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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 685 records · Page 38Linked to original sources
PubMed1989

The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes.

Three distinct human endothelin-related genes were cloned by screening a genomic DNA library under a low hybridization stringency with a synthetic oligonucleotide probe encoding a portion of the endothelin sequence. Genomic Southern blot analysis with the same oligonucleotide probe showed three corresponding chromosomal loci not only in the human genome but also in porcine and rat genomes. The nucleotide sequences of the three human genes were highly conserved within the regions encoding the 21-residue (mature) endothelins, in spite of the fact that the immediately upstream exon sequences, which encode a part of the propeptides, retained little similarity. Moreover, each of the human genes predicted a putative 21-residue peptide, similar to but distinct from each other: (i) the "classical" endothelin (ET-1), (ii) [Trp6,Leu7]endothelin (ET-2), and (iii) [Thr2,Phe4,Thr5,Tyr6, Lys7,Tyr14]endothelin (ET-3). Synthetic ET-1, ET-2, and ET-3 were prepared according to the deduced amino acid sequences, and the biological activities were assayed by contraction of isolated porcine coronary artery strips and by intravenous injection to anesthetized rats. All these synthetic peptides produced strong vasoconstrictor and pressor responses. However, the quantitative profiles of the pharmacological activities were considerably different among the three isopeptides, suggesting the possible existence of endothelin receptor subtypes.

Animals↗
PubMed1989

Physicochemical properties of 57 kDa thyroid hormone binding protein from rat liver nuclei.

The nuclear thyroid hormone binding protein (NTHB) with the molecular weight of 57 kDa was obtained from rat liver nuclear extracts by using HPLC and DEAE-Sephadex A-25 ion exchange chromatography methods. Fluorescein isothiocyanate-labeled 3,5,3'-triiodo-L-thyronine (F-T3) was used as a fluorescent probe to identify the hormone binding protein. Purified NTHB has a single binding site for T3 with the apparent binding constant of (3.3 +/- 0.7) X 10(8) M-1. NTHB is an acidic protein with a pI of 5.0. The secondary structure of NTHB is characterized by about 42% helical and 18% beta-structure from CD measurements.

Animals↗
PubMed1989

Conversion of big endothelin-1 to 21-residue endothelin-1 is essential for expression of full vasoconstrictor activity: structure-activity relationships of big endothelin-1.

The vasoconstrictor activities of porcine big endothelin-1 (big ET-1), a 39-residue intermediate predicted from cDNA sequence analysis, and of its shorter derivative, big ET-1 [1-25], were characterized in vitro by measuring the contraction of porcine coronary artery strips. Synthetic big ET-1 [1-39] and big ET-1 [1-25] induced a slow developing, long-lasting, and strong vasoconstriction as in the case of 21-residue ET-1. However, the contractile molar potencies of big ET-1 [1-39] and big ET-1 [1-25] were approximately 140- and 50-fold lower than that of ET-1, respectively. These results indicate that the conversion of big ET-1 to "mature" ET-1 is essential for the expression of the full vasoconstrictor activity, suggesting the physiological importance of the unusual proteolytic processing catalyzed by the putative "ET converting enzyme."

Animals↗
PubMed1989

Elimination of intravenously injected endothelin-1 from the circulation of the rat.

The rate of elimination and the fate of endothelin-1 (ET-1) from the circulating blood was studied in urethane-anesthetized rats by intravenous injection of [125I]-labeled ET-1. The vasoconstrictor activities of the iodinated ET-1 were confirmed to be similar to those of native ET-1. Following i.v. bolus injection of 30 pmol/kg of [125I]-ET-1 into the femoral vein, the total radioactivity of the right atrial blood decayed rapidly, with a half-life of 7 min. At 5 min after the injection, the administered radioactivity distributed chiefly to the parenchyma of the lungs, kidneys, and liver. The analysis of the chemical form of labeled peptides from the plasma by reverse-phase high-performance liquid chromatography (HPLC) demonstrated no appreciable amount of degraded forms of [125I]-ET-1 in the blood for up to 60 min. [125I]-ET-1 was also stable for up to 60 min upon incubation in vitro with heparinized rat blood at 37 degrees C. Even when the same amount of labeled ET-1 was injected together with a pressor dose (1,500 pmol/kg) of cold ET-1, the half-life of the radioactivity in the bloodstream was exactly identical to that for [125I]-ET-1 alone. Nevertheless, the pressor response continued for more than 90 min after i.v. bolus injection of 1500 pmol/kg of ET-1 to the rat. These results clearly indicate that the elimination of ET-1 from circulating blood and the ET-1-induced pressor response are not in parallel, and the relatively rapid disappearance of ET-1 from the bloodstream is mostly due to the removal of the peptide by the parenchymal tissues, in the anesthetized rat. The long-lasting pressor action of ET-1 may be ascribed to our previous finding that the dissociation of ET-1 from its specific binding sites on vascular smooth muscle cells is extremely slow.

Animals↗
PubMed1989

Endothelin-1 acts in cerebral arteries from the adventitial but not from the luminal side.

The in vivo vasoconstrictor effect of endothelin-1 (ET-1) was investigated on feline and canine basilar arteries. The basilar artery caliber was angiographically measured after either vertebral artery perfusion or cisternal injection of the peptide. In both cats and dogs, ET-1 (5-500 pmol) induced a dose-dependent basilar artery contraction in vivo when applied intracisternally. The vasoconstriction was extremely long lasting; no significant recovery of vessel caliber was observed up to 12 h after injection. In contrast, bolus injection of ET-1 up to 3 nmol into the vertebral artery had no appreciable effect on the basilar artery caliber. These observations suggest that ET-1 acts in cerebral vessels from the adventitial but not from the luminal side, possibly due to the presence of the blood-brain barrier. The long-lasting nature of the ET-1-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1989

Calcitonin gene-related peptide-binding sites of porcine cardiac muscles and coronary arteries: solubilization and characterization.

Calcitonin gene-related peptide (CGRP)-binding sites were solubilized, using digitonin, from the porcine spinal cord, atria, and coronary arteries. The specific binding of 125I-human alpha-CGRP to the solubilized binding sites was inhibited by human alpha- and beta-CGRP and by rat alpha-CGRP, but not by angiotensin II or human calcitonin. Scatchard plot analysis of saturation gave the same KD value for CGRP in the crude membrane fractions of the tissues examined. The affinity of CGRP to the binding sites was decreased by solubilization in the atria and coronary arteries, but not in the spinal cord. Affinity labeling followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed distinct molecular sizes of the specific binding sites among the tissues; 70K for the spinal cord, 70K and 90K for the coronary arteries, and 70K and 120K for the atria. These results indicate that the molecular characteristics of the specific binding sites of CGRP in the cardiovascular system are distinct from those in the central nervous system.

Animals↗
PubMed1989

Periodontal disease prevalence in different age groups in Japan as assessed according to the CPITN.

A CPITN survey was conducted involving 12,832 Japanese subjects from 7 to 64 years of age. Subjects under 18 were schoolchildren, and 18-year-old and older subjects represented various social backgrounds, having been randomly selected from both urban and rural Japan. Fifty percent of the 7-yr-old children had signs of periodontal disease, and this percentage increased with increasing age. In those under 14, this increase in periodontal disease was mainly due to an increase in the proportion of children developing dental calculus. Subjects with 6 mm or deeper pockets were observed starting from the 20-29-yr-old age group. In subjects over this age, the prevalence of periodontal disease was higher in men than in women. The percentages of subjects having pathologic pockets had increased remarkably in the 30-44-yr-olds. In the 45-64-yr-old group, almost all subjects had some sign of periodontal disease, and the percentage of those with 4 or 5 mm pockets and 6 mm or deeper pockets were 37% and 21%, respectively.

Adolescent↗
PubMed1989

Mechanism of contraction to endothelin in isolated porcine coronary artery.

To elucidate the mechanisms of action of endothelin (ET) on vascular smooth muscles, the contractile responses of the isolated porcine coronary artery to ET were precisely investigated. ET produced concentration-dependent vasoconstrictions that were not mediated by biogenic amines, arachidonate metabolites, or endothelium-derived contractile factors. The maximum response to ET was identical to the response to K+ depolarization. The vasoconstrictor activity of ET was at least one or two orders of magnitude more potent than other vasoconstrictors (BAY K 8644, histamine, acetylcholine, and prostaglandin F2 alpha) examined. The action of ET was antagonized by a dihydropyridine Ca2+ antagonist, nicardipine, in a competitive fashion. ET-induced vasoconstriction was not mediated by membrane depolarization. A small amount of ET (2 x 10(-10) M) caused a leftward shift of the concentration-response relationship for K+. ET (5 x 10(-10), 5 x 10(-8) M) accelerated 45Ca2+ uptake to the smooth muscle cells, which were inhibited by nicardipine. However, ET did not affect the specific binding of [125I]iodipine to the smooth muscle cell membrane. These results suggest that ET produces vasoconstriction via ultimately accelerating Ca2+ influx through voltage-dependent Ca2+ channels but that the binding site is distinct from that of dihydropyridines.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Effects on the urinary level of gamma-carboxyglutamic acid caused by the administration of antibiotics with N-methyl thiotetrazole side chains to patients with infectious diseases.

A comparative study was conducted of the urinary level of gamma-carboxyglutamic acid (gamma-Gla) in patients with infectious diseases to investigate the mechanism of hemorrhagic diathesis occurrence resulting in post-administrative side effects of cephem-group antibiotics. The results showed that the group of administered antibiotics with N-methyl thiotetrazole (NMTT) side chains exhibited decreases in the urinary level of gamma-Gla. Especially, in the aged group of patients (over 65) with non-carcinoma infectious diseases, significant decreases in the urinary level of gamma-Gla were observed. From the above, it is considered that the administration of antibiotics with NMTT side chains has an effect of prohibiting the vitamin K function.

1-Carboxyglutamic Acid↗
PubMed1989

Interleukin-1 production by polymorphonuclear leukocytes during the course of acute inflammation in rabbits.

Inflammation-induced immune enhancement was observed when an antigen was introduced during an early period of casein-induced inflammation. An immune potentiation factor was detected at the early inflammatory site of mice and rabbits. This immune potentiation factor of rabbits was identified as interleukin-1 (IL-1) in respect of either its biologic activities or its molecular structure. Expression of IL-1 mRNA was observed only in peritoneal exudate cells from the early inflammatory site in parallel with the generation of the immune potentiation activity. The inflammation-induced immune potentiation was assumed to be mediated by newly synthesized IL-1 at the early inflammatory site. By using immunocytochemical staining, it was definitely proved with respect to a single cell level that the polymorphonuclear leukocytes were the major cells in synthesizing IL-1 at the casein-induced inflammation in rabbits.

Acute Disease↗
PubMed1989

Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina.

To examine whether or not magnesium suppresses coronary spasm, the effect of magnesium infusion on anginal attacks induced by hyperventilation was studied in 20 patients with variant angina. In all patients, anginal attacks associated with ischemic ST segment changes on the electrocardiogram were repeatedly induced by hyperventilation. The study was performed in the early morning successively for 3 days. On days 1 and 3 (control studies), 50 minutes before the hyperventilation test, a 5% glucose solution was infused as a placebo. On day 2 (magnesium study), 50 minutes before the hyperventilation test, magnesium sulfate (0.27 mM/kg body wt) was infused during a 20-minute period. During the control studies, anginal attack was induced by hyperventilation in all 20 patients, whereas during the magnesium study, anginal attack was induced by hyperventilation in only six (30%) of the 20 patients (p less than 0.001 vs. control studies). The changes in arterial blood pH and PCO2 caused by hyperventilation were not significant between the control study and the magnesium study. Mean serum magnesium concentration increased from 2.2 +/- 0.2 to 6.0 +/- 0.5 mg/dl immediately after infusing magnesium and was 4.5 +/- 0.6 mg/dl before the hyperventilation test during the magnesium study. We conclude that magnesium suppresses anginal attacks induced by hyperventilation in patients with variant angina.

Aged↗
PubMed1989

Characteristics of pressor response to endothelin in spontaneously hypertensive and Wistar-Kyoto rats.

Endothelin, an endothelium-derived vasoconstrictor peptide, and angiotensin II were intravenously injected into the femoral vein of normotensive Wistar-Kyoto (WKY) rats that had been anesthetized with urethane. Blood pressure and heart rate were recorded from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. Endothelin showed a potent, dose-dependent pressor action. The dose-response relations for the increase in blood pressure of rats receiving endothelin were comparable with those of rats receiving angiotensin II. However, endothelin showed far more long-lasting effects. Endothelin-induced responses consisted of three phases: a rapid and transient depressor phase and then two phases of pressor (transient and long-lasting) response. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+ channel blocker, markedly attenuated the slow phase of the pressor response but only slightly attenuated the rapid one. The pressor action of endothelin was not inhibited by continuous infusions of saralasin, which almost abolished the angiotensin II-induced pressor response. Endothelin-induced pressor response was also not attenuated by indomethacin, a prostaglandin synthesis inhibitor. These data provide evidence that endothelin produces a unique, potent, and long-lasting pressor response, which appears to be in part related to the activation of Ca2+ channels. In 12-week-old spontaneously hypertensive rats (SHR), the maximal pressor response to endothelin was slightly but significantly greater than that in age-matched WKY rats, but the dose dependency of the response was approximately consistent with that in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1989

Endothelin acts in feline and canine cerebral arteries from the adventitial side.

We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73 +/- 4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. Our observations suggest that endothelin acts in cerebral vessels from the adventitial side, not from the luminal side, possibly due to the presence of the blood-arterial wall barrier. The long-lasting nature of endothelin-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1989

[Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates].

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.

Animals↗
PubMed1989

[Pharmacological study of TJ-8007 (tsumura-zokumeito) (II): Protective effect of TJ-8007 against cerebral ischemia].

It has been demonstrated that TJ-8007 (Tsumura-Zokumeito, A traditional Chinese medicine) has a protective effect against cerebral anoxia. This study was done to elucidate the protective mechanism of TJ-8007 against cerebral ischemia and anoxia. TJ-8007 (0.3 approximately 3.0 g/kg, p.o.) inhibited the rise in the cumulative mortality rate after ligation of the bilateral carotid artery (BCA) in mice. TJ-8007 also significantly prolonged the survival time at the dose of 3.0 g/kg, p.o. However, TJ-8007 (1.0 or 3.0 g/kg, p.o.) did not affect the mean survival time after ligation of BCA in Mongolian gerbils and the gasping movement in a decapitated mouse head that served as a complete ischemic model. Ifenprodil (30 mg/kg, p.o.) also showed the protective effect only against ischemic death after ligation of BCA in mice. TJ-8007 (1.0 or 3.0 g/kg, p.o.) increased the vertebral blood flow, but showed no effect on the internal carotid blood flow in anesthetized dogs. These results suggest that the mechanism for the cerebral protective effect of TJ-8007 may be due to its ameliorating action on the cerebral circulation.

Animals↗
PubMed1989

Stimulation of phagocytic activity of leukocytes and macrophages by traxanox sodium in mice and rats.

Phagocytosis of yeast particles by mouse peritoneal macrophages or rat peritoneal polymorphonuclear leukocytes was enhanced by traxanox sodium in vitro. Traxanox sodium (30 and 100 mg/kg, p.o.) enhanced phagocytosis of yeast particles by leukocytes and macrophages in vivo or ex vivo. On the other hand, prednisolone, isoproterenol and theophylline inhibited phagocytosis by leukocytes and macrophages under the same conditions. Traxanox sodium (30 mg/kg, p.o.) prevented the suppression of phagocytosis by the above drugs. Combined with theophylline, isoproterenol synergistically inhibited phagocytosis by leukocytes in vivo. Traxanox sodium (100 mg/kg, p.o.) administered alone had no influence on carbon clearance in normal mice. However, traxanox sodium (1-30 mg/kg, p.o.) prevented the suppression of carbon clearance by the treatment with carrageenan, but not by the treatment with ethyl palmitate. These results suggest that traxanox sodium stimulates the phagocytic activity of leukocytes or macrophages and prevents the drug-induced suppression of the phagocytic activity of these cells.

Animals↗
PubMed1989

Pressor response to endothelin in guinea pigs.

Endothelin (ET), an endothelium-derived vasoconstrictor peptide, was injected into the jugular vein (i.v.) of guinea pigs anesthetized with urethane. Blood pressure was measured from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. ET showed a potent, dose-dependent pressor action in guinea pigs. However, the initial, transient depressor response which is observed in rats was not produced in guinea pigs. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+-channel blocker, significantly inhibited the ET-induced pressor response. These results suggest that ET causes a potent pressor response, which appears to be related to the activation of Ca2+ channels.

Animals↗