Activator protein-1 in epiretinal membranes of patients with proliferative diabetic retinopathy.
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Cell Membrane↗
Biomedical subjects
C Harada
Publications and source records attributed to C Harada.
Production of methyl-oxonium ion and its complexes in the core-excited (HC(O)OCH3)n clusters: H/H+ transfer from the alpha carbonyl.
Dissociation of free methyl-formate (MF), HC(O)OCH3, and its clusters (MF)n, (HC(O)OCH3)n, induced by core-level excitation was studied near the oxygen K edge by time-of-flight fragment-mass spectroscopy. Besides the protonated clusters, (MF)nH+ with n < or = 15, we identified the production for another series of (MF)mCH3OH2+ with m < or = 14 as well as methyl-oxonium ion, CH3OH2+, characteristic of hydrogen transfer reactions in the cationic clusters. Here; specifically labeled methyl-formate-d (MFD), DC(O)OCH3 was also used to examine the core-excited dissociation mechanisms. Deuterium-labeled experiments indicated that MFD+ with low internal energies, partially generated after the core excitation, produces CH3OD+ via a site-specific deuterium transfer from the alpha carbonyl in the molecular cation and that CH3OD2+ can be formed via the successive transfer of another deuterium from the neighbor molecule in the clusters. The deuteron (proton) transfer was also found to take place preferentially from the alpha carbonyl of the neighbor molecule for the production of deuteronated (MFD)nD+, (protonated (MF)nH+), clusters. The minimal energy requirement paths were examined for dimer (MF)2+ cation to support the present dissociation mechanisms of core-excited (MF)n clusters using ab initio molecular-orbital calculations.
Journal Article↗
Activation of nuclear factor-kappa B in the conjunctiva with the epithelial scraping of the mouse cornea and human epidemic keratoconjunctivitis.
AIM: To examine the expression of p65, one of nuclear factor-kappa B (NF-kappa B), in the conjunctival epithelium of the C57Bl6 mouse and a patient with epidemic keratoconjunctivitis (EKC). METHODS: Normal and epithelial scraped cornea obtained 6 hours after the injury were processed for paraffin section. Samples of a normal and an EKC conjunctival epithelium were obtained using impression cytology. Both samples were analysed by immunocytochemistry using anti-p65 antibody. RESULTS: Immunocytochemistry with the anti-NF-kappa B p65 antibody revealed that p65 was localised in the cytoplasm of the conjunctival epithelium in the C57Bl6 mouse without the treatment. Six hours after the scraping of the cornea, p65 protein was expressed in the nuclei of the conjunctival epithelium. p65 was localised in the cytoplasm of the conjunctival epithelium in the human normal eye. p65 protein was expressed in the nuclei of the conjunctival epithelial cells in the EKC patient. CONCLUSION: These findings suggest that NF-kappa B was activated in the conjunctiva in the epithelial scraping of the mouse cornea and in human EKC.
Animals↗
Intracerebroventricular administration of histamine H3 receptor antagonists decreases seizures in rat models of epilepsia.
The effects of histamine H3 antagonists on amygdaloid kindled and maximal electroshock seizures in rats were studied to determine their potential as new antiepileptic drugs. Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus and a stainless steel guide cannula for drug administration was implanted into the lateral ventricle. In amygdaloid kindled seizures, electrodes were implanted into the right amygdala and electroencephalogram was recorded bipolarly; stimulation was applied bipolarly every day by a constant current stimulator and continued until a generalized convulsion was obtained. In the maximal electroshock (MES) seizure test, electroconvulsion was induced by stimulating animals through ear-clip electrodes, and the durations of tonic and clonic seizures were measured. Thioperamide, clobenpropit, iodophenpropit, VUF5514, VUF5515 and VUF4929 caused a dose-dependent inhibition of both seizure stage and afterdischarge (AD) duration of amygdaloid kindled seizures. The duration of tonic seizure induced by MES was also inhibited by H3 antagonists, but the duration of clonic seizures were unchanged. Among the H3 antagonists tested, clobenpropit and iodophenpropit were somewhat more potent than the other drugs on amygdaloid kindled seizures and MES seizures, respectively. These results indicate that some H3 antagonists may be useful as antiepileptic drugs, especially for secondary generalized seizures and/or tonic-clonic seizures in humans.
Amygdala↗
NF-kappaB in epiretinal membranes after human diabetic retinopathy.
AIMS/HYPOTHESIS: Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to examine whether or not nuclear factor kappa B (NF-kappaB), a transcription factor that can be activated by various pathological conditions, is involved in the formation of ERMs after PDR. METHODS: ERM samples were obtained by vitrectomy from 22 cases with PDR aged 56+/-11 years with 18+/-10 years of diabetes and 15 cases with idiopathic ERM. They were processed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. In addition, 5 ERM samples from PDR patients aged 51+/-16 years with 15+/-6 years of diabetes were processed for immunohistochemical analysis. RESULTS: NF-kappaB mRNA expression levels were higher (20 out of 22 cases vs. 9 out of 15 subjects in idiopathic ERM, p<0.05) in PDR subjects. Immunohistochemical analysis showed NF-kappaB protein expression in all the 5 ERMs derived from PDR patients, and that region was partially double-labelled with interleukin-8 (IL-8) and von Willebrand factor (vWF). CONCLUSIONS/INTERPRETATION: These results suggest a possibility that NF-kappaB is involved in the formation of ERMs after PDR, especially for the development of vascular endothelial cell component.
Adult↗
Potential role of glial cell line-derived neurotrophic factor receptors in Müller glial cells during light-induced retinal degeneration.
Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and their receptors (GFRalpha1, GFRalpha2 and Ret) play an important role in the survival of neurons in the central and peripheral nervous system. For example, GDNF as well as other trophic factors promotes photoreceptor survival during retinal degeneration. Recent studies have proposed that part of neurotophic rescue of photoreceptors may be indirect, mediated by interaction of the neurotrophic factors with other cell types, that in turn release secondary factors that act directly on photoreceptors. In the present study, we examined the GDNF receptor expression in control and light-damaged retina, and found that GFRalpha2 protein is upregulated in retina-specific Müller glial cells during photoreceptor degeneration. We also examined the effect of GDNF or NTN on cultured Müller cells. Exogenous GDNF increased brain-derived neurotrophic factor, basic fibroblast growth factor and GDNF, but not NTN mRNA production. On the other hand, NTN increased NTN, but not GDNF mRNA production in cultured Müller cells. These observations suggest that GDNF, NTN and their receptors are involved in the regulation of trophic factor production in retinal glial cells, and that functional glia-neuron network may utilize GDNF family for the protection of neural cells during retinal degeneration.
Animals↗
Impossibility of injection through an epidural catheter caused by an incorrect connection of catheter and connector.
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Anesthesia, Epidural↗
Proliferation in the posterior region of the lens of c-maf-/- mice.
PURPOSE: To examine the involvement of the c-maf gene in the proliferation of the lens cells. METHODS: Eyes of the E13 and E18 stages of the wild-type and c-maf-/- mice were analyzed by BrdU incorporation assay, TUNEL assay and immunocytochemistry using a anti-P27(KIP1) and a anti-P57(KIP2) antibody. RESULTS: In the E13 and E18 c-maf mutant lens, BrdU-positive cells were detected at the posterior region of the lens. Cell-cycle inhibitor P27(KIP1) and P57(KIP2) were expressed in the equatorial and posterior region of the lens of both wild-type and c-maf-/- lenses. CONCLUSION: These results suggest that the expression of c-maf is required for differentiation and cell cycle arrest of lens fiber cells. It is also suggested that P27(KIP1) and P57(KIP2) were not involved in the continued proliferation of posterior region of the c-maf-/- lens.
Animals↗
N-acetylated-alpha-linked-acidic dipeptidase inhibitor has a neuroprotective effect on mouse retinal ganglion cells after pressure-induced ischemia.
Excessive glutamate receptor activation is thought to be involved in the retinal ganglion cell (RGC) death after ischemic injury. In this study, we examined the effect of 2-PMPA (2-(phosphonomethyl)pentanedioic acid) on RGC survival in an ischemia-reperfusion model using C57BL/6 mouse eyes. 2-PMPA is a NAALADase (N-acetylated-alpha-linked-acidic dipeptidase) inhibitor, an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-aspartyl-glutamate) to N-acetyl-aspartate and glutamate. 100mg/kg 2-PMPA were given with intraperitoneal injections 30 min before ischemia followed per hour injection for 3h. 2-PMPA increased surviving RGCs as well as retinal thickness after pressure-induced retinal ischemia. In addition, neuroprotection afforded by 2-PMPA was greater than that of N-methyl-D-aspartate receptor blocker. These data indicate that NAALADase inhibition may be useful in retinal disorders in which excessive amino acid transmission is pathogenic.
Animals↗
Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration.
Prolonged or high-intensity exposure to visible light leads to photoreceptor cell death. In this study, we demonstrate a novel pathway of light-induced photoreceptor apoptosis involving the low-affinity neurotrophin receptor p75 (p75NTR). Retinal degeneration upregulated both p75NTR and the high-affinity neurotrophin receptor TrkC in different parts of Müller glial cells. Exogenous neurotrophin-3 (NT-3) increased, but nerve growth factor (NGF) decreased basic fibroblast growth factor (bFGF) production in Müller cells, which can directly rescue photoreceptor apoptosis. Blockade of p75NTR prevented bFGF reduction and resulted in both structural and functional photoreceptor survival in vivo. Furthermore, the absence of p75NTR significantly prevented light-induced photoreceptor apoptosis. These observations implicate glial cells in the determination of neural cell survival, and suggest functional glial-neuronal cell interactions as new therapeutic targets for neurodegeneration.
Animals↗
Light-induced retinal degeneration suppresses developmental progression of flip-to-flop alternative splicing in GluR1.
AMPA receptors are hetero-oligomers composed of subsets of four distinct subunits, termed GluR1, GluR2, GluR3, and GluR4. Using quantitative reverse transcription-PCR analysis, we have found that light-induced degeneration of rat retina dramatically suppresses developmental progression of the flip-to-flop alternative splicing switch of retinal GluR1 mRNA. When animals were raised under standard conditions of a 12 hr light/dark cycle (LD 12:12), the flop-to-flip ratio in GluR1 and GluR2 dramatically increased between postnatal day 10 (P10) and P28, and the ratios continued to increase gradually up to P84. When animals were raised in complete darkness, this increase was delayed in GluR1 between P21 and P42. In addition, the increase of the flop-to-flip ratio in GluR1 was strongly suppressed after P21 under conditions of continuous illumination from P2. This is significant because P21 is just after the eye opening and is the timing of the onset of light-induced retinal degeneration. This suppression of the increase of the flop-to-flip ratio was specific to GluR1 and was not observed in GluR2-4. Immunocytochemistry and immunoblot analysis suggested no changes in either the distribution or expression of GluR1 protein in the light-damaged retina measured at P84. When rats were raised under continuous illumination from P2 to P21 followed by LD 12:12 from P22 to P84, retinal degeneration did not progress after P22. In such animals the flop-to-flip ratio, once decreased to approximately 50% of the control (LD 12:12) at P21, was restored to the control level at P84. These findings demonstrate that developmental progression of the flip-to-flop exon switch in retinal GluR1 is affected by lighting conditions, and that light-induced retinal degeneration contributes to the mechanism of suppression of this splicing switch.
Alternative Splicing↗
Functions of the two glutamate transporters GLAST and GLT-1 in the retina.
In the retina, the glutamate transporter GLAST is expressed in Müller cells, whereas the glutamate transporter GLT-1 is found only in cones and various types of bipolar cells. To investigate the functional role of this differential distribution of glutamate transporters, we have analyzed GLAST and GLT-1 mutant mice. In GLAST-deficient mice, the electroretinogram b-wave and oscillatory potentials are reduced and retinal damage after ischemia is exacerbated, whereas GLT-1-deficient mice show almost normal electroretinograms and mild increased retinal damage after ischemia. These results demonstrate that GLAST is required for normal signal transmission between photoreceptors and bipolar cells and that both GLAST and GLT-1 play a neuroprotective role during ischemia in the retina.
ATP-Binding Cassette Transporters↗
A case of bilateral optic neuropathy and recurrent transverse myelopathy associated with perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA).
A case involving a 52-year-old man having bilateral optic neuropathy and recurrent transverse myelopathy is reported. His clinical features resembled multiple sclerosis, but neuroimaging failed to show evidence of demyelination or inflammation in the brain or the optic nerves. The patient experienced sudden visual loss despite massive steroid therapy. Positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) is suggestive that optic neuropathy and recurrent transverse myelopathy may have been caused by some common inflammatory processes associated with p-ANCA, however, having a different etiology from multiple sclerosis.
Antibodies, Antineutrophil Cytoplasmic↗
Neural responses to electrical stimulation of the cochlea in guinea pigs.
A special bridge circuit was constructed to compensate stimulus artifact to determine the effects of an alternating current (AC) in the range of 3 to 20 kHz and direct current (DC) stimulation on the activity of cochlear nerve fibers. When AC and DC stimulation of the same fiber were compared, a greater current intensity was required to change the spike rate with AC stimulation than DC stimulation. While positive DC stimulation reduced activity, negative DC stimulation increased the spike rate. AC stimuli excited fibers in a manner similar to that observed with negative DC stimulation. Thresholds increased with stimulus frequency, suggesting that the effects of AC stimulation on the discharge rate are independent of the CF (characteristic frequency) of a fiber. The effects of short-time AC and DC stimulation on cochlear fiber activity lasted only during the stimulation, and the spontaneous activity did not significantly differ before and after electrical stimulation.
Animals↗
Latent menstrual cycle in pre-menarcheal monozygotic twins.
The distribution of menarcheal interval-length between cotwins in 67 pairs of female identical twins in Tokyo was found to cluster at fairly constant intervals. When delayed in one twin, the menarche occurred in the second twin at intervals of approximately 28 days after that of the earlier twin. This finding suggests the existence of a latent lunar or menstrual cycle in pre-menarcheal girls, evidence for which was detected by recording the menarcheal intervals between MZ cotwins in days.
Adolescent↗
Recording eye movement during stepping in place with a CCD (charge-coupled device) imagesensor.
A new system for recording eye movements using a charge-coupled device (CCD) imagesensor in a video camera, in which less than 0.5 degree of horizontal and vertical eye movements can be recorded, was applied in 7 subjects. Eye movements were recorded while they stepped in place. We observed 5 normal subjects, a patient with horizontal and vertical oscillopsia during walking, and one with a chronic limp. In the normal adults, the amplitude of vertical eye movement was less than 0.5 degree, and the horizontal eye movement was less than 2 degrees. The mean amplitude of horizontal and vertical eye movements in the subject who limped was larger than that of normal subjects. The patient who complained of vertical oscillopsia during walking showed the largest amplitude of vertical eye movement among any subject tested. The vertical oscillopsia in the patient was due to the largest amplitude of vertical eye movement. This system for recording eye movements will be useful in analyzing the mechanism of gaze fixation during walking.
Adult↗
[Effects of temperature and pH on hydrolysis of monoacetoacetin in an aqueous phase].
The kinetics of hydrolysis of monoacetoacetin (MAA; 1,2-dihydroxy-3-acetoacetyloxypropane) in 300 mM phosphate buffer was studied by means of high performance liquid chromatography. MAA was hydrolyzed to glycerin (Glyc) and acetoacetate (AA), the latter of which furthermore decomposed to acetone (Acet) and CO2 at high temperature. The rate constant, k1, for the reaction of MAA-->AA+Glyc increased with increases in temperature and pH. On the other hand, another one, k2, for the reaction of AA-->Acet+CO2 increased with an increase in temperature but showed a minimum around pH 7.5 when pH was changed at a given temperature. The activation energy for k1 was almost constant in the range of studied pHs (5-8) but the pre-exponential factor, k1,0, increased with an increase in pH. It was concluded that the decomposition reaction of MAA is consecutive in a sequence of MAA-->AA-->Acet. Calculated concentrations of MAA, AA, and Acet through the obtained k1 and k2 together with a given initial concentration of MAA (= 40 mM) were compared with those experimentally observed on the time course of the hydrolysis. They were in good agreement with each other.
Acetoacetates↗
[A comparison of time resolution among auditory, tactile and promontory electrical stimulation--superiority of cochlear implants as human communication aids].
Our previous reports showed that second formant information, using a speech coding method, could be transmitted through an electrode on the promontory. However, second formant information can also be transmitted by tactile stimulation. Therefore, to find out whether electrical stimulation of the auditory nerve would be superior to tactile stimulation for our speech coding method, the time resolutions of the two modes of stimulation were compared. The results showed that the time resolution of electrical promontory stimulation was three times better than the time resolution of tactile stimulation of the finger. This indicates that electrical stimulation of the auditory nerve is much better for our speech coding method than tactile stimulation of the finger.
Cochlea↗