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Biomedical subjects

K Mizukawa

Publications and source records attributed to K Mizukawa.

At least 19 recordsLinked to original sources
PubMed1997

Possible involvement of free radical scavenging properties in the action of tumor necrosis factor-alpha.

Constitutive production of hydroxyl radicals from four established cancer cell lines was detected as spin adducts of 5,5-dimethyl-l-pyroline-N-oxide (DMPO), using an electron spin resonance spectrometer. The generated hydroxyl radicals was decreased in three out of four cancer cell lines when incubated in vitro for 3 h with TNF-alpha No direct scavenging effect of TNF-alpha on hydroxyl radicals or superoxide anions was observed in the in vitro radical generation system. The modulation of intracellular reactive oxygen species of these cancer cells by adding menadione or CuDIPS to the culture medium changed the antiproliferative effect of TNF-alpha on the cells. The ultrastructural localization of the radical-generating sites in cancer cells was visualized using the diaminobenzidine/horseradish peroxide histochemical system at the electron microscopic level. The hydrogen peroxide-dependent formation of electron-dense materials localized at the mitochondrial membranes was decreased after the treatment of the cancer cells with TNF-alpha. These data indicate that the reduction of radical generation in cancer cells by TNF-alpha may be an early mechanism that contributes to the antiproliferative effect of this cytokine on some cancer cells.

Cell Division↗
PubMed1997

[Highly reproducible technique for the estimation of trabecular bone density: three slice method on peripheral quantitative CT].

The reproducibility of bone mineral density (BMD) measurements with peripheral quantitative CT has been limited by the repositioning error. In this study, 1 mm-step 3-slice scan data were used to compensate for this error in trabecular BMD of the distal radius. The assessment was based on the liner relations between the cross-sectional area and trabecular bone mineral content and trabecular area ratio, on the condition that the trabecular bone is defined by a BMD value. The estimated reproducible errors of less than 2% under clinical conditions indicate that the method is reliable for follow-up examination.

Adult↗
PubMed1996

Changes in cellular ultrastructure induced by gamma-interferon in K562 cells may be prerequisite for apoptosis.

We report here the time-course of electron microscopic changes induced by gamma-interferon (IFN-gamma) in the human erythromyeloid leukemia cell line K562. In K562 cells treated with IFN-gamma for 6h, the nuclei were polygonal in shape and microvilli were far more abundant on cell membranes compared with control K562 cells, and invaginations were often seen in the cell membranes. There was a reduction in the number of cell-membrane microvilli and an increase in the number of lysosomal bodies in the cytoplasm of K562 cells treated with IFN-gamma for 12h. After treatment with IFN-gamma for 24h, the cell membrane microvilli disappeared, large numbers of cellular organelles were observed, such as mitochondria and lysosomes, and the cytoplasm became electron-dense. Cytoplasmic vesicles and vacuoles were also observed. These vesicles may correspond to an intermediate step in the ultimate cellular disintegration associated with apoptosis caused by IFN-gamma.

Apoptosis↗
PubMed1995

Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713 prevents delayed neuronal death in the gerbil hippocampus.

We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries after light ether anesthesia. Pyramidal cells had been decreased to 27% of sham-operated controls and the number of hypertrophic astrocytes expressing glial fibrillary acidic protein (GFAP) markedly increased in the hippocampal CA1 subfield 14 days after ischemia. However, post-ischemic administration of ENA-713 (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced decrease in the number of pyramidal cells by 47% of sham-operated controls, furthermore, it reduced the ischemia-induced accumulation of GFAP-positive astrocyte in the CA1 region. Together with previous results showing that ENA-713 protected against the ischemia-induced cholinergic abnormalities in the gerbil brain and improved cholinergic dysfunctions in the senescent rat brain, our present findings suggest that ENA-713 prove to be useful for treatment with senile dementia such as cerebrovascular dementia.

Animals↗
PubMed1995

Adhesion of composite to porcelain with various surface conditions.

This study evaluated the adhesion of composite resin to five different surface conditions of porcelain samples that were treated with three kinds of silane agents. Two of these were commercially available Porcelain Liner M and Tokuso Ceramic Primer, and one was an experimental agent. The commercially available silane agents gave high bond strengths without hydrofluoric acid etching, which gave the greatest roughness on the porcelain surface. One component of these commercially available silane agents was gamma-methacryloxypropyl trimethoxysilane, and the other was the carboxylic acid. As a result of the effective formation of siloxane bonds by mixing with acid solution, porcelain surface conditions did not affect the bond strengths.

Analysis of Variance↗
PubMed1995

Retrieval of a migrated detachable coil--case report.

A 74-year-old female presented with intraventricular and subarachnoid hemorrhage due to probable rupture of a basilar artery (BA) aneurysm or a superior cerebellar artery (SCA) aneurysm. She was treated by endovascular therapy using detachable coils through the BA. The BA aneurysm was completely occluded, but part of a coil migrated into the BA from the SCA aneurysm during the procedure. The migrated coil was retrieved using a snare type endovascular retrieving device. The snare loop required concentric closure around the coil by simultaneous pulling of the corewire and a slight forward movement of the tip of the snare catheter. The SCA aneurysm was successfully occluded 1 week later using a shorter coil.

Aged↗
PubMed1994

Limited diffusibility of gene products directed by a single nucleus in the cytoplasm of multinucleated myofibres.

Two types of beta-galactosidase genes, whose products are distributed in the nucleus (N beta-gal) or cytoplasm (C beta-gal), were injected with fructose intramuscularly into the quadriceps of adult mice. Regionally restricted and overlapped distributions of both gene products were observed in the myofibres. These findings indicate that N beta-gal is incorporated into the nucleus responsible for its synthesis and that C beta-gal becomes located in the vicinity of the nucleus after its synthesis. This restricted location of C beta-gal in myofibres remained unchanged during the development of infant mouse muscle. Thus, the gene products directed by the nucleus of myofibres seem to show limited diffusibility, suggesting a universal localization of subcellular domains in myofibres.

Animals↗
PubMed1994

Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia.

The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia.

Acetylcholine↗
PubMed1994

Striatal grafts in infarct striatopallidum increase GABA release, reorganize GABAA receptor and improve water-maze learning in the rat.

We grafted fetal striatal cells in ischemic rat models, and investigated graft survival/growth, GABA release, GABAA receptor reorganization and functional recovery. One hour intraluminal occlusion of the middle cerebral artery (MCA) induced ischemic infarct in the lateral part of the striatum and adjacent cortex. In ischemic rats, the acquisition of Morris' water-maze learning was significantly slower than that of control rats. In these animals GABA level in the globus pallidus, detected by microdialysis, was about the half of that of controls. However, after the grafts of fetal striatal cells in the striatopallidum, the acquisition was improved, thus no difference was observed in the time course of learning curves in control and grafted animals. GABA level recovered to almost normal level by the graft. It further increased by the treatment of a GABA uptake blocker (nipecotic acids) in the perfusion. In the grafts, GABAA receptor organization detected by autoradiography using [3H] labeled SR95531 was restored for more than 1 year after the graft. Data suggest that fetal striatal cell grafts in infarct striatum may partially reconstruct striatopallidal GABA projection and reorganize GABAA receptor. This might be a basis of improvement of function.

Animals↗
PubMed1994

Atrial natriuretic polypeptide (ANP)-immunoreactivity and specific atrial granules in cardiac myocytes of stroke-prone spontaneously hypertensive rat (SHRSP).

The distribution of atrial natriuretic polypeptide (ANP) and atrial specific granules in the myocytes of the atria and ventricles of an experimental animal model, stroke-prone spontaneously hypertensive rats (SHRSP) and a control, Wistar Kyoto rats (WKY), was examined using immunocytochemical and electron microscopic techniques. In the atria of both SHRSP and WKY, ANP-immunoreactivity was recognized in the perinuclear regions of essentially all cardiac myocytes. In the ventricles of WKY, ANP-immunoreactivity was hardly seen except for the impulse-conducting system. However, in the ventricles of SHRSP, almost all cardiac myocytes possessed immunoreaction products which were scattered evenly throughout the cytoplasm; this distribution pattern differed from that of the atrial wall of this strain.

Animals↗
PubMed1993

The preventive effect of cyclosporin A, an immunosuppressant, on the late onset reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischemia.

We previously reported that a late onset reduction of muscarinic acetylcholine receptors (LORMAR) occurs in the gerbil hippocampus after 5 min of transient ischemia. This reduction begins as late as 7 days post-ischemia and accompanies the accumulation of glia, but is subsequent to completion of the disappearance of CA1 pyramidal cells. In the present study, we showed that this LORMAR was prevented by daily post-ischemic administration of the immunosuppressant cyclosporin A (CsA). The effectiveness of CsA against the LORMAR indicates that an immune mechanism may be involved in the progressive brain damage occurring after transient ischemia.

Animals↗
PubMed1993

A cerebral ischemia model produced by injection of microspheres via the external carotid artery in freely moving rats.

We produced an improved microembolism model of cerebral focal ischemia by injection of 1000-2000 microspheres (50 +/- 5 microns diameter) via a tube retrogradely inserted into the right external carotid artery in freely moving rats. The group injected with 2000 spheres showed a much more severe mortality rate as well as neurological signs than did the 1000-sphere group. Brain water content of the 2000-sphere group was examined and found to show an increase from 4 to 24 h after embolization in the right hemisphere, indicating serious brain edema. Severe neurological signs and individual deaths by embolization were most likely related to the extent of development of brain edema. Examination of learning behavior by shuttle-box avoidance revealed partial but significant impairment of learning in the 1000-sphere group. Autoradiographic studies for muscarinic acetylcholine receptors and protein kinase C binding sites were conducted. Both these binding sites decreased in number, but protein kinase C seems to be more susceptible to ischemic injury than muscarinic acetylcholine receptors. The observation was considered to be closely related with an impairment of learning. The present study suggests that our microembolism model in freely moving rats is useful for investigations of the early phase and late phase of cerebral ischemia.

Animals↗
PubMed1993

Differing roles of protein kinase C on the signal transduction of tumour necrosis factor-alpha and -beta on PANC-1 cells: in vitro autoradiographic investigation.

We investigated alterations in protein kinase C (PKC) activity of PANC-1 cells following treatment with tumour necrosis factor (TNF)-alpha or TNF-beta by an in vitro autoradiographic method. Binding studies performed on whole cells using [3H]phorbol-12,13-dibutyrate (PDBu) as a ligand revealed strong activation of PKC by TNFs within 30 min. The effect was similar to that seen after 30 min treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). After treatment for 24 h, TNF-beta caused a marked down-regulation of PKC similar to that seen after 24 h treatment with TPA; significant activation persisted, however, in the cells treated for 24 h with TNF-alpha. Our data suggest that PKC activation may play a more important role in the TNF-alpha signal transduction pathway than in that of TNF-beta.

Autoradiography↗
PubMed1993

Swinglock removable partial denture and biting forces in partially edentulous patients. Comparison of individual biting forces with and without swinglock removable partial denture.

Several studies have shown that swinglock removable partial dentures are effective for stability of the abutment teeth and the surrounding tissues including alveolar bone. This efficacy has been thought to be due to the dynamic structure of the swinglock attachment. Individual biting force was measured to determine the physiological efficacy of teeth splints by use of the attachment. The results showed that individual biting forces with the swinglock removable partial denture were 10-25% higher than those without the denture. Furthermore, statistical analysis showed that the individual biting forces with the swinglock removable partial denture were significantly higher. The swinglock attachment can stabilize partially edentulous dentition by splinting all residual teeth. In addition, when physical forces are applied to the abutment teeth and the artificial teeth, this attachment can deliver and distribute the stress to the other abutment teeth and alveolar mucosa. The present findings suggest that the swinglock attachment augments the ability to withstand physical forces such as those occurring during biting and mastication.

Bite Force↗
PubMed1992

Post-ischemic administration of bifemelane hydrochloride prohibits ischemia-induced depletion of the muscarinic M1-receptor and its mRNA in the gerbil hippocampus.

Parallel determinations of muscarinic cholinergic M1 receptor (M1-R) binding and of M1-R mRNA levels were carried out in the gerbil hippocampus 14 days after 5 min of transient ischemia. Both were reduced in the ischemic tissue to about 50% of the levels found in sham-operated controls, indicating that the late loss of M1-R is probably dependent on decreased synthesis. Three administrations of bifemelane hydrochloride (15 mg/kg, i.p., just after ischemia and 6 and 12 h later) completely prevented neuronal death in the hippocampus and ischemia-induced losses of hippocampal M1-R and its mRNA. Since vascular dementia may depend upon the ischemia-induced losses in cholinergic communication in the hippocampus, these findings suggest that it may be possible to prevent its occurrence by post-ischemic treatment with bifemelane hydrochloride.

Animals↗
PubMed1992

Abnormal expression of embryonic neural cell adhesion molecule (N-CAM) in the developing mouse cerebellum after neonatal administration of cytosine arabinoside.

We have previously found that neonatal administration of cytosine arabinoside (Ara-C) induces cerebellar malformation, including arrest of granule cell migration and destruction of glial palisade. In the present study, the expression of neural cell adhesion molecule (N-CAM) and its distribution were examined in the mouse malformed cerebellum induced by neonatal Ara-C administration. Western blot analysis demonstrated that, in the control group, the embryonic form of N-CAM (E-N-CAM) was expressed in the 7-day-old mouse (P7) cerebellum, but not in the P14 cerebellum which exhibited only the adult form of N-CAM (A-N-CAM). On the other hand, E-N-CAM was expressed in the Ara-C treated cerebellum not only at P7 but also at P14. Immunohistochemical studies revealed that E-N-CAM was observed in the area below the external granular layer (EGL) of the P7 cerebellum in both the control and Ara-C treated mice. In contrast, E-N-CAM immunoreactivity was found in the arrested EGL cells in the Ara-C treated cerebellum of P14 mice but not in the age-matched controls. Therefore, E-N-CAM was aberrantly expressed in the arrested EGL at P14. From the present and previous findings, it was speculated that the aberrant expression of E-N-CAM in the arrested EGL cells is attributed to abnormal cellular interactions, probably arrested EGL cell-to-Bergmann glia.

Animals↗