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Biomedical subjects

K Kageyama

Publications and source records attributed to K Kageyama.

At least 37 records · Page 2Linked to original sources
PubMed1999

Extrusion polymerization: catalyzed synthesis of crystalline linear polyethylene nanofibers within a mesoporous silica

Crystalline nanofibers of linear polyethylene with an ultrahigh molecular weight (6,200,000) and a diameter of 30 to 50 nanometers were formed by the polymerization of ethylene with mesoporous silica fiber-supported titanocene, with methylalumoxane as a cocatalyst. Small-angle x-ray scattering analysis indicated that the polyethylene fibers consist predominantly of extended-chain crystals. This observation indicates a potential utility of the honeycomb-like porous framework as an extruder for nanofabrication of polymeric materials.

Journal Article↗
PubMed1999

Urocortin messenger ribonucleic acid: tissue distribution in the rat and regulation in thymus by lipopolysaccharide and glucocorticoids.

Urocortin (Ucn), a new mammalian member of the CRF family, is a candidate endogenous ligand for type 2 CRF receptors. In a survey of peripheral tissues from adult male rats, we found that Ucn messenger RNA (mRNA) was abundant in the gastrointestinal tract and immune tissues such as thymus and spleen. We next tested the hypothesis that levels of Ucn mRNA levels in thymus and spleen would be altered after immune activation. As measured by ribonculease protection assay, lipopolysaccharide (LPS) induced a 2-fold time-dependent increase in thymic Ucn mRNA levels within 6 h. By contrast, splenic Ucn mRNA levels decreased after LPS. Because LPS activates the hypothalamus-pituitary-adrenal (HPA) axis, we examined whether the effects of LPS on Ucn mRNA might be mediated through changes in HPA axis hormones. Ucn mRNA in thymus, but not spleen, was significantly increased after ACTH injection; however, LPS did not increase Ucn expression in the thymus of adrenalectomized rats with corticosterone replacement, despite substantial increases in ACTH. Finally, sc injection of corticosterone stimulated Ucn mRNA comparably to that of LPS. Together, these results suggest that Ucn mRNA expression can increase after immune activation in a corticosterone-dependent manner, and that such changes in Ucn mRNA may be an additional consequence of HPA axis activation.

Animals↗
PubMed1999

Antimetastatic and anti-invasive ability of phospho-ascorbyl palmitate through intracellular ascorbate enrichment and the resultant antioxidant action.

A lipophilic and auto-oxidation-resistant derivative of ascorbic acid (Asc), Asc-2-O-phosphate-6-O-palmitate (Asc2P6Plm), was shown to exert an invasion-inhibitory action as promptly as 30-40 min for 50% inhibition and 60-90 min for 80% inhibition after entering fibrosarcoma HT-1080 cells. Invasive inhibition of 95-97% was accomplished by Asc2P6Plm of doses exhibiting no cytotoxicity under the same conditions. Asc2P6Plm was dephosphorylated and esterolyzed to Asc, which enriched the intracellular Asc dose dependently in invasion-suppressed cells, contrasting with no detectable Asc in invasive cells fed without Asc2P6Plm. Intracellular dehydroAsc (DehAsc), unexpectedly, amounted to 1.02-1.65-fold as much as intracellular Asc, suggesting that invasive cells underwent oxidative stress, the repression of which resulted in both inhibition of tumor invasion and oxidative conversion of Asc to DehAsc. Correspondingly, intracellular oxidants fluorometrically detected with a redox indicator CDCFH were more abundant in invasive cells than in invasion-suppressed cells fed with Asc2P6Plm. Invasion inhibitory effects of Asc2P6Plm necessitated the extensive inhibition of the major gelatinases MMP-9 and MMP-2, as shown by zymography and Western blots, but did not necessitate direct expression of the metastasis suppressor gene nm23, taking as long as 6-18 h in contrast to a prompt action of Asc2P6Plm. Antimetastatic effects on melanoma B16BL6 cells were given dose dependently by intravenous administration or pretreatment with Asc2P6Plm. Thus, Asc2P6Plm is anticipated as an antimetastatic agent via the potent antioxidant activity.

Animals↗
PubMed1998

Serotonin stimulates corticotropin-releasing factor gene expression in the hypothalamic paraventricular nucleus of conscious rats.

To examine the direct effects of serotonin (5-HT) on the release and synthesis of corticotropin-releasing factor (CRF) in the hypothalamic paraventricular nucleus (PVN), 5-HT was microinjected just onto the bilateral PVN of conscious rats. Plasma adrenocorticotropic hormone (ACTH) levels peaked at 30 min and returned to the basal levels in 90 min. Northern blot analysis revealed that the CRF messenger RNA (mRNA) level in the PVN as well as the proopiomelanocortin mRNA level in the anterior pituitary significantly increased 120 min after the 5-HT injections (50-250 nmol/side). Pretreatment with intracerebroventricular (i.c.v.) injection of pindobind 5-HT1A (5 nmol) or LY-278584 (500 nmol) completely abolished the 5-HT-induced ACTH response, whereas LY-53857 (100 nmol) was without effect. These results suggest that 5-HT stimulates CRF release, which has interactions with 5-HT1A and 5-HT3 receptors on CRF neurons in the PVN, and activates CRF synthesis in conscious rats.

Adrenocorticotropic Hormone↗
PubMed1998

Naturally occurring 2'-O-methylpurine nucleosides with hypotensive properties.

2'-O-Methylinosine (1) has been isolated for the first time and shown to be an intrinsic hypotensive principle. Its probable in vivo precursor, 2'-O-methyladenosine (3), showed stronger and even orally potent hypotensive activity. Resistance of the methyladenosine (3) against adenosine deaminase is thought to contribute to its long-lasting activity. The effect of both nucleosides (1 and 3) was not accompanied with any significant change in heart rate, which is often observed with adenosine.

Adenosine↗
PubMed1998

Studies on in vitro effect of free fatty acids on water content and osmotic fragility of rabbit (Lepus cuniculus) erythrocytes.

The effects of free fatty acids in the blood on osmotic fragility and water content of erythrocytes when combined with hyperthermia were investigated. The isotonic buffer, containing the fatty acid, was added to the erythrocyte suspension to a final concentration of 200 microM/L. The samples were kept for one hour in an incubator at 37 degrees C or 42 degrees C. The osmotic fragility of erythrocytes was determined by coil planet centrifuge system and intracellular water content was measured by gas-liquid chromatography. A high concentration of unsaturated fatty acid and hyperthermia caused the increase in intracellular water and the decrease in osmotic resistance of the red blood cells compared to saturated fatty acid and the control. The present experiment demonstrated that unsaturated fatty acid was one of the principal chemical and metabolic factors which caused sports anemia.

Animals↗
PubMed1998

A hypopituitary patient who attained tall stature without growth hormone.

We describe an unusual patient with hypopituitarism who attained tall stature even without growth hormone (GH). A 37-year-old man was devoid of secondary sexual characteristics, but manifested tall stature with a eunuchoidal feature. Serum levels of GH, insulin-like growth factor-I, gonadotropins and testosterone were all below normal. GH secretion was not enhanced by any provocative stimulus. Adrenocorticotropic hormone increased after administration of corticotropin releasing hormone, but not after insulin-induced hypoglycemia. Thyrotropin increased in response to thyrotropin releasing hormone, but both free T3 and T4 did not rise. Magnetic resonance imaging disclosed a transected pituitary stalk. The present patient had hypopituitarism due to perinatal problems but had grown with the aid of non-GH growth-promoting factors, which suggests that man may be able to achieve statural growth even without GH.

Adult↗
PubMed1998

[Osmotic fragility test of erythrocytes with a coil planet centrifuge].

The measurement of osmotic fragility of erythrocytes has been applied to the diagnosis of hemolytic diseases, studies of membrane permeability and alternations leading to destruction of erythrocytes. Almost 30 years have gone by since the coil planet centrifuge system was devised for measuring the osmotic fragility of erythrocytes. Many excellent studies by means of this centrifuge system have been published. Prominent investigations are reviewed as follows: in relation to the osmotic fragility, various liver diseases, angina pectoris, trapping the aged erythrocytes, tumor, lactic acid, unsaturated fatty acids, free cholesterol, exercise and lead exposure level were examined.

Angina Pectoris↗
PubMed1997

Moderately controlled transport of ascorbate into aortic endothelial cells against slowdown of the cell cycle, decreasing of the concentration or increasing of coexistent glucose as compared with dehydroascorbate.

Uptake of L-[1-(14)C]ascorbic acid (Asc) of 12.5-200 microM for 1 h into bovine aortic endothelial BAE-2 cells grown to confluence was as low as 43-64% (per cell) of uptake into the cells grown to nearly one-fourth confluence. [14C]Asc undergoing transmembrane uptake was concentrated and accumulated in the cell less efficiently ([Asc]in/ex = 8-13) at confluence than at subconfluence ([Asc]in/ex = 15-24). The declined Asc uptake at confluence is attributable to slowdown of the cell cycle, because a similar decrease in [Asc]in/ex was shown by subconfluent cells precultured in serum-insufficient medium, resulting in an increase in G1 phase and concurrent decreases in S and G2 + M phase distributions as determined by flow cytometry. [1-(14)C]Dehydroascorbic acid (DehAsc) was taken up and accumulated as Asc, after metabolic reduction, without detectable DehAsc. The [Asc]in/ex values for DehAsc at confluence were as low as 15-69% of those at subconfluence in contrast to the values as retentive as 62-75% for Asc, suggesting the moderate control of Asc uptake against slowdown of the cell cycle. At either confluence or subconfluence, dose-dependence for DehAsc uptake was more marked than for Asc uptake as shown by an uphill slope in a curve of doses versus [Asc]in/ex for DehAsc in contrast to a downhill slope for Asc, suggesting the moderate control for Asc uptake against fluctuation of the dose. Increasing of coexistent glucose of 5 mM to 20-40 mM, plasma concentrations in diabetic patients, declined DehAsc uptake to 46-48%, which was less moderately controlled than Asc uptake retained to 59-73%. Asc uptake did not compete with DehAsc uptake, suggesting different transporter proteins for Asc and DehAsc. Thus, Asc uptake into the aortic endothelial cells is more moderately controlled against slowdown of the cell cycle, decreasing of the extracellular concentrations or increasing of coexistent glucose than DehAsc uptake, suggesting a homeostatic advantage of Asc over DehAsc in terms of retention of intracellular Asc contents within a definite range.

Animals↗
PubMed1997

Enhanced protection against peroxidation-induced mortality of aortic endothelial cells by ascorbic acid-2-O-phosphate abundantly accumulated in the cell as the dephosphorylated form.

Bovine aortic endothelial BAE-2 cells exposed to the peroxidizing agent, tert-butylhydroperoxide (t-BuOOH) or 2,4-nonadienal (NDE), suffered from disruption of cell membrane integrity and from reduction of mitochondrial dehydrogenase activity as assessed by fluorometry using ethidium homodimer and photometry using WST-1, respectively. The cells were protected from t-BuOOH-induced injury more markedly by L-ascorbic acid-2-O-phosphate (Asc2P) stably masked at the 2,3-enediol moiety, which is responsible for the antioxidant ability of L-ascorbic acid (Asc), than by Asc itself. In contrast, NDE-induced membrane disruption but not mitochondrial dysfunction was prevented by Asc2P, whereas Asc exhibited no prevention against both types of injury. The amount of intracellular Asc was 7.2- to 9.0-fold larger in Asc2P-administered BAE-2 cells, where the intact from Asc2P was not detected, than in Asc-administered cells as assessed by HPLC of cell extract with detection by coulometric ECD and UV. During transmembrane influx into the cell, Asc2P was concentrated as highly as 70- to 90-fold relative to the extracellular Asc2P concentration, whereas Asc was 8- to 13-fold concentrated as estimated based on an intracellular water content of 0.59 pL/cell determined by [14C]PEG/gas chromatography. Thus, Asc2P but not Asc is highly concentrated in the aqueous phase of the cell after prompt dephosphorylation, and may thereby render the cell more resistant to t-BuOOH-peroxidation assumedly via scavenging of intracellular reactive oxygen species than to peroxidation with the less hydrophilic agent NDE.

Animals↗
PubMed1997

Effects of fenthion, isoxathion, dichlorvos and propaphos on the serum cholinesterase isoenzyme patterns of dogs.

The serum cholinesterase (ChE) isoenzyme patterns consist of 5 bands for normal beagle dogs. We examined the ChE isoenzyme patterns and ChE activities of 4 groups, each of which consisted of 4 dogs, given the organophosphate (OP) compounds fenthion (P = S type), isoxathion (P = S type), dichlorvos (P = O type) or propaphos (P = O type) po at 220, 75, 120 or 90 mg/kg respectively. Blood samples were collected for 30 d after the OP administrations. ChE isoenzyme bands 4 and 5 were inhibited 12 h after fenthion and isoxathion administration; dichlorvos and propaphos produced suppression of main bands 4 and 5 20 min after administration. This change was effective to differentiate the type of OP administered (P = S and P = O), while the main ChE isoenzyme bands of dog serum reflected inhibition of serum ChE activity.

Animals↗
PubMed1997

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

OBJECTIVE: A coll planet centrifuge is an apparatus for the dynamic measurement of erythrocyte osmotic fragility, and it was applied to the observation of altered erythrocyte osmotic fragility induced by the lactic acid. Changes in intracellular water content of red cells were also measured according to the method, based on gas-liquid chromatography. EXPERIMENTAL DESIGN: Blood was withdrawn from the animal by cardiac puncture before and after lactic acid injection. The lactic acid was injected to rabbit through the auricular vein till the final concentration for the circulating blood was 0.7 mg/ml. RESULTS: The water content in the red cells before the lactic acid injection was between 71.37% and 73.33%. It increased after the lactic acid injection and reached the maximum of 102% of the original content. Hemolysis of erythrocytes before the injection of lactic acid began at 108.3 to 110.3 mOsm and ended at 77.0 to 81.0 mOsm, and after the injection it began at 117.0 to 120.7 mOsm and ended at 84.5 to 87.3 mOsm. CONCLUSIONS: In the present experiment the decrease in pH of the blood in lactic acid administered rabbits was too small to cause any changes in the osmotic fragility, suggesting that changes of the erythrocyte membrane properties, owing to the presence of lactic acid in the blood had occurred.

Animals↗
PubMed1997

Cytotoxicity to tumors by alpha, beta-dihydric long-chain fatty alcohols isolated from esterolysates of uncytotoxic sheep cutaneous wax: the dependence on the molecular hydrophobicity balance of N- or iso-alkyl moiety bulkiness and two hydroxyl groups.

Wool fatty alcohols (WF-Alc; C10-C33), separated by esterolysis of wool grease secreted from sheep sebaceous gland, inhibited growth of mouse Ehrlich ascites carcinoma (EAC) cells in contrast to no inhibition by unesterolysed wool grease. WF-Alc was fractionated by molecular distillation and subsequent octadecylsilica (ODS) gel liquid chromatography, showing that most of the growth-inhibitory activity was found in the most hydrophilic fraction with the lowest boiling-point (MW 200-300; C12-C20), ODS-HPLC of the fraction showed that most of the activity resided in two homogeneous fractions identified by GC-MS and 13C-/1H-NMR as alpha, beta-dihydric saturated fatty alcohols such as 1,2-hexadecanediol (n-C16(OH)2) and 16-methyl-1,2-heptadecanediol (iso-C18(OH)2), respectively. EAC cells implanted into mice were inhibited markedly by n-C16(OH)2 possessing a cytolysing ability and slightly by iso-C18(OH)2, but hardly by other alkyl-alpha, beta-diols (C12-C24) contained in WF-Alc. Thus, the antitumor activity of WF-Alc was exhibited only after saponification of uncytotoxic wool grease, showing necessity of unesterified hydroxyl groups, and was dependent upon the molecular hydrophobicity balance attributed to both hydroxyl groups and n- or iso-alkyl moiety bulkiness specified out of diverse species of fatty alcohols contained in WF-Alc.

Animals↗
PubMed1997

[In vitro effects of free fatty acids on water content and osmotic fragility of erythrocytes in rabbits].

The effects of free fatty acids in the blood on osmotic fragility and water content of erythrocytes when combined with hyperthermia were investigated. The isotonic buffer, containing the fatty acid, was added to the erythrocyte suspension to a final concentration of 200 microM/l. The samples were kept for one hour in an incubator at 37 or 42 degrees C. The osmotic fragility of erythrocytes was determined by Coil Planet Centrifuge System and intracellular water content was measured by gas-liquid chromatography. A high concentration of linoleic acid and hyperthermia caused the increase in intracellular water and the decrease in osmotic resistance of the red blood cells. The present experiment demonstrated that unsaturated fatty acid was one of the principal chemical and metabolic factors which cause sports anemia.

Animals↗
PubMed1996

Promotive action of acylated ascorbate on cellular DNA synthesis and growth at low doses in contrast to inhibitory action at high doses or upon combination with hyperthermia.

Effects of 6-O-palmitoyl ascorbate (ascorbate) developed to increase the antitumour activity of ascorbic acid on DNA synthesis and proliferation of Ehrlich ascites tumour cells were investigated. Treatment of the cells with the acylated ascorbate at 25-50 microM for 1 h resulted in no effect on DNA synthesis, assayed by pulse incorporation of [3H]thymidine after a culture period of 20 h, but led to 49%-87% enhanced DNA synthesis after 4 days, suggesting that long-term culture is required for promotion by ascorbate to occur. At a dose as high as 75 microM acylated ascorbate, however, cellular DNA synthesis was 64% inhibited after 20 h and 99% after 4 days. The results suggest that acylated ascorbate exhibits a dual action on DNA synthesis: promotion at low doses and inhibition at high doses, both of which are potentiated in a time-dependent manner. In contrast to the above-mentioned results at 37 degrees C, acylated ascorbate at 25-75 microM inhibited but did not promote DNA synthesis at 42 degrees C whatever the culture period. Similar results were exhibited when proliferation of cells cultured for a long period was investigated. At 37 degrees C, 50 microM acylated ascorbate increased the number of the cells to 3.6 times the control values after 8 days and to 1.9 times after 11 days; in contrast, a 75-microM dose decreased the cell number considerably. Combination with hyperthermia (42 degrees C) suppressed the increase and cell growth was completely inhibited at 75 microM.

Acylation↗
PubMed1995

Experimental infection of SPF piglets with porcine reproductive and respiratory syndrome (PRRS) viruses isolated from two farms.

Porcine reproductive and respiratory syndrome (PRRS) viruses were isolated from pig samples obtained from two farms characterized by an increased number of stillbirth and high mortality in new-born piglets (farm A), and respiratory distress with high mortality in weaning and growing pigs (farm B) in 1993, respectively. When primary specific pathogen-free piglets, 5-day-old or 13-day-old, were experimentally inoculated with the isolates, they showed clinical signs of depress, anorexia, pyrexia, diarrhea, sitting posture and periocular edema. Rate of the weight gain was reduced in the inoculated piglets compared with the non-inoculated pig. There were no apparent differences in clinical signs between the piglets inoculated with the virus samples derived from farms A and B. Microscopically, the most prominent changes observed in experimentally inoculated piglets were interstitial pneumonia, nonpurulent myocarditis and catarrhal lymphnoditis post inoculation day (PID) 28. Viruses were recovered from tissues collected from the inoculated piglets on PID 7 or 28. Furthermore, the viruses were continuously recovered from the sera from PID 7 to PID 28. Antibodies measured by indirect immunofluorescence assay to PRRS virus were first detected in sera on PID 14, and the antibody titer rose to 1:1280 on PID 28.

Animals↗
PubMed1995

[Beta-adrenergic receptor-mediated changes in subcellular localization of G protein beta subunits in perfused rat hearts].

G proteins serve as transducers between cell surface receptors and intracellular effectors. They consist of three subunits, termed alpha, beta, and gamma. Recently, it has been recognized that the beta gamma subunits play an active role such as activation of beta-adrenergic receptor kinase (beta ARK). The desensitization and down-regulation of beta-adrenergic receptors have been observed in the heart failure. beta ARK is one of the components involved in desensitization of beta-adrenergic receptor and it is reported, recently, that G protein beta gamma subunits bind beta ARK through the pleckstrin homology domain. Therefore, we investigated the effects of beta-adrenergic receptor stimulation on steady-state level of G protein beta subunits (G beta) in the rat heart. The whole rat heart was preliminarily perfused for 10 min by Langendorff's technique at 60 mmHg of hydrostatic pressure with Krebs-Henseleit bicarbonate buffer, and then perfused for 30 min in the same buffer with or without 10 microM isoproterenol (ISO), 0.1mM epinephrine (EPI), 10 microM ISO with 0.1mM propranolol (PROP), or 10 microM ISO with 10 microM CGP20712A (CGP). Immunoblotting using isoform-specific antisera against G protein beta subunits revealed that the rat heart contains at least three G protein beta subunits, beta 1, beta 2 and beta 3 at molecular weight of between 35,000 and 37,000. The level of G beta 3 in the cytosol dramatically decreased in the presence of ISO alone or ISO with CGP. G beta 3 decreased in the presence of EPI as well. Propranolol could block ISO-induced decrease of G beta 3 in the cytosol. In contrast, the levels of G beta 1 and G beta 2 didn't change in the presence of ISO or EPI. On the other hand, in membrane fractions the level of G beta 3 significantly increased in the presence of ISO or EPI. ISO with PROP or ISO with CGP did not change the level of G beta 3 in membrane fractions. The levels of G beta 1 and G beta 2 did not change in the presence of ISO or EPI in membrane fractions. Taken together, beta-adrenoceptor agonist might induce isoform-specific translocation of G beta 3 from the cytosol to the membrane.

Animals↗