PubMed Health⌕ Search

Biomedical subjects

H Inomata

Publications and source records attributed to H Inomata.

At least 19 recordsLinked to original sources
PubMed1997

Expression of vascular endothelial growth factor in experimental choroidal neovascularization.

BACKGROUND: Although the choroidal neovascularization (CNV) is a common pathologic feature of a number of different eye diseases, its pathological mechanisms have not been fully elucidated. We investigated the expression of vascular endothelial growth factor (VEGF) in CNV using an experimental primate model. METHOD: CNV was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 1, 3, 7 or 14 days after photocoagulation and examined immunohistochemically for VEGF, macrophage antigen, von Willebrand factor and glial fibrillary acidic protein (GFAP). Expression of VEGF mRNA was examined by in situ hybridization. RESULTS: One day after photocoagulation, the normal structure of the outer portion of the retina and the inner portion of the choroid was destroyed. Three days after photocoagulation, choroidal vascular endothelial cells migrated into the subretinal space through the defect in Bruch's membrane. Increased expression of VEGF was detected in the accumulating macrophages, migrating retinal pigment epithelial (RPE) cells and Müller cells. Maximal expression of VEGF was observed between 3 and 7 days after wounding, and many newly formed vessels extended into the subretinal space 7-14 days after photocoagulation. CONCLUSION: VEGF derived from RPE cells, macrophages and Müller cells may play a role in the formation of CNV.

Animals↗
PubMed1997

Effect of electric pulses and antiproliferative drugs on cultured bovine retinal pigment epithelial cells.

PURPOSE: The effect of antiproliferative agents with high voltage electric pulses (EP) on the proliferation of retinal pigment epithelial (RPE) cells was investigated. METHODS: Bovine RPE cells were cultured and exposed briefly to an antiproliferative agent: 0.005 to 500 microM of bleomycin (BLM), 0.005 to 500 microM of mitomycin C (MMC) or 0.05 to 5000 microM of 5-fluorouracil (5-FU) with or without high voltage electric pulses (EP: 2,000V/cm, 98 microseconds, 8 pulses). Streptomycin (SM) was used as a negative control. Cell proliferation with or without antiproliferative agents was assessed on day 3. DNA fragmentation was assessed by flow cytometric analysis. RESULTS: Treatment with BLM, MMC or 5-FU inhibited cell proliferation in a dose-dependent manner, with and without EP (p < 0.05). EP enhanced the inhibitory effect of BLM as much as 3,000 times (ID50: BLM without EP; 163.7 microM, BLM with EP; 0.0574 microM, MMC without EP; 132.4 microM, MMC with EP; 26.2 microM, 5-FU without EP; 616.4 microM, 5-FU with EP; 873.8 microM). EP treatment showed an inhibitory effect of BLM on cell proliferation more prominently than BLM alone. The cell numbers of 0.5 microM BLM treatment without EP were 87.4 +/- 11.7% (mean +/- SD), whereas the cell numbers of 0.5 microM BLM with EP were 21.1 +/- 2.16% (p < 0.005). BLM treatment with EP increased the apoptosis like DNA fragmentation in the flow cytometric DNA histogram, showing dominant accumulation in the A0 region, which is the population of DNA fragmentation. (The cell population of the A0 region: control, 3.4%; EP alone, 18.9%; BLM treatment without EP, 32.0%; with EP, 93.8%.) CONCLUSIONS: EP treatment enhances the inhibitory effect of BLM on RPE cell proliferation. The combination of electric pulse and BLM treatment can localize the drug effect and reduce the necessary dose of the antiproliferative agent in comparison to BLM treatment alone.

Animals↗
PubMed1997

Immunoelectron microscopic localization of the HNK-1 carbohydrate epitope in the anterior segment of pseudoexfoliation and normal eyes.

PURPOSE: To study the presence of the cell-adhesion related HNK-1 carbohydrate epitope in the anterior segment of pseudoexfoliation and normal eyes by immunoelectron microscopy. METHODS: Anterior segment tissue of 6 autopsy eyes with pseudoexfoliation (PEX) syndrome (5 eyes without glaucoma and 1 with glaucoma), and 6 normal autopsy eyes without PEX syndrome were studied by an electron microscopic immunogold technique using a monoclonal antibody to the HNK-1 epitope. RESULTS: In both normal and PEX eyes, the HNK-1 epitope could be immunolocalized to the basement membranes of both ciliary epithelia and posterior iris pigmented epithelium, to the lens capsule and zonular lamella, and to the pigmented epithelial cells of iris and ciliary body. Within the inner connective tissue layer of the ciliary body, the gold label was mainly associated with the periphery of elastic fibers and microfibrillar bundles. PEX material on the surfaces of posterior iris, ciliary body, anterior lens capsule, zonular fibers, and uveal part of the trabecular meshwork reacted strongly with the HNK-1 antibody. In contrast, PEX material accumulations within the iris stroma or the juxtacanalicular tissue of the trabecular meshwork showed only weak immunoreactivity, while PEX material in the conjunctiva was totally negative. CONCLUSIONS: The wide distribution of the HNK-1 epitope in anterior segment tissues and its association with a variety of extracellular and cellular structures was ultrastructurally demonstrated. In PEX syndrome, the varying labelling density of PEX fibers indicates a deviating carbohydrate composition in different locations of the eye. The HNK-1 epitope might be involved in the adhesiveness of PEX deposits on intraocular surfaces.

Aged↗
PubMed1997

[Nomenclature of the macular area].

There is a confusion in terminology of macular area of the retina. Particularly in Japanese, the word "fovea" has been used both for clinical term of the very center of the fovea (foveola) and for the anatomical term of fovea centralis. Therefore, whenever the term "fovea" is used in ophthalmology, one has to specify which meaning the word is being used for. This is the main reason why we propose to revise the nomenclature of the macular area. Based upon the historic background of histological findings regarding the macular area of the retina, the most suitable term instead for clinical use is discussed. In conclusion, we propose the term "macular foveola" or simply "foveola" for clinical use in place of the term "fovea". In this revision, the clinical terms will be macular area, macula (lutea), and macular foveola or foveola, and the anatomical terms, area centralis, macula (lutea), fovea centralis, and foveola. We hope this will eliminate the confusion in terminology of the macular area.

Fovea Centralis↗
PubMed1996

Ultrastructural age-related changes on the posterior iris surface. A possible relationship to the pathogenesis of exfoliation.

OBJECTIVES: To verify the presence of age-related changes in the human iris and to determine whether such changes could be related to the pathogenesis of the exfoliation syndrome. DESIGN: Ultrastructural examination of the posterior surface of the normal iris in 9 enucleated eyes. PATIENTS OR OTHER PARTICIPANTS: Eyes of persons aged 1 day, 3 months, and 3, 9, 27, 52, 59, 59, and 65 years. MAIN OUTCOME MEASURE: The presence of aging changes in the iris. RESULTS: Aging changes included duplication of the basal lamina of posterior iris pigment epithelial cells, formation of atrophic invaginations in the posterior cell membranes containing interlacing basal lamina, formation (or deposition) of microfibrils 11 to 13 nm in diameter, with a banding periodicity of 12 to 16 nm, deposition of electron-dense material in relation to the basal lamina and/or microfibrils, and the presence of some fine granular material overlying the basal lamina. CONCLUSION: These changes have been consistently described before in association with exfoliation material, which suggests the possibility that exfoliation is an eventual aging process.

Adult↗
PubMed1996

The ultrastructure of parapapillary chorioretinal atrophy in eyes with secondary angle closure glaucoma.

BACKGROUND: The present study was performed to investigate the ultrastructure of deep retinal layers and choroid corresponding to the parapapillary chorioretinal atrophy in eyes with secondary angle-closure glaucoma. METHODS: The glaucomatous eyes included two eyes enucleated due to iris ring melanoma with high intraocular pressure and one eye with neovascular glaucoma enucleated due to ocular pain. The control eyes included one eye enucleated due to choroidal malignant melanoma with normal intraocular pressure and one eye enucleated during surgery for supramandibular carcinoma. These eyes were studied with light and electron microscopy. RESULTS: In the region of parapapillary chorioretinal atrophy of glaucomatous eyes, the retinal pigment epithelial cells showed degenerative changes, such as loss of basal infoldings and microvilli, degenerated mitochondria, vacuolar degeneration and irregular distribution of melanin granules. The photoreceptors were decreased in number in this area of glaucomatous eyes. The lumen of the choriocapillary vessels adjacent to the optic nerve was collapsed. CONCLUSION: These results elucidate the fine structures of deep retina and choroid in the region of parapapillary chorioretinal atrophy of glaucomatous eyes, and suggest that the reduced choroidal perfusion might be the pathogenetic mechanism of glaucomatous parapapillary chorioretinal atrophy.

Adult↗
PubMed1996

Vitiligo in Vogt-Koyanagi-Harada disease: immunohistological analysis of inflammatory site.

BACKGROUND: Vogt-Koyanagi-Harada disease (VKH) consists of uveitis with associated non-ocular symptoms, such as vitiligo or central nervous system disorders. A cell-mediated immune disorder is believed to play an important role in VKH; however, the skin lesion has not been well studied. Therefore, for this study, we examined the skin of a 56-year-old Japanese man with Vogt-Koyanagi-Harada disease (VKH). METHODS: Skin biopsy specimens from the patient's vitiligo were obtained 1 month after the onset of ocular symptoms. Immunohistochemical analysis of the specimens study was performed using the following monoclonal antibodies: anti-T cell, anti-B cell, anti-major histocompatibility complex class II (HLA-DR), anti-T helper/inducer (CD4), and anti-T suppressor/ cytotoxic lymphocytes (CD8). RESULTS: Histopathologic analysis revealed mononuclear cell infiltration of the slightly edematous dermis, especially surrounding the hair follicles and sweat glands. Melaninladen cells in the epidermis were partially lost. The infiltrating mononuclear cells consisted primarily of T lymphocytes with a smaller number of B lymphocytes. Most showed expression of HLA-DR. CD4-positive lymphocytes were dominant over CD8-positive cells (3:1). CONCLUSIONS: The results indicate that vitiligo of VKH is infiltrated by mostly activated helper/inducer lymphocytes and that cell-mediated immunity plays an important role in the pathogenesis of the dermal lesions of VKH as well.

Antibodies, Monoclonal↗
PubMed1996

Histologic findings and prognosis of uveal malignant melanoma in japanese patients.

PURPOSE: To determine factors of uveal malignant melanoma that would help to predict prognosis in Japanese patients. METHODS: From 1969 to 1994, 23 eyes with uveal malignant melanoma were enucleated from 23 Japanese patients, and 16 of these patients were studied. In the 16 patients, enucleated eyes were evaluated for tumor characteristics, including cell type and microvascular architecture. Patient records were reviewed for follow-up therapy and outcome. Mortality rate was evaluated four years after enucleation. RESULTS: In Japanese patients with uveal malignant melanoma, the average tumor size was larger (average largest diameter, 11.36 mm; average increase, 6.25 mm) and the average patient age was younger (55.2 years old) than previously reported for white populations. Patients with spindle cell type melanoma tended to have a better prognosis than those with epithelioid cell type (four-year mortality rates: spindle cell type, 0%; mixed cell type, 43%; epithelioid cell type, 66%). Microvascular architecture patterns interpreted as either network or closed loop patterns were associated with a poorer prognosis (network pattern, P = .03; closed loop pattern, P = .005). CONCLUSIONS: The prognosis for Japanese patients with uveal malignant melanoma is poorer, and epithelioid cell-type melanoma is more common, than has been reported in white populations. Mitotic figures are well correlated with poor prognosis, as are two microvascular patterns, the network pattern and the closed loop pattern.

Adult↗
PubMed1996

Ciliary body band width as an indicator of goniodysgenesis.

PURPOSE: To evaluate the gonioscopic signs indicative of underdevelopment of the iridocorneal angle and thereby obtain a correct diagnosis of goniodysgenetic glaucoma. METHODS: We examined morphologically the iridocorneal angle of 28 enucleated human eyes, including those from premature infants as well as from older subjects. The ratio of the ciliary body band width to the width of the posterior limbus (the distance between the termination of Descemet's membrane and the iris root), termed the theoretic C/L ratio, was calculated by drawing on light micrographs. Data were compared for three age groups: premature infants, children, and subjects older than 9 years. We also examined clinically the appearance of the ciliary body band on gonioscopy in 135 eyes of 69 younger patients having primary glaucoma with open iridocorneal angles and in 94 eyes of 47 age-matched control subjects. RESULTS: The theoretic C/L ratio +/-SD was 1.4% +/- 2.7% in premature infants, 24.0% +/- 5.4% in children, and 36.7% +/- 8.0% in the older subjects. There was a statistically significant difference between each of the three groups (between premature infants and children, P < .001; between children and older subjects, P < .005; between premature infants and older subjects, P < .001). On gonioscopy, 105 of 135 glaucomatous eyes (77.8%) and 13 of 94 control eyes (13.8%) showed either an invisible or very narrow ciliary body band (P < .0001). CONCLUSION: The ciliary body band seen on gonioscopy provides an indicator of the development of the iridocorneal angle. An invisible or very narrow ciliary body band represents an underdevelopment of the angle.

Adolescent↗
PubMed1996

Ultrasound biomicroscopic analysis of transient shallow anterior chamber in Vogt-Koyanagi-Harada syndrome.

PURPOSE: To evaluate the mechanism of formation of the transient shallow anterior chamber in Vogt-Koyanagi-Harada syndrome. METHODS: Two patients with Vogt-Koyanagi-Harada syndrome with shallow anterior chambers were examined with an ultrasound biomicroscope. RESULTS: A ciliochoroidal detachment, which was not obvious on ophthalmoscopic examination, was clearly demonstrated in both patients by ultra-sound biomicroscopy. The detachment disappeared after systemic corticosteroid therapy. CONCLUSION: The shallowing of the anterior chamber in two patients with Vogt-Koyanagi-Harada syndrome was caused by suprachoroidal effusion secondary to inflammation of the uvea.

Anterior Chamber↗
PubMed1996

Neovascular tissue in the intertrabecular spaces in eyes with neovascular glaucoma.

AIMS/BACKGROUND: To investigate histological changes in the trabecular meshwork in eyes with neovascular glaucoma. METHODS: Light and electron microscopic studies were carried out on the trabecular meshwork of three enucleated eyes with neovascular glaucoma. The presence and distribution of factor VIII in the trabecular meshwork was assessed using the ABC method. RESULTS: Peripheral anterior synechiae covering the trabecular meshwork were detected in two eyes, which would explain the rise in intraocular pressure. In the third the angle was not completely closed by peripheral anterior synechiae. The spaces between the trabecular beams were lined by a single layer of vascular endothelium, and were filled with red blood cells in this patient. Factor VIII was positively stained in the endothelial cells, lining both these spaces and Schlemm's canal. A basal lamina and microfibrils were detected just beneath the newly formed vascular endothelial cells. CONCLUSION: The neovascular tissue found in the trabecular spaces might be one of the factors responsible for intraocular pressure elevation in eyes with neovascular glaucoma.

Adult↗
PubMed1996

Mechanisms of ionic currents involved in suppressive effect of isoprenaline on the action potential of guinea-pig vas deferens in normal Krebs solution.

The effects of beta-adrenoceptor stimulation by isoprenaline (ISO) on action potential and membrane current were studied in the guinea-pig vas deferens in normal Krebs solution by using a double sucrose gap method. In current-clamp experiments, ISO produced the membrane hyperpolarization by reducing the resistance and modified the pattern of multi-spike activity elicited by long depolarizing currents; an initial spike potential was reduced in the amplitude and the rate of rising phases and the slope of diastolic depolarization was slowered, leading to a prolongation of the spike discharge interval. In voltage-clamp experiments, ISO greatly enhanced the late outward K+ current (Ik2) by increasing the conductance, but hardly affected the peak outward K+ current (Ik1). ISO also reduced the inward Ca2+ current (Ica) by decreasing the conductance (ga) as well as by reducing the driving force for Ca2+. While it increased the leakage conductance (g1) due to K+ associated with hyperpolarizing voltage steps. In the preparations treated with Ca2+ channel blocker such as D-600, the enhanced effect of ISO on the Ik was still prominent, suggesting that Ca2+ and K+ channels appear to be independently regulated during beta-adrenoceptor stimulation. These results suggest that ISO exerts depressant actions on the vas deferens muscle by reduction of the Ica as well as by prominent enhancement of the Ik2 via beta-adrenoceptor activation.

Action Potentials↗
PubMed1996

Enhancement by dibutyryl cyclic AMP of voltage-dependent Ca2+ and K+ currents in the guinea-pig vas deferens.

This study was designed to investigate a possible role for intracellular cyclic AMP involved in agonist-induced changes in electrical activity of smooth muscle of the guinea-pig vas deferens. The action of dibutyryl adenosine 3', 5'-phosphate (dibutyryl cyclic AMP) (up to 30 microM) was examined in current- and voltage-clamp, using the double sucrose gap method. Under current-clamp, dibutyryl cyclic AMP clearly shortens the duration of action potential by hastening the rates of depolarization and of repolarization and increases the peak amplitude. Under voltage-clamp, dibutyryl cyclic AMP enhances the maximum ICa by increasing the conductance (ga), but without affecting its reversal potential (Ea) and kinetics in preparations in normal Krebs solution as well as in preparations in tetraethylammonium chloride loading solution. In normal Krebs solution, dibutyryl cyclic AMP also enhances the peak (Ib') and late outward K+ currents (Ib) by increasing the conductances (gb') and (gb), respectively. These results indicate that in vas deferens smooth muscle intracellular cyclic AMP may be of functional significance for activation of voltage-dependent peak and late IK channels as well as activation of voltage-dependent ICa channel.

Action Potentials↗
PubMed1996

Distribution and characterization of proteoglycans associated with exfoliation material.

PURPOSE: To examine the distribution of proteoglycans in the exfoliation materials in order to investigate the nature of the materials. METHODS: The anterior parts of two eyes with exfoliation syndrome were examined by electron microscopy after staining with cupromeronic blue (cmb). Some specimens were treated with enzymes and/or nitrous acid prior to staining. The effects of the enzymes were evaluated statistically by counting the density of the cmb-positive filaments in the exfoliation materials, using a computer. One eye with exfoliation syndrome stained with alcian blue was observed with light microscopy. RESULTS: Exfoliation materials were observed along the epithelial cells of the iris and ciliary body, and in the trabecular meshwork and zonules. In tissue specimens treated with cmb, electron-dense filaments were seen associated with the exfoliation materials. Microfibrils in the trabecular meshwork and iris, and zonular fibrils themselves were free of any filament staining, while the exfoliation materials located closely to the fibrils contained the electron-dense filaments. In the tissue specimens treated with chondroitinase AC, chondroitinase B, chondroitinase ABC or nitrous acid before cmb staining, the amount of the filament associated with exfoliation materials decreased in comparison to the controls. Digestion with keratinase did not demonstrate any significant changes in staining. A combination treatment with chondroitinase ABC and nitrous acid eliminated almost all filaments associated with the exfoliation materials. In the eye stained with alcian blue, the zonules that did not stain for the dye demonstrated an accumulation of exfoliation materials that stained strongly for alcian blue. CONCLUSIONS: Exfoliation materials contain chondroitin sulfate, dermatan sulfate, heparan sulfate proteoglycans. Depositions of proteoglycans on the microfibrils may be closely associated with the formation of exfoliation materials.

Aged↗
PubMed1996

The temporal and spatial vascular endothelial growth factor expression in retinal vasculogenesis of rat neonates.

Vascular endothelial growth factor (VEGF) has been identified as an endothelial cell-specific mitogen with potent angiogenic properties. VEGF is overexpressed in pathologic angiogenesis observed in tumor growth, rheumatoid arthritis, and retinal angiogenic diseases such as diabetic retinopathy and retinopathy of prematurity. VEGF expression in physiologic angiogenesis, i.e., vasculogenesis, has also been reported in the embryonic organs such as brain, kidney, spleen, and lung. However, the details of VEGF expression in vasculogenesis remain largely unclear. To determine if VEGF contributes to vasculogenesis in the developing tissues, VEGF expression was studied by both immunohistochemistry and in situ hybridization in newborn rat retinas on postnatal days 3, 7, 14, and 30. Vasculogenesis was assessed by both the ink perfusion method and a histologic examination. To identify the cell types of VEGF-expressing cells, immunohistochemistry for cell markers such as glial fibrillary acidic protein and von Willebrand factor was performed. On postnatal days 3 and 7, when retinal vasculogenesis was active, VEGF mRNA and protein(s) were prominently expressed in the ganglion cell and the inner nuclear layers. In rats, as well as humans, these two layers are where the retinal vessels develop, and these two layers depend solely on the retinal vessels. In addition to the ganglion and the inner nuclear layers, VEGF protein(s) were located in the endothelial cells of the developing vessels and the angioblasts, i.e., endothelial precursors. On postnatal day 14, when vasculogenesis became inactive, VEGF mRNA expression markedly decreased. These results indicated that VEGF expression in the developing retinas is temporally and spatially correlated with retinal vasculogenesis.

Animals↗
PubMed1996

The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas.

In the retinas of streptozotocin-induced diabetic rats, the relationship between the expression of vascular endothelial growth factor (VEGF) and the breakdown of the blood-retinal barrier (BRB) was investigated. VEGF mRNA expression was examined by in situ hybridization and VEGF protein expression was examined by immunohistochemistry. BRB breakdown was immunohistochemically demonstrated by detecting extravasation of albumin. In diabetic retinas, VEGF mRNA was expressed by the following cells: (a) ganglion cells, (b) glial cells such as astrocytes and Muller cells, whose cell processes are closely associated with retinal vessels, (c) smooth muscle cells and pericytes in the vessel walls, and (d) the retinal pigment epithelium. In diabetic retinas, BRB breakdown was immunohistochemically detected, and VEGF protein expression was markedly increased in comparison to that in the control retinas. The rates of both BRB breakdown and VEGF immunoreactivity increased in proportion to the duration of diabetes. In addition, the rate of BRB breakdown was much higher in vessels with VEGF immunoreactivity than in vessels without VEGF immunoreactivity. These findings indicate that VEGF has a major promoting effect on BRB breakdown in simple diabetic retinopathy. VEGF immunoreactivity was distributed throughout all layers of the retinas, and were most prominently observed in the nerve fiber layer, especially near the optic disc and around large vessels. These two regions coincide with the sites wherein BRB breakdown is clinically detected by fluorescein angiography in diabetic patients. Neovascularization in proliferative diabetic retinopathy is also most commonly observed in these two regions. Because VEGF promotes endothelial proliferation, these findings suggest that VEGF plays a role in the budding of retinal neovascularization and, as a result, could induce proliferative diabetic retinopathy.

Animals↗