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ABSTRACT: We present a case of idiopathic orbital inflammatory disease with dilatation and tortuosity of the retinal veins.
A 74-year-old man presented at his local eye hospital with left conjunctival edema and pain. He was referred to our hospital. At the initial examination, the intraocular pressure was 19 mmHg OD and 40 mmHg OS. Examination of the left eye revealed conjunctival edema with dilated and tortuous blood vessels, and dilatation and tortuousity of the retinal veins. Magnetic resonance imaging showed marked thickening of the left extraocular muscles, and suspected compression of the left superior and inferior ophthalmic veins. We diagnosed left idiopathic orbital inflammatory disease, and administered a tapering course of prednisolone starting at 40 mg daily. Thirteen days later, the conjunctival findings improved, but the left fundus showed signs of non-ischaemic central retinal vein occlusion. Subsequently, the dilatation and tortuousity of the retinal veins gradually improved. At the final examination, recurrence was not noted.
We report a case of idiopathic orbital inflammatory diseases with central retinal vein occlusion. The dilatation and tortuousity of the conjunctiva and central retinal vein occlusion improved with steroid therapy only. These Conditions improved because the inflammatory swelling of the extraocular muscle disappeared and the pressure to the vein was relieved.
Nippon Ganka Gakkai zasshi 02/2011; 115(2):142-6.
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ABSTRACT: To investigate the effects of transcorneal electrical stimulation (TES) on eyes that have a branch retinal artery occlusion (BRAO).
We studied two eyes having a BRAO, with an interval between the onset of symptoms and the beginning of treatment of >16 weeks (longstanding cases), and in three eyes with an interval of <16 weeks (fresh cases). The visual functions of the eyes were assessed by the best-corrected visual acuity (BCVA), multifocal electroretinograms (mfERGs), and automated static perimetry with the Humphrey field analyzer (HFA). The mfERGs were recorded before and 1 month after the TES, and perimetry with the HFA was done before and at 1 and 3 months after the TES. The amplitudes and implicit times of the N1, P1, and N2 components of the mfERGs were analyzed.
TES did not alter the BCVA significantly in all eyes, but it led to a significant increase in the amplitude of the N2 wave of the mfERGs (P < 0.01). The amplitude of the N1-P1 was also increased but not significantly. The implicit times of N1 (P < 0.01) and P1 (P < 0.05) were significantly shorter than that before the TES. The mean deviation of the HFA was increased after the TES but only in the longstanding cases.
Our results indicate that TES improves the visual function in eyes with BRAO, mainly in longstanding cases.
Clinical Ophthalmology 01/2011; 5:397-402.
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ABSTRACT: IL-33, a member of the IL-1 family of cytokines, is the ligand for ST2 (IL-33Ralpha chain). IL-33 has the capacity to induce T(h)2 cytokine production from T(h)2 cells, mast cells and basophils, indicating that IL-33 has the potential to induce T(h)2 cytokine-mediated allergic inflammation of the eye. Thus, we tested the pathological role of IL-33 in allergic conjunctivitis (AC). As reported elsewhere, animals immunized with ragweed pollen (RW)/alum and boosted with RW/PBS developed AC promptly (within 15 min) and conjunctival eosinophilic inflammation after a delay (within 24 h) in response to eye drop challenge with RW. Furthermore, RW-immunized mice, when topically challenged with both RW and IL-33, developed more striking eosinophilia in their conjunctiva without exacerbation of the clinical AC score. This in vivo IL-33 treatment significantly increased the capacity of T cells in the cervical lymph nodes of RW-immunized mice to produce IL-4, IL-5 and IL-13 upon challenge with anti-CD3 and anti-CD28 antibodies in vitro. Furthermore, the infiltrating cells were largely eosinophils and a small proportion of CD4(+) T cells, both of which express ST2. We also found that even splenic eosinophils express ST2 and show increased expression in response to IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-33. Eosinophils, stimulated with IL-5 and/or GM-CSF, are responsive to IL-33, which induces production of IL-4 and chemokines. Finally, we showed that conjunctival tissues constitutively express biologically active IL-33, suggesting that IL-33 might play a crucial role in the induction and augmentation of AC.
International Immunology 06/2010; 22(6):479-89. · 3.41 Impact Factor
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Hiroto Ishikawa,,
Naohiro Ikeda,,
Sanae Kanno,,
Tomohiro Ikeda,, Osamu Mimura,,
Mari Dezawa
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ABSTRACT: In considering ways that physics has helped advance biology and medicine, what typically comes to mind are the various tools used by researchers and clinicians. We think of the optics put to work in microscopes, endoscopes, and lasers; the advanced diagnostics permitted through magnetic, x-ray, and ultrasound imaging; and even the nanotools, that allow us to tinker with molecules. We build these instruments in accordance with the closest thing to absolute truths we know, the laws of physics, but seldom do we apply those same constants of physics to the study of our own carbon-based beings, such as fluidics applied to the flow of blood, or the laws of motion and energy applied to working muscle.
Instead of considering one aspect or the other,Handbook of Physics in Medicine and Biology explores the full gamut of physics’ relationship to biology and medicine in more than 40 chapters, written by experts from the lab to the clinic.
The book begins with a basic description of specific biological features and delves into the physics of explicit anatomical structures starting with the cell. Later chapters look at the body's senses, organs, and systems, continuing to explain biological functions in the language of physics.
The text then details various analytical modalities such as imaging and diagnostic methods. A final section turns to future perspectives related to tissue engineering, including the biophysics of prostheses and regenerative medicine.
The editor’s approach throughout is to address the major healthcare challenges, including tissue engineering and reproductive medicine, as well as development of artificial organs and prosthetic devices. The contents are organized by organ type and biological function, which is given a clear description in terms of electric, mechanical, thermodynamic, and hydrodynamic properties. In addition to the physical descriptions, each chapter discusses principles of related clinical diagnostic methods and technological aspects of therapeutic applications. The final section on regenerative engineering, emphasizes biochemical and physiochemical factors that are important to improving or replacing biological functions. Chapters cover materials used for a broad range of applications associated with the replacement or repair of tissues or entire tissue structures.
04/2010; , ISBN: 1420075241
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ABSTRACT: The visual efficiency scale currently adopted to determine the legal grade of visual disability associated with visual field loss in Japan is not appropriate for the evaluation of disability regarding daily living activities. We investigated whether Esterman disability score (EDS) is suitable for the assessment of mobility difficulty in patients with visual field loss.
The correlation between the EDS calculated from Goldmann's kinetic visual field and the degree of subjective mobility difficulty determined by a questionnaire was investigated in 164 patients with visual field loss. The correlation between the EDS determined using a program built into the Humphrey field analyzer and that calculated from Goldmann's kinetic visual field was also investigated.
The EDS based on the kinetic visual field was correlated well with the degree of subjective mobility difficulty, and the EDS measured using the Humphrey field analyzer could be estimated from the kinetic visual field-based EDS.
Instead of the currently adopted visual efficiency scale, EDS should be employed for the assessment of mobility difficulty in patients with visual field loss, also to establish new judgment criteria concerning the visual field.
Nippon Ganka Gakkai zasshi 01/2010; 114(1):14-22.
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ABSTRACT: A case of acute lymphoblastic leukemia in which a variety of ophthalmic findings were observed.
A 27-year-old woman with acute lymphoblastic leukemia. Ocular findings were Roth's spot and serous retinal detachment. Fluorescein angiography revealed no clear leak point. Subsequently, the serous retinal detachment disappeared. Within 4 months after the initial diagnosis, cytomegalovirus (CMV) retinitis occurred, and further keratoconjunctivitis and serous retinal detachment recurred due to Graft-versus-Host Disease (GVHD), thus resulting in death 4 months later.
Cases in which patients with leukemia complicated by serous retinal detachment during the course often result in death. In the present case, CMV retinitis and keratoconjunctivitis occurred due to GVHD after serous retinal detachment, thus resulting in death 8 months after the initial diagnosis, therefore if serous retinal detachment is observed in a leukemia patient, it is necessary to perform periodical ophthalmologic examinations even after the ocular symptoms disappear.
Nippon Ganka Gakkai zasshi 01/2010; 114(1):28-33.
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ABSTRACT: To evaluate the pharmacological properties of cilostazol (CLZ), we examined its intraocular pressure (IOP) -lowering effect. CLZ is an inhibitor of Type III phosphodiesterase that increases intracellular cyclic AMP levels by restraining platelet aggregation, and has a potential protective effect against atherosclerosis. We attempted to apply it for use as an anti-glaucoma agent; however, the application of CLZ in the ophthalmic field is limited due to its poor water solubility. We attempted to enhance CLZ solubility using 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). The solubility of CLZ increased with increasing HPbetaCD concentrations, and 0.05% CLZ was dissolved in 10% HPbetaCD. Moreover, fine particle suspension of 0.5% CLZ in 5% HPbetaCD (soluble CLZ: ca. 0.027%) were prepared using a Microfluidizer, an impact-type emulsifying comminution device. In an in vitro transcorneal penetration experiment through the rabbit cornea, the CLZ penetration rate was dependent on the CLZ content of the solutions and suspensions. When a 0.05% CLZ ophthalmic solution was instilled into a rabbit eye, the absorption rate constant for CLZ into an aqueous humor was 0.0059+/-0.001 min(-1), and the elimination rate constant was 0.048+/-0.024 min(-1). Also CLZ ophthalmic solutions and fine particle suspension were examined to for their ability to reduce enhanced intraocular pressure (IOP) of rabbits in a darkroom. The instillation of 0.05% CLZ ophthalmic solutions and 0.5% CLZ fine particle suspensions into rabbit eyes reduced the enhanced IOP. These results demonstrate that the instillation of CLZ ophthalmic solutions and fine particle suspensions may represent an effective anti-glaucoma formulation.
Journal of oleo science 01/2010; 59(8):423-30. · 1.42 Impact Factor
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ABSTRACT: The aim of this article is to investigate the effect of transcorneal electrical stimulation (TES) on chorioretinal blood flow in healthy human subjects.
The chorioretinal blood flow of 10 healthy subjects was measured before and after TES by laser speckle flowgraphy and expressed as the square blur rate (SBR). The chorioretinal blood flow was determined before and immediately after TES and 0.5, 1, 1.5, 2, 2.5, 3, 24, and 40 h after TES in three different areas: the margin of the optic disc, a point located midway between the optic disc and macula, and the macula area. The SBR of the stimulated eye is expressed relative to the value of the fellow eye. The mean standardized blur ratio was calculated as the ratio of the standardized SBR to the baseline SBR. The changes of intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were determined after each measurement of the SBR. The ocular perfusion pressure (OPP) was calculated from BP and IOP.
The mean standardized blur ratio at the optic disc did not change significantly throughout the course of the experiment. However, the mean standardized blur ratio midway between the optic disc and macula and at the macula area were significantly higher after TES than that after sham stimulation at 3 and 24 h (P < 0.05, P < 0.01, respectively). At all times, the mean BP, PR, IOP, and OPP were not significantly different from the prestimulation values.
TES increases the chorioretinal blood flow in normal subjects with minimal effects on the systemic blood circulation and the IOP. The increase in chorioretinal blood flow may be one of the beneficial effects that TES has on ischemic retinal diseases.
Clinical Ophthalmology 01/2010; 4:1441-6.
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ABSTRACT: The ectopic distribution of synaptic ribbons in dendrites of mouse retinal bipolar cells was examined by using genetic ablation of metabotropic glutamate receptor subtype 6 (mGluR6), electron microscopy, and immunocytochemistry. Ectopic ribbons were observed in dendrites of rod and ON-cone bipolar cells in the mGluR6-deficient mouse but not in those of wild-type mice. The number of rod spherules facing the ectopic ribbons in mGluR6-deficient rod bipolar dendrites increased gradually during early growth and reached a plateau level of about 20% at 12 weeks. These ectopic ribbons were immunopositive for RIBEYE, a ribbon-specific protein, but the associated vesicles were immunonegative for synaptophysin, a synaptic-vesicle-specific protein. The presence of ectopic ribbons was correlated with an increase in the roundness of the invaginating dendrites of the rod bipolar cells. We further confirmed ectopic ribbons in dendrites of OFF-cone bipolar cells in wild-type retinas. Of the four types of OFF-cone bipolar cells (T1-T4), only the T2-type, which had a greater number of synaptic ribbons at the axon terminal and a thicker axon cylinder than the other types, had ectopic ribbons. Light-adapted experiments revealed that, in wild-type mice under enhanced-light adaptation (considered similar to the mGluR6-deficient state), the roundness in the invaginating dendrites and axon terminals of rod bipolar cells increased, but no ectopic ribbons were detected. Based on these findings and known mechanisms for neurotransmitter release and protein trafficking, the possible mechanisms underlying the ectopic ribbons are discussed on the basis of intracellular transport for the replenishment of synaptic proteins.
Cell and Tissue Research 10/2009; 338(3):355-75. · 3.11 Impact Factor
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ABSTRACT: To determine whether pyroglutamic acid (PGA) enhances the survival of retinal ganglion cells (RGCs) after optic nerve (ON) transection in vivo and RGCs in culture.
The RGCs of rats were retrogradely labeled by Fluorogold (FG)-soaked sponges placed on both superior colliculi. Seven days later, the ON was transected, and PGA was immediately injected into the vitreous. Seven or fourteen days later, the number of FG-labeled RGCs was counted on flat-mounted retinas to obtain the mean densities of FG-labeled RGCs. To determine whether the survival effect of PGA was related to excitatory amino acid transporter (EAAT), L-trans-pyrrolidine-2,4 dicarboxylate (PDC), a nonselective glutamate transport inhibitor, was injected into vitreous with the PGA. In primary retinal cultures, RGCs were identified as cells that were immunopositive to beta III tubulin three days after beginning the culture with and without PDC.
The mean density of FG-labeled RGCs was reduced from 2249 +/- 210 to 920 +/- 202 cells/mm(2) (p < 0.001) on day 7 after the ON transection. The mean density RGCs was significantly higher at 1213 +/- 159 cells/mm(2) after 0.5% PGA injection immediately after the ON transaction than eyes injected with the vehicle at 1007 +/- 122 cells/mm(2) (p = 0.035). One percent PGA was the most effective concentration for survival-promoting effects on RGCs, and the mean density of the RGCs was 1464 +/- 102/mm(2) (p < 0.001). Fourteen days after 1% PGA, the mean density of FG-labeled RGCs was significantly higher than that with vehicle (204 +/- 23/mm(2) versus 145 +/- 17 cells/mm(2); p < 0.01). Simultaneous application of 1% PGA and PDC blocked the survival effects of PGA on day 7 after ON transection. The presence of PGA increased the number of beta III tubulin-positive cells.
PGA promotes the survival of axotomized RGCs in adult mammalian retinas possibly mediated by the EAATs.
Current eye research 07/2009; 34(7):598-605. · 1.51 Impact Factor
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ABSTRACT: To investigate whether electrical stimulation promoted axonal regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) crush in adult rats.
Transcorneal electrical stimulation (TES), which stimulates the retina with current from a corneal contact lens electrode, was used to stimulate the eye. TES was applied for 1 h immediately after ON crush. Axonal regeneration was determined by anterograde labeling of RGC axons. To examine whether the axonal regeneration was mediated by insulin-like growth factor 1 (IGF-1) receptors, an IGF-1 receptor antagonist, JB3, was injected intraperitoneally before each TES application. Immunostaining for IGF-1 was performed to examine the effects of TES. To test the survival-promoting effects of TES applied daily, the mean density of retrogradely labeled RGCs was determined on day 12 after ON crush.
Compared with sham stimulation, the mean number of regenerating axons significantly increased at 250 microm distal from the lesion and increased IGF-1 immunoreactivity was observed in retinas treated daily with TES. Preinjection of an IGF-1 receptor antagonist significantly blocked axonal regeneration by TES applied daily. TES applied daily also markedly enhanced the survival of RGCs 12 days after ON crush.
TES applied daily promotes both axonal regeneration and survival of RGCs after ON crush.
Japanese Journal of Ophthalmology 06/2009; 53(3):257-66. · 0.92 Impact Factor
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ABSTRACT: The development of a device to enable the visually disabled to differentiate eye drops and their dose.
The new instrument is composed of a voice generator and a two-dimensional bar-code reader (LS9208). We designed voice outputs for the visually disabled to state when (number of times) and where (right, left, or both) to administer eye drops. We then determined the minimum bar-code size that can be recognized. After attaching bar-codes of the appropriate size to the lateral or bottom surface of the eye drops container, the readability of the bar-codes was compared.
The minimum discrimination bar-code size was 6 mm high x 8.5 mm long. Bar-codes on the bottom surface could be more easily recognized than bar-codes on the side.
Our newly-developed device using bar-codes enables visually disabled persons to differentiate eye drops and their doses.
Nippon Ganka Gakkai zasshi 02/2009; 113(1):5-10.
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ABSTRACT: Interleukin-18 (IL-18) is a pleiotropic cytokine expressed in both immune and non-immune cells. In the present study, we demonstrate an anti-apoptotic role of IL-18 in normal human neonatal foreskin epidermal keratinocytes (NHEK-F). Cultured NHEK-F spontaneously produced the active form of IL-18. Treatment of NHEK-F cells with anti-IL-18 receptor alpha-chain neutralizing antibody increased apoptosis and caspase-3 activity. Exogenous IL-18 augmented phosphorylation of Akt and activation of NF-kappaB. The promotion of Akt phosphorylation by IL-18 was abolished by LY294002, a PI3K inhibitor, but not SN50, an NF-kappaB inhibitor, indicating that IL-18 functions via the PI3K/Akt pathway and independently of NF-kappaB. In addition, IL-18 was found to augment expression of anti-apoptotic proteins, Bcl-2, XIAP and glucose regulated protein78/BiP, while anti-IL-18 receptor alpha-chain neutralizing antibody suppressed expression of Bcl-2, XIAP, glucose regulated protein94 and protein disulfide isomerase. Taken together, these results indicate that IL-18 plays an important role in keratinocyte survival.
The Journal of Dermatology 09/2008; 35(8):514-24. · 1.49 Impact Factor
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ABSTRACT: Cilostazol (CLZ), a selective inhibitor of cyclic nucleotide phosphodiesterase 3, has been shown to reduce neuronal cell death after a transient cerebral infarction. The mechanism for this reduction was suggested to be an elevation of intracellular cAMP or an inhibition of tumor necrosis factor alpha. Optic nerve injury leads to retinal ganglion cell (RGC) death possibly from a deprivation of neurotrophic factors and/or the down-regulation of intracellular cAMP. The purpose of this study was to determine if CLZ can rescue RGCs after optic nerve transection by inhibiting cyclic nucleotide phosphodiesterase 3. To examine this, the mean densities of surviving RGCs after optic nerve transection were determined in retinas that received an intravitreal injection of CLZ and in retinas that received vehicle. Our results showed that the density of surviving RGCs in the retina with intravitreal CLZ were significantly higher than that with vehicle injection on day 7. The CLZ was effective in promoting the survival at more than 0.05% concentration. The neuroprotective effects induced by 0.05% CLZ could be observed even 14 days after optic nerve transection. Furthermore, combined application of protein kinase A (PKA) inhibitor, KT5720 (10 microM) and 0.05% CLZ significantly decreased the density of surviving RGCs compared to that with only 0.05% CLZ. Based on these data, we concluded that CLZ enhances the survival of axotomized RGC in vivo, possibly depending on the activation of PKA pathway.
Neuroscience Letters 06/2008; 436(2):116-9. · 2.11 Impact Factor
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ABSTRACT: Purpose: To report electrophysiological and psychophysical findings in an unusual case with acute loss of the peripheral visual field bilaterally.
Methods: A 19-year-old woman underwent fundus photography, fluorescein angiography, visual field testing, determination of full-field electroretinograms (ERGs) and multifocal ERGs (mfERGs), and rod-cone perimetry in addition to routine ophthalmologic examinations.
Results: Findings of fundus examination and fluorescein angiography were completely normal, and best-corrected visual acuity was 1.0 in both eyes. However, static perimetry revealed a temporal field defect in the right eye and an arcuate scotoma in the left eye. Full-field ERG cone responses were significantly reduced, but rod responses were normal in both eyes. Psychophysical rod-cone perimetry demonstrated that the peripheral cone system was impaired whereas the rod sensitivity was completely normal. mfERGs showed that the local cone responses were well preserved in the central retina but were severely reduced in the peripheral retina in both eyes.
Conclusions: These results indicate that there is an unusual retinopathy showing acute dysfunction of the peripheral cone system bilaterally whereas the rod system is functioning normally.
Retinal Cases & Brief Reports 12/2007; 2(3):193-195.
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ABSTRACT: The cornea is sensitive to nociceptive stimuli and receives dense sensory innervations from the trigeminal ganglion, which also innervates the upper eyelid. We investigated the morphological and immunohistochemical characterization of the trigeminal ganglion neurons innervating the cornea and upper eyelid. We injected the retrograde tracer Fluoro-Gold (FG) into the cornea and the retrograde tracer cholera toxin subunit b (CTb) into the upper eyelid of the same animal. Less than 10% of the FG-labeled neurons were also labeled with CTb. The FG-labeled neurons were small (29.6+/-0.6microm), while the CTb-labeled neurons were large (36.1+/-0.5microm). We also characterized the neurons in the trigeminal ganglion with the retrograde tracer FG following its injection into the cornea or the upper eyelid, and immunohistochemical double-labeling with nociception-related neuronal markers, such as calcitonin gene-related peptides (CGRP), transient receptor potentiated vanilloid 1 (TRPV1), and substance P (SP). About 27% of the neurons innervating the cornea were double-labeled with CGRP, about 23% with TRPV1, and about 8% with SP. About 4% of the neurons innervating the upper eyelid were double-labeled for CGRP, about 11% for TRPV1, and 3% for SP. Thus, the percentages of double-labeled neurons for the neurons innervating the cornea were higher than those for the neurons innervating the upper eyelid. These results indicate that the cornea and the upper eyelid receive innervations mainly from different neurons of the trigeminal ganglia. The cornea is innervated by many characteristic sensory neurons containing nociception-related neuronal markers.
Journal of Chemical Neuroanatomy 12/2007; 34(3-4):95-101. · 2.43 Impact Factor
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ABSTRACT: Xylazine, an alpha-2 adrenergic agonist, activates the endogenous trophic factors and neuronal survival signaling. Here, we tested the regenerative effect of xylazine on damaged optic nerve axons in adult rats. After optic nerve crush, xylazine was intraperitoneally injected into three groups of rats: a single administration immediately after the crush, intermittent administration, and daily administration. On day 14, the regenerated axons were quantitatively evaluated by anterograde labeling. Everyday administration but neither single nor intermittent administration markedly increased the number of labeled axons beyond the crush site, with upregulation of growth-associated protein-43 in the ganglion cell layer and the regenerated axons. It was concluded that xylazine promotes axonal regeneration in damaged optic nerves of adult rats.
Neuroreport 11/2006; 17(14):1525-9. · 1.66 Impact Factor
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ABSTRACT: Both extracellular superoxide dismutase (EC-SOD) and heparin binding EGF like growth factor (HB-EGF) are produced in smooth muscle cells of the arterial wall, and are thought to play pathological roles in atherosclerosis with heparin binding characteristics. EC-SOD treatment clearly reduced the H2O2 induced expression of HB-EGF in rat aortic smooth muscle cells (RASMC). EC-SOD also inhibited the induction of HB-EGF by 12-O-tetradecanoylphorbol-13-acetate (TPA) in RASMC by 60%. Both H2O2 and TPA increased intracellular ROS levels, and EC-SOD inhibited ROS generation only for the case of H2O2 but not TPA. Treatment of the cells with heparin alone decreased HB-EGF expression by 20%, whereas EC-SOD alone and a co-incubation with EC-SOD and heparin suppressed the induction by 60 and 70%, respectively. These results suggest that EC-SOD is related to the EGF signaling in two ways, competition for HSPG with HB-EGF and as an ROS scavenger.
Free Radical Research 07/2006; 40(6):589-95. · 2.88 Impact Factor
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ABSTRACT: We investigated the role of monocyte chemoattractant protein-1 (MCP-1) in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular permeability and the underlying molecular mechanism of VEGF-induced endothelial MCP-1 expression in vitro and in vivo.
We used an anti-MCP-1 neutralizing antibody for specific inhibition of MCP-1. VEGF increased tubule formation in the angiogenesis assay and vascular permeability in the Miles assay, and these effects were markedly inhibited by anti-MCP-1 antibody. Using a luciferase MCP-1 promoter-gene assay, we found that the activator protein-1 (AP-1) binding site of the MCP-1 promoter region contributes to the increase in MCP-1 promoter activity by VEGF. To specifically inhibit AP-1, we used recombinant adenovirus containing a dominant-negative c-Jun (Ad-DN-c-Jun). Ad-DN-c-Jun inhibited VEGF-induced endothelial MCP-1 mRNA expression and promoter activity in vitro. In vivo gene transfer of DN-c-Jun into rat carotid artery, with the hemagglutinating virus of the Japan liposome method, significantly blocked VEGF-induced MCP-1 and macrophage/monocyte (ED1) expression in endothelium.
These results reveal that endothelial MCP-1 induced by VEGF seems to participate in angiogenesis, vascular leakage, or arteriosclerosis. AP-1 plays a critical role in the molecular mechanism underlying induction of MCP-1 by VEGF.
Arteriosclerosis Thrombosis and Vascular Biology 12/2003; 23(11):1996-2001. · 6.37 Impact Factor
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ABSTRACT: We have revealed previously that the survival rate of beta cells of cat retinal ganglion cells (RGCs) rapidly decreased to 29% on day 7 after optic nerve transection, whereas that of alpha cells slowly decreased to 64% on day 14 (Watanabe et al., 2001). The reason that beta cells die more rapidly than alpha cells was not clear. In the present study, we tested the possibility that the rapid death of beta cells is attributable to apoptosis, as shown for some axotomized RGCs in rats. The following results were obtained. First, the proportion of pyknotic cells in Nissl-stained cat retinas started to increase sharply starting on day 4 and reached a peak on day 6 after optic nerve transection. The time course of occurrence of pyknotic cells corresponded well with that of the rapid death of axotomized beta cells. Secondly, the proportion of pyknotic cells was the highest in the area centralis (AC), in which beta cells are densely distributed. The preferential death of axotomized RGCs in the AC was also confirmed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining in cross sections. Thirdly, after the intravitreal injection of caspase 3 inhibitor (z-DEVD-cmk) the survival of axotomized beta cells on day 7 was significantly enhanced, whereas no such survival-promoting effect was obtained in axotomized alpha cells. Taken together, these results suggest that the rapid death of axotomized beta cells is attributable mainly to apoptosis, which is mediated by caspase 3.
Journal of Neuroscience 06/2003; 23(10):4023-8. · 7.11 Impact Factor
