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H Maeno

Publications and source records attributed to H Maeno.

At least 37 records · Page 2Linked to original sources
PubMed1992

[A case of recurrent pulmonary alveolar proteinosis treated by pulmonary lavage: were the remissions due to the natural course or due to the lavage?].

We report a 39-year-old male with pulmonary alveolar proteinosis. Although no abnormal shadows were seen on regular check-up chest roentgenogram one year previously, diffuse alveolar filling shadows were noted on admission, suggesting fairly acute progression of the disease. He was treated with bronchoalveolar lavage of each segment of both lungs by flexible fiberoptic bronchoscope under local anesthesia. Following this treatment, the shadows on X-ray film and shortness of breath resolved. Oxygen tension of arterial blood, pulmonary function, and serum CEA recovered to almost within normal ranges. The shadows deteriorated twice, but therapeutic lavage performed at the outpatient clinic was effective on each occasion. He thus received 3 series of bronchoalveolar lavage over a period of more than 3 years. We followed the clinical course of this patient for 6 years, and he remained well 3 years after the final treatment.

Adult↗
PubMed1986

Functional and metabolic properties in hearts from aged spontaneously hypertensive rats.

The effect of long-term pressure overload on myocardial functional and metabolic alterations was investigated in hearts from spontaneously hypertensive rats of 16 weeks (young SHR) and 44 weeks (aged SHR) and age matched normotensive Wistar Kyoto strain rats (young WKY, aged WKY). The hearts were perfused by working heart mode and whole heart ischemia was induced by one-way valve. Following 20 min of ischemia, the hearts were reperfused for 30 min. The heart-body weight ratio in both SHR groups was significantly higher than in the respective age-matched WKY groups. Coronary flow relative to heart weight in both SHR groups was significantly lower than that of the respective age-matched WKY during both preischemic and reperfused periods. There was no significant difference in the recovery rate of cardiac output between young and aged WKY, whereas the young and aged SHR revealed significantly less recovery than their respective age-matched WKY. Tissue creatine phosphate and energy charge in both aged groups were significantly lower than in the young groups. These results indicate that long-term pressure overload increases susceptibility to ischemia and decreases the myocardial reserve presumably resulting from relative ischemia, whereas deterioration was minimal in the normotensive aged rat heart.

Aging↗
PubMed1984

Low density lipoprotein-lowering and high density lipoprotein-elevating effects of nicardipine in rats.

Oral administration of a calcium antagonist, nicardipine hydrochloride (simply designated as nicardipine), in doses of 10-100 mg/kg tended to decrease total serum cholesterol and to increase high density lipoprotein (HDL) cholesterol in the normal rat. These effects of nicardipine were much greater than those of clofibrate, a standard cholesterol-lowering drug. Neither nicardipine nor clofibrate caused significant alteration in serum triglyceride and phospholipid. In hypercholesterolemic rats, nicardipine increased significantly HDL cholesterol with a reduction of total serum cholesterol, whereas clofibrate did not change HDL cholesterol. Separation of serum lipoproteins either by ultracentrifugation in various densities of KBr-NaCl solution or by polyacrylamide gel electrophoresis demonstrated that nicardipine increased preferentially HDL2 (density: 1.063-1.125), with a reduction of the low density lipoprotein (LDL) (density: 1.006-1.063) level in hypercholesterolemic rats. Serum triglyceride and liver phospholipid were increased slightly by nicardipine with no clear dose-dependency. Clofibrate also increased serum triglyceride. In normal rats, neither nicardipine nor nicotinic acid inhibited sterol biosynthesis from [1-14C]acetate in the liver, whereas clofibrate inhibited sterol production. Oral administration of [4-14C]cholesterol to hypercholesterolemic rats indicated that nicardipine had no inhibitory effect on the intestinal absorption of cholesterol.

Acetates↗
PubMed1983

Kinetics of antisecretory action of a new H2-antagonist, YM-11170, in conscious dogs.

The antisecretory property of YM-11170 was compared with that of cimetidine and atropine in the Heidenhain pouch dog. YM-11170 inhibited competitively dimaprit-induced gastric acid secretion in doses of 33 and 100 nmol/kg per h and its antisecretory potency was 148 times more pronounced than that of cimetidine. The secretory action of pentagastrin and methacholine was also inhibited by YM-11170 and cimetidine with doses similar to those required for the inhibition of dimaprit action although the inhibition by the H2-antagonists was not of the surmountable type. Atropine inhibited gastric secretion stimulated by methacholine and pentagastrin more strongly than that stimulated by dimaprit. It is concluded that YM-11170 is a competitive antagonist of dimaprit-induced gastric secretion in vivo and that the activity of the H2-antagonists in blocking gastric H2-receptors may reflect their inhibitory effect on the acid response to pentagastrin and methacholine.

Animals↗
PubMed1983

Effect of a new potent H2-receptor antagonist 3[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-N2- sulfamoylpropionamidine (YM-11170) on gastric mucosal histamine-sensitive adenylate cyclase from guinea pig.

The effect of 3[[[2-[(diaminomethylene)amino]-4- thiazolyl]methyl]thio]-N2-sulfamoylpropionamidine (YM-11170), a new thiazole H2-receptor antagonist bearing propionamidine at the terminus of a side chain, on histamine-sensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] of gastric mucosa from the guinea pig was studied and compared with that of cimetidine. YM-11170 displaced the concentration-stimulation curve of histamine-sensitive adenylate cyclase to the right with a pA2 of 7.65 (Ki = 2.25 X 10(-8) M). Stimulation of gastric adenylate cyclase by 0.1 mM histamine was competitively inhibited by YM-11170 and cimetidine in a dose-dependent manner, with IC50 values of 5.9 X 10(-7) M and 1.4 X 10(-5) M respectively. Hippocampal histamine-sensitive adenylate cyclase in the presence of 0.1 mM histamine was also competitively inhibited by YM-11170 with an IC50 of 1.1 X 10(-7) M. YM-11170 did not affect Gpp(NH)p-, NaF-, PGE2-stimulated or basal activity of the gastric adenylate cyclase. These data, together with other results, indicate that YM-11170 is a highly selective and potent H2-receptor antagonist which competes with histamine at the receptor site on the histamine-sensitive adenylate cyclase.

Adenylyl Cyclases↗
PubMed1983

Selective binding of YM-09151-2, a new potent neuroleptic, to D2-dopaminergic receptors.

Effects of YM-09151-2 and five other neuroleptics (haloperidol, spiperone, chlorpromazine, sulpiride and clozapine) on the binding of [3H]-ligands to nine different receptors (alpha 1-adrenergic, alpha 2-adrenergic, beta-adrenergic, muscarinic, D2-dopaminergic, H1-histaminergic, 5HT1-serotonergic, 5HT2-serotonergic and opiate receptors) and on dopamine-sensitive adenylate cyclase were determined using brain membranes in the rat, guinea-pig and dog. The affinity of YM-09151-2 for D2-receptors with a Ki value of 0.1 nM was more than 1000-times higher than that for the other receptors and dopamine-sensitive adenylate cyclase, and it was the greatest among the neuroleptics tested.

Adenylyl Cyclases↗
PubMed1983

Dopamine receptor system involving adenylate cyclase in canine caudate nucleus.

Two distinct dopamine binding sites, referred to as D1 and D2, exist in canine caudate nucleus, as characterized by [3H]dopamine binding to the synaptic membrane fraction. D1 has the low affinity for dopamine with the dissociation constant of a few micromolar, whereas the affinity for D2 is about two orders of magnitude greater. Classical neuroleptics such as haloperidol and chlorpromazine have no selectivity in the inhibition of D1 and D2 binding, whereas a number of 2-methoxy benzamide derivatives which have been synthesized in our laboratories exhibit rather different selectivity. Correlation between the selectivity of those benzamide derivatives for the two sites and the inhibition of apomorphine-induced stereotypy in rats suggests that D1 is more responsible for the stereotypy. Photoaffinity labeling of D1 and D2 with [3H]dopamine demonstrates that the two sites are distinct entities. In the D1 system, the adenylate cyclase which is responsive to Gpp(NH)p can be dissociable by the treatment with GTP-Sepharose into a guanine nucleotide binding unit and a catalytic unit which is insensitive to Gpp(NH)p. The catalytic unit restores the responsiveness to Gpp(NH)p after preincubation with the nucleotide binding unit. Furthermore, endogenous cAMP-dependent phosphorylation of two particular proteins (protein Ia and Ib) is shown, which may be at least partly responsible for stereotypy and dopamine turnover in the caudate nucleus.

Adenylyl Cyclases↗
PubMed1983

Aminophenyl ether compound (YM-95831), a new hypolipidemic agent with a high density lipoprotein elevating activity in rats.

A single oral dose of a new hypolipidemic agent, 4-(cis-p-menthan-8)benzanilide (YM-95831) exhibited a marked elevation of high density lipoprotein (HDL) cholesterol with great reduction of serum total cholesterol in rats which were fed hypercholesterolemic diet. Reduction of serum total cholesterol preceded the increase in HDL, reached a peak at 16 h and was still significant even after 112 h. When YM-95831 was orally given daily for 4 days to the hypercholesterolemic rats, the dose required to reduce serum total cholesterol by 50% was about 6 mg/kg. Clofibrate was more than 10 times less potent than YM-95831 in the hypolipidemic activity. Nicotinic acid was virtually ineffective. HDL cholesterol was doubled by YM-95831 of about 3 mg/kg, but not significantly influenced by clofibrate of 200 mg/kg. Nicotinic acid at 400 mg/kg increased 1.5 times HDL cholesterol. Polyacrylamide gel electrophoresis of the serum demonstrated the decrease in beta-lipoprotein and the increase in alpha-lipoproteins by YM-95831. In hypercholesterolemic rats. YM-95831 increased preferentially HDL2 (d: 1.063-1.125) without significant alteration of a HDL3 (d: 1.125-1.21) level. YM-95831 tempted to decrease liver total cholesterol. Nicotinic acid significantly decreased the cholesterol whereas clofibrate exhibited no alteration. These results indicate that YM-95831 is a potent and long-lasting hypolipidemic agent with a potent HDL cholesterol elevating activity.

Anilides↗
PubMed1982

Dopamine receptors in canine caudate nucleus.

Physiological, pharmacological, histochemical and biochemical studies indicate that dopamine receptors are heterogenous in the central nervous system with each individual functions. This review describes pharmacological and biochemical characteristics of dopamine receptors, particularly in canine caudate nucleus, which have been studied in our laboratory with a brief comparison to the current studies by other workers in similar research fields. Two distinct dopamine receptors have been characterized by means of [3H]dopamine binding to the synaptic membranes from canine caudate nucleus. One of the receptors with a Kd of about 3 muM for dopamine may be associated with adenylate cyclase and referred to as D2 receptor. The other receptor with a Kd of about 10 nM for dopamine is independent of adenylate cyclase and referred to as D2. A photochemical irreversible association of [3H]dopamine with the membraneous receptors makes it possible to separate D1 and D2 receptors from one another by gel filtration on a Sephadex G-200 column after solubilization with Lubrol PX. On the basis of selective inhibition of [3H]dopamine binding to D1 and D2 receptors, dopamine antagonists can be classified into three classes: D1-selective (YM-09151-2), D2-selective (sulpiride) and nonselective (haloperidol, chlorpromazine). Effects of these typical antagonists on the metabolism of rat brain dopamine suggest that D1 receptor is more closely associated with the neuroleptic-induced increase in dopamine turnover. Studies with 28 benzamide derivatives and some classical neuroleptics reveal that apomorphine-induced stereotypy displays a greater association with D1 than with D2 receptors. Dopamine-sensitive adenylate cyclase in canine caudate nucleus can be solubilized with Lubrol PX in a sensitive form to either dopamine. Gpp(NH)p or fluoride Sephadex G-200 gel filtration separates adenylate cyclase from D1 receptors with a concomitant loss of dopamine sensitivity. Addition of the D1 receptor fraction to the adenylate cyclase restores the responsiveness to dopamine. The solubilized dopamine-unresponsive adenylate cyclase can be further separated into two distinct fractions by a batch-wise treatment with GTP-sepharose: a catalytic unit which does not respond to fluoride, and a guanine nucleotide regulatory protein. The regulatory protein confers distinct responsiveness to Gpp(NH)p and fluoride upon adenylate cyclase. These results indicate that dopamine-sensitive adenylate cyclase is composed of at least three distinct units; D1 receptor, guanine nucleotide regulatory protein and adenylate cyclase.

Adenosine Triphosphate↗
PubMed1982

Pharmacological studies on a new benzamide derivative, YM-09151-2, with potential neuroleptic properties.

The electrophysiological properties and cataleptogenicity of YM-09151-2 (N-[(2RS, 3RS)-1-benzyl-2-methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-methylaminobenzamide) were studied in the cat. This drug inhibited the EEG arousal response to electrical stimulation of the mesencephalic reticular formation with the same potency as that of haloperidol, whereas chlorpromazine revealed a more potent central depressant action. The duration of the afterdischarge induced by electrical stimulation of the amygdaloid nucleus was initially shortened and thereafter prolonged by both YM-09151-2 and haloperidol. However, YM-09151-2 was less effective than haloperidol and chlorpromazine in both augmenting the spindle bursts produced by electrical stimulation of the caudate nucleus and antagonizing the inhibitory effect of L-DOPA on the caudate spindle, indicating a smaller effect of YM-09151-2 on the extrapyramidal dopaminergic system than that of the two neuroleptic drugs. In fact, YM-09151-2 produced no cataleptic behaviour in the cat even at a dose of 5 mg/kg (s.c.), although haloperidol and chlorpromazine caused catalepsy in doses of 0.5 and 5 mg/kg (s.c.), respectively. Sulpiride, chemically related to YM-09151-2, showed much weaker central actions than YM-09151-2. The results indicate that a new benzamide, YM-09151-2, has a potent neuroleptic effect with a slight central depressant activity and that the cataleptogenicity of the compound is weaker than that of haloperidol and of chlorpromazine.

Amygdala↗
PubMed1982

Effects of porcine calcitonin on behavioral and electrophysiological responses elicited by electrical stimulation of the tooth pulp in rabbits.

Effects of porcine calcitonin on both behavioral and electrophysiological responses of rabbits to painful stimuli were examined. The behavioral pain response (licking reaction) to electrical stimulation of the tooth pulp was suppressed dose dependently by intracerebroventricular administration of calcitonin, 8 and 17 U/kg, but not by intravenous injection of 7.5-50 U/kg of the peptide. The duration of action of intracerebroventricular calcitonin was over 90 min. The EEG arousal response and the development of the long latency cortical potential evoked by electrical stimulation of the tooth pulp in gallamine-immobilized rabbits, were inhibited by intracerebroventricular calcitonin, 17 U/kg, for the period of over 90 min but not by the intravenous injection of 50 U/kg. Morphine, 2 mg/kg i.v., inhibited all of the responses for 30 min or longer. The EEG arousal response induced by sound stimulation was not affected by calcitonin or morphine. Naloxone (0.5 mg/kg i.v.), an opiate antagonist, showed no influence upon the inhibitory effects of calcitonin in licking reaction, EEG arousal response and evoked potential, though it completely antagonized the effects of morphine. The results suggest that the analgesic effect of intracerebroventricular porcine calcitonin can be attributed to blocking of pain pathways in the central nervous system in a manner distinct from the narcotic analgesic.

Animals↗
PubMed1982

Relaxant actions of PGE2 and its derivative (YPG-209) on canine tracheal smooth muscle and their enhancement of Ca++ uptake by the microsomal fraction.

The spasmogenic action of tetraethylammonium on canine tracheal smooth muscle was dependent on the extracellular Ca++ concentration. Acetylcholine, on the contrary, produced partial contraction for a certain period of time after removal of extracellular Ca++, suggesting the release of Ca++ from intracellular Ca++ stores into the cytosol. PGE2, 16(S)-methyl-20-methoxy-PGE2 (YPG-209), verapamil, and dibutyryl cyclic AMP relaxed the acetylcholine-induced contraction of the trachea. Pretreatment with prostaglandins or dibutyryl cyclic AMP more efficiently suppressed acetylcholine-induced contraction, whereas verapamil blocked the spasmogenic action of tetraethylammonium in a relatively selective manner. The prostaglandins and dibutyryl cyclic AMP also inhibited the spasmogenic action of acetylcholine in a Ca++-free medium. Influx of 45Ca into tracheal smooth muscle which was produced by 83 mM KCl plus 20 mM tetraethylammonium was not significantly affected by prostaglandins as measured by the lanthanum method. In addition, PGE2 increased ATP-dependent Ca++ uptake by the microsomes from tracheal smooth muscle. These results suggest that prostaglandins induce relaxation of the airway smooth muscle mainly through affecting the intracellular Ca++ movement such as by enhancement of sequestration of Ca++ to the microsomes.

Animals↗
PubMed1982

Vasodilator and hypotensive effects of the optical isomers of nicardipine (YC-93), a new Ca2+-antagonist.

Vasodilator and hypotensive effects of (+) and (-) nicardipine were investigated in anesthetized dogs. When administered intravenously, (+) nicardipine was 3 times as potent as the (-) isomer in increasing vertebral blood flow and in lowering mean blood pressure. When injected into the vertebral artery, (+) nicardipine was also 3 times as potent as the (-) isomer in increasing vertebral blood flow. Upon both routes of administration, the duration of the action after (+) nicardipine was longer than that after the (-) isomer. However, there were no differences of plasma nicardipine levels after intravenous injection of both isomers to conscious beagle dogs. The LD50 values of (+) nicardipine in mice and rats upon intravenous injection were only 1.5-2 times smaller than those of the (-) isomer. These results indicate that there exists a stereoselectivity of vasodilator and hypotensive actions among the nicardipine isomers.

Animals↗