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Biomedical subjects

T Toyoda

Publications and source records attributed to T Toyoda.

At least 181 records · Page 10Linked to original sources
PubMed1988

Mechanism of action of nicotine in isolated urinary bladder of guinea-pig.

1. Nicotine produced a transient contraction of isolated strips of guinea-pig urinary bladder. The response to nicotine was antagonized by the nicotinic receptor antagonist, hexamethonium but was insensitive to tetrodotoxin. 2. The nicotine-induced contraction was potentiated by the cholinesterase inhibitor, physostigmine, and was reduced to 50% and 70% by the muscarinic cholinoceptor antagonist, atropine and the sympathetic neurone blocking drug, guanethidine, respectively. Chemical denervation with 6-hydroxydopamine abolished the inhibitory effect of guanethidine. Simultaneous treatment with atropine and guanethidine did not abolish the response to nicotine, but the degree of inhibition was comparable to that obtained with atropine alone. 3. The nicotine-induced contraction was insensitive to bunazosin and yohimbine (alpha 1- and alpha 2-adrenoceptor antagonists, respectively), and exogenously applied noradrenaline did not cause a contraction even in the presence of blockade of noradrenaline uptake mechanisms with desipramine and normetanephrine and of beta-adrenoceptors with propranolol, suggesting a non-adrenergic nature of the sympathomimetic effect of nicotine in this tissue. 4. The nicotine-induced contraction in the presence of atropine was abolished after desensitization of P2-purinoceptors with alpha, beta-methylene adenosine 5'-triphosphate, a slowly degradable ATP analogue selective for P2-purinoceptors. By this desensitization, the response to ATP, but not to histamine, was also abolished. 5. A cyclo-oxygenase inhibitor flurbiprofen partially inhibited the nicotine-induced contraction. The degree of the inhibition was more pronounced in the presence of atropine than in its absence. Flurbiprofen antagonized the response to exogenously applied ATP in an unsurmountable manner, but not that to carbachol. 6. The present results suggest that nicotine might induce a contraction through an interaction with nicotinic receptors located on the terminals of, possibly, (i) parasympathetic cholinergic, (ii) sympathetic non-adrenergic and (iii) non-sympathetic purinergic nerves in guinea-pig detrusor preparations, and that a portion of the contraction due to the purine nucleotide released is possibly potentiated by intramural prostaglandin(s). Parasympathetic cholinergic output might be modulated by an unknown excitatory substance released by nicotine from sympathetic nerve. 7. Nicotine reveals a latent excitatory effect of the sympathetic hypogastric nerve which innervates guinea-pig detrusor.

Animals↗
PubMed1988

Identification of amino acids relevant to three antigenic determinants on the fusion protein of Newcastle disease virus that are involved in fusion inhibition and neutralization.

Nucleotide sequence analysis of F protein antigenic variants of Newcastle disease virus mapped three distinct antigenic determinants to positions 343, 72, and 161 on the protein. The high fusion-inhibiting and neutralizing capacities of all of the monoclonal antibodies used for selection suggested close functional and structural relationships of the three positions with the fusion-inducing N-terminal region of the F1 subunit. The former two positions were located at the cysteine cluster domain near the C terminus of the F1 subunit and at the major hydrophilic domain in the F2 subunit, respectively, and both domains appeared to represent the major antigenic determinants of paramyxovirus F protein.

Amino Acid Sequence↗
PubMed1988

Fibrinopeptide A (FPA) levels in atrial fibrillation and the effects of heparin administration.

It has been reported that a patient with atrial fibrillation (AF) is in the hypercoagulable state and that this state results in a high incidence of systemic thromboembolisms. In this paper, we have investigated plasma fibrinopeptide A (FPA) levels and the effects of subcutaneous administration of heparin on these levels in patients with AF. Forty-five patients with hypertension (HT) or mitral stenosis (MS) were classified into four groups according to whether they had AF complications; i.e. HT with normal sinus rhythm (NSR), HT with AF, MS with NSR and MS with AF. Patients with AF demonstrated significantly higher plasma FPA levels and lower plasma antithrombin III (AT III) activities than those with NSR. When low dose heparin was administered to patients with AF, plasma FPA levels were decreased to the near normal range, accompanied by an increase in heparin-AT III complex activity and heparin concentration 0.5-1.0 h after injection. These levels were maintained for 5 h. From these results it was concluded that patients with AF were in the hypercoagulable state and that the measurement of plasma FPA levels provided a possibility to detect the underlying activation of blood coagulation.

Atrial Fibrillation↗
PubMed1988

Anti-cancer therapy with valine-depleted amino acid imbalance solution.

For the purpose of developing amino acid imbalance solution applicable to cancer treatment, we prepared seven kinds of amino acid imbalance solutions based on a 10% balanced amino acid solution and investigated the anti-tumor effects of each solution. The administration of valine-depleted amino acid solution for 8 days at a daily dose of 53 ml/rat (79.5 kcal/rat) resulted in the most significant inhibitory effects on the growth of hepatoma (AH109A) and mammary tumors (MRMT-1), the rate being 82.8% and 90.8%, respectively. Side effects observed were inhibition of increases in host body weight, weight loss of the spleen and thymus, loss of hair, and a decrease in the amounts of total plasma protein and albumin. When the daily dosage of valine-depleted amino acid solution was reduced to 40 ml/rat (58.3 kcal/rat), anti-tumor effects were still noticed, while side effects were abated. These findings indicate that side effects accompanying the use of this solution can be alleviated by controlling the ingredients of the solution as well as the amount administered. It is thus suggested that valine-depleted amino acid imbalance solution is a valuable tool in the treatment of cancer.

Amino Acids↗
PubMed1987

Effect of inhibition of Na+-K+ ATPase on the prostacyclin generation of cultured human vascular endothelial cells.

Prostacyclin (PGI2) generation of cultured human vascular endothelial cells (VEC) was observed coincidentally with the increase of 45Ca net influx. Ca ionophore A23187 enhanced not only PGI2 generation and 45Ca net influx but also 45Ca efflux. PGI2 generation was completely abolished by the pretreatment with Ca++ immobilizer, TMB-8. A Na+-K+ ATPase inhibitor, ouabain increased 45Ca net influx, but decreased 45Ca efflux, and enhanced PGI2 generation. These observation indicate that PGI2 generation of VEC may be regulated by not only Ca++ but also Na+, and it was suggested that enhanced PGI2 generation by ouabain might be derived from the increased cytosolic Ca++concentration by the decreased Ca++ efflux, and it was considered to be originated from the suppression of Na+-Ca++ exchange systems by the increased intracellular Na+ concentration via inhibition of Na+-K+ ATPase activity by ouabain. Enhancement of PGI2 generation of VEC by the increased ouabain like substances (OLS) in hypertension is suspected to be beneficial on the maintenance of vascular homeostasis.

Calcimycin↗
PubMed1987

Effects of angiotensin I converting enzyme (ACE) related substances upon the vascular prostacyclin generation.

We investigated the interaction of angiotensin I (AI) converting enzyme (ACE) related substances to prostacyclin (PGI2) generation and ACE activity using cultured human vascular endothelial cells (EC) and rat aortic rings (AR). In case of cultured EC, AI and bradykinin (BK) increased PGI2 generation and at the same time ACE released from EC, however angiotensin II (AII) did not show any effect on both of them. When the EC were pretreated by captopril both of basal PGI2 production and ACE activity were reduced but the enhancing effects on PGI2 generation by AI or BK were preserved. On the other hand in the experimental system with AR, not only AI or BK but also AII increased PGI2 generation and the higher concentration of captopril inhibited PGI2 generation. When the EC were removed, the enhancing effect by AII was diminished and the mechanical stimulation to AR remarkably increased PGI2. From these experimental studies, we obtained the results that (1) the reported hypothesis that the vasodilative effect of captopril would be developed by the enhanced PGI2 generation was not confirmed in our systems of EC and AR. (2) AII did not affect on PGI2 generation of EC. Therefore the enhanced PGI2 generation by AII in AR was considered to be mainly derived from the mechanical stimulation to EC by the AII induced smooth muscle cells contraction. (3) It was speculated that the enhanced PGI2 generation by AI or BK might be modulated through their activating effect on ACE as an autoregulatory mechanism.

Angiotensin I↗
PubMed1987

Detection of polycistronic transcripts in Newcastle disease virus infected cells and identification of their sequence content.

The synthesis of six to seven polycistronic transcripts of Newcastle disease virus (NDV) in BHK cells was detected by Northern hybridization using cDNA clones generated by reverse transcription of five NDV mRNAs. Within the molecular weight range resolved by the gel electrophoresis system employed, four of the transcripts were suggested to be distronic, containing sequences of two genes, NP-P, P-M, M-F0 and F0-HN, respectively. In addition, tricistronic molecules of M-F0-HN and possibly of NP-P-M as well as P-M-F0 appeared to develop, although they were very low in amount. These data suggest a gene order of NP-P-M-F0-HN on the NDV genome. The polycistronic as well as monocistronic transcripts were generated with an almost constant proportion in amount throughout the virus replication. Further, at least several of them were also generated under the conditions where only the primary transcription was allowed by inhibiting de novo protein synthesis. Therefore, it appears likely that there is no distinct temporal control in NDV genome expression.

Amino Acid Sequence↗
PubMed1987

Structural comparison of the cleavage-activation site of the fusion glycoprotein between virulent and avirulent strains of Newcastle disease virus.

The nucleotide sequence of the mRNA encoding the fusion (F0) protein of a virulent strain of Newcastle disease virus was determined. A single open reading frame in the sequence encodes a protein of 553 amino acids with a calculated molecular weight of 59058. The amino acid sequence predicted several structural features involving the fusion-inducing hydrophobic stretch (residues 117-142) and the cleavage-activation site (residues 112-116) to generate the disulfide-linked F1 and F2 subunits. The cleavage-activation site as well as a part of the fusion-inducing sequence were compared among a series of virulent and avirulent strains by the chain-termination method using a synthetic oligonucleotide primer. It was found that without exception, the cleavage-activation site of virulent strains consisted of two dibasic residues with an intervening glutamine, Arg-Arg-Gln-Arg-Arg, whereas the corresponding region of avirulent strains was made of a sequence with single basic residues scattered among uncharged residues, Gly-LysArg-Gln-GlySer-Arg. On the basis of these observations and the previous results showing a strict correlation between the pathogenicity and the cleavability of the fusion protein of NDV (Y. Nagai, H-D. Klenk, and R. Rott, Virology, 72, 494-508, 1976), we propose the importance of the dibasic residues for efficient proteolytic activation of the fusion protein and for the pantropic property of NDV. Some strains were found to have Leu-Ile-Gly as the N-terminus of F1, whereas others contained Phe-Ile-Gly, indicating that Phe-X-Gly is not always conserved at F1 N-terminus of paramyxovirus.

Amino Acid Sequence↗
PubMed1987

Antigenic characterization of the internal proteins of Newcastle disease virus by monoclonal antibodies.

We have prepared and characterized monoclonal antibodies against the three internal structural proteins, M, P and NP, of Newcastle disease virus. At least two non-overlapping antigenic sites were delineated on the M protein, four on the P, and two on the NP by competitive binding assay. One of the two non-overlapping antigenic sites on the M protein was found to be a cluster of at least three distinct epitopes. Enhancement of antibody binding by the binding of a second antibody was observed with the M protein. The reactivity of these monoclonal antibodies with heterologous strains was studied by enzyme-linked immunosorbent assay. The results indicated that there are both highly conserved antigenic sites and those subject to remarkable change on both M and P proteins. On the other hand, NP appeared to be antigenically more stable.

Antibodies, Monoclonal↗
PubMed1987

Effects of angiotensin I converting enzyme (ACE)-related substances on prostacyclin generation and ACE activity of human vascular endothelial cells and rat aortic rings.

The effects of angiotensin I (ANG I) converting enzyme (ACE)-related substances on prostacyclin (PGI2) generation were investigated using cultured human vascular endothelial cells (EC) and rat aortic rings. ANG I or bradykinin (BK) increased while captopril decreased PGI2 generation and ACE activity of EC, whereas ANG II was without effect. The enhancement of PGI2 generation induced by ANG I or BK was not affected by the pretreatment with captopril. In rat aortic rings, ANG I, ANG II, and BK enhanced whereas captopril (10(-3) M) attenuated PGI2 generation. Mechanical stimulation of aortic rings stimulated PGI2 generation. These results suggest that (a) the conversion of ANG I to ANG II did not enhance PGI2 generation in EC; (b) the ANG II stimulated PGI2 generation of aortic rings was partially derived by mechanical stimulation of EC, probably originating from the contraction of smooth muscle cells by ANG II; (c) captopril directly inhibited PGI2 generation; and (d) in EC, the stimulation of PGI2 generation by ANG I or BK is probably regulated by an activating effect on ACE as an autoregulatory mechanism.

Animals↗
PubMed1987

Regulation of prostacyclin generation by angiotensin converting enzyme related substances in cultured human vascular endothelial cells.

The regulation of prostacyclin (PGI2) generation by angiotensin I-converting enzyme (ACE) related substances was investigated using cultured human vascular endothelial cells. Angiotensin I (AI) or bradykinin (BK) increased PGI2 generation and ACE activity, while the ACE inhibitor, captopril decreased both of them, and angiotensin II (AII) did not show any effect. The increasing rate of PGI2 generation induced by AI or BK was not affected by the pretreatment with captopril. These results suggest that the accumulation of AI or BK via the inhibition of ACE by captopril did not cause the enhancement of PGI2 generation. Rather, it was proposed that the enhanced PGI2 generation by AI or BK might be regulated by ACE activation derived from these substances, as an autoregulation mechanism.

Angiotensin I↗
PubMed1986

Modulation of prostacyclin generation in cultured human vascular endothelial cells and the effects of human alpha-natriuretic polypeptide.

Vascular endothelial cells have been known to possess not only a barrier function but also other biologically important functions maintaining vascular homeostasis. Among these, the generation of prostacyclin is one of the most conspicuous functions, and the modulation of its synthesis and liberation has been of interest with reference to the interaction with several vasoactive substances, including human atrial alpha-natriuretic polypeptide. This paper investigates the regulatory mechanism of prostacyclin generation using cultured human vascular endothelial cells as far as Ca2+ flux, (Na+ + K+)-ATPase activity, and Na+-Ca2+ exchange systems are concerned. Through these experimental studies the following results were obtained. Prostacyclin generation was triggered by an increase of Ca2+ influx, and an increase in intracellular Na+ also enhanced it, and this was accompanied by a decreased Ca2+ efflux arising from suppression of Na+-Ca2+ exchange systems. (Na+ + K+)-ATPase activity as well as prostacyclin generation was also enhanced by the increase of intracellular Na+. These results indicate a possible link between the mechanism which generates prostacyclin in the human vascular endothelial cells and the mobilization of electrolytes; however, in this aspect human atrial alpha-natriuretic polypeptide had no effect on the endothelial cells.

Atrial Natriuretic Factor↗
PubMed1986

Studies on the adaptation of mumps virus to chick embryo.

About 15 serial passages of wild type mumps virus (Sasazaki strain) in the amnion sac of chick embryo (CE) yielded a CE-adapted strain which was poorly replicative and did not form plaques in Vero cells where the wild strain grew well. In the course of this limited replication of the CE-adapted strain in Vero cells, we have analysed the viral protein and RNA synthesis. It was found that protein synthesis took place very efficiently at least early in infection by 12 h. The subsequent rate of synthesis remained, however, at a low level without showing the progressively increasing synthesis observed with the wild strain. Furthermore, 50S genomic RNA was synthesized early in the limited infection, but the subsequent synthesis was markedly suppressed. In addition, the other virus-specific RNA species could not be detected throughout. Thus the amplified RNA synthesis observed in the permissive CE cells and in the wild strain-infection of Vero cells seemed not to occur in the limited replication. Neither interferon nor DI (defective interfering) RNA was involved in the limited virus growth. When Vero cells were infected with the wild strain 6 to 8 h before inoculation of CE-adapted strain, growth restriction was overcome and the yield of the latter virus was greatly enhanced by a factor more than 10(3). These results suggest that through adaptation to CE, mumps virus may be altered in such a way that there is a restriction, probably at a step (s) involved in amplification of the viral RNA synthesis in Vero cells and that the restriction may be overcome by the simultaneous genome expression of the prototype wild strain.

Animals↗