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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 631 records · Page 35Linked to original sources
PubMed1993

Carbamylcholine-induced morphological changes and spatial dynamics of [Ca2+]c in Harderian glands of guinea pigs: calcium-dependent lipid secretion and contraction of myoepithelial cells.

To determine whether lipid-secreting cells have cytosolic Ca2+ concentration ([Ca2+]c)-related secretory mechanisms, morphological changes and intracellular calcium dynamics of Harderian glands of guinea pigs stimulated by secretagogue were studied by electron microscopy and Fura-2/AM digital image analysis. Control glandular cells contained large lipid vacuoles that were bordered by multi-layered membranes. Rough-surfaced endoplasmic reticulum, mitochondria, and smooth-surfaced endoplasmic reticulum may be involved in lipid vacuole formation. Myoepithelial cells surrounded alveoli. After carbamylcholine (CCh, 10(-6), 10(-5), and 10(-3) M) stimulation, lipid materials within the membranous structures were frequently discharged by an exocytotic mechanism. Conspicuous deformation of glandular cells caused by vigorous contraction of myoepithelial cells was observed in isolated alveoli after 10(-6) M CCh stimulation, whereas the deformities of glandular tissues perfused via vessels were small even after 10(-3) M CCh stimulation. Connective tissue between glandular alveoli inhibited unbridled myoepithelial-cell contraction. Fura-2/AM digital imaging analysis revealed that CCh stimulation caused an increase in [Ca2+]c in isolated alveoli. The morphological reactions and changes in [Ca2+]c were prevented by atropine. When extracellular calcium ions were absent, enhanced extrusion of lipid vacuoles, myoepithelial-cell contraction, and a rise in [Ca2+]c after CCh stimulation were not observed. Nicotine and catecholamines had no effect on the secretion or on the dynamics of [Ca2+]c. It can be concluded that acetylcholine elicits exocytosis in glandular cells and contraction of the myoepithelial cells of Harderian glands, accompanied by an increase in [Ca2+]c. The dynamics of [Ca2+]c of the gland alveoli are mostly dependent on extracellular Ca2+.

Animals↗
PubMed1993

The enhancement of catecholamine-induced Cl- current by cyclic GMP revealed using photolabile caged compounds in guinea-pig ventricular cells.

Whole cell currents were recorded in single myocytes dissociated from guinea-pig ventricles, and caged compounds were loaded intracellularly through the patch electrodes. Flash photolysis of caged cyclic GMP (cGMP) increased the amplitudes of both catecholamine-induced Cl- (ICl) and Ca2+ currents (ICa) which were pre-activated by submaximum doses of isoprenaline. Transient activation of ICl by photo-release of cyclic AMP (cAMP) showed a half decay time (t1/2) of 16.7 +/- 1.4 sec (mean +/- S.E.M., n = 14). This decay was markedly delayed by inhibiting phosphodiesterases using 3-isobutyl-1-methyl-xanthine (IBMX). The intracellular application of cGMP (10-50 microM) also prolonged the decay of the ICl response to caged cAMP (t1/2 = 38.0 +/- 7.1 sec, n = 12). These findings strongly support the hypothesis that cGMP facilitates the beta-adrenergic response of ionic currents through the inhibition of phosphodiesterase in mammalian cardiac myocytes.

Animals↗
PubMed1993

Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5.

A male infant with partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5 (46,XY,rec(5), dup q,inv(5)(p15.1q35.1)pat) is reported together with the oral findings. The phenotype was chiefly the cri-du-chat syndrome. Severe retardation of mental and motor development, microencephaly, cardiac malformation, crying and facial appearance unique to the cri-du-chat syndrome were observed. Perioral and intraoral findings included thin upper lip, down-turning corners of mouth, micrognathia, shallow palate, and cleft of soft palate. Anterior deciduous teeth were small and canine deciduous teeth were conic. The row of deciduous teeth showed a flat arch-like shape that was very wide but short in length. No abnormality was noted in the number of deciduous teeth or the timing of eruption.

Adult↗
PubMed1993

Elevation of the extracellular glutamate concentration in the hippocampus after total cerebral ischemia related to the deterioration of the recovery in EEG and evoked potentials in dogs.

The concentrations of extracellular glutamate (Glu), aspartate (Asp) and glycine (Gly) were measured by microdialysis method in the cortex and hippocampus before, during and after 15 min of total cerebral ischemia in dogs. The correlations between the concentrations of amino acids and the changes in EEG and evoked potentials (EP) after ischemia were evaluated. Total cerebral ischemia was achieved by occluding the ascending aorta and the caval veins. The concentrations of Glu in the hippocampus significantly increased from 1.73 +/- 0.59 (mean +/- SEM) nmol.ml(-1) at pre-ischemia to 5.46 +/- 1.34 (P < 0.05) during ischemia and 14.37 +/- 3.70 (P < 0.01) 0-15 min after ischemia, and returned to the pre-ischemic level 30 min after ischemia. The concentration of hippocampal Glu 0-15 min after ischemia had significant negative correlations with the EEG-EP scores (0 = serious deterioration of electrical function and 6 = normal electrical function) 30 min, 3 hr and 5 hr after ischemia (r = -0.69, P < 0.05 : r = -0.67, P < 0.05 : r = -0.70, P < 0.05, respectively). The increase of the extracellular Glu concentration in the hippocampus immediately after ischemia may aggravate the neurological outcome after total cerebral ischemia.

Journal Article↗
PubMed1993

Alkaline phosphodiesterase I release from eucaryotic plasma membranes by phosphatidylinositol-specific phospholipase C. III. The release from tumor cells.

1. Alkaline phosphodiesterase I release from two tumor cell lines, KB III or AH-130 cells, by the action of phosphatidylinositol-specific phospholipase C (PIPLC) of Bacillus thuringiensis was studied. 2. A significant amount of alkaline phosphodiesterase I was released from both the cell suspension and homogenate of KB III cells, but not from AH-130 cells. 3. The release of the enzyme from KB III cells was dependent on, or proportional to, the reaction time and the PIPLC or cell concentrations. 4. Alkaline phosphatase and 5'-nucleotidase were also released from KB III cells, while gamma-glutamyl transpeptidase and dipeptidyl peptidase IV were not solubilized. The enzyme release by the action of PIPLC was suppressed when purified anti-PIPLC antibody was added to the reaction mixture. This suggests that the enzyme release must be due to the direct action of PIPLC on KB III cells. 5. The alkaline phosphodiesterase I released from KB III cells had a mol. wt of 240,000 and was activated by Mg2+, but strongly inhibited by EDTA and thiol reagents and by 5'-nucleotide-containing compounds. Although KB III cells were derived from Homo sapiens tumor, the released alkaline phosphodiesterase I appeared to be very similar to enzymes obtained from normal tissues of Rattus norvegicus.

5'-Nucleotidase↗
PubMed1993

Immunological analysis of the rats with anterior hypothalamic lesions.

We have previously identified the suppression of lymphocyte blastogenesis and the acceleration of growth of subcutaneous tumors by bilateral anterior hypothalamic lesions in rats. The present study was performed to clarify the changes in lymphocyte subsets and natural killer (NK) activity after making the lesions. The influence on immunological memory was also studied. The CD4/CD8 ratio of peripheral blood lymphocytes and spleen cells, T cell receptor alpha beta-positive cells of the thymocytes and NK activity of the spleen cells decreased significantly. Major histocompatibility complex (MHC) antigen expression on RBL-1 cells injected intraperitoneally into pre-immunized rats was also suppressed. These results suggest that the anterior hypothalamus has some influences on the control of the cellular immunological functions at the peripheral level, on the maturation of T cells at the level of thymus and on the antigen recognition by T cell receptors and MHC antigens.

Animals↗
PubMed1993

Radiosensitization of SCCVII tumours and normal tissues by nicotinamide and carbogen: analysis by micronucleus assay.

The radiosensitizing effect on SCCVII tumours of carbogen (95% O2 + 5% CO2) combined with nicotinamide was investigated using the micronucleus assay and an in vivo/in vitro colony formation assay following single irradiation. The effects on intestinal crypt cells and bone marrow cells were also examined in mice. The frequency of micronuclei in tumours increased with an increase in the nicotinamide dose (administered 1 h before the irradiation of 5 Gy) from 0.1 to 1.0 mg/g, and showed a 1.3-fold increase at 1.0 mg/g when compared with radiation alone. The micronucleus frequency showed a more marked increase following irradiation combined with nicotinamide and carbogen inhalation starting 15 min before irradiation. The radiosensitizing effect reached a plateau at a nicotinamide dose of 0.1 mg/g in combination with carbogen, giving an enhancement ratio (ER) of 1.8 relative to radiation alone at 2 Gy. In the radiation dose range of 5-20 Gy, ERs of 1.8-1.9 and 1.5 (at a 10% cell-survival level) were obtained for the combination of 0.1 or 1.0 mg/g nicotinamide and carbogen and for carbogen alone, respectively. A slight increase in the regeneration response of the jejunum and the bone marrow was observed following irradiation combined with 0.1 mg/g nicotinamide and carbogen, yielding ERs of 1.07 for the jejunum and 1.15 for the bone marrow. Thus, the nicotinamide/carbogen combination, with its large therapeutic gain factor at low doses and proven low toxicity in humans, seems to improve the response of cancer to radiotherapy.

Animals↗
PubMed1993

Neurite outgrowth from N18TG2 neuroblastoma induced by H-7, a protein kinase inhibitor, in the presence of colchicine.

Our previous studies have demonstrated that the protein kinase inhibitor H-7 promotes neurite outgrowth from mouse neuroblastoma N18TG2 cells as well as from primary cerebellar cells, and also that the neurites induced by H-7 were more tolerant of colchicine (COL) than those induced by dibutyryl cAMP (dB-cAMP). In the present study, we tested the effects of H-7 and dB-cAMP on neurite growth from N18TG2 cells in the presence of COL. We found that only H-7 promoted neurite formation in the presence of COL. The percentage of cells with neurites induced by H-7 in the presence of COL (H-7 + COL) was similar to that induced by H-7 alone. The neurites induced by H-7 + COL grew straight. They were very thin (less than 1 micron in diameter) and had round varicosities, as did the neurites induced by H-7 alone. By transmission electron microscopy, the neurites induced by H-7 + COL were found to contain longitudinally arranged intermediate filaments (IF). Microtubules (MT) were not observed within the neurites. We also examined the effect of cytochalasin B (CB) on the neurites induced by H-7 + COL and by H-7 alone. The neurites induced by H-7 + COL were tolerant to CB, but those induced by H-7 were resorbed completely within 24 h after CB was applied. Neurites tolerant to CB contained longitudinally IF. Simultaneous application of CB with H-7 + COL or with H-7 alone did not induce neurite formation.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system.

N-CAM is abundantly expressed in the nervous system in the form of numerous structural variants with characteristic distribution patterns and functional properties. N-CAM-180, the variant having the largest cytoplasmic domain, is expressed by all neurons. The N-CAM-180-specific exon 18 has been deleted to generate homozygous mice unable to express this N-CAM form. The most conspicuous mutant phenotype was in the olfactory bulb, where granule cells were both reduced in number and disorganized. In addition, precursors of these cells were found to be accumulated at their origin in the subependymal zone at the lateral ventricle. Analysis of the mutant in this region suggests that the mutant phenotype involves a defect in cell migration, possibly through specific loss of the polysialylated form of N-CAM-180, which is expressed in the migration pathway. Subtle but distinct abnormalities also were observed in other regions of the brain.

Actins↗
PubMed1993

Determination of the target volume of HeLa cells treated with platinum-195m radiolabeled trans-diaminedichloroplatinum(II): a comparison with cis-diaminedichloroplatinum(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled trans-diaminedichloroplatinum(II) (TDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with TDDP at 37 degrees C for 1, 2 and 3 h were 163.7, 65.8 and 24.9 microM, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules was determined after the cells were fractionated using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes, expressed as the reciprocals of the D0 values, were calculated for each fraction. The results suggested that DNA and high molecular weight RNAs (except t-RNA), under some limited condition, could be the target molecules for cell killing by TDDP. The target volumes for DNA were 1.31 x 10(3), 3.01 x 10(3) and 6.26 x 10(3) nucleotides for 1, 2 and 3 h treated cells, respectively. Cell killing effects of TDDP were lower than CDDP by a factor of 39.5, 19.0 and 16.5 for 1, 2 and 3 h treatments at 37 degrees C, respectively, when viewed from the stand point of the target volume, while those from the mean lethal dose (D0) were 17.6, 9.8 and 6.7, respectively.

Cell Survival↗
PubMed1993

Effects of retinoic acid on steroid and vitamin D3 receptors in cultured mouse osteosarcoma cells.

The effect of retinoic acid (RA) on the expression of osteoblast-related genes as well as on steroid/vitamin D3 receptor contents was examined using cultured osteosarcoma cell line (BFO cells). Northern blot analysis revealed that mRNAs encoding osteocalcin, pro-alpha 1 (I) collagen and bone morphogenetic protein 4 (BMP-4) are expressed in BFO cells. Stimulation with RA, however, failed to alter their mRNA content, although the transcripts for retinoic acid receptor (RAR)-alpha and -gamma were present in BFO cells. In addition, alkaline phosphatase activity (AP) was significantly but modestly increased by RA treatment. These results suggest BFO cells have well differentiated osteoblastic properties. In contrast to the effects of RA on osteoblast-related gene regulation, RA was found to increase the quantity of estrogen receptor as well as of 1,25-dihydroxy vitamin D3 receptor (VDR) in BFO cells. The quantities, assessed by ligand binding assays, were approximately 200% more than those of the controls after 24 h stimulation with 10(-9)-10(-8) M RA. These RA effects on ER and VDR seem to be specific, since glucocorticoid receptor quantities were not affected by RA treatment. These results suggest that RA regulates ER and VDR quantities in BFO cells.

Alkaline Phosphatase↗
PubMed1993

Effect of fixation conditions on the granule morphology of rat antral gastrin cells: an ultrastructural and immunocytochemical study.

After fixation at pH = 7 or pH = 5 the gastrin (G) cells in the rat pyloric antrum were investigated by conventional and immunoelectron microscopy. After fixation at pH = 7 G cells contained numerous electron-lucent granules, a few electron-dense and intermediate granules while G cells had numerous electron-dense and intermediate granules, and a few electron-lucent granules after fixation at pH = 5. Preembedding immunoelectron microscopy revealed that in G cells after fixation at pH = 7, gastrin immunoreactivity was mainly seen in the cytoplasm, cores of a few electron-dense and intermediate granules and in the periphery but not within the numerous electron-lucent granules; in G cells after fixation at pH = 5, gastrin immunoreactivity was mainly visible in the cores of numerous intermediate and electron-dense granules, in the periphery of a few electron-lucent granules, but weakly in the cytoplasm. Therefore, the variable electron density of G cells may reflect differences in the degree of the leakage of contents from the gastrum-containing granules into the cytoplasm during fixation. This phenomenon may be related to the acidity of the granule substances during intragranular maturation.

Animals↗
PubMed1993

Elevated plasma fibronectin concentrations in patients with ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum.

Fibronectin is a glycoprotein involved in a wide variety of cellular activities, including the development of bone tissues. To study the relevance of fibronectin to the development of ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF), plasma fibronectin concentrations in 30 consecutive patients with OPLL or OLF and 20 age-and-sex-matched control subjects were measured with an immunonephelometric method. Plasma fibronectin concentrations were significantly elevated in the patients with OPLL or OLF, independently of associated endocrinologic abnormalities, when compared with the control subjects. Because fibronectin is one of the essential factors in endochondral ossification, it is probable that the higher fibronectin concentration in plasma acts as a promoter of the development of OPLL and OLF.

Causality↗
PubMed1993

Antimetastatic activity of polymeric RGDT peptides conjugated with poly(ethylene glycol).

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n = 2 to 4), at a dose of 500 micrograms exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and anti-metastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis ("anti adhesion therapy").

Amino Acid Sequence↗