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Biomedical subjects

K Namikawa

Publications and source records attributed to K Namikawa.

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

Discordant expression of c-Ret and glial cell line-derived neurotrophic factor receptor alpha-1 mRNAs in response to motor nerve injury in neonate rats.

Adult motoneurons can survive following axotomy, whereas neonate motoneurons result in cell death. Following hypoglossal nerve axotomy in neonate rat, Glial cell line-Derived Neurotrophic Factor (GDNF) receptor alpha-1 (GFRalpha-1) mRNA expression was dramatically suppressed in the injured motoneurons, while a slight increase of c-Ret mRNA expression was observed. In adult, both GFRalpha-1 and c-Ret mRNAs increased substantially after axotomy. The present result suggests that the difference of motoneuron fate after axotomy may be partly due to the coordinate or discordant responses of GFRalpha-1 and c-Ret expression to nerve injury.

Aging↗
PubMed1999

Expressed-sequence-tag approach to identify differentially expressed genes following peripheral nerve axotomy.

Gene expression profiles in the rat hypoglossal nucleus after axotomy were demonstrated using expressed-sequence-tag (EST) approach. To demonstrate the gene-expression profiles after axotomy, nerve-transected hypoglossal nuclei were dissected and collected from about 1000 rats, with which a cDNA library was constructed. More than 750 clones were sub-cloned and sequenced from the library. The clones which hit frequently are likely to be associated with mitochondrial respiratory chain, cytoskeletal protein and protein synthesis. One hundred three clones from among the sequenced clones were further processed for histological screening using unilateral-hypoglossal nerve-transected brain sections by in situ hybridization histochemistry. In situ hybridization study revealed that 26% of clones examined showed upregulated expression of mRNA in response to axotomy. They included genes encoding proteins associated with glucose, lipid and protein metabolism, cytoskeleton, neurotransmission and immune reaction. The present EST analysis may have an advantage in targeting genes which are associated with nerve injury with a good efficacy, as compared with other methods such as differential display and subtraction.

Animals↗
PubMed1999

[Effects of allopurinol for oxidative injury of cisplatin-induced nephrotoxicity in mice].

The effects of allopurinol (Allop) on the lipid peroxidation in the nephrotoxicity of an antitumor drug, cisplatin (CDDP) were studied in mice. CDDP was administered intraperitoneally to two groups (CDDP + Allop group and CDDP + CMC-Na group) at single doses of 10 mg/kg, and mice were sacrificed 3 days after CDDP administration. The body weights of the CDDP-administered group gradually decreased to approximately 78% of the values of the control group (saline + Allop group and saline + CMC-Na group) within 3 days. Plasma urea nitrogen and creatinine, especially in the CDDP + Allop group, increased after 3 days. Lipid peroxides in the blood and kidney were monitored by measuring the production of malondialdehyde (MDA), which increased in the CDDP + CMC-Na group. On the other hand, MDA levels in the CDDP + Allop group increased in the kidney but remained unchanged in the blood. Changes were observed in tissue glutathione (reduced form, GSH; oxidized form, GSSG) levels in the CDDP + Allop group but not in the CDDP + CMC-Na group. Histomorphological examination demonstrated the degeneration of the proximal tubuli in the CDDP-administered groups. Especially in the CDDP + Allop group, the increase of mesangium cells in the glomeruli was observed. From these results, it was suggested that Allop was not able to inhibit CDDP-induced lipid peroxidation in the kidney, and the kidney function became more severely impaired by the administration of Allop.

Allopurinol↗
PubMed1999

Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons.

Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression.

Adenoviridae↗
PubMed1998

Up-regulation of thioredoxin expression in motor neurons after nerve injury.

A substantial up-regulation of thioredoxin, a dithiol/disulfide oxido-reductase, in adult rat motoneurons following hypoglossal nerve axotomy, was demonstrated by using both in situ hybridization and immunohistochemistry. Although thioredoxin is normally accumulated more in the nucleus of a motoneuron rather than in the cytoplasm, a dramatic increase of thioredoxin in the cytoplasmic region after nerve injury was observed. The up-regulation of mRNA lasted more than 9 weeks, whereas, the detectable up-regulation of protein was observed for more than 5 weeks.

Animals↗
PubMed1998

Effect of the lipid peroxide reaction caused by repeated cold stress on cisplatin-induced nephrotoxicity.

The peroxide reaction in mouse kidney was examined in order to determine the relationship between the lipid peroxide reaction caused by SART (specific alternation of rhythm in temperature) stress and that caused by drug administration. After exerting SART stress for one wk on 6-wk-old male ddY mice (stress group), the peroxide reaction generated by the administration of a single dose of cis-diamminedichloroplatinum (cisplatin: CDDP, 10 mg/kg, i.p.) into SART-stressed mice (stress + CDDP group) was compared with the reaction of CDDP-administered nonstressed mice (CDDP group), saline-administered nonstressed mice (saline group), and saline-administered SART-stressed mice (stress + saline group). Lipid peroxidation in the kidneys was significantly higher in the stress group upon cessation of stress exertion than in the normal group. However, no significant difference in the lipid peroxide level after administration of CDDP was observed between the CDDP groups. The renal glutathione levels were significantly different between the CDDP groups and the saline administered groups. These results indicate that the peroxide reaction is generated in the kidneys by stress, but stress has no effect on the peroxide damage caused by CDDP administration. However, the contribution of stress to renal function impairment requires further evaluation.

Animals↗
PubMed1998

Enhanced expression of 14-3-3 family members in injured motoneurons.

An increase in 14-3-3 mRNA expression after hypoglossal nerve injury was demonstrated by RNA finger printing using the arbitrary primed polymerase chain reaction (RAP-PCR). RAP-PCR was carried out to compare differences in mRNA expression between axotomized (6 h after the transection) and normal hypoglossal nuclei in mice. The expression of several gene fragments was increased after nerve injury; one fragment was identified as 14-3-3 which is an activator of Raf-1. Since a family of 14-3-3 genes are identified in the rat, we examined the expression of five members of the rat 14-3-3 family after injury (beta, gamma, zeta, eta and theta). Among these family members, a substantial up-regulation in mRNA expression was observed for the zeta and θ forms. Subsequent emulsion autoradiography of hybridization tissue sections revealed an increase in zeta and theta mRNA in injured motoneurons. Since 14-3-3 has the ability to dimerize and activate Raf-1, the up-regulation of 14-3-3 expression would be expected to facilitate the Ras-Erk signal pathway by Raf-1 activation. Our previous results have demonstrated that Shc, Erk1 and Mek1 mRNAs are up-regulated during nerve regeneration, whereas PKA which inhibits the Ras-Erk pathway via Raf-1 was down-regulated. Taken together, the present results suggest that enhancement in expression of molecules involved in the Ras-Erk signaling is required for peripheral nerve regeneration.

14-3-3 Proteins↗
PubMed1998

Enhancement of extracellular glutamate scavenge system in injured motoneurons.

An increase in glutamine synthetase (GS) mRNA expression after peripheral motor nerve injury was demonstrated by differential display PCR using single arbitrary primer coupled with in situ hybridization screening called in situ display. Differential display PCR was carried out to compare differences in mRNA expression between axotomized (6 h after the transection) and normal hypoglossal nuclei in mice. Several gene fragments were increased after nerve injury; one was identified as GS. Subsequent emulsion autoradiography of hybridization tissue sections revealed that the increase in GS mRNA was observed in injured motoneurons. As GS is a key enzyme participating in the metabolism of the major excitatory neurotransmitter glutamate, we examined the significance of increased GS expression on glutamate-uptake kinetics. GS-transfected human embryonic kidney cells showed an up-regulation in glutamate-uptake kinetics. Therefore, newly expressed GS together with an increased expression of the neuronal glutamate transporter EAAC1 in the injured motoneurons accelerates glutamate uptake. The present results may suggest that the glutamate-uptake system involving the neuronal glutamate transporter and GS in injured neurons is enhanced so as to provide resistance against neurotoxic glutamate accumulation during the early process of nerve regeneration.

Animals↗
PubMed1997

5,6-Cis-penems: broad-spectrum anti-methicillin-resistant Staphylococcus aureus beta-lactam antibiotics.

5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-binding protein 2a of MRSA and to form stable acyl intermediates with beta-lactamases by blocking the deacylating water molecule.

Anti-Bacterial Agents↗
PubMed1997

X-ray reflectivity at the L edges of Gd.

Preparations are underway for the experimental investigation of the roughness of magnetic interfaces in rare-earth multilayers by combining the grazing-angle X-ray scattering technique with the resonant magnetic scattering of hard X-rays. Theoretical considerations show that for small scattering angles, 2theta, the asymmetry ratio, A = [I(+) - I(-)]/[I(+) + I(-)], depends on 2theta and varies as 1/cos theta. The first step towards the goal of determining the magnetic roughness has been taken by measuring the chemical roughness (via specular reflectivity) of a Gd thin-film sample at five photon energies close to the L(3) absorption edge, which yielded the dispersion corrections, f' and f'', to the Gd atomic form factor in good agreement with the calculation of Cromer & Liberman [J. Chem. Phys. (1970), 53, 1891-1898].

Journal Article↗
PubMed1997

Differential display reveals transcriptional up-regulation of the motor molecules for both anterograde and retrograde axonal transport during nerve regeneration.

RNA fingerprinting using an arbitrary primed polymerase chain reaction was carried out to compare differences in expression of mRNAs between axotomized and normal hypoglossal motoneurons in the mouse. In this survey, the kinesin light chain (KLC) was identified as a nerve injury-associated molecule. This was also confirmed by in situ hybridization using hemihypoglossal nerve-transected brain sections. In order to identify the exact species of molecules belonging to the KLC family, in situ hybridization was carried out with oligonucleotide probes specific to rat KLC A, KLC B and KLC C, using the rat hypoglossal nerve injury model. In addition, expression of both ubiquitous and neuron-specific kinesin heavy chain and cytoplasmic dynein which is a retrograde motor, was also examined. Expression of all the members of the KLC (A-C) family and dynein was up-regulated during nerve regeneration, whereas the abundant expression of the neuron-specific KHC mRNA was not changed. The present results indicate that the molecules associated with both anterograde and retrograde axonal transport are up-regulated in their expression during efferent motor nerve regeneration, suggesting that the retrograde transport of growth factors and anterograde transport of vesicles, providing membrane material, could be increased during motor nerve regeneration.

Amino Acid Sequence↗
PubMed1995

Up-regulation of PKA RI alpha subunit mRNA in rat skeletal muscle after nerve injury.

Localization of all subunits of cAMP dependent protein kinase (PKA) mRNAs and their changes of expression after denervation were examined in rat tongue skeletal muscle by in situ hybridization histochemistry. Among all PKA subunits only RI alpha subunit mRNA was detected in the skeletal muscle, whereas positive signal of all subunits mRNA were observed in some haematocytes or lymphocytes within the tongue tissue. The RI alpha mRNA was distributed in a restricted area near the endplate. The mRNA level was substantially induced by the hypoglossal nerve transection, suggesting that the up-regulation of RI alpha mRNA leading to the down-regulation of PKA activity may contribute to some intracellular signalling modulation or to muscle specific gene transcription after the denervation.

Acetylcholinesterase↗
PubMed1995

Evaluation of an improved ileus monitoring system for intestinal motility.

To observe the recovery of normal intestinal movement and the effects of peristalsis-promoting agents in patients with intestinal obstruction, an ileus monitoring system using the balloon method was simultaneously compared with that using the infusion method in 24 patients. To initiate the balloon ileus monitoring system, measurement was started at a setting of 0 after connecting a transducer to the balloon inflation channel of a decompression tube. The recording sensitivity was 20 mmHg/cm, and the speed of recording was 5 mm/min. The sensitivity of the infusion method was found to be 0.70 +/- 0.17 times that of the balloon method, and therefore the balloon method was considered to be more accurate. The findings of this study show how useful this ileus monitoring system is for observing the motility of intestinal obstruction.

Endoscopes, Gastrointestinal↗
PubMed1995

Relationship between age and nephrotoxicity following single low-dose cisplatin (CDDP) injection in rats.

We studied nephrotoxicity following a single injection of cisplatin (CDDP) at low dose (1 mg/kg) in two groups of rats aged 52 weeks (adult, A group) and 9 weeks (young, Y group). Renal platinum (Pt) was detectable in both groups 3 h after the CDDP injection, and, from 6 h to 3 d after injection, its level in the A group was higher than that in the Y group. Compared with the levels in age-matched normal rats (non-treated rats examined at time zero), the plasma urea nitrogen and creatinine levels in the A group were significantly increased, beginning 3 d after CDDP injection, while those in the Y group showed little change for 10 d after injection. Beginning 3 d after CDDP injection, the level of renal metallothionein in the Y group increased, while that in the A group decreased remarkably. The renal tissue levels of the heavy metals Zn, Cu, Mn showed similar patterns. There were no significant changes in the renal lipid peroxide (LPO) level in either the A and Y group at any time measured after CDDP injection compared with the value in the respective age-matched untreated group. Morphological evaluation demonstrated degeneration of the proximal tubules in the A group 3 d after CDDP injection. These results suggested that the renal disorders observed following CDDP injection in the A group were caused by mechanisms other than LPO such as decreased tissue metabolic function associated with aging.

Aging↗
PubMed1994

Experimental quantitative evaluation of transvascular removal of unnecessary substances in brain edema fluid.

We developed a model by which the transvascular removal of unnecessary substances in brain edema fluid could be measured quantitatively and chronologically. Brain stab wounds were produced in Wistar rats by insertion of paired microdialysis probes in the unilateral caudatoputamen. Homovanillic acid (HVA) was administered by microdialysis from one probe, and the HVA clearance was measured by HPLC analysis of perfusate from the other probe. Using this model, we evaluated the site of removal and whether the removal processes were affected by anesthesia or an elevated plasma concentration of the substance. As a result, 1) Probenecid did not change HVA clearance although this inhibits HVA removal via subarachnoid vessels. Therefore, HVA removal in this model was considered mainly due to intraparenchymal transvascular efflux. 2) There was no alteration in HVA removal induced by anesthesia or intravenous HVA injection. Consequently, this efflux mechanism seems to be a rather stable protective process, and seems to play a considerable role in brain microenvironmental homeostasis.

Animals↗
PubMed1994

Accumulation of platinum in the intervertebral discs and vertebrae of ovarian tumor-bearing patients treated with cisplatin.

Platinum was determined by the inductively coupled plasma mass spectrometry (ICP-MS) in the intervertebral discs and vertebrae of ovarian tumor bearing patients treated with cis-diamminedichloro-platinum (II) (cisplatin). Platinum was 0.05 ng/mL at the absolute detection limit, and platinum was undetectable in the intervertebral discs and vertebrae of human specimens without cisplatin treatments. On the other hand, platinum was detected in the intervertebral discs and vertebrae of patients administered cisplatin, and platinum concentration was at levels of 1.06-10.31 micrograms/g dry tissue in the intervertebral discs and 0.60-1.28 micrograms/g dry tissue in the vertebrae, respectively. The platinum level of intervertebral discs was 4.3-fold higher than that of the vertebrae. Thus, platinum accumulates greatly in the intervertebral discs and somewhat in the vertebrae after administering cisplatin to patients for therapy.

Adenocarcinoma↗
PubMed1994

Nephrotoxicity induced by adenine and its analogs: relationship between structure and renal injury.

Twenty-four adenine analogs were administered to mice and the relationship between the structure of analogs and the occurrence of renal injury was examined. Plasma urea nitrogen (UN) and creatinine levels were measured 24 h after oral administration of analogs. Both levels increased in the adenine-, 8-azaadenine-, isoguanine-, or 6-dimethyl aminopurine (6-DMAP)-administered group, but did not increase in the other analog groups. From light microscopy, the damages of tubuli, mainly of proximal tubuli, were observed in the kidneys of these four groups. The common property of these compounds is the strong basicity of nitrogen which binds the 6-position of the purine ring. Furthermore, UN and creatinine increased time-dependently with intravenous administration of isoguanine. When adenine was intravenously administered, UN slightly increased at 1 h, but creatinine was unchanged. No changes were observed in the 6-DMAP- or 8-azaadenine-administered group. The basicity of nitrogen which binds to the 6-position of the purine ring is thus considered to be related to the occurrence of renal injury with oral administration, and isoguanine has high affinity with the kidney.

Adenine↗