Biomedical subjects

Koji Ohno

Publications and source records attributed to Koji Ohno.

18 recordsLinked to original sources

PubMed2005

Cyclooxygenase-1 mediates the final stage of morphine-induced delayed cardioprotection in concert with cyclooxygenase-2.

OBJECTIVES: We sought to investigate the time course of morphine-induced delayed cardioprotection and examine the role of cyclooxygenase (COX) in this cardioprotective effect. BACKGROUND: Cyclooxygenase-2 has been shown to be essential for the delayed cardioprotection induced by ischemic preconditioning and delta-opioid agonists. METHODS: Male mice were subjected to 45 min of coronary artery occlusion followed by 120 min of reperfusion. Expressions of COX-2 and COX-1 were assessed by Western blotting, and the myocardial prostaglandin (PG)E2 and 6-keto-PGF(1-alpha) contents were measured using enzyme immunoassays. RESULTS: A powerful infarct-sparing effect appeared 24 and 48 h after morphine preconditioning and faded after 72 h. After 24 h, the anti-infarct effect was associated with enhanced myocardial levels of COX-2, PGE2, and 6-keto-PGF(1-alpha), and no changes in COX-1 protein levels were found. Cardioprotection and increases in PGE2 and 6-keto-PGF(1-alpha) were completely abolished by the COX-2-selective inhibitor NS-398 and the non-selective COX inhibitor indomethacin, whereas the COX-1-selective inhibitor SC-560 had no effect. After 48 h, up-regulation of myocardial PGE2 and 6-keto-PGF(1-alpha) was also observed, and COX-1 expression was enhanced markedly, but only a slight increase in COX-2 expression was apparent. Cardioprotection and the increases in PGE2 and 6-keto-PGF(1-alpha) 48 h after morphine administration were abrogated only by indomethacin, and not by SC-560 or NS-398. CONCLUSIONS: Morphine confers delayed cardioprotection via a COX-dependent pathway; COX-2 is essential for the cardioprotection observed in the initial stage (24 h), whereas, in the final stage (48 h), cardioprotection is mediated by COX-1 in concert with COX-2.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

The differential expression patterns of messenger RNAs encoding Nogo-A and Nogo-receptor in the rat central nervous system.

Nogo-A and Nogo-receptor have been considered to play pivotal roles in controlling axonal regeneration and neuronal plasticity. We investigated the total distribution of Nogo-A and Nogo-receptor mRNAs in the adult rat central nervous system using in situ hybridization histochemistry. Nogo-A is abundantly expressed in both neurons and oligodendrocytes throughout the central nervous system. Interestingly, we could not find any neuron which lacks Nogo-A mRNA expression, indicating that Nogo-A mRNA is universally expressed in all neurons. In contrast, Nogo-R mRNA expression was very restricted. Nogo-R mRNA was expressed in the olfactory bulb, hippocampus, tentia tecta, some amygdala nuclei, cerebral cortex, some thalamic nuclei, medial habenular, whereas we could not detect it in the other regions. Interestingly, we did not detect Nogo-R mRNA in monoaminergic neurons, which are known to have high regenerative capacity, in the substantia nigra, ventral tegmental area, locus caeruleus, and raphe nuclei. In addition, although neurons in the reticular thalamus and cerebellar nuclei are also known to show high capacity for regeneration, Nogo-R mRNA was not detected there. These data indicate that Nogo-A and Nogo-R mRNAs were differentially expressed in the central nervous system, and suggest that the lack of Nogo-R expression in a given neuron might be necessary to keep its high regenerative capacity.

Animals↗

PubMed2005

Differential expression of KCC2 accounts for the differential GABA responses between relay and intrinsic neurons in the early postnatal rat olfactory bulb.

The rat olfactory bulb is anatomically immature at birth, and considerable neurogenesis and synaptogenesis are known to take place postnatally. In addition, significant physiological changes have also been reported in this period. For example, granule cell-mediated inhibition following electrical stimulations to the lateral olfactory tract is robust during the first postnatal week, and then decreases abruptly after the second week. However, the mechanism underlying this enhanced inhibition remains to be elucidated. To know the cause of this phenomenon, we investigated the expression patterns of cation-Cl(-) co-transporters (KCC1, KCC2 and NKCC1) mRNAs, which are responsible for the regulation of [Cl(-)](i). In addition, responses to gamma-aminobutyric acid (GABA) were measured by gramicidin-perforated patch-clamp recordings and Ca(2+) imaging using fura-2. We found that in the early postnatal period, mitral cells expressing KCC2 mRNA were inhibited by GABA, while granule cells lacking KCC2 mRNA expression were depolarized or excited by GABA. These results indicate that transient GABA-mediated excitation on granule cells might be the main cause of the enhanced inhibition on mitral cells, and suggest that these differential GABA responses between relay and intrinsic neurons play pivotal roles in the early postnatal rat olfactory bulb.

Animals↗

PubMed2005

[Long-term clinical course of laser in situ keratomileusis--two year follow-up].

PURPOSE: To evaluate the cases that were treated with laser in situ keratomileusis (LASIK) and who were follwed up for a full 2-year period without fail. MATERIALS AND METHODS: LASIK was performed in 62 eyes of 35 patients between June 1997 and March 1999. Mean age was 29.1 years and the preoperative mean spherical equivalent refraction was -6.90 +/- 2.49 (mean +/- standard deviation) diopter (D). Five aspects were studied as follows. RESULTS: 1. SAFETY: 26 eyes (41.9%) gained 1 line or more in best corrected visual acuity. Twenty eyes (32.3%) were unchanged. Sixteen eyes(25.8%) lost 1 line. No eye lost 2 lines or more. The safety index was 1.04. 2. EFFICACY: The efficacy index was 0.85. 3. Predictability: Forty-eight eyes (77.4%) were predictable within +/- 0.5 D, and 55 eyes (88.7%) were within +/- 1.0 D. 4. Stability: Manifest refraction was relatively stable after 3 months. 5. Complication: No complications were experienced. CONCLUSIONS: Our 2-year follow-up showed that postoperatively LASIK was safe and effective.

Adolescent↗

PubMed2004

Synectin in the nervous system: expression pattern and potential as a binding partner of neurotrophin receptors.

To assess the potential for functional interaction between synectin and neurotrophin receptors (Trk receptors) in the nervous system, we characterized synectin expression in the rat brain. Synectin is widely expressed in the brain and its expression levels are regulated both temporally and spatially, correlating with those of Trk receptors. Biochemical studies indicated that synectin interacts with TrkB but not with TrkC in the developing brain. We also found that axotomized motoneurons upregulate synectin mRNA expression as well as TrkB mRNA. These data suggest that synectin plays a role in neural development and regeneration in association with TrkB.

Adaptor Proteins, Signal Transducing↗

PubMed2004

The neuronal glycine transporter 2 interacts with the PDZ domain protein syntenin-1.

The glycine transporter subtype 2 (GlyT2) is localized at glycinergic axon terminals where it mediates the re-uptake of glycine from the extracellular space. In this study, we used the yeast two-hybrid system to search for proteins that interact with the cytoplasmic carboxy terminal tail region of GlyT2. Screening of a rat brain cDNA library identified the PDZ domain protein syntenin-1 as an intracellular binding partner of GlyT2. In pull-down experiments, the interaction between GlyT2 and syntenin-1 was found to involve the C-terminal amino acid residues of GlyT2 and the PDZ2 domain of syntenin-1. Syntenin-1 is widely expressed in brain and co-localizes with GlyT2 in brainstem sections. Furthermore, syntenin-1 binds syntaxin 1A, which is known to regulate the plasma membrane insertion of GlyT2. Thus, syntenin-1 may be an in vivo binding partner of GlyT2 that regulates its trafficking and/or presynaptic localization in glycinergic neurons.

Amino Acid Sequence↗

PubMed2003

Changes in chloride homeostasis-regulating gene expressions in the rat hippocampus following amygdala kindling.

In a rat kindling model, we examined expression patterns of NKCC1, KCC1, KCC2, and CLC-2. In the dentate granule cell layer, there was an activity-dependent increase in NKCC1 mRNA but significant decreases in KCC1 and CLC-2 mRNAs. In addition, CLC-2 mRNA expression was markedly decreased in CA1 pyramidal layer. These results suggest that an increase in [Cl-]i and a resultant reduction in GABAergic inhibition may occur in hippocampus of epileptic rats.

Amygdala↗

PubMed2003

Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition.

The glycine transporter subtype 1 (GlyT1) is widely expressed in astroglial cells throughout the mammalian central nervous system and has been implicated in the regulation of N-methyl-D-aspartate (NMDA) receptor activity. Newborn mice deficient in GlyT1 are anatomically normal but show severe motor and respiratory deficits and die during the first postnatal day. In brainstem slices from GlyT1-deficient mice, in vitro respiratory activity is strikingly reduced but normalized by the glycine receptor (GlyR) antagonist strychnine. Conversely, glycine or the GlyT1 inhibitor sarcosine suppress respiratory activity in slices from wild-type mice. Thus, during early postnatal life, GlyT1 is essential for regulating glycine concentrations at inhibitory GlyRs, and GlyT1 deletion generates symptoms found in human glycine encephalopathy.

Amino Acid Transport Systems, Neutral↗

PubMed2003

Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality.

The glycine transporter subtype 2 (GlyT2) is localized in the axon terminals of glycinergic neurons. Mice deficient in GlyT2 are normal at birth but during the second postnatal week develop a lethal neuromotor deficiency that resembles severe forms of human hyperekplexia (hereditary startle disease) and is characterized by spasticity, tremor, and an inability to right. Histological and immunological analyses failed to reveal anatomical or biochemical abnormalities, but the amplitudes of glycinergic miniature inhibitory currents (mIPSCs) were strikingly reduced in hypoglossal motoneurons and dissociated spinal neurons from GlyT2-deficient mice. Thus, postnatal GlyT2 function is crucial for efficient transmitter loading of synaptic vesicles in glycinergic nerve terminals, and the GlyT2 gene constitutes a candidate disease gene in human hyperekplexia patients.

Amino Acid Transport Systems, Neutral↗

PubMed2003

The alteration of odor-induced c-Fos immunoreactivity in the rat olfactory bulb after olfactory nerve transection.

We used the rats in which one olfactory nerve had been transected and observed the odor (Propionic acid) -induced c-Fos immunoreactivity in the bulb at different times (2, 4, 8 weeks) after nerve transection. The exposure to odor produced a strong cluster of c-Fos positive cells in the mediodorsal region of the intact bulb. On the other hand, the transected bulb showed much less reactivity 2 weeks after neurectomy; however, a large number of positive cells were observed in the whole of the bulb from 4 weeks after neurectomy. Furthermore, we measured the levels of mRNA for tyrosine hydroxylase (TH), which was the marker of odor-induced olfactory nerve activity in the bulb, by using real-time PCR. The level of TH mRNA decreased on the transected side at 2 weeks but recovered to the level of the contralateral side at 4 weeks after neurectomy. We firstly demonstrated that projection mapping of odor receptors was altered after olfactory nerve transection by using an immunohistochemical method.

Animals↗

PubMed2003

Clinical outcomes of wavefront-guided laser in situ keratomileusis: 6-month follow-up.

PURPOSE: To evaluate the clinical outcomes 6 months after wavefront-guided laser in situ keratomileusis (LASIK) for myopia in Japan. SETTING: Department of Ophthalmology, Sanno Hospital, Tokyo, Japan. METHODS: This prospective study comprised 22 eyes of 12 patients treated with wavefront-guided LASIK who were available for evaluation at 6 months. The mean patient age was 31.2 years +/- 8.4 (SD) (range 23 to 50 years), and the mean preoperative spherical equivalent refraction was -7.30 +/- 2.72 diopters (D) (range -2.75 to -11.88 D). In all cases, preoperative wavefront analysis was performed with a Hartmann-Shack aberrometer and the Technolas 217z flying-spot excimer laser system (Bausch & Lomb) was used with 1.0 mm and 2.0 mm spot sizes and an active eye tracker with a 120 Hz tracking rate. The clinical outcomes of wavefront-guided LASIK were evaluated in terms of safety, efficacy, predictability, stability, complications, and preoperative and postoperative aberrations. RESULTS: At 6 months, 10 eyes had no change in best spectacle-correct visual acuity and 10 gained 1 or more lines. The safety index was 1.11 and the efficacy index, 0.82. Slight undercorrections were observed in highly myopic eyes. In all eyes, the postoperative refraction tended slightly toward myopia for 3 months and stabilized after that. No complication such as epithelial ingrowth, diffuse lamellar keratitis, or infection was observed. Comparison of the preoperative and postoperative aberrations showed that 2nd-order aberrations decreased and higher-order aberrations increased. In the 3rd order, aberrations increased in the high-myopia group (-6.0 D or worse) and decreased in the low to moderate-myopia group (better than -6.0 D). CONCLUSION: Wavefront-guided LASIK was a good option for refractive surgery, although a longer follow-up in a larger study is required.

Adult↗

PubMed2003

[Late onset diffuse lamellar keratitis].

BACKGROUND: Diffuse lamellar keratitis (DLK) is marked by the presence of diffuse or multifocal infiltrates confined to the laser in situ keratomileusis(LASIK) interface. These infiltrates are culture-negative, and the etiology is thought to be noninfectious. Most cases of DLK occur within the first week or two following surgery. CASE: We describe two cases of diffuse lamellar keratitis that occurred 3 months after LASIK. These patients were treated with intensive topical corticosteroids. RESULTS: We treated the patients with topical corticosteroids, with rapid improvement in patient symptoms, visual acuity, and slit-lamp biomicroscopy. CONCLUSION: DLK may occur three months after LASIK.

Female↗

PubMed2003

Glycine transporter isoforms in the mammalian central nervous system: structures, functions and therapeutic promises.

The amino acid glycine (Gly) serves as a neurotransmitter at excitatory and inhibitory synapses in the mammalian central nervous system. Gly concentrations at post-synaptic neurotransmitter receptors are regulated by Na+/Cl(-)-dependent Gly transporters, which are expressed in neurons and in glial cells. Recent evidence suggests that these transporters are promising targets for the treatment of psychiatric and neurological disorders, such as schizophrenia and pain. Here, recent research on the structure, regulation and pharmacology of mammalian Gly transporters is reviewed.

Amino Acid Transport Systems, Neutral↗

PubMed2002

Induction of NMDA and GABAA receptor-mediated Ca2+ oscillations with KCC2 mRNA downregulation in injured facial motoneurons.

To clarify the changes that occur in gamma-aminobutyric acid type A (GABA(A)) receptor-mediated effects and contribute to alterations in the network activities after neuronal injury, we studied intracellular Ca(2+) concentration ([Ca(2+)](i)) dynamics in a rat facial-nerve-transection model. In facial motoneurons, an elevation of the resting [Ca(2+)](i), GABA-mediated [Ca(2+)](i) transients, enhancement of the glutamate-evoked [Ca(2+)](i) increases, and spontaneous [Ca(2+)](i) oscillations were induced by axotomy. All these axotomy-induced modifications were abolished by the GABA(A)-receptor antagonist bicuculline and N-methyl-d-aspartate (NMDA)-receptor antagonist d(-)-2-amino-5-phosphonopentanoic acid. A downregulation of K(+)-Cl(-) cotransporter (KCC2) mRNA, an increase in intracellular Cl(-) concentration ([Cl(-)](i)), and transformation of GABAergic hyperpolarization to depolarization were also induced by axotomy. We suggest that in axotomized neurons KCC2 downregulation impairs Cl(-) homeostasis and makes GABA act depolarizing, resulting in endogenous GABA inducing [Ca(2+)](i) oscillations via facilitation of NMDA-receptor activation. Such GABA(A)-receptor-mediated [Ca(2+)](i) oscillations may play a role in neural survival and regeneration.

Animals↗

PubMed2002

Cyclic AMP-mediated modulation of epileptiform afterdischarge generation in rat hippocampal slices.

This study assessed the effects of drugs which manipulate the cAMP system on afterdischarges (ADs) induced in the CA1 region of rat hippocampal slices. The adenylate cyclase activator forskolin (50 microM) and the phosphodiesterase inhibitor rolipram (0.1 and 1 microM) enhanced AD generation. These effects were reversed by the cAMP-dependent protein kinase inhibitors H-89 (5 microM) and Rp-cAMPS (100 microM). These findings suggest that AD generation can be modulated through cAMP generation and the subsequent activation of the cAMP-dependent protein kinase.

Action Potentials↗

PubMed2002

Effects of antiepileptic drugs on afterdischarge generation in rat hippocampal slices.

We have recently reported that ictal-like afterdischarges (ADs) analogous to those in in vivo kindling models are induced by high-frequency stimulation (100 Hz, 1s) to the stratum radiatum of the CA1 region of rat hippocampal slices. To test whether this model can also serve as an in vitro seizure model for temporal lobe epilepsy, we examined the effects of antiepileptic drugs on this model and compared them with their effects on seizures in patients with temporal lobe epilepsy. ADs were progressively enhanced following repetitive high-frequency stimulations to slices treated with 4-aminopyridine, a proconvulsive A-type potassium channel blocker. Bath application of phenytoin (1-100 microM) and carbamazepine (1-100 microM) suppressed AD generation in a concentration-dependent manner. At a clinically relevant concentration of 10 microM, phenytoin reduced the number of spikes in an AD to 50.6% and carbamazepine to 39.7% of the control values. On the other hand, ethosuximide had no effect on AD generation at a concentration of 1 mM, which is clinically effective against absence seizures, but enhanced it at a toxic concentration of 10 mM. These findings indicate that the pharmacological profiles of antiepileptic drugs applied to our model correspond to those applied to seizures in patients with temporal lobe epilepsy. We therefore conclude that this model can be a useful in vitro model for the ictal manifestation of temporal lobe epilepsy.

4-Aminopyridine↗

PubMed2002

Amygdala kindling induces upregulation of mRNA for NKCC1, a Na(+), K(+)-2Cl(-) cotransporter, in the rat piriform cortex.

GABA, the main inhibitory neurotransmitter in the brain, elicits a hyperpolarizing response by activation of the GABA(A)-receptor/chloride-channel complex under conditions of normal Cl(-) homeostasis. Thus the pathogenesis of epilepsy could involve an impairment of GABA(A)-receptor-mediated inhibition due to a collapse of the Cl(-) gradient. We examined the expression patterns of Cl(-) transporters and a Cl(-) channel in a rat amygdala-kindling model. Activity-dependent increases were observed in the mRNA for NKCC1, an inwardly-directed Cl(-) transporter, in the piriform cortex. This suggests that an increase in [Cl(-)](i) and a resultant reduction in GABAergic inhibition may occur in the kindled piriform cortex.

Amygdala↗

PubMedDate not supplied

Late-onset diffuse lamellar keratitis.

BACKGROUND: Diffuse lamellar keratitis (DLK) is marked by the presence of diffuse or multifocal infiltrates confined to the laser in situ keratomileusis (LASIK) interface. These infiltrates are culture-negative, and the etiology is thought to be noninfectious. Most cases of DLK occur within the first week or 2 following surgery. CASES: We described 2 cases of DLK that occurred 3 months after LASIK. These patients were treated with intensive topical corticosteroids. RESULTS: Treatment with topical corticosteroid was instituted, with rapid improvement in patient symptoms, visual acuity, and slit-lamp biomicroscopic findings. CONCLUSION: DLK may occur as late as 3 months after LASIK.

Administration, Topical↗