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Biomedical subjects

T Toyoda

Publications and source records attributed to T Toyoda.

At least 163 records · Page 9Linked to original sources
PubMed1989

Newcastle disease virus evolution. I. Multiple lineages defined by sequence variability of the hemagglutinin-neuraminidase gene.

We compared the hemagglutinin-neuraminidase gene sequence among 13 strains of Newcastle disease virus (NDV) isolated over the last 50 years. Although overall homology was remarkably high, the sequence variability demonstrated the existence of at least three distinct lineages, which must have co-circulated for considerable periods. The sequence variability also appears to reflect some accumulation of mutations over time. Strictly correlating with the lineages, the translation products could be classified into three size classes. One class lacked the interchain disulfide bond, and another represented unusual precursor protein of biologically inactive form. The lineages correlated to some extent with virulence and place of isolation of the strains. However, antigenic variations, which were neither cumulative nor progressive, did not correlate with the lineages. These analyses showing multiple lineages were greatly facilitated by a precise calculation of synonymous substitutions, which had been largely free from selective pressures and had occurred frequently and evenly throughout the coding region.

Amino Acid Sequence↗
PubMed1989

Newcastle disease virus evolution. II. Lack of gene recombination in generating virulent and avirulent strains.

Sequence analysis and comparison of the fusion glycoprotein genes of 11 Newcastle disease virus (NDV) isolates indicated a high degree of functional and structural constraint exerted on the change of the glycoprotein. However, synonymous nucleotide substitutions occurred frequently throughout the coding region. Facilitated by an analysis of synonymous difference (Ks) in pairwise strain comparison, we defined the branching orders of the strains and identified three distinct evolutionary lineages correlating with the virulence as expressed by mean death time (MDT) for chick embryo. The typically virulent strains with MDT of about 50 hr were associated with one lineage, while the typically nonvirulent strains with MDT of infinity were of another lineage. The third lineage consisted of both virulent and avirulent strains whose MDTs lay on a continuum from 50 to 120 hr. Synonymous substitutions were found to occur with almost the same rates in the adjacent hemagglutinin-neuraminidase and membrane protein genes as in the fusion protein gene, and the branching orders based upon the Ks for these genes were essentially identical to those derived from the fusion protein gene. Therefore, no gene exchange by recombination seems to have occurred to generate the strains of distinct lineages. Rather, the different strains appear to have evolved through various degrees of accumulation of point mutations. Besides these evolutionary features, the present study strongly supports the importance of the previously identified signals for gene expression and for the proteolytic activation of the gene product.

Animals↗
PubMed1989

Application of thrombin-antithrombin III complex for detecting a latent hypercoagulable state in patients with coronary artery disease.

It is thought that a hypercoagulable state contributes to the pathogenesis of coronary artery disease (CAD), but few sensitive markers have been available for detecting the state. In the present study the plasma level of thrombin-antithrombin III complex (TAT), a specific indicator of thrombin generation in blood, was investigated before and after a submaximal exercise test in 18 patients with CAD and in 12 healthy controls. The mean (+/- SEM) value of plasma TAT before the exercise was 3.30 (0.81) ng/ml in the patient group and 1.49 (0.08) ng/ml in controls, and its level increased to 29.22 (5.74) ng/ml and 12.07 (2.89) ng/ml after the exercise, respectively. Thus, the TAT value in the patient group was higher than that in the controls both before and after the exercise. However, no differences could be found between the groups in the following parameters; prothrombin time, activated partial thromboplastin time, antithrombin III, fibrinogen, FDP, plasminogen, alpha 2-plasmin inhibitor, and alpha 2-macroglobulin. Through these results it was concluded that plasma TAT level could be a sensitive marker for latent activation of blood coagulation, and also that the results of these experiments showed that patients with CAD were in a latent hypercoagulable state.

Adolescent↗
PubMed1989

Detection of impaired fibrinolytic activity in coronary artery disease--electrophoretic and immuno-blotting analysis of tissue plasminogen activator.

In present study, we investigated the fibrinolytic activities and plasma antigen levels of tissue plasminogen activator (tPA) before or after a submaximal exercise in patients with coronary artery disease (CAD). We also investigated tPA phenotypes in plasma by electrophoretic and immuno-blotting analysis. Euglobulin fractions obtained from plasma were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting analysis. There were no differences in plasma antigen levels of tPA between the study group and controls before or after the exercise, however CAD patients showed lower fibrinolytic activities after the exercise than controls. SDS-PAGE followed by immuno-blotting with an antisera against human tPA revealed two bands at molecular weights (m.w.) of 70,000 and 120,000. The band at m.w. of 70,000 corresponded to free tPA and that of 120,000 was considered to be identical to a complex of tPA with its inhibitor. Furthermore, we found a decrease in free tPA in the patients with low fibrinolytic activities. From these results it was concluded that impaired fibrinolytic activities, probably due to decreased free tPA, observed in CAD patients, might be an important factor in the pathogenesis of CAD.

Adult↗
PubMed1989

[A case of gall bladder cancer with high level alpha-fetoprotein].

A case of primary gall bladder tumor with high level AFP were demonstrated, which showed hepatocellular carcinoma like pattern with trabecular proliferation histologically, positive AFP stain of cancer cells by a peroxidase conjugated antibody method immunohistochemically. This case was no metastasis with liver and lymph nodes.

Aged↗
PubMed1989

[A case of immotile cilia syndrome and a review of Japanese cases].

A case of immotile cilia syndrome (ICS) is presented. A 34-year-old male, who had suffered from recurrent bronchitis, sinusitis and otitis media since early childhood, was admitted to Keio University Hospital complaining of productive cough and infertility. A saccharin test showed prolonged nasal clearance time, and semen analysis revealed immotile sperm. By electron microscopic observation of cilia of the nasal mucous epithelium and the sperm, inner and outer dynein arm defect, abnormal microtubular arrangement and compound cilia were detected and he was diagnosed as ICS. Thirty eight Japanese cases of ICS collected from the literature were analyzed concerning clinical manifestations, airway clearance, family history and ciliary ultrastructural abnormalities (Table 2, 3). Recurrent bronchitis, male infertility, chronic sinusitis, otitis and decrease in airway clearance were very common in these patients. Female infertility was more common than anticipated. The prevalence rate of situs inversus was more than 50%, probably due to more attention having been paid to Kartagener's syndrome in Japan. Recent studies show that the cilia of this syndrome is not always immotile but characterized by hypomotility or asynchrony, and have attempted to determine the relationship between each ciliary ultrastructural abnormality and motility pattern. It is necessary that more patients including incomplete and mild cases should be investigated.

Adult↗
PubMed1989

[A case report of biventricular assistance by means of ventricular assist device and IABP in postoperative biventricular failure].

Three patients with biventricular failure were managed postoperatively with the aid of a right ventricular assist device (RVAD) and intraaortic balloon pumping (IABP) with favorable results. Among these three cases, two had multiple rheumatic valvular disease with cardiac cachexia and underwent combined valve replacement. Another who was suffered from heart failure with a large ventricular septal defect and tricuspid regurgitation had a VSD closure and tricuspid valve replacement. In all patients, the weaning from pump oxygenator was difficult even with large doses of catecholamine. Therefore, the pump oxygenator was switched to RVAD for right ventricular assistance and IABP for left ventricular assistance because these patients had had right ventricular failure dominant biventricular failure preoperatively. Though case 2 was lost 64 days after the surgery by retroperitoneal bleeding due to inadequate anticoagulant treatment, the other two cases recovered successfully from postoperative biventricular failure and were discharged from the hospital. The indications of this method and the criteria for RVAD weaning were discussed.

Aged↗
PubMed1989

[The effect of aortic valve translocation and a few problems].

Aortic valve endocarditis is frequently associated with an aortic root abscess, so that it is difficult to insert a prosthetic valve. Between April, 1983 and June, 1988 we treated four out of seven patients with aortic valve endocarditis by translocation of the aortic valve, closure of the native coronary ostia, and placement of saphenous vein grafts on the coronary arteries. In each case, the operation was undertaken because of rapidly progressing heart failure. Infection was due to alpha-Streptococcus in two instances, to Staphylococcus epidermidis and fungus in the other cases. In one of the four patients, the prosthetic aortic valve was sutured to the ascending aorta and two saphenous vein grafts were placed on the proximal coronary arteries. In the other three patients, the composite Woven Dacron graft was used to replace the ascending aorta and two saphenous vein grafts were placed on the distal coronary arteries. One patient died one year postoperatively of LOS because of rapidly progressing coronary grafts ostial stenosis. The other three patients survived and doing well with satisfactory hemodynamic function and no infection. Translocation of the aortic valve for infective aortic valve endocarditis is a useful operative technique when conventional aortic valve replacement technique cannot be utilize.

Adult↗
PubMed1988

Structural features unique to each of the three antigenic sites on the hemagglutinin-neuraminidase protein of Newcastle disease virus.

Antigenic variants of D26 strain of Newcastle disease virus (NDV) were selected with monoclonal antibodies directed to the three nonoverlapping antigenic sites on the hemagglutinin-neuraminidase (HN) protein, and their HN genes were sequenced to identify the amino acids important for the integrity of each site. Seven variants for site I, which is immunodominant and conserved among NDV strains, had a change of glutamic acid at position 347, mostly to lysine, and in a single case, to glycine. In the second group of two variants for site IV, a change of asparagine to aspartic acid was found at position 481. This resulted in elimination of the oligosaccharide attached to this asparagine residue of the parental virus. Together with the finding that the site IV was destroyed by treatment with endoglycosidase F, it was suggested that the oligosaccharide is important for maintaining the structure of site IV. The oligosaccharide appeared to contribute to exposing a nearby determinant by conferring hydrophilicity on it. A variant for site II had also a nonconservative mutation resulting in the change of glutamic acid to valine at position 495. The site I recognized by antibodies which inhibit neuraminidase activity with a small substrate neuraminlactose was located closer to the predicted sialic acid-binding site than to the other sites recognized by antibodies lacking the enzyme-inhibiting capacity. The sequence of the parental virus HN gene revealed that the HNo precursor for the HN protein is an extra-long protein whose C terminus is elongated by 45 amino acids, compared with the usual HN protein sequenced in parallel.

Amino Acid Sequence↗
PubMed1988

Characterization of nicotine-induced contraction in the canine bronchus.

1. The modes of action of nicotine on the dog bronchial smooth muscle preparation was investigated, in order to compare with those on the bronchial preparations from the guinea-pig, rabbit and monkey. 2. Nicotine induced a contraction in the dog bronchial preparation, and this response was abolished by hexamethonium and atropine and potentiated by physostigmine. 3. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and due to the release of acetylcholine. 4. Tetrodotoxin did not inhibit the contractile response to nicotine in the dog bronchial preparation, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 5. The present observations in the dog bronchial preparations coincided with those in the rabbit and monkey bronchi but not with the findings in the guinea-pig bronchus.

Animals↗
PubMed1988

Mechanism of methotrexate-sensitivity of choriocarcinoma cells in culture.

Four cell lines established from choriocarcinoma were compared for sensitivity to methotrexate (MTX). In this paper, we have compared the relative gene copy number of dihydrofolate reductase (DHFR), the target enzyme of methotrexate (MTX), in order to clarify whether or not amplification of the gene is involved in the relative resistance to MTX observed for one of the cell lines, designated NaUCC-1, which is 4- to 5-fold more resistant to MTX as compared with the other cell lines and exhibits a reduced uptake of [3H]MTX. Neither dot blot nor Southern blot hybridization revealed any significant difference in the gene copy number among the four cell lines. Therefore, the resistance to MTX of the NaUCC-1 line is explained by a reduced uptake of the drug, rather than amplification of the target gene.

Animals↗