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Biomedical subjects

T Toyoda

Publications and source records attributed to T Toyoda.

At least 199 records · Page 11Linked to original sources

Inhibition of the assembly of Newcastle disease virus by monensin.

Monensin inhibits the intracellular transport of the glycoproteins of Newcastle disease virus between cis and trans Golgi stacks of infected BHK cells, as evidenced by its effect upon their post-translational modifications such as fatty acid acylation, glycosylation and proteolytic cleavage. Thus the drug has markedly altered the subcellular distribution of the glycoproteins so that they accumulate in the internal smooth membranes but are virtually absent in the plasma membrane. These glycoproteins that accumulated in intracellular membranes have a cytoplasmic domain susceptible to protease digestion and thus are transmembranous. Under such conditions, the behavior of M protein, which plays a crucial role in virus assembly (Y. Nagai et al., 1976, Virology 69, 523-538), has been analyzed. It has been found that the M protein can neither associate with the internal membranes nor bind to the plasma membrane. Thus no virus budding has been observed, either at the plasma membranes or at internal membranes. These results substantiate the view that the interaction between M and glycoproteins is of great importance for virus assembly and suggest further that this interaction is possibly only when the glycoproteins have been incorporated into the plasma membrane.

Animals↗

Topological and operational delineation of antigenic sites on the HN glycoprotein of Newcastle disease virus and their structural requirements.

Monoclonal antibodies to the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus have identified four antigenic sites on the glycoprotein, which are topologically and operationally discriminated from one another. To define the metabolisms and cellular compartments required for formation of the individual antigenic sites, a panel of monoclonal antibodies were examined for their reactivity with the nascent and variously processed forms of the antigen molecules in combination with the use of inhibitors of glycosylation (tunicamycin and N-methyl-1-deoxynojirimycin) and glycoprotein transport (carbonyl cyanide m-chlorophenylhydrazone and monensin). Reactivity was also examined with the antigen molecules deglycosylated by endoglycosidase F and with the antigen molecules reduced by 2-mercaptoethanol. The results taken together suggest that posttranslational organization of the glycoprotein is important for all four of the antigenic sites. At the same time, there appeared to be marked site-specific requirements with respect to glycosylation and disulfide bond formation. However, all of these metabolic requirements were found to be provided within the rough endoplasmic reticulum, and no further processing of the antigen molecules appeared to be necessary for the formation of any of the antigenic sites.

Amino Acid Sequence↗

Prostacyclin generation by cultured human vascular endothelial cells with reference to angiotensin I-converting enzyme.

Prostacyclin (PGI2) generation has been known to be regulated by several endogenous vasoactive substances, and in this study the relationship between angiotensin I-converting enzyme (ACE) related substances and PGI2 generation was investigated using cultured human vascular endothelial cells. Addition of angiotensin I (AI) or bradykinin (BK) enhanced PGI2 generation and increased the level of ACE activity in the culture medium, while the addition of ACE inhibitor (captopril) caused a dose dependent suppression of PGI2 generation and ACE activity. The enhancement of PGI2 generation induced by AI or BK was not affected by pretreatment with captopril, and angiotensin II (AII) did not show any effect on either PGI2 generation or ACE activity. Through these experimental results, the conversion of AI to AII by ACE was considered not to cause the enhancement of PGI2 generation. Captopril solely inhibited PGI2 generation and the reported hypothesis that captopril enhances PGI2 generation by the accumulation of AI or BK via inhibition of ACE was not confirmed in this experimental system. Rather, it is proposed that AI or BK induced PGI2 generation may be regulated by the increased breakdown of AI or BK, as an autoregulation mechanism, that is derived from increased ACE activity by AI or BK.

Angiotensin I↗

A difference in mode of antagonism between optical isomers of a potent selective alpha 1-adrenoceptor blocker (YM-12617) and norepinephrine in isolated rabbit iris dilator and aorta.

Optical isomers of YM-12617, a potent and selective alpha 1-adrenoceptor blocker, were tested on the rabbit iris dilator and aorta. The order of potency was R(-)-isomer greater than racemate greater than S(+)-isomer. The R(-)-isomer and racemate behaved as an essentially irreversible antagonist to norepinephrine in the iris dilator where the efficacy of norepinephrine was small, although the S(+)-isomer was a competitive antagonist. These drugs behaved as a competitive antagonist of norepinephrine in the aorta where the efficacy of norepinephrine was large.

Adrenergic alpha-Antagonists↗

Studies on hepatobiliary lymph flow with radioactive colloid--for lymph node metastasis resection of carcinoma of the bifurcation of hepatic duct.

Hepatobiliary lymphoscintigraphy by Technetium 99m-rhenium colloid (99mTc-Re colloid) using a fine needle guided by ultrasonography was performed on 12 patients who underwent resection of the hepatoduodenal ligament lymph nodes. Histological examination revealed no lymph node metastasis in 8 patients. In 4 patients in whom 99mTc-Re colloid was injected into the left medial inferior hepatic segment, periarterial lymph nodes showed higher isotope uptake count than periductal nodes, and lymph nodes around the common hepatic artery revealed higher values than superior posterior pancreatoduodenal nodes. On the contrary, in 3 patients in whom the isotope was injected into the right anterior inferior segment, periductal lymph nodes had higher values than periarterial nodes, and superior posterior pancreatoduodenal lymph nodes showed higher values than those around the common hepatic artery. In one patient in whom the isotope was injected into both right and left segments, superior posterior pancreatoduodenal lymph nodes showed similar values to those around the common hepatic artery. Periportal lymph nodes tended to have values between those of periarterial and periductal ones. Lymph node metastases were confirmed in 4 patients in whom the relationships mentioned above was not always observed, and periportal lymph nodes showed the highest values among the three.

Adenocarcinoma↗

Clinicopathological study of carcinoma of the bifurcation of hepatic duct.

Ten cases of carcinoma of the bifurcation of hepatic duct were studied, 9 were resected and one case was autopsied. They were classified into two types according to the type of infiltration: Type 1 included cases, in which cancer cells were demonstrated in the mucosal or submucosal layer at a distance greater than 11 mm from the main tumors. Type 2 included the cases less than 11 mm distant. Histologic type and gross configuration had no correlation with the type of infiltration. Concerning hepatic infiltration, vascular invasion, serosal invasion and perineural invasion, Type 1 was more extensive than Type 2. Three Type 2 cases were all curatively resected, while all except one Type 1 were noncuratively resected. Three cases where the tips of the bile duct appeared to form a V and were connected through a narrow, long, stenotic bile duct on the preoperative cholangiographic figure were all Type 1. In these cases, cancer cells were thought to infiltrate into bilateral hepatic lobes, and as cancer cells would remain if only lobectomy is done, trisegmentectomy should be performed.

Aged↗

Transcriptive complex of Newcastle disease virus. II. Structural and functional assembly associated with the cytoskeletal framework.

The transcriptive complex, the nucleocapsid with the viral RNA-synthesizing activity, of Newcastle disease virus (NDV) contains three protein components, the major structural subunit (NP) and two associated proteins (P and L) involved in the RNA synthesis. We studied the pathway of these proteins from synthesis to assembly into the complex by pulse-chase labeling of infected cells followed by detergent extraction of the cells to separate soluble and cytoskeletal fractions. Most molecules of NP and P (and probably L) became associated with the cytoskeletal framework immediately after their synthesis. Most of the remaining molecules were initially found in the soluble fraction, but joined the cytoskeletal framework within several minutes. Once attached, none of the proteins left the cytoskeleton, and it was here that they assembled with 50 S viral RNA into nucleocapsids. The nucleocapsids thus formed remained bound to the cytoskeletal framework and were found by in situ autoradiography to exhibit viral RNA synthesis on the framework. These results suggested that the cytoskeletal framework could actively participate in the structural and functional assembly of NDV transcriptive complex.

Animals↗

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male.

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph1 translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph1 translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph1 translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph1 translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.

Adult↗

Postoperative cancer therapy for patients with carcinoma of the thoracic esophagus: an attempt of aggressive chemotherapy combined with proper nutritional support for patients with distant node metastasis.

The prognosis of patients with advanced thoracic esophageal carcinoma is still poor. In general, patients having distant lymph-node metastasis do not survive for more than 3 years. Therefore, a new therapeutic regimen employing aggressive chemotherapy for these patients has been attempted. In this regimen, three kinds of anticancer drugs Pepleomycin, and twice as much as Adriamycin and Mitomycin of the conventional level for a short period of time are used. Eleven cases were treated with this chemotherapy under active enteral and parenteral nutritional support of 45 to 50 kcal/kg daily. Two patients over 70 years of age died of pneumonitis. Four patients with recurrence of cancer in the lungs, liver and cervical nodes died after 10, 12, 13 and 14 months following surgery, respectively. Five patients have been alive for more than 2 years. These results indicate that this therapy is more effective than other conventional therapies. It has been shown that aggressive chemotherapy combined with proper nutritional support is effective for patients with node metastasis.

Antineoplastic Combined Chemotherapy Protocols↗

[Cytophotometric DNA analysis of the early and superficial esophageal cancer].

Although it is widely known that early esophageal cancer (n-) patients have a favorable prognosis after surgery and the superficial esophageal cancer (n+) patients have a poor one, the differences between them have not been found out under the microscopic examination of the primary lesion. Cytophotometric DNA analysis of the primary lesion was done to search for the differences between early and superficial esophageal cancer. Significant differences were obtained in the mean DNA value (p less than 0.01), the percentage of nuclei beyond tetraploid (p less than 0.001) and the product of 2 indices above (p less than 0.001). The result suggests that cytophotometric DNA analysis is a useful means for differentiating the early esophageal cancer from the superficial esophageal cancer and that the most suitable perioperative combined therapy can be chosen through the Feulgen-stained biopsy specimen.

Aged↗