PubMed Health⌕ Search

Biomedical subjects

H Inomata

Publications and source records attributed to H Inomata.

At least 55 records · Page 3Linked to original sources

Electroporation and bleomycin in glaucoma-filtering surgery.

PURPOSE: To develop a new treatment in glaucoma-filtering surgery using combined treatment with electroporation and the antiproliferative drug bleomycin. METHODS: Pigmented rabbits were treated with both bleomycin (10 micrograms/ml) and localized electric pulses (EP) using a special probe (5 V/cm, 100 msec, 8 pulses) (n = 10; group A). After EP treatment, bleomycin was washed out with 50 ml balanced salt solution, and then a posterior lip sclerectomy was performed on the same area. We also studied rabbits undergoing a posterior lip sclerectomy with bleomycin treatment alone (n = 10; group B), a posterior lip sclerectomy with EP treatment alone (n = 5; group C) and a posterior lip sclerectomy alone using the same operation (n = 5; group D, negative control). The intraocular pressure (IOP) was measured before and 1, 3, 5, 7, 10, 15, and 20 days after surgery. The formation of blebs, the conjunctiva, and the cornea were periodically examined by slit-lamp biomicrography. RESULTS: In every group, the IOP decreased until day 7, and no significant difference was observed among the four groups. In groups B, C, and D (control), the IOP increased gradually from day 10 and thereafter returned to the preoperative level after 15 days. However, in group A, the IOP remained lower than the preoperative level for 20 days; it was also significantly lower than each of the other three groups (P < 0.01). The survival rate of a filtering bleb was significantly higher in group A than in groups B, C, or D, but the survival rate in group B was not higher than groups C or D. No adverse effects were clinically observed in the ocular tissue, such as the cornea and conjunctiva. CONCLUSIONS: The combined treatment with EP and bleomycin was found to decrease IOP more prominently than EP or bleomycin treatment alone in filtering surgery. This treatment thus makes filtering surgery effective by decreasing the dose of the antiproliferative drug and by possibly localizing the drug delivery.

Animals↗

[Intraocular neovascularization].

To investigate the mechanism of intraocular neovascularization, we studied how vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are expressed in the ocular tissues under hypoxic conditions. Prior to proliferation of vascular endothelial cells resulting in neovascularization, the retinal tissues such as pericytes, retinal glial cells, ganglion cells, and ciliary epithelium react directly to hypoxia expressing VEGF and/or IL-8 and stimulate endothelial cell proliferation in a paracrine manner. We demonstrated that transcription factor activator protein-1 (AP-1) is activated for expression of VEGF messenger ribonuculeic acid (mRNA) and in a similar way nuclear factor kappa B (NF-kappa B) is activated for expression of IL-8 mRNA. However, hypoxia-induced expression of VEGF and/ or IL-8 is only one aspect of the complicated processes in intraocular neovascularization. We hope that further detailed analysis of the mechanism will make it possible to inhibit and treat clinically intraocular neovascularization in the near future.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[Inhibitory effect of vitamin E succinate on the proliferation of cultured bovine choroidal endothelial cells].

We report the effect of vitamin E succinate (VE succinate) on the proliferation of cultured bovine choroidal endothelial cells (BCECs). BCECs were incubated with a medium containing vitamin E (VE) or one of the VE derivatives gamma-tocopherol, VE phosphate, VE succinate, VE nicotinate, VE acetate, or trolox, at a concentration of 10 microM. The proliferation of BCECs was assessed by 3H-thymidine uptake and cell counting. Especially in VE and VE succinate, the proliferation assay was performed on BCECs at two different stages, that is, the proliferating stage and the quiescent stage. The effect of protein kinase C (PKC) stimulator phorbol ester (PMA) on the VE succinate-induced inhibition of BCEC proliferation was also examined. VE succinate was found to significantly inhibit BCEC proliferation at a concentration of 10 microM or greater both by 3H-thymidine uptake assay and by cell counting. This inhibitory effect was not noted in other VE derivatives. The inhibitory effect was the most prominent in the proliferating BCECs and co culture of PMA. VE succinate inhibits the proliferation of cultured BCECs and PKC is involved in this action at least in part.

Animals↗

Differential effects of diltiazem and nitroglycerin on cytosolic Ca2+ concentration and on force in the bovine ophthalmic artery.

PURPOSE: To determine the mechanisms of inhibition by diltiazem (Dil) and nitroglycerin (NG) of the contraction induced by serotonin (5-HT) in the ophthalmic artery. METHODS: Using front-surface fluorometry of fura-2 and the medial strips of the bovine ophthalmic artery, [Ca2+]i and force were monitored simultaneously. Changes in the force at a constant [Ca2+]i were determined by use of receptor-coupled membrane permeabilization with alpha-toxin. RESULTS: In the presence of extracellular Ca2+, 5-HT (10(-5) M) induced an initial transient and subsequently lower steady state elevation of [Ca2+]i. The transient elevation of [Ca2+]i was dependent on both intracellular and extracellular [Ca2+]i, whereas the steady state elevation was dependent on only extracellular Ca2+. For a given level of elevation of [Ca2+]i, 5-HT produced a greater force than the depolarization with high external K+ (118 mM) solution. In the permeabilized ophthalmic artery smooth muscle, 5-HT enhanced the contractile response to constant cytosolic Ca2+ (pCa 6.5) in the presence of guanosine triphosphate (GTP, 10 microM), but not in its absence. Therefore, 5-HT induces [Ca2+]i elevation, depending on both extracellular (Ca2+ influx) and intracellular Ca2+ (Ca2+ release), and it potentiates the Ca2+ sensitivity of the contractile apparatus through the activation of G-proteins. 5-HT-induced release of Ca2+ from the store was inhibited by NG, but not by Dil, in a concentration-dependent manner. However, neither NG nor Dil inhibited caffeine (20 mM)-induced release of Ca2+ from the store. Dil (10 microM) and NG (10 microM) inhibited in a concentration-dependent manner the steady state elevations of [Ca2+]i (Ca2+ influx) and force induced by 5-HT (10 microM) in the presence of extracellular Ca2+. Dil equally inhibited the steady state elevations of [Ca2+]i and force induced by 5-HT, whereas NG inhibited the force to a greater extent than expected from the reduction in [Ca2+]i. In the permeabilized ophthalmic artery smooth muscle, NG (10 microM), but not Dil (10 microM), decreased the force development induced by GTP (10 microM) and 5-HT (10 microM) at constant [Ca2+]i (pCa 6.5). These results indicate that NG, but not Dil, decreases the Ca2+ sensitivity of contractile apparatus. CONCLUSIONS: The authors found that 5-HT contracts the ophthalmic artery smooth muscle by the elevation of [Ca2+]i mediated by the release of intracellular Ca2+ and the influx of extracellular Ca2+, as well as by an increase in the Ca2+ sensitivity of the contractile apparatus through the activation of G-proteins, and that Dil relaxes 5-HT-mediated contraction of ophthalmic artery primarily by inhibiting the Ca2+ influx and, hence, by decreasing [Ca2+]i without having any effect on the Ca2+ sensitivity of the contractile apparatus. Nitroglycerin relaxes the ophthalmic artery not only by decreasing [Ca2+]i (inhibition of both the Ca2+ release and Ca2+ influx) but also by decreasing the Ca2+ sensitivity of the contractile apparatus.

Animals↗