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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 631 records · Page 35Linked to original sources
PubMed1985

Studies on YM-12617: a selective and potent antagonist of postsynaptic alpha 1-adrenoceptors.

YM-12617, 5-[2-[[2-(2-ethoxyphenoxy)ethyl]-amino]propyl]-2 -methoxybenzenesulfonamide HCl is a structurally new type of extremely potent alpha 1-adrenoceptor antagonist. Its alpha-adrenoceptor blocking properties have been compared with those of prazosin, phentolamine and yohimbine using both pharmacological and 3H-ligand binding techniques in vitro and in vivo. In the isolated rabbit aorta, a tissue known to contain mainly alpha 1-adrenoceptors at postjunctional sites, YM-12617 competitively antagonized noradrenaline-induced contraction with a pA2 value of 10.11. Although YM-12617 was also a competitive antagonist toward clonidine at prejunctional alpha 2-adrenoceptors in the isolated rat vas deferens, its affinity for these receptors (pA2 = 6.41) was 5,000 times lower than that displayed for the postjunctional alpha 1-adrenoceptors in the isolated rabbit aorta. YM-12617 displaced both 3H-WB 4101 and 3H-clonidine binding to rat brain membranes; however, the affinity of YM-12617 for alpha 1-adrenoceptors (pKi = 9.64) was 3800 times higher than that for alpha 2-adrenoceptors (pKi = 6.06). Based on pA2 values obtained in the isolated tissues and pKi values in the binding assays, YM-12617 was 2-18, 36-117 and 1,740-5,750 times more potent than prazosin, phentolamine and yohimbine in antagonizing alpha 1-adrenoceptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1985

alpha 1-Adrenoceptor subtype mediating contraction of the smooth muscle in the lower urinary tract and prostate of rabbits.

The alpha-adrenoceptor subtype mediating contraction of the smooth muscle in the urinary bladder base (trigone), proximal urethra and prostate isolated from male rabbits was investigated by comparing the responsiveness to alpha-adrenoceptor agonists and antagonists under condition where beta-adrenoceptors and neuronal and extraneuronal uptakes were inhibited. Noradrenaline (non-selective), phenylephrine (alpha 1-selective) and clonidine (alpha 2-selective) caused a dose-dependent contraction in the trigone, urethra and prostate. Phenylephrine acted as a full agonist whereas clonidine was a partial agonist. YM-12617 and prazosin (alpha 1-selective), phentolamine (non-selective) and yohimbine (alpha 2-selective) produced dose-dependent shifts to the right of the dose-response curves for noradrenaline, phenylephrine and clonidine in the all three tissues. YM-12617 (pA2 = 9.77, 9.67 and 9.73 for trigone, urethra and prostate, respectively), prazosin (pA2 = 8.26, 8.20 and 8.08), phentolamine (pA2 = 7.67, 7.62 and 7.45) and yohimbine (pA2 = 6.30, 6.30 and 5.94) showed constant pA2 values irrespective of the agonists and tissues used, suggesting that only a single subclass of alpha-adrenoceptors is present. The actual pA2 values for these antagonists are comparable to those reported previously in tissues said to contain mainly alpha 1-adrenoceptors. Thus, we concluded that the postsynaptic alpha-adrenoceptors of the rabbit trigone, urethra and prostate mediating contraction belong to the alpha 1-subtype.

Adrenergic alpha-Agonists↗
PubMed1985

Nonfunctioning adrenocortical carcinoma in a young girl.

A 9 year old Japanese girl was admitted complaining of left hypochondrial pain and a large upper left abdominal tumor. There were no clinical or laboratory signs of hormonal abnormality. Intravenous pyelography showed marked compression and deformity of the kidney by a tumor. This tumor was excised together with the left kidney. The pathological diagnosis was adrenocortical carcinoma. Postoperatively, the child was given neither irradiation nor chemotherapy. Twenty-one months after the surgery, there was a hepatic metastasis, and she died 40 months after surgery from a combination of hepatic metastases and local tumor recurrence.

Adrenal Cortex Hormones↗
PubMed1985

A pharmacological study of alpha adrenergic receptor subtypes in smooth muscle of human urinary bladder base and prostatic urethra.

Postsynaptic alpha adrenergic receptor subtypes mediating contraction of human urinary bladder base and prostatic urethra were investigated in vitro. Alpha adrenergic receptor agonists, noradrenaline and phenylephrine, induced contraction dose-dependently in these tissues. Alpha adrenergic receptor antagonists, prazosin and yohimbine, competitively antagonized the contraction induced by these agonists in the bladder base as well as prostatic urethra. The mean pA2 values for the antagonists in the bladder base and prostatic urethra were as follows: 8.89 and 8.96 for prazosin and 6.30 and 6.45 for yohimbine, respectively. Comparison of pA2 values of prazosin and yohimbine in both the tissues with those values found in the literature for these compounds in a variety of tissues containing alpha-1 or alpha-2 adrenergic receptor indicates that the postsynaptic alpha adrenergic receptor subtype in the human urinary bladder base and prostatic urethra is the alpha-1 type, not the alpha-2 type.

Aged↗
PubMed1985

Effects of neurosurgical treatment on diffuse slow spike and wave complex: a case of left frontal mass lesion with diffuse slow spike and wave complex (DSSW).

A 10-year-old girl with a mass lesion in the left deep frontal lobe was reported. Clinically, seizures occurred at 3 years and 8 months and became intractable around the age of 5.5 years. EEG initially showed focal spikes on the left fronto-central area and later developed into diffuse slow spike and wave complexes (DSSW). Her seizures were clinically different from those in Lennox-Gastaut syndrome. After a left frontal lobectomy, her intractable seizures completely disappeared with marked EEG improvement and without any neurological deficit. Radiological findings before the operation suggested that the expanding effects extended to the deep temporal structures, adjacent to the frontal lobe. These structures, deep frontal and temporal lobes, both or either, were assumed to be involved in generating DSSW in this case.

Child↗
PubMed1985

Constant number of immunogloblin G positive plasma cells around the penicilli in murine spleen with increasing age.

The splenic lymphoid tissue of mice reared in a conventional environment regressed with increasing age. Immunogloblin G positive plasma cells gathered along the penicilli in the senile spleen as well as in the adult control spleen. The number of plasma cells around the penicilli showed no difference in the senile spleen as compared to the adult spleen. Since mature plasma cells remain in the lymph node for a short time only and seldom divide there, our results indicate that the transformation from B lymphocyte to plasma cell is not affected by age.

Aging↗
PubMed1985

Urinary excretion characteristics of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate.

Urinary excretion characteristics of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), following intravenous administration was studied in rats. Three types of MMC-D, conjugates with dextrans of molecular weights of 10000, 70000 and 500000, were tested and urine concentration of MMC, dextran and spacer were determined by three analytical methods, i.e., bioassay, anthrone method and radioactivity counting. MMC was assayed separately as a free form and conjugated form based on antimicrobiological activity. MMC administered as a free form was excreted rapidly into urine but only a small amount of MMC was excreted following the administration of MMC-D. The excreted amount of MMC in a conjugated form varied with the size of carrier dextran while similar sustained excretion was observed regardless of the carrier size. The excretion of carrier dextran determined by anthrone method was confined as the molecular weight was increased. The effect of molecular weight was also observed in the case of spacer-introduced dextran (dextran-C6 spacer) and original dextran. Compared with neutral dextran, cationic MMC-D and anionic dextran-C6 spacer exhibited diminished excretion, indicating the effect of charge on urinary excretion. The urinary recovery of radioactivity was almost in accordance with that of carrier dextran. However, the urinary recovery of MMC based on biological activity was considerably lower than that of carrier dextran. It was suggested that MMC-D underwent inactivation to a great extent before releasing active MMC in the body. The effect of physicochemical properties such as molecular weight and electric charge on the urinary excretion of the polymeric prodrug was thus elucidated.

Animals↗
PubMed1985

Autonomic and antihypertensive activity of oral amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor blocking agent in conscious rats.

The autonomic and antihypertensive activities of amosulalol (YM-09538) were studied in conscious rats. Single oral administration of amosulalol antagonized the phenylephrine-induced pressor and isoproterenol-induced positive chronotropic responses with DR10 values of 11.5 and 13.6 mg/kg in pithed rats, respectively, indicating that the compound inhibits both alpha 1- and beta 1-adrenoceptors to almost the same extent in agreement with previously reported results in vitro. Amosulalol was approximately 50 times less potent than prazosin and 12 times more potent than labetalol at alpha 1-adrenoceptors, and it was approximately as effective as labetalol and 2 times more potent than propranolol at beta 1-adrenoceptors. In spontaneously hypertensive rats (SHR), renal hypertensive rats and DOCA/salt hypertensive rats, a single oral administration of amosulalol (3-30 mg/kg) lowered acutely systolic blood pressure with a duration of over 6 hr and was found to be approximately 50 times less potent than prazosin and 3 times more potent than labetalol in lowering blood pressure. Propranolol did not cause such an immediate hypotensive effect. Amosulalol and labetalol did not increase heart rate, whereas prazosin induced a tachycardia in the hypertensive rats. Repeated oral administrations of amosulalol and labetalol (50 mg/kg/day, b.i.d., for 12 weeks) produced not only an antihypertensive effect without evidence of tolerance, but also reductions in plasma renin activity (PRA) and heart rate in SHR with established hypertension. We conclude that alpha-adrenoceptor blockade by amosulalol might account for its antihypertensive activity and that its beta-adrenoceptor blockade might inhibit reflexogenic increases in heart rate and PRA due to the reduction in blood pressure.

Adrenergic alpha-Antagonists↗
PubMed1985

Effect of microelectrophoretically applied acetylcholine, noradrenaline, dopamine and serotonin on the discharge of paraventricular oxytocinergic neurones in the rat.

The effects of microelectrophoretic applications of neurotransmitter substances and their antagonists on the activity of paraventricular oxytocinergic neurones were studied in urethane anesthetized lactating rats. Oxytocinergic neurones were identified by their antidromic response to the stimulation of the neurohypophysis and by their characteristic high frequency discharge of action potentials approximately 15-20s before reflex milk ejection. Acetylcholine (ACh) excited the majority (75%) of paraventricular oxytocinergic neurones, and none of the cells was inhibited in its activity by ACh. In about half of the oxytocinergic cells, atropine and hexamethonium reduced the number of action potentials during the burst discharge preceding reflex milk ejection. Noradrenaline (NE), dopamine (DA) and serotonin (5-HT) reduced the activity of most (75-100%) of oxytocinergic neurones, and none of the cells was excited by these catecholamines. These results suggest that paraventricular oxytocinergic neurones receive excitatory cholinergic inputs and inhibitory noradrenergic, dopaminergic and serotonergic inputs.

Acetylcholine↗
PubMed1985

Reducing terminals of urinary chondroitin sulfate.

Human urinary chondroitin sulfate isolated from the cetylpyridinium chloride-complex of the non-dialyzable fraction of the pooled urine was subjected to ethanol fractionation, successive enzymic digestion with neuraminidase and mucopolysaccharidases, and anion exchange chromatography. The gas liquid chromatographic analyses of the acetyl and butaneboronic acid ester derivatives of the reduced terminal sugar units after treatment with sodium borohydride plus hydrolysis revealed that 42% of the urinary chondroitin sulfate was bound to peptide through xylose. The reducing terminal sugar units of the peptide-free form consisted of 34.6% of xylose, 22.4% of galactose, 16.4% of glucose of unknown origin and 26.6% of glucuronic acid. These observations showed that the xyloside, galactoside and glucuronide linkages at non-terminal sites of carbohydrate chains of chondroitin sulfate were cleaved in tissues. It was thus suggested that the endo-types of beta-xylosidase, beta-galactosidase and beta-glucuronidase, which act on proteochondroitin sulfate are present in tissues.

Amino Acids↗
PubMed1985

Release of oxytocin during suckling and parturition in the rat.

A highly sensitive and specific radioimmunoassay (RIA) for oxytocin was developed and used to measure oxytocin concentrations during both suckling and parturition in individual rats. In urethane-anaesthetized rats, the suckling stimuli, provided by ten pups, induced intermittent increases in intramammary pressure of about 10 mmHg. This was associated with a significant (P less than 0.01) increase in serum oxytocin levels from 19.5 +/- 4.5 (S.E.M., n = 9) to 49.1 +/- 7.4 pmol/l (n = 9) in the samples taken within 30 s from the time of the peak in the pressure. These rises in serum oxytocin returned rapidly to the basal levels as expected from the short half-life (1.46 min) of oxytocin in general circulation. On day 22 or 23 of gestation, serum oxytocin levels remained stable until 0-0.5 h before the first fetus was expelled. They then increased significantly (P less than 0.01) from 27.6 +/- 4.6 pmol/l (n = 19) in samples taken 0-0.5 h before to 45.1 +/- 5.6 pmol/l in samples taken after the expulsion of the first fetus and gradually increased until the last fetus was expelled. Serum oxytocin concentrations then declined but remained higher than those observed before the first fetus had been born until at least 1-1.5 h after the expulsion of the last fetus. Thus, this oxytocin RIA revealed increased concentrations of the hormone in blood during both suckling and parturition in the rat.

Animals↗
PubMed1985

Functional development of the oxytocin release mechanism and its role in the initiation of parturition in the rat.

Developmental changes in levels of oxytocin in the blood and the pituitary gland and in oxytocin responses to oxytocin-releasing stimuli were investigated in the rat from the fetus close to term to the 40-day-old young adult. The oxytocin content of the pituitary gland rose gradually from fetuses of 21 days of gestation to 40-day-old rats. Pituitary oxytocin levels expressed in terms of body weight also increased up to day 25 after birth and declined slightly thereafter. In contrast, serum concentrations of oxytocin increased from day 21 of pregnancy up to day 5 after birth but were stable thereafter. Oxytocin levels in both blood and the pituitary gland were equal in 23-day-old fetuses and 1-day-old infants born on day 22 of pregnancy. There was no difference in serum and pituitary oxytocin levels in newborn pups and unborn littermates of day 22 or 23 of gestation. The i.p. injection of hypertonic saline induced a significant increase in serum oxytocin levels on day 5 and later, but no effect in the fetus on day 22 of gestation and in the 1-day-old infant. The responsiveness to the osmotic stimuli increased after 5 days of age. The i.p. injection of diethyldithiocarbamate, a noradrenaline synthesis inhibitor, or phenobarbitone was effective in raising blood oxytocin levels only in rats older than 10 and 20 days of age respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

[Topical application of mitomycin C conjugated with dextran (MMC-D): a high molecular weight derivative of mitomycin C].

Mitomycin C conjugated with dextran (MMC-D), with a molecular weight of about 500,000, was synthesized for intraoperative topical application. MMC-D contained approximately 10% mitomycin C (MMC) and released active MMC by hydrolysis with a half-life of 24 hours in vivo. In experimental studies, MMC-D was retained at the injection site for about 48 hours and transferred to the lymphatic system. Sixteen patients suffering from advanced abdominal cancers were treated with MMC-D (5-10mg eq. MMC) by intraoperative direct injection or percutaneous injection under sonography. Objective tumor responses were observed in 9 of 16 cases. No serious side-effect was observed other than temporary fever, localized pain and mild leukopenia. MMC-D diffused from the center of the tumor releasing active MMC which was transferred to the lymphatic system. Local application of MMC-D was therefore considered to be effective for the treatment of solid tumors.

Aged↗
PubMed1985

[Clinicopathological studies on disseminated carcinomatosis of the bone marrow occurring through metastasis of gastric carcinoma].

Five cases of gastric carcinoma (one woman) were investigated. The average age of the patients was 44 and the clinical manifestation were lumbago, melena and fatigue. Two cases were Borrmann III, and other were Borrmann IV, IIc and IIc advanced, respectively. Three were signet-ring cell carcinoma and the other two were moderately differentiated and well-differentiated adenocarcinoma, respectively. All patients showed leukoerythroblastosis. Bone marrow specimens revealed myelofibrosis in three cases, while adenocarcinoma cells were also found in three. MHA or DIC was found in three patients, all of whom died of bleeding tendency. Mean survival time was 2.6 months. Thus, bone marrow carcinomatosis proved to be very severe.

Adenocarcinoma↗