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Biomedical subjects

M Ohno

Publications and source records attributed to M Ohno.

At least 487 records · Page 27Linked to original sources
PubMed1988

A sensitive radioimmunoassay of alpha human atrial natriuretic polypeptide using monoclonal antibody recognizing human form ring structure.

A monoclonal antibody (C351) against alpha human atrial natriuretic polypeptide (alpha hANP) recognizing human form ring structure was established and applied to a radioimmunoassay of plasma alpha hANP. The minimum detectable amount in terms of 10% radioligand displacement relative to zero dose were 0.28 fmol/tube, corresponding to 0.7 fmol/ml in plasma after extraction using Sep-Pak C18 cartridges. When the mean plasma levels at recumbent position in fasted morning were compared in 10 young (less than 30 years) and 10 elderly (greater than or equal to 50 years) healthy subjects taking normal sodium diet, it was slightly higher in the latter (3.2 +/- 0.4 vs 4.7 +/- 0.5 fmol/ml, mean +/- SE, p less than 0.05). After i.v. infusion of hypertonic saline (2.5% NaCl) at a rate of 0.24 ml/kg/min for 20 min in 6 normal subjects (26 to 35 years), it was increased from 4.1 +/- 0.4 to 5.9 +/- 0.7 fmol/ml (p less than 0.01). In 6 patients with essential hypertension (34 to 57 years), it was elevated with high salt intake, i.e. 3.3 +/- 0.3, 3.9 +/- 1.03 and 7.6 +/- 1.5 fmol/ml under 34, 170 and 340 mEq NaCl/day for 7 days, respectively. From these results, the radioimmunoassay of plasma IR-alpha hANP using MAb C351 seems to be quite suitable to detect rather small changes at low plasma concentrations and to investigate a physiological importance of alpha hANP in man.

Adult↗
PubMed1988

Effect of DG5128 on epinephrine and glucagon induced glucose output from the isolated perfused rat liver.

The effect of a specific alpha 2-adrenergic antagonist 2-[2-(4,5-dihydro-1.H-imidazol-2-yl)-1-phenyl-ethyl] pyridine dihydrochloride sesquihydrate (DG5128), on the glucose output by epinephrine and/or glucagon was studied using the perfused rat liver. The administration of DG5128 alone did not affect the glucose output. However, DG5128 produced a significant inhibition of the increased glucose output when induced by 10(-6) M epinephrine alone or 10(-6) M epinephrine plus 1.4 x 10(-10) M glucagon. There were no significant changes of the glucose output by 1.4 x 10(-10) M or 7.0 x 10(-11) M glucagon alone. On the other hand, addition of 1 mU/ml insulin to the perfusate suppressed the 7.0 x 10(-11) M glucagon-induced glucose output, but failed to decrease the 1.4 x 10(-10) M glucagon effect. DG5128 suppressed further the glucagon (7.0 x 10(-11) M)-induced increase of glucose output in the presence of insulin. These results suggest that DG5128 produces a hypoglycemic effect partly through an inhibition of the increased hepatic glucose output elicited by epinephrine and glucagon.

Animals↗
PubMed1988

Anti-serotonin action in combination with noradrenaline-stimulating action is important for inhibiting muricide in midbrain raphe-lesioned rats.

The present study was designed to examine the possible involvement of both an anti-serotonin action and a catecholamine-stimulating action in the mechanism of the inhibition of the muricide in rats with lesions of the midbrain raphe. Serotonin antagonists, such as cyproheptadine (10 mg/kg), cinanserin (10 mg/kg) and pirenperone (1 mg/kg), given alone showed little suppression of muricide in rats with raphe lesions, although the first two drugs were inhibitory at very large doses. Methamphetamine showed no inhibition of muricide at 0.32 mg/kg (i.p.), but exerted a marked inhibition of muricide when combined with the above serotonin antagonists. In addition, the dose-response curve for cyproheptadine and cinanserin was shifted markedly to the left when combined with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) (100 mg/kg i.p.), but not with lisuride (0.32 mg/kg i.p.). Similarly, pirenperone produced a marked inhibition of muricide at doses of 0.32-1.8 mg/kg (i.p.) when combined with L-threo-DOPS, but not when combined with lisuride. These results suggest that the combination of an anti-serotonin action with noradrenergic activation is important for inhibiting muricide, at least in rats with raphe lesions. A similar mechanism also seems to be valid for the anti-muricidal effect of antidepressant drugs.

Aggression↗
PubMed1988

Purification and characterization of L-amino acid oxidase from the venom of Trimeresurus mucrosquamatus (Taiwan habu snake).

L-Amino acid oxidase (EC.1.4.3.2) was purified to homogeneity via four steps consisting of Sephadex G-100, CM-Toyopearl 650M, and first and second granulated hydroxyapatite column chromatographies. The mol. wt of the enzyme was 140,000 when estimated by analytical gel filtration and was 70,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the enzyme is composed of two identical subunits. The enzyme has an absorption spectrum characteristic of flavoprotein, contains 2 moles of FMN per mole of enzyme and has an isoelectric point of 5.4. The enzyme oxidatively deaminated hydrophobic amino acids such as Leu, Met, Phe, and Tyr while basic amino acids except for Lys were also oxidized though at slower rates. This specificity was generally similar, with some exceptions, to that of the enzyme from Trimeresurus flavoviridis venom. For oxidative deamination of Leu, Km and maximum velocity of the enzyme were 1.17 mM and 9.9 units/mg, respectively, at pH 7.6. The activity was inhibited almost completely by heavy metal ions, some aromatic benzoates and sulfhydryl reagents but not by metal-chelating agents.

Amino Acid Oxidoreductases↗
PubMed1988

Tryptophan residue essential for activity of Naja naja atra phospholipase A2.

When Naja naja atra phospholipase A2, which contains three tryptophan residues at the 18th, 19th, and 61st positions, was oxidized with N-bromosuccinimide at pH 4.0, its activity decreased in a convex manner with increase in the extent of oxidation of tryptophan residues. The curve shape showed that the tryptophan residue oxidized last is most responsible for the activity. The order of accessibilities of the three tryptophan residues, which was analyzed according to the method reported previously (Mohri et al. (1876) J. Biochem. 100, 883-893), was Trp-61 greater than Trp-19 greater than Trp-18. Thus, Trp-18 was evaluated to be essential for activity. Difference spectra of phospholipase A2 produced by titrating with laurylphosphorylcholine in the presence of Ca2+, which are due in large part to perturbation of the tryptophan residue(s), were retained with phospholipase A2 derivatives containing 1.2 and 2.0 mol of tryptophan residues oxidized but not with the derivative containing 3.0 mol of tryptophan residues oxidized. Such observations led us to assume that Trp-18 is involved in the specific site that interacts with phospholipid.

Amino Acid Sequence↗
PubMed1988

Amino acid sequence of a coagulant enzyme, flavoxobin, from Trimeresurus flavoviridis venom.

The amino acid sequence of a coagulant enzyme, named flavoxobin, isolated from the venom of Trimeresurus flavoviridis (the habu snake) was determined by sequencing the S-pyridylethylated derivative of the protein and its peptides generated by chemical (cyanogen bromide and hydroxylamine) and enzymatic (clostripain, Staphylococcus aureus V8 protease, Achromobacter protease I, and elastase) cleavages. Hydrazinolysis was also employed to determine the C-terminal amino acid. The enzyme consisted of 236 amino acids and had a calculated molecular weight of 25,744. Flavoxobin was found to be highly (69%) homologous in sequence to batroxobin, a coagulant enzyme from the venom of Bothrops atrox, and 27, 39, and 31% homologous to bovine thrombin, bovine trypsin, and human kallikrein, respectively. The sequence around the active site serine residue deduced from the homology relationship was Phe-Asp-Ser-Gly-Thr, which is different from the common sequence, Gly-Asp-Ser-Gly-Gly, for most serine proteases. Flavoxobin appears to be similar in secondary structure composition to batroxobin.

Amino Acid Sequence↗
PubMed1988

Hydrolysis of platelet activating factor and its methylated analogs by acetylhydrolases.

We examined the substrate specificity of PAF-degrading enzymes from various sources using platelet activating factor (PAF) and its synthetic analogs. The results were as follows: 1) Tissue-originated acetylhydrolases, such as rat kidney soluble enzyme, deacetylated 1S-methyl-1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (1S-Me-PAF) slightly more rapidly than PAF, whereas plasma acetylhydrolase hydrolyzed PAF more effectively than 1S-Me-PAF. 2) Rat polymorphonuclear leukocytes, monocytes, and lymphocytes homogenates showed an appreciable acetylhydrolase activity, the substrate specificity of which resembled that of the plasma enzyme. 3) Pleural exudates in an experimental pleurisy induced in rats by carrageenan contained an acetylhydrolase activity, the properties of which were similar to those of the plasma enzyme. 4) An extracellular phospholipase A2 activity, which was also observed in the pleural exudate and required Ca2+ ion for maximum activity, seemed not to participate in the deacetylation of PAF, since addition of EDTA did not affect the PAF deacetylation catalyzed by the pleural exudate. These findings indicate that the inactivation reaction of PAF present in the extracellular space is mainly catalyzed by plasma acetylhydrolase, which yields lysoPAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1988

Is salt sensitivity in essential hypertension affected by ageing?

To investigate the question of whether the salt sensitivity of blood pressure in human essential hypertension is affected by ageing, the salt-sensitivity index was determined in 54 hospitalized patients with essential hypertension, aged 26-67 years (mean +/- s.d. 46.9 +/- 9.5 years) as well as plasma inhibition of Na+,K+-ATPase (sodium-pump inhibitor), erythrocyte sodium and potassium concentrations and fractional excretion of lithium. The salt-sensitivity index was calculated as the percentage change in mean blood pressure when the dietary sodium content was increased from 34 mmol/day (low sodium) to 340 mmol/day (high sodium) for 8 days each. Despite wide range of ages, age showed no correlation with the salt-sensitivity index, the sodium-pump inhibitor, the erythrocyte Na+:K+ ratio or fractional excretion of lithium. Furthermore, the distribution of the salt-sensitivity index did not differ between older (greater than or equal to 45 years old) and younger (less than 45 years old) age groups. In contrast, the distribution of this index was correlated positively with the change in sodium pump inhibition induced by a sodium load (r = 0.415, P less than 0.05) and negatively with the fractional excretion of lithium (r = -0.725, P less than 0.01). The erythrocyte Na+:K+ ratio tended to be higher in patients with a salt-sensitivity index of 10% than in those with an index of less than 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Urinary normetanephrine and metanephrine measured by radioimmunoassay for the diagnosis of pheochromocytoma: utility of 24-hour and random 1-hour urine determinations.

To validate the clinical usefulness of recently developed normetanephrine (NM) and metanephrine (M) RIA for the diagnosis of pheochromocytoma, urinary excretion of catecholamines and these metabolites were determined in 30 normal subjects, 40 patients with essential hypertension, 30 patients who were suspected to have but ultimately proven not to have a pheochromocytoma (pheochromocytoma-suspect), and 31 patients with a surgically verified pheochromocytoma. Abnormally high catecholamine excretion (epinephrine plus norepinephrine) was found in patients with pheochromocytoma compared with that in the normal subjects and the essential hypertension group. However, 3 of 31 patients with pheochromocytoma had urinary catecholamine excretion that overlapped the values in the pheochromocytoma-suspect group. Both urinary NM and M excretion also were elevated in patients with pheochromocytoma, but in 4 of 31 patients with pheochromocytoma urinary M excretion was within the range found in 1 or more of the other groups. Total M (NM plus M) excretion of more than 5485 nmol/day (as NM) was found in all patients with pheochromocytoma, and all patients had values that were higher than the highest values in the normal subjects or the patients with no evidence of pheochromocytoma. To save time and simplify the diagnostic work-up of patients suspected of having a pheochromocytoma, we also determined the NM and M concentrations in randomly voided 1-h urine samples in 24 patients with pheochromocytomas, 31 patients with essential hypertension, and 16 normal subjects. Abnormally high total M excretion was found in all patients with pheochromocytomas, and there was no overlap with the values in the patients with essential hypertension or the normal subjects. We conclude that total M measurements in both 24-h and random 1-h urine samples are useful in diagnosing pheochromocytomas.

Adolescent↗
PubMed1988

Periodic fluctuation of blood pressure and its management in a patient with pheochromocytoma. Case report and review of the literature.

The case of a 69 year old man with a right adrenal pheochromocytoma who manifested cyclic fluctuations of blood pressure with a cycle length of 9 to 13 min is reported. We collected and reviewed 14 similar cases previously reported in the literature. In these cases, right adrenal pheochromocytoma was most common, while 1 case involved the left adrenal and 2 cases were of extra-adrenal origin. The incidence in males was twice that in females and the median age was 45.3 years. Although a good correlation between the blood pressure and plasma norepinephrine concentrations was observed in our patient, the exact mechanism for the cyclic fluctuations of blood pressure is not known. In our patient, both YM-09538 and bunazosin were effective in controlling severe hypertension preoperatively. YM-09538 induced significant increases in urinary norepinephrine concentrations (1327 +/- 238 micrograms/day), while bunazosin induced a significant decrement in urinary norepinephrine concentrations (475 +/- 188 micrograms/day) compared with pretreatment levels (900 +/- 42 micrograms/day) (p less than 0.01). These observations indicated that bunazosin as a postsynaptic alpha-adrenergic receptor blocker interfered with release of norepinephrine from the tumor and thus might be beneficial in the management of elevated blood pressure in patients with pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1988

Tetrodotoxin-unaffected depolarization of frog muscles induced by the venom of jellyfish (Genus aurelia).

In the isolated frog muscle, the proteinaceous venom extracted from jellyfish (genus Aurelia) produced 1) a complete and irreversible block of indirectly and directly elicited muscle twitch and 2) an irreversible depolarization of the muscle membrane. This venom-induced depolarization was effectively reversed or prevented by the substitution of choline for sodium in Ringer solution, but not by the introduction of tetrodotoxin (TTX), a sodium channel blocker. The mechanism of muscle membrane depolarization appears to involve probably an increase in membrane permeability to sodium ion as shown by the decrease in membrane resistance. These results suggest that the venom forms a pore which has sodium selectivity or activates a TTX-insensitive sodium channel which is different from the known sodium channel.

Aminopyridines↗
PubMed1988

Electroencephalographic effects of the new antidepressant paroxetine in the rabbit.

The electroencephalographic (EEG) effect of (-)-trans-4-(4'-fluorophenyl)-3-(3',4'-methylene-dioxyphenoxy-met hyl)piperidine hydrochloride (paroxetine, BRL 29060A) a new antidepressant, was investigated in conscious rabbits with chronic electrode implants and was compared with those of imipramine and amitriptyline. Paroxetine induced an arousal pattern of the spontaneous EEG consisting of low voltage fast waves in the cortex and synchronization of hippocampal theta waves with decreased amplitude, while imipramine and amitriptyline elicited drowsy patterns of the spontaneous EEG. Paroxetine failed to suppress the EEG arousal responses induced not only by auditory stimulation but also by electrical stimulation of the mesencephalic reticular formation, centromedian thalamus and posterior hypothalamus, whereas imipramine and amitriptyline markedly inhibited these responses. The EEG arousal response induced by i.v. injection of physostigmine 0.2 mg/kg was slightly enhanced by paroxetine, while the response was significantly suppressed by imipramine and amitriptyline. Paroxetine, imipramine and amitriptyline showed no significant effect on the photic driving response and recruiting response. Paroxetine did not show any effects on the limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation, while imipramine and amitriptyline caused an initial suppression followed by slight enhancement of these afterdischarges. These results indicate paroxetine to be an antidepressant of a new type which induces a sustained arousal pattern of the spontaneous EEG and has no central anticholinergic action.

Amitriptyline↗
PubMed1988

New therapeutic approach to aortic dissection complicated by cardiac tamponade.

The management of aortic dissection with cardiac tamponade may result in increased blood pressure and thereby itself make the aortic dissection worse. Nevertheless, it is important to prevent cardiac failure caused by cardiac tamponade. We describe a case of aortic dissection with cardiac tamponade. Echocardiography and aortography showed DeBakey IIIb-type aortic dissection with retrograde dissection, complicated by cardiac tamponade and aortic insufficiency. To treat this condition, a new therapeutic approach was undertaken. A vasodilator was administered, then pericardiocentesis guided by echocardiography was performed. To prevent abrupt elevation of blood pressure in response to the relief of cardiac tamponade, the pericardial aspiration was carried out slowly--it took four hours for the complete drainage of 415 ml of blood--and a vasodilator, sodium nitroprusside, was administered. After drainage, cardiac function was reversed fully, and the systolic pressure was controlled under 140 mmHg. Then, using extra-corporeal circulation, the surgical procedure was performed successfully. We conclude that it is useful to treat cardiac tamponade by controlling blood pressure with slow drainage and use of a vasodilator in preparation for performing the surgical procedure.

Aortic Dissection↗