Conservation and divergence of RAS protein function during evolution.
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Animals↗
Biomedical subjects
T Toda
Publications and source records attributed to T Toda.
Ultrastructure of human umbilical artery and vein. Characterization and quantification of lipid laden cells.
Intimal thickening and lipid accumulation, which occur in atherosclerosis, were observed in fifteen human umbilical vessels. Quantification of lipid laden cells was done electron-microscopically. Within 1 month after birth, lipid laden cells originating from macrophages were observed in the umbilical artery, while those originating from smooth muscle cells were seen in the umbilical artery and vein. Lipid droplet formation appeared to be independent and different in macrophages and smooth muscle cells; the latter cells were stimulated to produce lipid droplets by hypoxia and the former cells by blood components.
Age Factors↗
Coronary arterial lesions in piglets from sows fed moderate excesses of vitamin D.
Ultrastructural studies were conducted on the coronary arteries of 6 week-old piglets from sows which received diets containing either 25 micrograms or 3.7 micrograms of vitamin D3 per pound of basal ration. The subendothelial space which was rich in mucopolysaccharide and newly formed tiny elastic fibers, contained numerous macrophages, some of which possessed lipid droplets. Degenerated smooth muscle cells with pyknotic nuclei or vesiculated organelles, and mitotic smooth muscle cells were occasionally seen in the coronary artery. Piglets from sows which were fed high doses of vitamin D had more degenerated smooth muscle cells without stainable lipid and lipid containing cells in their coronary arteries than piglets from sows which were fed low doses of vitamin D. These results suggested that an excess dietary intake of vitamin D by pregnant animals may have potential angiotoxic effects on the coronary arteries of their offsprings.
Animals↗
Comparative study of the atherogenecity of dietary trans, saturated and unsaturated fatty acids on swine coronary arteries.
Three groups of two-month-old swine were fed on basal diets supplemented with either oleic acid-rich safflower oil, lard or hydrogenated soybean oil in order to monitor the atherogenecity of various dietary fatty acids. The level of plasma triglyceride was highest in the safflower oil group and the level of plasma cholesterol was highest in the lard group. The degree of intimal thickening of the coronary arteries was most severe in the safflower oil group and lease severe in the hydrogenated fat group. Both the lard- and safflower oil-supplemented groups displayed lipid-rich coronary arterial lesions. The thickened intima of these two groups contained numerous activated smooth muscle cells, degenerated cells with or without stainable lipid and abundant cell debris. Cellular changes were less conspicuous in the coronary arteries from the hydrogenated fat group than in those from the other two groups.
Adipose Tissue↗
[Right ventricular dysplasia: clinical characteristics of five patients].
The purpose of this study was to elucidate the clinical features of right ventricular (RV) dysplasia, a recently described clinical entity characterized by RV myopathic changes and ventricular tachycardia of left bundle branch block morphology. Five cases were reported, in which the diagnosis was established according to the criteria of Marcus. Case 1, a 33-year-old man, was referred to us for evaluation of his paroxysmal ventricular tachycardia of five years duration. Case 2, a 38-year-old man, was admitted because of shock caused by ventricular tachycardia. In both cases, the QRS configurations during ventricular tachycardia were those of the left bundle branch block pattern, and electrocardiograms during sinus rhythm showed T wave inversions in the right precordial leads and late ventricular potentials. Two-dimensional echocardiography, radionuclide angiography and contrast angiography disclosed RV dilatation and dysfunction with normal left ventricular (LV) function. The biopsied myocardium from the right and left ventricles in Case 2 revealed myocytolysis, a paucity of myofibrils and proliferation of collagen fibers. Case 3, a 73-year-old woman began to experience exertional dyspnea since 16 years of age. Her treatment consisted of bed rest, diuretics and digitalis. In December 1983, her New York Heart Association functional class was III, and physical examinations disclosed a Levine III/VI systolic murmur suggestive of tricuspid regurgitation, jugular vein dilatation, hepatomegaly, and pretibial edema. Electrocardiogram showed atrial fibrillation, incomplete right bundle branch block and T wave inversions in the precordial leads. Chest radiograph revealed marked cardiomegaly (cardiothoracic ratio of 92%). Echocardiography, radionuclide angiography and contrast angiography revealed marked RV dilatation, depressed ejection fraction (RV end-diastolic volume index of 342 ml/m2, and RV ejection fraction of 28%). Case 4, a 20-year-old man, was admitted with a chief complaint of palpitation. Case 5, a 19-year-old man, was referred to us for the evaluation of asymptomatic cardiomegaly, and his cardiothoracic ratio was 54%. A 12-lead electrocardiogram showed right bundle branch block and T wave inversions in the right precordial leads. Ambulatory electrocardiography revealed frequent premature ventricular complexes of the left bundle branch block pattern. Echocardiography, radionuclide angiography, and contrast angiography disclosed RV dilatation and dysfunction in both cases, and mild LV dilatation and dysfunction (LV end-diastolic volume index of 149 ml/m2, LV ejection fraction of 48%) in Case 4.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
[Phase II study of (2''R)-4'-0-tetrahydropyranyladriamycin (THP) in gastrointestinal cancer].
A phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP) was performed on 37 patients with gastrointestinal cancer in 6 co-operative study institutions. Twenty-five patients out of 37 were evaluable for response according to the Koyama-Saito's criteria. THP was administered weekly at doses of 10 to 30 mg/body or every 3 to 4 weeks at doses of 40 to 60 mg/body intravenously. Of the 14 patients with gastric cancer, we obtained one complete response and 3 partial responses (response rate 28.6%), and of the 6 patients with rectal cancer, we obtained one partial response (16.7%). Leukopenia of less than 3 X 10(3)/mm3 and erythrocytopenia of less than 300 X 10(4)/mm3 were seen in 48% and 26% of cases. Neither cardiotoxicity nor hair loss were seen. These results suggest that THP is useful in the treatment of patients with gastrointestinal cancer.
Adult↗
Levamisole in postoperative adjuvant immunochemotherapy for gastric cancer. A randomized controlled study of the MMC + Tegafur regimen with or without levamisole. Report I.
The usefulness of LMS in postoperative immunochemotherapy of gastric cancer was investigated. In compliance with the protocol, MMC was given at a dose of 20 mg on the day of gastrectomy, and an additional 10 mg on the next day IV. The patients receiving 600 mg Tegafur daily were then divided into two groups according to whether LMS was also given or not. LMS was administered for 3 days before the operation in a daily dose of 150 mg and for 1 year or more after operation according to a schedule of 3 days' administration followed by an 11-day interval. The 2-year follow-up demonstrated that in stage III patients, the LMS (+) regimen was superior to the LMS (-) regimen, since the former prolonged the relapse-free interval significantly. The survival rate for stage III disease was also significantly higher in the LMS (+) than in the LMS (-) group. There was no significant difference in the incidence of subjective or objective side-effects between two groups. The incidence of agranulocytosis was comparable in the two groups.
Adult↗
Silver stain for proteins on a cellulose acetate membrane.
A rapid and sensitive silver staining method to detect proteins on a cellulose acetate membrane has been established. This method is achieved by modification of the silver-based color staining for detection of proteins in polyacrylamide gels [D. W. Sammons, L. D. Adams, and E. E. Nishizawa, Electrophoresis 2, 135-141 (1981)] and applied to our new type of two-dimensional electrophoresis for analysis of proteins on a cellulose acetate sheet [T. Toda, T. Fujita, and M. Ohashi, Anal. Biochem. 119, 167-176 (1982)]. Maximal sensitivity of silver stain for proteins on a cellulose acetate membrane can be obtained by an optimal balance between deposition of silver on the protein and on the background. Certain kinds of proteins are colored red, orange, or grayish-blue. The silver stain is 20-80 times more sensitive than Coomassie blue and some spots are visualized reproducibly by silver only. Densitometric evaluation of standard proteins stained with silver and Coomassie blue is also demonstrated. The method takes only 50 min to perform and is sensitive, simple, and reproducible.
Animals↗
Oxidation of fatty acid by heart mitochondria of chickens with endogenous hyperlipidemia.
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Animals↗
Ultrastructural changes in the comb and aorta of chicks fed excess testosterone.
The mode of cellular response to testosterone was monitored in the combs and aortas of chicks with the aid of an electron microscope. A 7-week treatment of 30 mg of testosterone per day had little effect on plasma lipid metabolism. However, this treatment resulted in the activation of fibroblasts in the comb, activation of fibroblast-like and smooth muscle cells in the aorta, and degeneration of smooth muscle cells in the aorta. A treatment of 150 mg of testosterone per day for 7 weeks induced hyperlipidemia and lipid-rich aortic lesions. The abdominal aorta had more activated and degenerated smooth muscle cells, with or without stainable lipid droplets, than the ascending aorta.
Animals↗
Molecular organization of the head of bacteriophage Teven: underlying design principles.
Structure and assembly of the bacteriophage T4 head are described as revealed by results obtained in this laboratory. Subunit arrangement of the major coat protein, soc and hoc in the head shell has been determined (Figs. 2 and 21). Two new approaches for studying the assembly pathway are presented: wild type infection at 19 degrees C and gene 23 cold sensitive mutants. We propose an assembly pathway in which the prehead is formed in one direction, starting from the neck and ending at the distal cap. The processes of proximal and distal capping of the head shell are distinctly different. Novel structural intermediates such as a naked core and cup-like particles are shown. A model on head length determination is presented, based on negative control by the core on distal capping. Interesting aspects in the maturation of the head are reviewed. An overall scheme of the head assembly is shown in Fig. 20. Comparative studies among Teven and RB phages showed that the particle morphology is strictly conserved while certain so-called non-essential and essential proteins are significantly varied. A phylogenetic relation among these phages is constructed from calculation of distances (Fig. 25).
Bacterial Proteins↗
The NDA3 gene of fission yeast encodes beta-tubulin: a cold-sensitive nda3 mutation reversibly blocks spindle formation and chromosome movement in mitosis.
The cells of a cold-sensitive mutant nda3-KM311 of the fission yeast Schizosaccharomyces pombe were arrested highly synchronously at a step similar to mitotic prophase when incubated at a restrictive temperature. DAPI staining and indirect immunofluorescence microscopy showed three condensed chromosomes but no spindle. Six minutes after the temperature shifted to a permissive one, the spindle appeared and elongated. The chromosomes were separated at a constant speed (relative velocity 1 micron/min), and the spindle disappeared after the chromosomes reached opposite ends of the cell. The NDA3 gene of S. pombe was cloned by transformation. The 2.6 kb Hind III genomic DNA that complemented the nda3 mutations had only one coding frame split with five short introns. The predicted amino acid sequence contained 448 residues, and was 75% homologous to that of chicken beta-tubulin.
Amino Acid Sequence↗
Identification of the pleiotropic cell division cycle gene NDA2 as one of two different alpha-tubulin genes in Schizosaccharomyces pombe.
Mutations in a cell-cycle gene NDA2 of Schizosaccharomyces pombe have pleiotropic effects on nuclear division, nuclear location, and thiabendazole sensitivity ( Toda et al., 1983). By transformation and nucleotide sequence determination, we identified NDA2 as one of two alpha-tubulin genes present in the genome of S. pombe. Two cloned sequences complemented cold-sensitive and thiabendazole-supersensitive nda2 mutations; one was derived from NDA2 that encodes alpha 1-tubulin, the other from an unidentified locus encoding alpha 2-tubulin. The predicted amino acid sequences showed that the alpha 1- and alpha 2-tubulins had respective residues of 455 and 449 (molecular weights 51,200 and 50,600). The homology to porcine alpha-tubulin was 76% in both cases. Frequent alterations took place in the two restricted regions. The alpha 1-tubulin (NDA2) clone had a 90 bp intervening sequence, the alpha 2-tubulin clone did not. RNA blot hybridization experiments indicated that both genes are transcribed. S. pombe tubulin was isolated by cycles of assembly and disassembly. Presumed alpha- and beta-tubulin polypeptide bands reacted with monoclonal antibodies specific for chicken alpha- and beta-tubulins.
Amino Acid Sequence↗
Hepatic mensenchymal hamartoma of an infant.
An 8-month-old boy was found to have a solitary hepatic mesenchymal hamartoma. Histologically, the lesion appeared as a large island of loose mesenchymal tissue with few cystic bile ducts and liver cells. Electronmicroscopy showed microvilli on the surface of tumor cells and desmosomes between the cells. Immunohistochemical studies showed that alpha-fetoprotein was localized in the proliferating liver cells and bile ductal epithelium of this neoplasm. This case is the 17th case of hepatic mesenchymal hamartoma reported in Japan.
Hamartoma↗
Ultrastructure of newly formed vessels in thrombi. Endothelium formation in human umbilical artery.
Thrombi with newly formed vessels in thirteen human umbilical arteries were studied. Red blood cells formed masses which were covered by fibrin within twelve hours after birth. By the second day, the intima including endothelial cells was denuded. In the junctional area between the thrombi and the original intima on the sixth day, red blood cells were surrounded by endothelial-like cells, which displayed junctional complexes and did not show any connection with intact endothelial cells. These cells also exhibited filaments with fusiform densities, suggesting a probable origin from vascular smooth muscle cells. Examination of older specimens indicated that these were precursor structures of functional capillaries found in mature thrombi.
Age Factors↗
Ultrastructure of aging human umbilical artery and vein.
Qualitative and quantitative changes in the human umbilical artery and vein were observed in 15 human specimens at different stages of development. Features such as intimal thickening and cellular lipid accumulation were found in umbilical vasculature. Cellular origin and quantification of lipid-containing cells were determined by electron microscopy. Within 1 month after birth, lipid-containing cells originating from macrophages were observed in the umbilical artery, while those originating from smooth muscle cells were observed in both the umbilical artery and vein. Lipid droplet formation appeared to be independent and different in macrophages and smooth muscle cells; the former cells were stimulated to produce lipid droplets primarily by plasma insudation and the latter cells primarily by hypoxia. These findings indicate that ultrastructural changes observed in closing umbilical vasculature may closely parallel and serve as a model for atherosclerotic changes which occur in mature vessels.
Aging↗
Electron microscopic comparison of the tunica media of the thoracic aorta between species.
Previous observations indicate that the tunica media of the thoracic aorta of chickens contains two populations of cells (smooth muscle cells and connective tissue cells), whereas that of the mammalian species only contains one cell type (smooth muscle cells). It was considered that this difference in chickens: a) might occur in other avian species; b) might be a common feature in other classes from phylum chordata which are inferior to mammalia; and c) might be a special adaptation for flying animals. In order to test these hypotheses, the cytology of the tunica media of thoracic aorta was studied in five mammals (human, pig, bat, rabbit, and rat), three avian species (chicken, turkey, and pigeon), one reptile (fresh water turtle), and one amphibian (frog). All animals exhibited smooth muscle cells in the tunica media of the aorta, but only the avian species demonstrated the second major cell type (interlamellar connective tissue cells). In the avian aorta the tunica media was composed of alternating layers of smooth muscle cells and fibroblast-like connective tissue cells separated by thick elastic lamellae. It is concluded that the presence of connective tissue cells in the tunica media of the aorta may be a distinctive characteristic of birds.
Animals↗
Spontaneous aortic lesions in marine turtles.
Marine turtles were found to have gross aortic aneurysmal dilations and multiple, raised grayish-white plaques which resembled both the aortic lesions of Marfan's syndrome in humans and those induced by chemical manipulation in animals. Smooth muscle cells in these aortic lesions displayed considerable functional as well as morphological similarity in their response to environmental injury in both turtles and humans.
Animals↗