Search PubMed⌕ Search

Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 523 records · Page 29Linked to original sources

Regression of atherosclerosis in normotensive and hypertensive rabbits. A quantitative analysis of cholesterol-induced aortic and coronary lesions with an image-processing system.

In the present study we attempted to quantitate the sequential changes occurring in cholesterol-induced aortic and coronary lesions in normotensive and ronovascular hypertensive rabbits, which were placed on a 0.5% cholesterol atherogenic diet for 16 weeks and observed for up to 104 months after withdrawal of the diet. After measuring the degree of surface involvement, a representative longitudinal section covering the whole length of the aorta was obtained, and histometric quantitative analysis was carried out using an image-processing system. Furthermore, ten continuous step-sections of the left coronary artery bed were prepared from each animal, and the degrees of luminal stenosis were estimated in all arterial segments contained. After withdrawal of the cholesterol diet, foam cell lesions of the aorta and coronary artery were gradually replaced by fibromuscular tissue. The hypertensive animals showed a greater degree of smooth muscle cell proliferation. Formation of atheroma occurred almost invariably after cessation of cholesterol feeding, and it was noted that hypertension aggravated the severity and extent of both aortic and coronary atherosclerosis. Upon histometric analysis, evidence of reduction of aortic lesions and significant reversal of luminal narrowing of the coronary artery were observed in normotensive as well as hypertensive animals. These results suggest that, even in hypertensive animals, substantial regression of both aortic and coronary atherosclerosis can be expected after normalization of hypercholesterolemia.

Animals↗

A comparison of academic performance of female and male optometry students at the University of Missouri-St. Louis.

The number of women entering optometry has risen steadily over the last 2 decades. The present study compares the academic performance of male and female optometry students in the 1984 through 1986 graduating classes at the University of Missouri-St. Louis School of Optometry. The female students had higher grade point averages upon entering optometry school than their male colleagues although they performed less well than the males on the Optometry College Admissions Test (OCAT) examination. An analysis of optometry grade point averages, class rank and honors received at graduation demonstrated that the women performed at least as well academically as their male counterparts.

Educational Status↗

Calmodulin activates inositol 1,4,5-trisphosphate 3-kinase activity in pig aortic smooth muscle.

The effects of calmodulin (CaM) on inositol 1,4,5-trisphosphate (InsP3) 3-kinase activity in pig aortic smooth muscle were examined. The cytosol fraction of muscle cells, containing 1.2-2.0 micrograms of CaM/mg of cytosol protein (thus 0.12-0.2%, w/w), showed a Ca2+-dependent InsP3 3-kinase activity, and there was no further activation by exogenous addition of CaM purified from dog brain. (NH4)2SO4 fractionation of the cytosol fraction revealed that a 20-60%-satd.-(NH4)2SO4 fraction was rich in the enzyme activity, and the activity without exogenous CaM was still dependent on Ca2+, although the CaM content in this fraction was minute (0.013-0.016%, w/w). The kinase activity observed in the absence of exogenous CaM became insensitive to Ca2+ when a 20-60%-satd.-(NH4)2SO4 fraction was applied to a DEAE-cellulose column, but exogenous addition of CaM increased the enzyme activity from 80-120 to 450 pmol/min per mg of protein, with addition of 10 microM free Ca2+. A fraction separated by DEAE-cellulose chromatography was applied to a CaM affinity column. The kinase activity was retained on the column in the presence of Ca2+, and was eluted by lowering the free Ca2+ concentration by adding EGTA. These results directly show that CaM activates InsP3 3-kinase activity and the enzyme becomes sensitive to Ca2+.

Animals↗

Activation of interleukin-2 receptor gene by forskolin and cyclic AMP analogues.

Forskolin (FK), a reversible activator of adenylate cyclase, markedly enhanced the expression of interleukin-2 receptor (IL-2-R) on a human natural killer (NK)-like cell line, YT. The FK-induced increase in IL-2-R on YT cells closely correlated with an increase in intracellular cyclic AMP (cAMP) level, and was mimicked by dibutyryl cyclic AMP (dbcAMP). FK induced both high and low affinity IL-2-R on the cells. Using a cDNA for the IL-2-R as a probe, the FK-induced IL-2-R expression was shown to be associated with an increase in IL-2-R mRNA. FK also enhanced the IL-2-R expression on a human T lymphotrophic virus I (HTLV-I) positive T-cell line (YTA-1H) and augmented the phorbol ester-induced expression of IL-2-R on HTLV-I negative T-cell lines (HSB-2 and HPB-ALL). These results suggest the possibility that the stimulation of adenylate cyclase may serve as a pathway leading to activation of the IL-2-R gene in certain types of lymphocytes.

Adenylyl Cyclases↗

Effect of guanosine triphosphate on the release and uptake of Ca2+ in saponin-permeabilized macrophages and the skeletal-muscle sarcoplasmic reticulum.

The effects of GTP, with or without polyethylene glycol (PEG), on the release and uptake of Ca2+ were examined by using saponin-treated macrophages and sarcoplasmic reticulum isolated from skeletal muscles. The application of GTP in concentrations in the range 0.1-10 microM induced a gradual, small but sustained release of Ca2+ from the saponin-treated macrophages. The addition of PEG to GTP markedly enhanced the GTP-mediated Ca2+ release. GTP at the same concentration ranges used for Ca2+ release decreased the amount of Ca2+ uptake, at a steady state, but stimulated the rate of Ca2+ accumulation in the presence of oxalate, the Ca2+-precipitating anion. The addition of PEG abolished the GTP-evoked stimulation of Ca2+ accumulation in the presence of oxalate. The stimulating effect on the rate of Ca2+ accumulation by GTP and its elimination by PEG were not due to changes in the permeability of oxalate by either GTP or PEG, or both. The Ca2+-releasing effect of GTP without PEG was enhanced by eliminating the uptake activity by decreasing the content of ATP. These results indicate that GTP has an inherent activity to release Ca2+ from non-mitochondrial intracellular stores of saponin-treated macrophages, and PEG enhances the GTP-mediated Ca2+ release, partly owing to its eliminating effect on GTP-stimulated Ca2+ uptake activity. These effects of GTP observed with saponin-permeabilized macrophages were not apparent in the isolated skeletal-muscle sarcoplasmic reticulum.

Animals↗

Some secular changes in body height and proportion of Japanese medical students.

Anthropometric dimensions of 738 medical students at Kyushu University in Japan were analyzed to determine secular changes of height and body proportions during a 20-year period. Since 1961, means of standing height, leg length, and ratio of leg length to standing height have increased, although the rate of increase from 1971 to 1981 has been rather slow. On the contrary, the mean sitting height X 100/standing height has declined during this same period. Compared with data on the Japanese general population, the medical students were considerably taller, but the difference has decreased.

Adult↗

Effect of guanosine triphosphate on the release of Ca2+ from intracellular store sites of saponin-treated human peripheral lymphocytes.

The effects of guanosine triphosphate (GTP) on the release and uptake of Ca2+ in nonmitochondrial intracellular store sites of human peripheral lymphocytes were examined. GTP in the presence of 3% polyethylene glycol released Ca2+ from the intracellular store sites of lymphocytes in a dose-dependent manner, and the maximal release was obtained at 10 microM GTP. GDP and 5'-GMP also enhanced the release of Ca2+. On the other hand, Ca2+ uptake in the presence of oxalate by saponin-treated lymphocytes was stimulated by GTP and this stimulation was abolished when polyethylene glycol was concomitantly present. The dose dependence of the stimulated Ca2+ uptake by GTP was much the same as that of the Ca2+ released by GTP. These results indicate that GTP has an inherent activity to release Ca2+ as well as to stimulate the uptake of Ca2+ in nonmitochondrial intracellular store sites of saponin-treated lymphocytes. The stimulatory effect of polyethylene glycol on GTP-mediated Ca2+ release may occur by inhibiting functions of the Ca2+ pump.

Biological Transport, Active↗

Activation by calmodulin of inositol-1,4,5-trisphosphate 3-kinase in guinea pig peritoneal macrophages.

The activity of inositol-1,4,5-trisphosphate 3-kinase in the cytosol fraction of guinea pig macrophages was assayed with special reference to the dependence on the free Ca2+ concentration. The enzyme activity, as assessed by the production of inositol 1,3,4,5-tetrakisphosphate was reversibly activated by free Ca2+ concentrations ranging from 10(-7) to 10(-6)M. The calmodulin antagonists, W-7 and chlorpromazine, inhibited the Ca2+-activated enzyme activity in a dose-dependent fashion, thereby indicating that calmodulin may be involved in the activation by Ca2+. The content of calmodulin in the cytosol fraction (about 2.8 micrograms/mg of cytosol protein) was markedly reduced to less than 0.03 microgram/mg of proteins by subfractionation by ammonium sulfate, followed by an anion-exchange chromatography. The subfraction obtained by the chromatography showed no Ca2+ dependence in the enzyme activity, while an exogenous addition of calmodulin with 10(-6)M Ca2+ increased the enzyme activity. The enzyme activity was retained on a calmodulin-affinity column in the presence of Ca2+, and was eluted from the column by lowering the free Ca2+ concentration by adding ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. These results clearly indicate that calmodulin activates the inositol-1,4,5-trisphosphate 3-kinase activity.

Animals↗

Aziridine biotransformation by microsomes and lethality to hepatocytes isolated from rat.

To clarify the relationship of aziridine biotransformation to their cytotoxic activities, the metabolism of optical isomers of typical cytotoxic and non-cytotoxic aziridines was studied in isolated hepatocytes, rat liver microsomes, mitochondria and L-1210 mouse leukemia cells. Cytotoxic 1-methyl-2-beta-naphthylaziridine (NAZ) gave nitrosomethane as one of the bioactivation products in isolated hepatocytes and simultaneously induced a marked decrease in cellular ATP followed by cell lethality. NAZ itself did not directly affect the respiratory function of mitochondria in isolated hepatocytes or in buffer solution, however, it inhibited the mitochondrial activity in the presence of microsomes in the buffer solution. Nitroso-t-butane or nitrosomethane dimer, used as a substitute for extremely labile nitrosomethane, strongly inhibited the respiration of mitochondria. On the other hand, optical isomers of 2-aziridinecarboxylic acid (AZC) which did not give nitrosomethane in isolated hepatocytes or microsomes also did not show cytotoxicity. Thus, the cytotoxicity of NAZ seems to be induced by bioactivation via cellular oxidases with the nitrosomethane generated being a major toxic component. This may occur with most of the cytotoxic aziridine derivatives.

Adenosine Triphosphate↗

Enumeration of terminal deoxynucleotidyl transferase positive cells in leukemia/lymphoma by flow cytometry.

The method to fix single cells in suspension and its application for the detection of TdT-positive cells by flow cytometry are described. In comparison to formalin-methanol fixation, formalin-acetone fixation resulted more formation of aggregated cells which caused non-specific staining. In our assay system 80% cells in human thymus were TdT-positive. Levels of TdT in normal human peripheral blood was 0.5 +/- 0.6% (means +/- 1 S.D., n = 50). A total of 104 patients with leukemia/lymphoma was examined for TdT. TdT-positive cells were detected in ALL (87.5% cases), AML (57.1% cases), CML-BC (58.3% cases) and ML (17.6% cases). Mean channel of fluorescence intensity of the TdT-staining in AML was significantly reduced in comparison with that in ALL. When antigen density of TdT was very low, fluorescence microscopy gave false negative results and flow cytometry could detect this dim fluorescence.

DNA Nucleotidylexotransferase↗

Regulation of coronary artery tone in relation to the activation of signal transductors that regulate calcium homeostasis.

Muscle tone of coronary arteries is regulated by free calcium concentration in the myoplasm. Various agonists, autacoids and putative peptides modify the calcium concentration directly or through actions of second messengers (signal transductors), such as cyclic guanosine monophosphate (GMP), cyclic adenosine monophosphate (AMP), inositol 1,4,5-trisphosphate, diacylglycerol or calmodulin. For example, acetylcholine (in the presence of intact endothelium cells), alpha-human natriuretic peptide or nitrate compounds increase the amount of cyclic GMP and isoproterenol, prostacyclin (prostaglandin I2) or vasoactive intestinal polypeptide increases cyclic AMP. Both cyclic nucleotides reduce free calcium concentration. On the other hand, acetylcholine (in the presence or absence of endothelium cells), norepinephrine or thromboxane A2 increases inositol 1,4,5-trisphosphate and diacylglycerol, thus causing the increase in the free calcium concentration, whereas vasoactive intestinal peptide and alpha-human natriuretic peptide reduce them. Calmodulin acts as an internal calcium receptor for regulation of the contractile machinary. Regulation of calcium homeostasis in relation to the muscle tone in the coronary arteries including other vascular tissues is discussed together with the role of second messengers.

Arteries↗