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Biomedical subjects

K Terao

Publications and source records attributed to K Terao.

At least 91 records · Page 5Linked to original sources
PubMed1994

Injury and recovery process of intestine caused by okadaic acid and related compounds.

The injuries and repair processes in the intestines of mice induced by dinophysistoxin 3 (DTX 3) were compared morphologically to those induced by okadaic acid (OA) and dinophysistoxin 1 (DTX 1). DTX 3 impaired intestinal villi by the oral route only, whereas OA and DTX 1 caused intestinal injury with both oral and intraperitoneal exposures. The character of the lesions caused by the 3 toxins and the recovery processes were highly similar. Within 5 min of dosing, the basal portion of the covering epithelium became homogeneous and peeled from the lamina propria, while the upper portion containing microvilli remained intact. There were two types of villous injury and recovery: 1) When the injuries were limited to the villi, new cells from the crypts moved upward and differentiated into columnar cells. 2) When injuries progressed into the glands of Lieberkuhn, clusters of crypt cells were exposed to the intestinal lumen, and in the most severe case they were completely separated. Villous fusion was often seen in the recovery process of the type 2 cases. Recovery from the injuries was almost completed within 2 days. When mice were pretreated with fusarenon-X, a mycotoxin which injuries undifferentiated crypt cells preferentially, the injury induced by OA to the intestinal crypts was exacerbated and the recovery was delayed.

Administration, Oral↗
PubMed1994

Effects of cyclochlorotine on myofibrils in cardiomyocytes and on actin filament bundles in fibroblasts in vitro.

The effects of cyclochlorotine (CC), a secondary metabolite of Penicillium islandicum, on cardiomyocytes and fibroblasts were investigated by fluorescent and electron microscopy. The in vitro application of CC on myocytes induced disruption of myofibrils and large accumulations of actin, myosin, alpha-actinin, and vinculin at the cellular processes. This agent also induced the formation of islands of myosin and alpha-actinin aggregates. Actin filament bundles in fibroblasts were either unaffected or disrupted completely, suggesting the presence of two, physiocochemically different, populations of fibroblasts. CC damage was dose-dependently reversible. Further studies will be required to explore the feasibility of using CC for analyzing the properties of contractile and/or cytoskeletal proteins.

Actins↗
PubMed1994

Decrease in spermidine content during logarithmic phase of cell growth delays spore formation of Bacillus subtilis.

Bacillus subtilis 168M contained a large amount of spermidine during the logarithmic phase of growth, but the amount decreased drastically during the stationary phase. The extracts, prepared from B. subtilis cells harvested in the logarithmic phase, contained activity of arginine decarboxylase (ADC) rather than the activity of ornithine decarboxylase. In the presence of alpha-difluoromethylarginine (DFMA), a specific and irreversible inhibitor of ADC, the amount of spermidine in B. subtilis during the logarithmic phase decreased to about 25% of the control cells. Under these conditions, spore formation of B. subtilis 168M delayed greatly without significant inhibition of cell growth. The decrease in spermidine content in the logarithmic phase rather than in the stationary phase was involved in the delay of sporulation. Electron microscopy of cells at 24 hrs. of culture confirmed the delay of spore formation by the decrease of spermidine content. Furthermore, the delay of sporulation was negated by the addition of spermidine. These data suggest that a large amount of spermidine existing during the logarithmic phase plays an important role in the sporulation of B. subtilis.

Arginine↗
PubMed1993

Correlation between the inhibition of cell growth by accumulated polyamines and the decrease of magnesium and ATP.

The mechanism of the antiproliferation effect of spermidine and spermine was studied using a cell culture system of mouse FM3A cells. The addition of either 10 mM spermidine or 2 mM spermine to the growth medium containing 0.9 mM Mg2+ greatly inhibited cell growth (more than 90%). A decrease in the Mg2+ concentration to 50 microM in the growth medium, but without the polyamine addition, did not influence cell growth. However, the concentrations of spermidine and spermine necessary for the inhibition of cell growth when cells were cultured in the presence of 50 microM Mg2+ were much smaller (2 mM spermidine and 0.15 mM spermine). Nevertheless, the amount of polyamines accumulating in cells which could cause the inhibition of cell growth was almost the same, regardless of the large difference in the added polyamine concentrations. At the early stage of polyamine accumulation, the inhibition of cell growth correlated with the decrease of Mg2+ content, but not with a decrease of the ATP content. The decrease in Mg2+ content correlated well with the inhibition of macromolecular synthesis, especially protein synthesis. Thus, the inhibition of cell growth at the early stage of polyamine accumulation was thought to be due to the inactivation of ribosomes through the replacement of Mg2+ on magnesium-binding sites by polyamines. The decrease in Mg2+ content was mainly caused by the inhibition of Mg2+ transport by polyamines. At the later stage of polyamine accumulation, a decrease in ATP content was also observed. This was followed by swelling of the mitochondria, which may be a symptom of the subsequent cell death.

Adenosine Triphosphate↗
PubMed1993

Metabolic characteristics of rat liver cytosolic 5SRNA.

5SRNA were purified from the cytosol, ribosomes, nucleoli and nucleoplasm of rat liver. The 5'-terminal and 3'-terminal sequences of these 5SRNA species were shown to be the same. The time course of changes in specific activities of these 5SRNA in rat liver, 20 min to 16 h after intraperitoneal injection of [14C]orotic acid, were investigated. The specific activity of cytosolic 5SRNA increased almost linearly for 3 h, without a lag, to a high value, then decreased rapidly. The specific activity of cytosolic 5SRNA was much higher than the specific activities of 5SRNA from the other cellular components over 45 min to 6 h after intraperitoneal injection, although at 20 min the specific activity was similar to that of nucleoplasmic 5SRNA. Thus, cytosolic 5SRNA of rat liver is characterized by a high rate of turnover, which was shown to be comparable to that of heterogeneous nuclear RNA. The specific activity of 5SRNA, 45 min to 6 h after intraperitoneal injection, was as follows; cytosolic > nucleoplasmic > nucleolar > ribosomal 5SRNA. The specific activity of nucleoplasmic RNA that migrated slightly slower than nucleoplasmic 5SRNA on PAGE was much higher than that of cytosolic 5SRNA or nucleoplasmic 5SRNA, and so may be the precursor of nucleoplasmic 5SRNA. Together, these results indicate that cytosolic 5SRNA is transferred from the nuclei to the cytosol immediately after maturation of the precursor of nucleoplasmic 5SRNA without entering the nucleoplasmic pool of 5SRNA.

Animals↗
PubMed1992

Injury of mouse lymphocytes caused by exogenous methyl linoleate hydroperoxides in vitro.

The incubation with methyl linoleate hydroperoxides (MLHPO), a model of lipid peroxides, depressed DNA, RNA and protein syntheses of mouse thymic lymphocytes and increased the amount of thiobarbituric acid-reactive substances in lymphocytes. These phenomena were also found in the splenic lymphoblasts in the DNA synthetic phase (S-phase) obtained by mitogen. Prior culturing with all-rac-alpha-tocopherol increased DNA synthesis in splenic lymphoblasts. Electron microscopically, cytoplasmic micro-organelles of splenic lymphoblasts in the S- and G2-phases were markedly destroyed as compared with nuclei. No discernible changes were observed in not-blastotransformed lymphocytes under these experimental conditions. These findings indicate that thymic lymphocytes and splenic lymphoblasts are affected by exogenous lipid peroxides, and cytoplasmic micro-organelles of splenic lymphoblasts might be markedly damaged by exogenous lipid peroxides as compared to their nuclei.

Animals↗
PubMed1992

Mechanism of the inhibition of cell growth by N1,N12-bis(ethyl)spermine.

The mechanism of the antiproliferation effect of N1,N12-bis(ethyl)spermine (BESPM) was studied in detail using mouse FM3A cells, since this polyamine analogue mimics the functions of spermine in several aspects [Igarashi, K., Kashiwagi, K., Fukuchi, J., Isobe, Y., Otomo, S. & Shirahata, A. (1990) Biochem. Biophys. Res. Commun. 172, 715-720]. Our results indicate that not only the decrease in sperimine and spermine caused by BESPM but also its accumulation play important roles on the inhibition of cell growth by BESPM, since BESPM accumulated in cells at a concentration fivefold that of spermidine in control cells. In comparison with the polaymine-deficient cells caused by alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase, and ethylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, the behavior of polyamine-deficient cells caused by BESPM was different as follows: the inhibition of cell growth by BESPM was not abrogated by spermine or spermidine; polyamine uptake, which is stimulated during polyamine deficiency, was greatly inhibited, while spermidine/spermine N1-acetyltransferase activity, which is inhibited during polyamine deficiency, was enhanced in BESPM-treated cells; thymidine kinase activity did not decrease in BESPM-treated cells; inhibition of cell growth and macromolecule synthesis by BESPM correlated with the swelling of mitochondria and the decrease in ATP content; BESPM caused cell death when incubated together for several days. The role of BESPM accumulation on inhibition of cell growth is discussed.

Adenosine Triphosphate↗
PubMed1992

Light and electron microscopic studies of the murine heart after repeated administrations of ciguatoxin or ciguatoxin-4c.

After repeated ip and oral administrations of ciguatoxin (CTX) and ciguatoxin-4c (CTX-4c), one of the derivatives of CTX, to male ICR mice at a dose of 0.1 microgram/kg for 15 days, resulted in marked swelling of cardiac cells and endothelial lining cells of blood capillaries in the heart was observed. Single doses caused no discernible pathological changes. Damage to the capillaries was followed by prominent effusion of serum and erythrocytes into the interstitial spaces of the myocardium occurred. Swelling of the endothelial lining cells of capillaries caused narrowing of the lumen and accumulation of blood platelets in capillaries, which resulted in multiple single cell necroses of cardiac muscle cells. Within 1 month after the treatments of these phycotoxins, myocytes and capillaries appeared to be normal. Effusion in the interstitial spaces resulted in formation of bundles of dense collagen, which persisted for 14 months. Diffuse interstitial fibrosis was prominent in septum and ventricles, accompanied by bilateral ventricular hypertrophy. A single dose of 0.7 micrograms/kg ip resulted in severe acute heart injuries, followed by diffuse myocardial fibrosis.

Animals↗
PubMed1992

Light and electron microscopic studies on experimental nocardia-toxicosis in mice.

An exotoxin (HS-6) produced by Nocardia otitidiscaviarum isolated from certain lesions of cutaneous nocardiosis of a male 82-year-old patient induced severe injuries in the pancreas, liver, stomach, small intestine, heart, thymus and kidney of male ICR mice. Mice given Nocardia-free preparation of HS-6 at a dose of 1 mg/kg of body weight developed several autophagic vacuoles in the pancreas and liver within 20 min after the i.p. injection. Thereafter, the autophagic vacuoles increased in number and size with time. About 24 hr after the administration of HS-6, the liver showed marked accumulation of fat droplets in the cytoplasm of the hepatocytes. Although they contained abundant autophagic vacuoles in the regions of RER, there were no lipomatoses in the acinar cells of the pancreas, those of the chief cells and smooth muscle cells of the stomach, Paneth cells, goblet cells, smooth muscle cells of the small intestine, and plasma cells in the digestive tract. Biochemical examinations revealed that HS-6 had no significant effect on the protein synthesis of reticulocytes. Inoculation of the Nocardia into the mouse peritoneal cavities caused marked granulomatoses in the pancreas, liver and regional lymph nodes, but did not develop autophagic vacuoles in RER regions of these organs.

Aged↗
PubMed1991

Resistance of Histoplasma capsulatum to killing by human neutrophils. Evasion of oxidative burst and lysosomal-fusion products.

The basis for resistance of yeast form of Histoplasma capsulatum to antifungal activity of human neutrophils was studied. In limiting dilution assays and short term coculture assays human neutrophils were ineffective in killing H. capsulatum whereas Candida albicans was readily killed. By contrast, in a cell free hydrogen peroxide-peroxidase-halide system H. capsulatum was as sensitive to killing as C. albicans. Moreover, lysate of human neutrophils effectively substituted for horse-radish peroxidase in a cell free system for killing H. capsulatum. H. capsulatum elicited significant products of the oxidative burst in human neutrophils as detected by luminol-enhanced chemiluminescence. However, the response was two-fold less (p less than 0.05) than that induced by C. albicans. Transmission electron microscopy studies showed that phagosome-lysosome fusion took place when neutrophils phagocytosed C. albicans or H. capsulatum. Taken together, these findings indicate that, even though H. capsulatum elicits an oxidative burst and phagosome-lysosome fusion within the phagosome, it is capable of evading damage in short term assays.

Cells, Cultured↗
PubMed1991

Light and electron microscopic studies of pathologic changes induced in mice by ciguatoxin poisoning.

Acute poisoning induced by ciguatoxin or ciguatoxin-4c in male ICR mice was examined by light and electron microscopy. Target organs were the heart, medulla of adrenal glands, autonomic nerves and penis. There were no significant differences between the toxicity of ciguatoxin and ciguatoxin-4c. Either i.p. injection or oral administration (0.7 micrograms/kg) resulted in marked swelling and focal necrosis of cardiac muscle cells and effusion into the interstitial space of the heart. Degeneration of cells in the medulla of the adrenal glands was also observed. Continuous erection of the penis was observed in about 15% of the mice suffering from ciguatoxicosis. Although severe diarrhea was brought about by the administration of these phycotoxins, no morphological alterations were seen in the mucosa and muscle layers of the small intestine except in autonomic nerve fibers and synapses. Atropine suppressed the symptoms of diarrhea but had no effect on the injury to the cardiac muscle. Reserpine aggravated the clinical signs and pathological findings. Guanethidine and 5-hydroxy dopamine as well as those undergoing bilateral adrenalectomy had no significant effects on the ciguatoxicosis.

Adrenal Medulla↗
PubMed1991

Occurrence of 5SrRNA in high molecular weight complexes of aminoacyl-tRNA synthetases in a rat liver supernatant.

The 5SrRNA in the rat liver postmicrosomal supernatant was investigated. Acrylamide gel electrophoresis and Northern blot analysis showed that most of the 5SrRNA was present in the fractions obtained on high molecular weight regions separated by Sephadex G-200 column chromatography of the supernatant, which contained the bulk of the methionyl-tRNA synthetase (Fraction I) and tyrosyl-tRNA synthetase (Fraction II). A high molecular weight complex containing nine aminoacyl-tRNA synthetases [Mirande, M., LeCorre, D., & Waller, J.-P. (1985) Eur. J. Biochem. 147, 281-289] was purified by fractional precipitation with polyethylene glycol 6000, gel filtration on Bio-Gel A-1.5m, and finally tRNA-Sepharose column chromatography, which gave two fractions. Fraction B showed the activities of nine aminoacyl-tRNA synthetases and gave protein bands corresponding to eight previously identified enzymes on SDS-PAGE. Fraction A, eluted with a lower KCl concentration than Fraction B, showed lower activities than fraction B of eight of the aminoacyl-tRNA synthetases, the exception being prolyl-tRNA synthetase. The staining patterns with ethidium bromide of the RNAs after PAGE showed 5SrRNA bands for Fraction A but not for Fraction B. However, Northern blot analysis indicated that 5SrRNA was present in both Fractions A and B. The staining pattern after SDS-PAGE of Fraction A with Coomassie Brilliant Blue showed several protein bands in addition to those observed for Fraction B, one of which, with a staining intensity comparable with those of other bands, was located at the same position as ribosomal protein L5, which is the protein moiety of the 5SrRNA-L5 protein complex of ribosomal 60S subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acyl-tRNA Synthetases↗
PubMed1991

Role of 5SrRNA as a positive effector of some aminoacyl-tRNA synthetases in macromolecular complexes, with specific reference to methionyl-tRNA synthetase.

1) Rat liver 5SrRNA enhanced the activity of methionyl-tRNA synthetase in the macromolecular aminoacyl-tRNA synthetase complex (Fraction B) purified from a rat liver supernatant. 5SrRNA-L5 protein complexes (5SrRNP) had similar effects, whereas other ribosomal RNAs and E. coli 5SrRNA had no effect. 2) 5SrRNA increased the activity of the complex for methionine-dependent ATP-PPi exchange. 3) 5SrRNA increased the activities of methionyl-, arginyl-, and isoleucyl-tRNA synthetases in the complex, but scarcely affected its leucyl-, lysyl-, and glutamyl-tRNA synthetase activities. 4) 5SrRNA increased the activities of the rat liver supernatant for the attachment of [35S]methionine, [3H]isoleucine, [3H]lysine, [3H]proline, [3H]threonine, [3H]tyrosine, and [3H]phenylalanine to endogenous tRNA markedly, and those for [3H]leucine, [3H]arginine, [3H]aspartic acid, and [3H]histidine slightly, but did not affect those for [3H]glutamic acid, [3H]glycine, [3H]valine, [3H]alanine, and [3H]tryptophan. 5) Preincubation of the rat liver supernatant with an antibody against Artemia salina ribosomal protein L5, that cross-reacted with the rat liver ribosomal protein L5, decreased the attachment of [35S]methionine and [3H]isoleucine to endogenous tRNA, and 5SrRNA and 5SRNP enhanced these activities of the supernatant preincubated with antibody. On the other hand, the antibody did not affect that for [3H]alanine. Immune dot blot analysis using the antibody against L5 showed the presence of immunologically the same protein as L5 in the liver supernatant. Northern blot analysis of RNA in the immunoprecipitate prepared from the liver supernatant incubated with the antibody against L5 indicated that 5SrRNA was complexed with L5.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Multiple alpha-globin genes in crab-eating macaques (Macaca fascicularis).

Alpha-globin genes in crab-eating macaques were found to be triplicated at high frequencies according to restriction-enzyme comparisons. The frequencies of triplicated alpha-globin genes in macaques originally from Malaysia and Indonesia were 0.432 and 0.275, respectively, while no triplication was found in individuals from either the Philippines or northern and central Thailand. Quadruplicated alpha-globin genes were also observed, at frequencies of 0.045 (Malaysia), 0.075 (Indonesia), and 0.021 (the Philippines). A single locus was detected in only one of 40 chromosomes from Indonesia (frequency 0.025).

Animals↗
PubMed1991

Depression of phagocytic activity of human polymorphonuclear leukocytes by methyl linoleate hydroperoxides.

Methyl linoleate hydroperoxides (MLHPO), a model for lipid hydroperoxides, decreased fungicidal activity of human polymorphonuclear leukocytes (PMN) for fungi of Candida albicans. When PMN was cultured with MLHPO, phagocytosis to fungi was depressed. Degree of the depression was dependent on the concentration of MLHPO and the treatment time with MLHPO. These findings indicate that phagocytic activity of human PMN can be depressed by lipid hydroperoxides.

Candida albicans↗
PubMed1991

Effects of hyperlipaemic serum on interleukin-2 (IL-2) production, IL-2 receptor expression, and T cell proliferation induced by IL-2 in cynomolgus monkeys.

The effect of hyperlipaemic serum on mitogen-induced T lymphocyte proliferation was investigated with cynomolgus monkeys. The mitogen-induced blastogenesis was remarkably inhibited when either hyperlipaemic or normal monkey lymphocytes were incubated with hyperlipaemic sera. Hyperlipaemic serum also inhibited ConA-induced interleukin 2 (IL-2) production as well as IL-2 receptor (IL-2R) expression of normal monkey lymphocytes. On the other hand, it showed slight inhibition of T-cell proliferation induced by adding recombinant human IL-2 to IL-2R-positive normal monkey lymphocytes. These results indicate that hyperlipaemic serum inhibited an early stage of T-cell autocrine activation pathway including IL-2 production and IL-2R expression.

Animals↗
PubMed1991

Genetic polymorphism of the vitamin D-binding protein (DBP) in crab-eating macaques (Macaca fascicularis).

Vitamin D-binding protein (DBP) of crab-eating macaques (Macaca fascicularis) was examined by means of three electrophoretic methods. DBP phenotypes were observed to be one or two bands in each method. All of DBP molecular variants could be detected by the simultaneous typing with these three methods. Family analysis suggested that DBP variants followed the mode of autosomal codominant inheritance. A total of 17 phenotypes governed by at least 11 alleles were observed in the populations of Malaysia, Indonesia, and the Philippines. The genetic variability was high in Malaysian and Indonesian populations but low in the Philippine population.

Alleles↗