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Biomedical subjects

K Kageyama

Publications and source records attributed to K Kageyama.

At least 55 records · Page 3Linked to original sources
PubMed1995

Enhanced inhibitory effects of hyperthermia combined with ascorbic acid on DNA synthesis in Ehrlich ascites tumor cells grown at a low cell density.

Effects of hyperthermia and cell densities on inhibitory activity of ascorbic acid on DNA synthesis in Ehrlich ascites tumor cells were studied. When cells at a low density of 5 x 10(3)/ml were treated with 75 microM ascorbic acid for 1 h, DNA synthesis was inhibited after treatment at 37 degrees C and the inhibition was significantly enhanced at 42 degrees C. At a cell density as high as 1 x 10(5)/ml, however, inhibition did not occur at 37 degrees C or 42 degrees C. In contrast, dehydroascorbic acid was inactive even at a low cell density under similar conditions. Inhibitory effects of ascorbic acid on DNA synthesis were also markedly enhanced by treatment at 40 degrees C. DNA synthesis was not inhibited in the absence of the drug. Furthermore, mice transplanted with cells treated with a combination of 75 microM ascorbic acid and hyperthermia at 42 degrees C, considerably prolonged their survival time in comparison with untreated cells. Addition of ascorbic acid to hyperthermia is suggested to be an advantageous treatment for cancer.

Animals↗
PubMed1995

Effect of lactic acid on water content and osmotic fragility of erythrocytes in vitro.

Effects of lactic acid in red blood cells on osmotic fragility and water content of erythrocytes after hyperthermia were investigated. The osmotic fragility of erythrocytes increased following one-hour incubation with the addition of lactic acid at both 37 degrees C and 42 degrees C and that also increased after heating in vitro at 42 degrees C compared with those incubated at 37 degrees C, whether the lactic acid was added or not. The water content increased with the addition of lactic acid after heating in vitro at 42 degrees C. A high concentration of lactic acid and hyperthermia seem to cause the increase of intracellular water and the decrease of osmotic resistance of the red blood cells.

Animals↗
PubMed1995

Differential susceptibility of epidermal keratinocytes and neuroblastoma cells to cytotoxicity of ultraviolet-B light irradiation prevented by the oxygen radical-scavenger ascorbate-2-phosphate but not by ascorbate.

Human or mouse epidermal keratinocytes NHEK or Pam212 was less susceptible to ultraviolet (UV)-B irradiation than mouse neuroblastoma NAs1 cells in culture, undergoing apoptosis-like cell death as shown by cell fragmentation and cell membrane integrity disruption. UV susceptibility was appreciably reduced by the reactive oxygen species (ROS)-scavenger L-ascorbic acid-2-phosphate (Asc2P) endowed with long-lasting functions but not by L-ascorbic acid (Asc) for each cell type. DehydroAsc reduced UV susceptibility of Pam212 or NAs1 established cell lines but not of normal diploid NHEK cells destined to be thereafter submitted to cellular senescence. The susceptibility reduction may not be ascribed to extracellular Asc2P or DehAsc, which was removed by aspirating and/or rinsing upon irradiation after the intracellular channelyzer analysis and dead cell-specific DNA-intercalator ethidium homodimer/fluorometry, respectively. Thus, the three cell types differed in UV susceptibility partly because of their different ROS-scavenging abilities, which may be potently promoted by Asc2P or dehydroAsc but not Asc.

Animals↗
PubMed1994

Neuropeptide Y potentiates the luteinizing hormone (LH) response to LH-releasing hormone in men.

It has been demonstrated in several animal species that neuropeptide Y (NPY) exerts a modulatory effect on luteinizing hormone (LH) secretion. However, whether NPY plays a similar role also in humans has yet to be determined. Therefore, in this study we examined the effect of human NPY on the anterior pituitary hormone secretion in 6 normal men. Intravenous bolus injection of 100 micrograms of human NPY alone did not affect the secretion of any anterior pituitary hormone or cortisol. However, when NPY (100 micrograms) was administered simultaneously with LH-releasing hormone (LHRH, 100 micrograms), a significant potentiation was observed for LHRH-induced LH secretion. Similarly, follicle-stimulating hormone (FSH) response to LHRH was slightly potentiated by the coadministration of NPY, although this effect was not statistically significant. This is the first study to demonstrate that NPY can augment the LHRH-induced LH secretion in humans.

Adult↗
PubMed1994

Microdynamics of the phospholipid bilayer in cardiomyopathic hamster heart cell membrane.

To investigate the microdynamics and the structural architecture of the membrane phospholipid bilayer during the course of cardiomyopathy, membrane fractions were prepared from hearts of cardiomyopathic Syrian hamsters (BIO 14.6) aged 4, 18 and 31 weeks and compared with age-matched control hamsters (F1b). Membrane cholesterol, phospholipids and phospholipid fatty acids were measured by thin-layer chromatography, gas-liquid chromatography and high performance liquid chromatography. Microdynamics of the phospholipid bilayer were determined by a nanosecond fluorometer using pulsed excitation of a fluorescent probe, diphenyl-hexatriene. At the age of 4 weeks, there was no difference in lipid compositions and microdynamics between the BIO 14.6 and F1b. At the age of 18 weeks, saturated fatty acids, 18:0 and 22:0 increased and 20:0, 20:2 and 32:4 decreased in the BIO 14.6. At the age of 31 weeks, adding to the above changes in phospholipid fatty acids, unsaturated fatty acids 20:4 and 22:6 decreased, moreover membrane phospholipids, especially phosphatidylinositol and phosphatidylethanolamine significantly decreased. The viscosity and the wobbling angle of phospholipid molecules were decreased significantly. We have previously demonstrated that intracellular Ca2+ accumulation might be responsible for the pathogenesis of cardiomyopathy. Thus, we conclude that cardiomyopathic membrane may alter its structure and function with age. These alterations in cell membranes might be involved in the cardiac hypertrophy and dysfunction through impaired Ca2+ handling in cardiomyopathic hamsters.

Animals↗
PubMed1993

Phosphatidylinositol metabolism in hypertrophic rat heart.

The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during cellular response to norepinephrine in pressure-overloaded hypertrophic rat heart. After stimulation with norepinephrine, the accumulations of IP3 and diacylglyceride significantly increased in isolated myocytes from stroke-prone spontaneously hypertensive rat (SHRSP) heart, indicating phosphatidylinositol-specific phospholipase C activity increased in SHRSP heart cells. Protein kinase C activity was also enhanced in SHRSP, with a marked increase in particulate activity. We determined the intracellular calcium concentration and found it to be higher in SHRSP than in Wistar-Kyoto (WKY) rats at 30-40 weeks of age. Ca2+ influx was also elevated in SHRSP stimulated by norepinephrine. In SHRSP heart, cytosolic Ca2+ concentration may rise quickly in response to some stimuli, such as alpha 1-adrenergic stimulation, which is shown to be one of the pathways that increases cytosolic Ca2+ levels in hypertrophied rat heart. These data suggest that a part of the phosphatidylinositol-turnover pathway, such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride-protein kinase C pathway, may play an important role in the development of hypertrophy in SHRSP heart.

Animals↗
PubMed1992

Rapid and simple gas chromatographic measurement of lactic acid in red blood cells, plasma, and tumor cells after hyperthermia.

The content of lactic acid in red blood cells, plasma, and Ehrlich ascites tumor cells were measured by a gas-liquid chromatography using a column with a terephtalic acid support coated with polyethylene glycol-6000. The lactic acid contents were directly determined in aqueous samples, because they were converted to a volatile derivative in the column. The method was rapid and simple, compared with previous methods which need time-consuming conversion of lactic acid to volatile derivatives. Our measurements showed the increase in the contents of intra- and extracellular lactic acid after hyperthermia.

Animals↗
PubMed1992

Helical volume CT and its clinical significance.

Helical Volume CT (HVCT) is an X-ray CT scanning technique in which the patient is scanned continuously while the couch-top is moved in the axial direction. It is performed using the Toshiba TCT-900S CT scanner jointly developed by the authors and Toshiba Corporation. This scanner features a large central opening, the inner surface of which is lined with a circular array of 2,304 detectors. The X-ray tube rotates outside the detector array at the rate of one revolution per second. Electrical power is supplied to the X-ray tube through a slip ring mechanism, permitting the X-ray to be continuously generated without any interscan delay. The X-ray tube and detectors move in a "nutate/rotate" pattern. The maximum scanning time is 30 seconds (equivalent to a single breath-hold). To improve image quality, the slice thickness can be selected to equal the distance over which the couch-top moves in one second. The clinical advantages of HVCT are as follows: (1) the examination time is significantly reduced (to minimize the patient's discomfort), (2) continuous data of anatomical structures can be obtained without artifacts due to respiratory motion, and (3) it is possible to obtain superior images for multiplanar reconstruction (MPR), cine-display, and three-dimensional reconstruction.

Humans↗
PubMed1989

Control by hyperthermia of ornithine decarboxylase in Ehrlich ascites tumor cells.

The effect of hyperthermia on the activity and the messenger RNA levels of ornithine decarboxylase (ODC), which has a rapid rate of turnover in cultured cells, was studied in Ehrlich ascites tumor cells. When the cells were incubated at 42 degrees C, elevation of ODC activity by a change of the medium was prevented. Total RNA was isolated from cells treated at 37 degrees C or 42 degrees C, and the relative abundance of the ODC mRNA was measured by Northern blot analysis. These levels in heat-treated cells were comparable to those in control cells. Inhibition by hyperthermia was reversible. The recovery was suppressed by cycloheximide but not by actinomycin D. In hyperthermic-treated cells, the biological half-life of ODC was 14 min, which was the same time as for cells cultured at 37 degrees C. These results suggest that hyperthermic treatment of Ehrlich ascites tumor cells suppressed ODC induction during translation, not during transcription or after translation.

Animals↗
PubMed1989

The maximum and minimum water content and cell volume of human erythrocytes in vitro.

The maximum and minimum water contents of human erythrocytes were measured after exposure to various osmotic pressures. Within a range of osmolarities, at which no haemolysis occurred, the water content reached its maximum, 78.1%, at 180 mosM and its minimum, 54.8%, at 800 mosM. Simultaneously, the mean cell volume increased to 98.5 microns 3 at 180 mosM and decreased to 77.2 microns 3 at 800 mosM.

Erythrocyte Volume↗
PubMed1989

Spontaneous olfactory neuroepithelioma in a domestic medaka (Oryzias latipes).

Tumors of the central nervous system in fish are rare, and only six cases of spontaneous olfactory neuroepithelioma have been reported. This is the seventh case, found in a medaka, Oryzias latipes. The tumor was noted near the right olfactory orifice and finally measured 1.5 mm in diameter. Histologically the tumor consisted of undifferentiated neuroblasts forming a few true rosettes. Mitosis was frequently observed. Tumor cells stained diffusely for neuron-specific enolase and sporadically for neurofilament proteins by immunohistochemical procedures. Additionally a few large tumor cells were positively stained for S-100 protein. Electron microscopy revealed that the tumor cells had extended cytoplasm in which parallel neurotubules and a few neuroendocrine granules were noted. In the perinuclear region, bundles of intermediate filaments and neuroendocrine granules were seen. Single cilia and a pair of centrioles were occasionally found, but no ciliated cells were found in this tumor. Some large tumor cells contained electron-dense intracytoplasmic inclusions which showed a crystalloid structure by high-magnification electron microscopy; however, this type of crystalloid has never been reported in neuronal tumors.

Animals↗
PubMed1989

Synergistic inhibition of DNA synthesis in Ehrlich ascites tumour cells by a combination of unsaturated fatty acids and hyperthermia.

Wide attention has been given to hyperthermia as a new measure for cancer treatment. Clinical trials of hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic we examine if fatty acids exert a synergistic effect on Ehrlich ascites tumour cells when combined with hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic acid and linoleic acid (unsaturated fatty acids) at 37 degrees C, the DNA synthesis of cells was significantly inhibited. Palmitic and stearic acids, which are saturated fatty acids, did not suppress DNA synthesis. Hyperthermic treatment without the presence of fatty acids at 42 degrees C for 1 h decreased DNA synthesis to 62% of the control level of 37 degrees C. The combination of an unsaturated fatty acid and hyperthermia synergistically suppressed DNA synthesis. When the cells were incubated in serum-free medium containing 0.1% albumin, unsaturated fatty acids were more effective in inhibiting DNA synthesis. However, saturated fatty acids had little or no effect on DNA synthesis in control or hyperthermia-treated cells. These results indicate that unsaturated fatty acids are useful for enhancing the inhibitory effect of hyperthermia on DNA synthesis, which may increase the in vitro antitumour effects of hyperthermia.

Animals↗
PubMed1989

Effect of acylated derivatives of ascorbate on ornithine decarboxylase induction in Ehrlich ascites tumor cells.

We studied the effects of 6-0-acylated derivatives of ascorbate on ornithine decarboxylase (ODC, E.C.4.1.1.17) activity and the ODC-mRNA level in Ehrlich ascites cells. These derivatives are known to inhibit cell growth. When cells grown to the stationary phase were diluted and stimulated with fresh medium containing 10% dialyzed fetal calf serum, the ODC activity increased rapidly and transiently with a peak at 4 hr. Ascorbate or 2,6-dipalmitoyl ascorbate had little or no effect on the induction of ODC, but 6-0-palmitoyl ascorbate (6P) suppressed the enzyme activity in a time- and dose-dependent way. 6-0-Stearoyl ascorbate had a similar effect. The amount of ODC-mRNA formed after growth stimulation was not affected by 6P. These results indicate that the treatment of Ehrlich ascites tumor cells with 6P caused dose-dependent suppression of ODC induction post-transcriptionally.

Acetylation↗
PubMed1988

Altered production of the active oxygen species is involved in enhanced cytotoxic action of acylated derivatives of ascorbate to tumor cells.

Our previous study shows that 6-O-acyl derivatives of L-ascorbic acid inhibits more markedly cell growth of mouse Ehrlich carcinoma than ascorbic acid. The present study shows that 6-O-palmitoyl ascorbic acid but not ascorbic acid prolongs the lifespan of mice into which tumors such as Meth A fibrosarcoma, MM46 mammary carcinoma, Ehrlich carcinoma and sarcoma 180 are implanted. The potentiated cytotoxicity of 6-O-palmitoyl ascorbic acid is not due to an increase in duration time of the cytotoxic action, because 6-O-palmitoyl ascorbic acid is gradually inactivated during contact with tumor cells and exhibits a similar action time curve to that of ascorbic acid as shown by clonal growth assay. Cytotoxicity of 6-O-palmitoyl ascorbic acid is markedly diminished by combined addition of catalase and superoxide dismutase (SOD), as shown by dye exclusion assay, whereas the cytotoxicity was slightly reduced by either enzyme alone but not by the specifically inactivated or heat-denatured enzymes. In contrast, cytotoxicity of ascorbic acid is abolished by catalyse but not SOD. Autooxidation of 6-O-palmitoyl ascorbic acid was not inhibited by catalase plus SOD. The results indicate that cytotoxicity of 6-O-palmitoyl ascorbic acid is attributed at least partly to both hydrogen peroxide (H2O2) and superoxide (O2-.) generated at the early stage. Cytotoxicity of 6-O-palmitoyl ascorbic acid is also appreciably attenuated by singlet oxygen (1O2) scavengers such as hydroquinone, 1,4-diazobicyclo-2,2,2-octane or sodium azide, but not by hydroxyl radical scavengers including butylated hydroxytoluene, D-mannitol, benzoic acid and ethanol. Thus, in contrast to cytotoxicity of ascorbic acid mediated entirely by H2O2 initially generated, acylated ascorbic acid produces a diversity of active oxygen species including H2O2, O2-. and other species secondarily generated via disproportion, which may be additively involved in the enhanced cytotoxic action.

Animals↗