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Biomedical subjects

H Inomata

Publications and source records attributed to H Inomata.

At least 19 recordsLinked to original sources

High D-glucose stimulates the cell cycle from the G1 to the S and M phases, but has no competent effect on the G0 phase, in vascular smooth muscle cells.

The effects of high (28mM) D-glucose (HG) on the cell cycle progression were investigated in rat aorta vascular smooth muscle cells (VSMCs) in primary culture, using an immunocytochemical analysis of cell-cycle-specific nuclear antigens. HG had no effect on the cell cycle of the serum-deprived G0 cells, whereas platelet-derived growth factor (PDGF) stimulated the entry of the G0 cells to the G1 phase without a further progression to the S and M phases. HG, but neither mannitol nor L-glucose, stimulated the progression of the PDGF-pretreated G1 cells to the S and M phases, which was blocked by calphostin-C, a protein kinase C (PKC) blocker. HG did not affect the cytosolic Ca2+ concentration ([Ca2+]i). These data suggest that HG has no competent effect on the G0 cells and acts as a progression growth factor (to stimulate the cell cycle from the G1 to the S/M) in VSMCs through the mechanism, which may be insensitive to [Ca2+]i and mediated by PKC.

Animals

Hypoxia-induced expression of vascular endothelial growth factor by retinal glial cells promotes in vitro angiogenesis.

To determine whether retinal glial cells (RGCs) participate in the paracrine regulation of retinal neovascularization, we investigated whether cultured RGCs synthesize and release vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) under normoxic or hypoxic conditions. Northern blot analysis demonstrated that cultured RGCs transcribed both VEGF mRNA with two molecular bands approximately 3.9 and 4.3 kilobases (kb), and bFGF mRNA with approximately 3.7 and 6.0 kb. The expression of VEGF mRNA was greatly enhanced by hypoxic cultivation (2% oxygen) when compared with normoxic cultivation (20% oxygen), while the expression of bFGF mRNA by RGCs was not significantly affected by hypoxia. The effects of RGCs-conditioned media (CM) on tritiated-thymidine incorporation and in vitro angiogenesis by retinal capillary endothelial cells (RECs) in producing the formation of capillary-like tubes in type I collagen gels, were evident in the observation that RGCs-CM harvested after hypoxic cultivation significantly enhanced tritiated-thymidine incorporation (1.9 times, P < 0.01) and in vitro angiogenesis (2.4 times, P < 0.01) compared with the normoxic RGCs-CM. These enhancing effects of RGCs-CM at hypoxia were suppressed by anti-VEGF neutralizing antibody. Furthermore, RECs were shown to express mRNA encoding the VEGF receptor flt-1 by northern blot analysis. These results suggest that VEGF expressed by RGCs under hypoxic conditions plays an integral role in the initiation and progression of retinal neovascularization in a paracrine manner.

Animals

Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels.

In rat diabetic retinas, we immunohistochemically looked for vascular endothelial growth factor (VEGF) which is also known as vascular permeability factor (VPF). In nondiabetic retinas, VEGF immunoreactivity was weak and restricted to the nerve fiber and ganglion cell layers. On the other hand, in diabetic retinas, VEGF immunoreactivity was markedly increased and was observed in all layers of the retina, especially in the perivascular area. Hyperpermeability of these vessels was confirmed by immunohistochemically detecting extravasation of albumin. These findings indicate that vascular endothelial growth factor plays an important role in blood-retinal barrier breakdown in diabetic retinopathy.

Actins

Proliferative vitreoretinopathy in Coats' disease. Clinicohistopathological case report.

We report the clinicohistopathological findings of the proliferative vitreoretinopathy in an eye with Coats' disease using the tissue obtained during surgery. A 28-year-old man, who had experienced poor vision in his right eye for a period of 4 years, was referred to our hospital. Examination revealed an extensive yellow exudate in the subretinal space and a tractional retinal detachment. Prominent teleangiectatic retinal vessels were also temporally present. Evident epiretinal membranes were present in the postequatorial area. We performed a scleral buckling, vitrectomy, membrane peeling, endophotocoagulation and silicone oil tamponade. A histological examination revealed that the epiretinal membrane consisted of collagen fibers, glial proliferation, foam cells and lymphocytes. The foam cell in the epiretinal membrane is a characteristic finding in an eye with Coats' disease.

Adult

Subretinal neovascularization in the rat induced by IRBP synthetic peptides.

The present study was undertaken to develop a new animal model of subretinal neovascularization that does not involve traumatic manipulation of the eye. Using this model, the mechanism of subretinal neovascularization and its penetration through Bruch's membrane, and the various factors that contribute to this process were then examined. Male Lewis rats were immunized with interphotoreceptor retinoid binding protein (IRBP) peptide R-4, and the eyes histologically examined at various times up to 45 days after immunization. On day 12 after immunization, inflammatory cells were identified primarily in the anterior segment of the eye, with scattered cells in the retina and choroid. The inflammation was most prominent on day 14, by which time many eyes showed serous retinal detachment. By day 18 the inflammation had declined in intensity, but branches of the retinal vessels were seen extending into the choroid. Examination on day 30 revealed even fewer inflammatory cells but an accumulation of retinal pigment epithelial cells and mononuclear cells was present in the subretinal space. Examination on day 45 revealed no appreciable inflammation, but typical new vessels were found in the eyes from five of the 13 rats (38%) examined at that point. Mild inflammation of the retinochoroidal tissue can induce subretinal new vessels in rats, and this model will be useful for further study of subretinal new vessel formation.

Amino Acid Sequence

Anterior chamber angle vascularization in Sturge-Weber syndrome. Report of a case.

The case of a 20-year-old woman with a left-sided facial hemangioma and a homolateral glaucoma is reported, complete with the histology of a trabeculectomy specimen. Her left eye had an episcleral hemangioma and goniodysgenetic features in the anterior chamber angle, while the intraocular pressure was measured to be 45 mmHg. The left optic disc showed a large cupping and the left visual field was constricted. The right eye had no glaucomatous changes. Histological examination of the trabeculectomy specimen by both light and electron microscopy showed multiple congenital anomalies. There was a cluster of blood vessels in the trabecular meshwork. Abnormal accumulations of fine granular extracellular matrixes were observed in both the juxtacanalicular connective tissue and around the vascular structures. The lumen of Schlemm's canal was subdivided into three or four parts with few giant vacuole structures. The endothelial cells lining the inner wall of Schlemm's canal contained a well-formed basal lamina with many villi projecting into the lumen. These findings suggest that the multiple anomalies observed in the trabecular tissue may contribute to the manifestation of glaucoma in Sturge-Weber syndrome.

Adult

Collagen types in human posterior capsule opacification.

The fibrous type of human posterior capsule opacification was examined by electron microscopy and immunoelectron microscopy to determine which types of collagen were present. The opacification consisted of lens epithelial cells and a large amount of extracellular matrix. The extracellular matrix comprised collagen fibrils and basal lamina-like material. Immunoelectron microscopy revealed that collagen types I, III, and IV were present. Types I and III were localized to the collagen fibrils. Type IV was present in the basal lamina of the lens epithelial cells and in the basal lamina-like material of the extracellular matrix.

Aged

Necrotizing retinitis in severe combined immunodeficiency mice following intracameral inoculation of herpes simplex virus type 1.

Necrotizing retinitis in severe combined immunodeficiency (SCID) mice following intracameral inoculation of herpes simplex virus type 1 provided an experimental model for acute retinal necrosis in AIDS and other immunocompromised patients. In order to assess the involvement of the immunological response in the pathogenesis, adoptive transfer experiments were conducted. Without transfer, SCID mice developed predominantly unilateral necrotizing retinitis and died within 10 days. Transfer of immune serum lengthened the survival time but resulted in bilateral necrotizing retinitis. Two of 5 mice transferred with CD4+ T cells and none of 7 transferred with CD8+ T cells developed bilateral necrotizing retinitis. Our results indicate that ipsilateral retinal necrosis occurs with or without a specific immunological response, and that antibodies and/or CD4+ T cells accelerate the contralateral retinal necrosis.

Animals

The diagnostic use of low molecular weight keratin expression in sebaceous carcinoma.

Sebaceous carcinoma is an infrequent skin tumor and its histological features sometimes closely resemble those of squamous cell carcinoma (SCC) and basal cell epithelioma (BCE), which often leads to a misdiagnosis. In the present immunohistochemical study, however, sebaceous carcinoma exhibited quite a different expression of keratins from SCC and BCE. We immunohistochemically examined 26 excised specimens of sebaceous carcinoma, 10 of SCC and 12 of BCE of the eyelids, using two monoclonal antibodies against high molecular weight keratins, 34 beta B4 (68kd) and 34 beta E12 (56kd, 56.5kd, 58kd), and two monoclonal antibodies against low molecular weight keratins, 35 beta H11 (54kd) and CAM5.2 (39kd, 43kd, 50kd). The cases of sebaceous carcinoma were positive with 34 beta B4 (23%), 34 beta E12 (54%), 35 beta H11 (81%) and CAM5.2 (73%). Of the four anti-keratin antibodies used in this study, 35 beta H11 was negative in all cases of SCC or BCE. These findings indicate that when sebaceous carcinoma is suspected, but no fat staining appropriate materials are available, a monoclonal antibody against low molecular weight keratin, 35 beta H11 (54kd), can be a useful tool to immunohistochemically rule out both SCC and BCE.

Adenocarcinoma, Sebaceous

Experimental rat model of neovascularization arising from the optic disk.

A consistent animal model of intraocular neovascularization was developed in the rat. A vitreous hemorrhage was induced by an experimental incision through the pars plana in the right eye of 24 rats. One month after the incision, 21 eyes produced a definite posthemorrhagic neovascularization arising from the optic disk. Histologically, the newly formed vessels consisted of endothelial cells forming lumina and surrounding smooth muscle cells. The proliferating activity of these cells was confirmed by immunohistochemical staining for proliferating cell nuclear antigen. An electron-microscopic examination also revealed mitotic activity and the cytoplasmic budding of immature endothelial cells. The 24 left eyes served as controls and showed no evidence of neovascularization.

Animals

A reassessment of histologic classification and an immunohistochemical study of 88 retinoblastomas. A special reference to the advent of bipolar-like cells.

BACKGROUND: Despite perpetual efforts of investigators, the histogenesis of retinoblastoma is still in dispute and histologic classification satisfactorily predictive of prognosis does not seem to be in use. METHODS: The authors studied 88 cases of retinoblastoma clinicopathologically and immunohistochemically, paying special attention to the presence of a "bipolar-like cell" element that would be used as one of the criteria for the diagnosis of differentiated retinoblastoma. RESULTS: Twelve cases of retinoblastoma with the bipolar-like cell element in the absence of rosettes and 41 cases of the tumor with rosettes were classified as differentiated retinoblastomas. The other 35 cases without rosettes or bipolar-like cells were classified as undifferentiated tumors. Tumor cells forming rosettes usually had positive results for synaptophysin and neuron-specific enolase (NSE) and negative results for glial fibrillary acidic protein (GFAP) and S-100 protein; however, undifferentiated cells had negative results for these four antibodies. The bipolar-like cells had positive results for synaptophysin and NSE but negative results for GFAP and S-100 protein. Twelve tumors with bipolar-like cells that lacked rosettes showed no optic nerve invasion, and the patients had a significantly better prognosis (100% 5-year survival rate) than 35 patients with undifferentiated tumors (71% 5-year survival rate) (P < 0.01). CONCLUSIONS: The findings support a neuronal origin of the tumor and indicate that, not only the rosettes symbolizing the photoreceptor differentiation, but also other neuronal elements, such as bipolar-like cells, can be used as criteria for histologic classification of retinoblastoma.

Adolescent

Possible involvement of Ca(2+)-related inward current in P2-purinoceptor-mediated depolarization of the guinea-pig vas deferens.

The effect of a Ca2+ antagonist or Ca2+ chelator on the membrane responses elicited by P2-purinoceptor activation was examined in current- and voltage-clamped muscle from the guinea-pig vas deferens. The non-hydrolyzable ATP-analogue 5'-adenylylimidophosphate (AMP-PNP) depolarized the membrane and the associated inward current. Superfusion with Ca(2+)-free solution containing Co2+ or EGTA markedly suppressed the AMP-PNP-induced membrane response, thereby suggesting that the inward current responsible for the depolarizing effect of AMP-PNP may involve activation of a Ca(2+)-related conductance.

Adenylyl Imidodiphosphate

Immunohistochemical detection of extravasated fibrinogen (fibrin) in human diabetic retina.

In diabetic retinopathy, breakdown of the blood-retinal barrier is an early functional disorder that can cause retinal edema, which in turn results in visual disturbance. Hard exudates, composed mainly of lipid and proteinaceous material, are one sign of chronic retinal edema caused by long-standing leakage from the vessels due to breakdown of the blood-retinal barrier. Utilizing diabetic retinas in which hard exudates were present, we performed immunohistochemical staining for fibrinogen. Because fibrinogen is a serum protein, its extravascular localization implies the existence of blood-retinal barrier breakdown. Our studies showed that the extravasated fibrinogen from blood-retinal barrier breakdown accumulated in the hard exudates and in areas of hemorrhage found primarily in the outer plexiform layer and was then phagocytosed by macrophages.

Aged

A case of amniotic band syndrome with bilateral epibulbar choristoma.

An autopsy case of amniotic band syndrome with bilateral epibulbar choristoma is described. The left eye reveals a complex choristoma and the right eye a dermis-like choristoma. Both choristomatous lesions included lenticular tissue suggesting that rupture of the amnion, which is the initial event of amniotic band syndrome, might have occurred at about the fourth week of gestation. Since the other systemic manifestations of amniotic band syndrome are considered to be compression deformities of the fetus caused by oligohydramnios or amniotic band, the occurrence of epibulbar choristomas in both eyes in this case suggests that a compression mechanism may play a role in the pathogenesis of epibulbar choristoma.

Adult

Goniodysgenesis of the eye with arthrogryposis multiplex congenita.

We report an autopsy case of 4-day-old male infant with arthrogryposis multiplex congenita studied by histological methods in respect to the ocular tissues. The eye examined was normal in size, and the retina, optic nerve, choroid, sclera and extracocular muscle showed no remarkable histological changes. However, the cornea was thickened, and the iris, trabecular tissue and ciliary body showed maldevelopmental changes, which were all compatible with goniodysgenesis. The clinical data of this case did not demonstrate any signs of congenital glaucoma, but the present study indicates that an infant with arthrogryposis multiplex congenita has a potential for infantile glaucoma with goniodysgenesis.

Abnormalities, Multiple

Concentration-related effects of extracellular application of ATP on the action potential and membrane currents of the guinea-pig vas deferens.

The ionic mechanisms underlying concentration-related alterations in the action potential configuration caused by ATP were studied using preparations of the guinea-pig vas deferens voltage-clamped by a double sucrose gap method. Under current-clamp conditions, ATP at concentration of 1.6 microM enhanced the rates of rise and of repolarisation of the action potential whereas at concentration of 1.6 mM it reduced both rates. Under voltage-clamp conditions, lower concentrations increased the maximum inward Ca current without altering kinetics or reversal potential. Higher concentrations reduced the maximum inward Ca current with slowing of rates of activations and inactivation, but also caused a negative shift in reversal potential without affecting conductance. These results suggest that a low ATP concentration activates the voltage-dependent Ca current channels and that the action of a high ATP concentration is related to the internal Ca ion concentration.

Action Potentials