia, by means of treadmill exercise testing and coronary angiography. Results of treadmill exercise testing showed ischemic ST depression in 41 of the 132 diabetic patients (mean age 61 +/- 4 years) and in 42 of the 140 nondiabetic control subjects (mean age 60 +/- 8 years) (31% vs 30%, p = NS). Coronary angiography was performed in 36 of 41 diabetic patients and 34 of 42 nondiabetic control subjects with positive results of treadmill exercise tests, who gave their consent. Among "treadmill-positive" subjects, diabetic patients had a prevalence of silent myocardial ischemia that was 2.2 times higher than that in nondiabetic control subjects (p less than 0.05). Diabetic patients who received insulin had a 2.6 times higher prevalence of silent myocardial ischemia than those who did not (p less than 0.05). Similarly diabetic patients with retinopathy has a 2.5 times higher prevalence of silent myocardial ischemia than those without it (p less than 0.05).

Aged↗
PubMed1992

[Molecular cardiopharmacology of selective inhibitors of cyclic nucleotide phosphodiesterase isozymes].

The existence of multiple isozymes of cyclic nucleotide phosphodiesterase (PDE) in many tissues including the heart has been demonstrated. Five isozyme families, each composed of several subtypes and having different tissue and subcellular distributions, have been characterized. Selective inhibitors of PDE III (cGMP-inhibited PDE) elevates the cAMP level which mediates positive inotropic actions with compartmentation of cAMP related to cardiac cell particulate structures. Both cardiac cytosolic and particulate PDE III were potently and selectively inhibited by the new cardiotonic agents competitively with respect to cAMP, except for vesnarinone. There might be at least two subtypes of PDE III, and vesnarinone may be a selective subtype inhibitor of PDE III in human heart. It was also reported that vesnarinone was beneficial in treating patients with congestive heart failure. Moreover, selective inhibitors of PDE III with ancillary properties such as calcium sensitization may prove to be more useful drugs for the treatment of heart failure.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1992

Malignant lymphoma in the mesentery with immune thrombocytopenia.

A 69-year-old man was referred to our hospital for further evaluation of an abdominal mass. After admission, he was suspected of having a malignant mesenteric tumor. Laboratory data disclosed thrombocytopenia with increased levels of platelet-associated immunoglobulin G. On surgery, the tumor involved the ileal mesentery, invading the urinary bladder and mucosal surface of the terminal ileum. The diagnosis of mesenteric lymphoma with immune thrombocytopenia was made. Complete remission was obtained after surgery and the subsequent three courses of combination chemotherapy. However, thrombocytopenia still persisted. This rare presentation is discussed with a review of the available literature.

Aged↗
PubMed1992

[Assessment of the rate of successful transcranial Doppler recording through the temporal windows in Japanese with special reference to aging and sex].

Transcranial Doppler method (TCD), newly developed in 1982, is ultrasound technology that measures physiologic parameters of blood flow in the major intracranial arteries. A major limitation of TCD is that, in some individuals, satisfactory recording is not possible, especially through the temporal windows. The purpose of the present study is to assess the rate of successful recording in TCD through the temporal ultrasonic windows in Japanese with special reference to aging and sex. In 423 Japanese (244 males and 179 females) aged from 25 to 93 years, measurement of blood flow velocity in basal cerebral arteries was performed by transcranial Doppler velocimeter with a 2 MHz pulsed wave Doppler probe. The signal was successfully recorded in 299 of 423 Japanese (71%). In Japanese males, successful measurement was more frequent (206/244; 84%) than in Japanese females (93/179; 52%). The rate of successful recording was evaluated in every decade from the twenties to the eighties, and it was found to decrease significantly according to age (100%, 94%, 91%, 74%, 66%, 67%, and 46%, respectively). In females, it significantly decreased in those older than 50 years old (100%, 100%, 93%, 61%, 36% 43%, and 27%, respectively), but not in males (100%, 88%, 89%, 81%, 88%, 83%, and 69%, respectively). These findings suggest that this noninvasive method has clinical usefulness for evaluating intracranial circulation but has limitation for assessing the intracranial lesions of elderly Japanese women.

Adult↗