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Biomedical subjects

K Munakata

Publications and source records attributed to K Munakata.

At least 73 records · Page 4Linked to original sources

Angiographic response to a vasodilating drug, nicorandil, in patients with coronary artery disease.

To investigate the usefulness of nicorandil as an antianginal drug, we compared the coronary vasodilatory response in nonstenotic coronary artery segments and the hemodynamic response in 26 coronary artery disease patients. Both responses were studied prior to sublingual administration of 10 mg of this drug and 10, 30 and 60 min afterward. The plasma nicorandil concentration was determined up to 120 min after administration. The mean coronary dilating ratio of nicorandil was 117% 30 min after administration (p less than 0.01) and showed a good correlation to the plasma nicorandil concentration. The mean maximum dilating ratio of each patient was 125%. There was no difference between individual coronary arteries or between proximal and distal segments in terms of the coronary artery dilating ratio. The plasma nicorandil concentration required for 120% dilation of the coronary arteries was 26 ng/ml, 89 ng/ml and 142 ng/ml for those cases with variant angina, exertional angina and postinfarction angina, respectively. Hemodynamic changes due to administration of this drug included a decrease in blood pressure, and a reduction in total peripheral resistance, rate-pressure product, pulmonary capillary pressure and stroke-work index. These results indicate that the antianginal effects of nicorandil are derived from its coronary vasodilatory action and an inhibitory effect on myocardial oxygen consumption.

Administration, Sublingual↗

[Role of the peptidergic nerves in Hirschsprung's disease and hypoganglionosis].

The purpose of this study is to examine the role of peptidergic nerves (VIP, Substance P, Neurotensin) in Hirschsprung's disease (aganglionosis) and hypoganglionosis in relation to the normoganlionic state of the colon using a mechanographic technique in vitro. The following results were obtained. 1) Normoganglionic muscle strips demonstrated the presence of intact non-adrenergic inhibitory nerve. The activities of such nerves, however, were reduced in hypoganglionic muscle strips, and were absent in aganglionic muscle strips. 2) Peptidergic nerve activities by VIP, substance P, and Neurotensin were present in normoganglionic muscle strips, while they were reduced in hypoganglionic muscle strips, and absent in aganglionic muscle strips. 3) VIP may act as a neurotransmitter-neuromodulator of non-adrenergic inhibitory nerve, while SP and Neurotensin may act as that of non-cholinergic excitatory nerve with some direct effect on the intestinal muscle.

Hirschsprung Disease↗

A case of progressive muscular dystrophy with numerous arterioluminal vessels.

A 48-year-old man had histologically demonstrated cardiac involvement associated with progressive muscular dystrophy. On coronary arteriography, numerous vascular communications between the coronary arteries and the left ventricular chamber were found. These vascular communications are considered to be the arterioluminal vessels. This is the first report of a case of progressive muscular dystrophy with numerous arterioluminal vessels.

Coronary Angiography↗

The degree of increment in plasma catecholamines in patients with mitral stenosis by mild exercise.

Although sympathetic excitation during mild exercise may readily occur in patients with mitral stenosis (MS), the degree of increment in plasma catecholamines has not been fully investigated. We imposed mild ergometric exercise (50 watts, 300 kg/min for 5 minutes) on five patients with mild MS (mitral valve area greater than or equal to 1.0 cm2) and eight with severe MS (mitral valve area less than 1.0 cm2) while they were undergoing cardiac catheterization. In patients with severe MS, total plasma catecholamine levels during exercise were remarkably higher (2821 +/- 783 [SEM] pg/ml) than in those with mild MS (957 +/- 113 pg/ml, p less than 0.05) and in seven control subjects (612 +/- 75 pg/ml, p less than 0.05). This marked increment could not be predicted by heart rate response, which did not differ between severe and mild MS (166 +/- 5 vs 153 +/- 10 bpm). In contrast with catecholamine change, the cardiac index in severe MS showed a very small increment. Results suggest that mild daily exercise can remarkably increase plasma catecholamine levels in severe MS, and this may accelerate various complications of this disorder.

Adult↗

Electrophysiological effects of flecainide on guinea pig ventricular muscle in high [K+]o, acidosis and hypoxia.

The electrophysiological effects of flecainide on the action potential were examined in guinea pig ventricular muscles using microelectrode recording methods. Under the control conditions, flecainide (0.5-1 microgram/ml) did not alter the resting potential, action potential duration (APD) or effective refractory period (ERP). The major effect of flecainide was on maximum upstroke velocity (Vmax), which was depressed in a dose-dependent manner. In high [K+] medium (potassium concentration = 10 mM), Vmax was depressed by 16.8% at a concentration of 1.0 microgram/ml (8.8% in normal [K+]o). In metabolic acidosis (pH = 6.89), it was depressed by 15.7% at the same concentration of the drug (8.3% in normal condition). The changes in ERP and ERP/APD90% in high [K+]o and metabolic acidosis were not significantly different from the normal condition. After hypoxic perfusion for 15 min, Vmax depression by flecainide was 16.3% (7.4% in control medium). The increase of ERP/APD90% was also greater in hypoxia. These data indicate that the most prominent effect of flecainide is Vmax depression which is enhanced under the high K+, acidic and hypoxic conditions. Therefore, it is suggested that flecainide may be most effective for ventricular arrhythmias occurring in myocardial ischemia.

Acidosis↗

Cholera toxin, a potent inducer of epidermal hyperplasia but with no tumor promoting activity in mouse skin carcinogenesis.

Intracutaneous injection of cholera toxin into mice induced epidermal hyperplasia to a greater extent than 12-O-tetradecanoylphorbol-13-acetate. It also induced adenylate cyclase and though weakly, ornithine decarboxylase of the epidermis. Cholera toxin, however, showed no tumor promoting activity in mouse skin carcinogenesis. In the single stage promotion, cholera toxin (50 ng) was injected once a week for 10 weeks into the skin of SENCAR mice initiated with 25 micrograms 7,12-dimethylbenz[a]anthracene, but no tumors developed. In the two-stage promotion test, cholera toxin (10-100 ng) was injected for one or two weeks into the initiated skin and then mezerein (4 micrograms) was applied twice a week for 18 weeks, but the toxin did not increase incidence or numbers of papillomas.

9,10-Dimethyl-1,2-benzanthracene↗

[Clinical and histologic studies of abnormal intramural plexus with special reference to hypoganglionosis].

Since April 1973, 230 patients, who were suspected of Hirschsprung's disease, have been examined by rectal mucosal biopsy, barium enema and ano-rectal manometry. Their rectal mucosal specimens have been taken both from the regions 2cm upwards and just above the dentate line, and have been studied by means of acetylcholinesterase (AChE)-staining and hematoxylin-eosin (H-E)-staining. Specimens obtained by rectal full-thickness biopsies or operations were examined by means of AChE-staining, H-E-staining and silver-impregnation. Eleven out of the 230 patients were histologically diagnosed as hypoganglionosis. All rectal mucosas of hypoganglionosis showed a few small submucous plexus. According to the findings of nerve fibers, however, cases of hypoganglionosis were divided into three groups. The recognition of nerve fibers partially proliferated in rectal mucosa at the newborn age leads the diagnosis to type A. The type B is diagnosed as Hirschsprung's disease only through the recognition of proliferations of nerve fibers in rectal mucosa after the suckling age. In type C, no proliferation of nerve fibers can be recognized even after the suckling age. An accurate diagnosis of type C can be, therefore, made only through the examinations of myenteric plexus in full-thickness rectal specimen. On barium enema, a narrow segment was definite in 7 cases of hypoganglionosis, but was indefinite in the remaining 4 cases. The diseased segments of intestines were limited to the rectum or the rectosigmoid colon in 10 cases. Recto-anal sphincteric reflex showed an atypical reflex in 6 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Secretion into the culture medium of a foreign gene product from Escherichia coli: use of the ompF gene for secretion of human beta-endorphin.

The ompF gene codes for a major outer membrane protein of Escherichia coli. A plasmid was constructed in which the structural gene for human beta-endorphin is preceded by the upstream region of the ompF gene consisting of the promoter region and the coding regions for the signal peptide and the N terminus of the OmpF protein. When the plasmid was introduced into E. coli N99, and OmpF-beta-endorphin fused peptide was synthesized and secreted into the culture medium through both the cytoplasmic and outer membranes. The OmpF signal peptide was cleaved correctly during the secretion, indicating that the export of the fused protein across the cytoplasmic membrane was dependent on the signal peptide. The secretion into the culture medium was apparently selective. Neither beta-lactamase nor alkaline phosphatase (both are periplasmic proteins) appeared in the culture medium in significant amounts. The mode of passage of the fused peptide across the outer membrane is discussed.

Bacterial Outer Membrane Proteins↗

Clinical and histologic studies of neuronal intestinal dysplasia.

Over a period of 10 years we have treated 10 patients with neuronal intestinal dysplasia (NID), including 3 in whom the entire intestinal tract was affected by NID, and one in whom small intestinal NID coexisted with total colonic aganglionosis. Three of these 4 patients have died and the one survivor requires parenteral feeding. The six patients with less extensive NID have all been treated successfully; three have required surgery (Duhamel procedure in 2 and colostomy in 1), but 3 responded to conservative measures. We have made detailed histologic studies, including acetylcholinesterase activity in all cases, silver impregnation studies in 4, and immunohistochemical investigation of the peptidergic innervation of the bowel in one case. Follow-up rectal biopsies have not shown any significant morphological changes with time, but functional improvement does occur and we suggest that the myenteric ganglia in NID may have the capacity for functional maturation.

Acetylcholinesterase↗

Effect of uniformly prolonged, and increased basic dispersion of repolarization on premature dispersion on ventricular surface in dogs: role of action potential duration and activation time differences.

Strong experimental evidence links ventricular fibrillation to an increased temporal dispersion of the recovery of excitability. The effect of an overall prolongation of repolarization and an increased basic dispersion of repolarization on premature dispersion was studied on ventricular surface in 10 dogs. Our observations reveal the operation of several fundamental electrophysiologic mechanisms controlling the conduction and the refractoriness in the ventricular myocardium in vivo. Action potential (AP) duration was influenced by the heart rate, the duration of the preceding AP and the proximity to the repolarization of the preceding AP. These effects can both slow, or enhance ventricular conduction, during propagation of premature impulses. This model may be applicable to several clinical situations where APs are prolonged (hypothermia, drug effects, changes in electrolytes) or when dispersion of refractoriness is increased (long QT-time syndrome, neural imbalance of the heart with and without heart disease.

Animals↗

Mechanism of ventricular arrhythmias caused by increased dispersion of repolarization.

To explain the mechanism of arrhythmias dependent predominantly on increased dispersion of repolarization, we created a model in which increased dispersion was induced by means of generalized hypothermia (29 degrees C) and regional warm blood (38-43 degrees C) perfusion (RWBP) via a coronary artery branch. In 23 open-chest dogs, hypothermia plus RWBP increased maximum dispersion of repolarization from 13 +/- 10 to 111 +/- 16 ms (P less than 0.001) due predominantly to the increased monophasic action potential duration (MAP) difference of six simultaneously recorded MAP's from the ventricular surface, from 10 +/- 15 to 97 +/- 16 ms (P less than 0.001). The maximal difference between activation times was not significantly changed while QRS duration increased from 47 +/- 6 to 52 +/- 7 ms (P less than 0.01). Ventricular arrhythmia (VA) did not occur spontaneously but was induced by a single ventricular premature stimulus (VPS) in all 23 dogs during hypothermia plus RWBP when dispersion reached a critical magnitude. The requirement of this critical magnitude of dispersion for the induction of VA was documented in 16 dogs by means of stepwise increments or decrements of dispersion. In four dogs an increase in atrial pacing rate by 24 beats/min-1 prevented induction of VA by decreasing dispersion from a critical magnitude of 103 +/- 5 ms to a nonarrhythmogenic value of 86 +/- 9 ms (P less than 0.05). In six dogs, we compared the stimulation-site dependent effects of VPS applied in the region with short and long MAPD. In all dogs VA was inducible only by VPS from the region with short MAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of mexiletine on action potential duration and its restitution in guinea pig ventricular muscles.

To clarify the mechanism of mexiletine-induced changes in action potential duration (APD), we studied the effects of mexiletine (2 micrograms/ml) on APD at 0 mV (APD0mV) and 90% (APD90%) repolarization and on restitution of premature responses in guinea pig ventricular muscle at three extracellular potassium concentrations [( K]0) and three stimulation rates using standard microelectrode techniques. The rates at which APD0mV and APD90% were shortened by mexiletine (S-APD0mV and S-APD90%) expressed as percent change from control were most pronounced at [K]0 = 5.4 mM. The percent changes at the three concentrations were 5.0 +/- 2.1% at a [K]0 of 2.7 mM, 6.0 +/- 3.2% at 5.4 mM and 1.8 +/- 1.2% at 10.0 mM for S-APD0mV and 2.0 +/- 1.9%, 4.7 +/- 2.0% and 1.3 +/- 1.5% for S-APD90% at the same concentrations, respectively. S-APD0mV and S-APD90% were more markedly affected when stimulated at a frequency of 1 Hz than when stimulated at 0.2 or 0.5 Hz. Mexiletine failed to produce any additional APD shortening beyond that produced by the introduction of tetrodotoxin (2.5 X 10(-6) M). Mexiletine and tetrodotoxin did not influence APD restitution that fitted a single exponential curve. We conclude that the shortening of APD by mexiletine results from inhibition of a tetrodotoxin-sensitive sodium current.

Action Potentials↗

A newly designed model for infection-induced bladder stone formation in the rat.

A newly designed urolithiasis model for rats, inducing a mild urinary tract infection, exhibiting reduced renal damage without pyelonephritis and causing reliable stone formation, was established. This was accomplished by implanting a zinc disc in the bladder and then performing transvesical inoculation of Proteus mirabilis into the bladder. Five days after challenge with 10(7) colony forming units (CFU) of P. mirabilis in each rat, the number of organisms in the bladder urine reached a level of over 10(5) colony forming units per ml. The infection was mostly restricted to the urinary tract organs. Infectious bladder stones were formed 5 days after infection and developed day by day, weighing 88.3 +/- 18.8 mg. on the 21st day. Blood urea nitrogen values stayed in the normal range in all test animals during this experiment. The main composition of the stones formed was shown to be struvite (MgNH4PO4 X 6H2O).

Animals↗