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T Otsuji

Publications and source records attributed to T Otsuji.

At least 19 recordsLinked to original sources
PubMed2005

Ocular structure and function in an aged monkey with spontaneous diabetes mellitus.

Diabetes mellitus develops spontaneously in middle-aged, obese rhesus monkeys, thus making them a good model for examining the effects of co-morbid factors on the development of end-organ damage. Changes in structure and function in the eyes of one monkey who spontaneously developed type 2 diabetes are reported here. This animal had concomitant hypertension, high levels of triglycerides and serum cholesterol, and a low fraction of high-density lipoprotein. The eyes showed intraretinal hemorrhages and large areas of retinal capillary nonperfusion. Indo-cyanin green (ICG) angiography revealed a large area of non- or poorly perfused choriocapillaris in one eye, and immunohistochemistry showed loss of viable choriocapillaries in this region. Both basal laminar deposits and hard drusen were present on areas of Bruch's membrane adjacent to nonviable choriocapillaris. Blood flow via the nasal posterior ciliary arteries to this section of choroid was not detectable by color duplex Doppler ultrasound, indicating contribution of extraocular vascular disease to ischemia in this eye. There was a severe decline in number of photoreceptor inner and outer segments, and corresponding reductions in the multifocal electroretinogram (ERG), in the areas of choriocapillaris loss. The ganzfeld ERG indicated loss in both inner and outer retinal function. Much of the ganglion cell layer was absent throughout the retina, possibly reflecting the effect of diabetes as well as chronic open angle glaucoma; the latter diagnosis supported by elevated intraocular pressures and excavated optic disks. In summary, high resolution, enzyme histochemical and histopathological analyses of a diabetic hypertensive monkey retina and choroid after serial functional in vivo analyses have demonstrated the relationship between vascular dysfunction and visual function loss. Choroidal vascular dysfunction in both large and small vessels was associated with age-related macular degeneration-like changes in Bruch's membrane and photoreceptor degeneration.

Aging↗
PubMed2004

Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy.

AIMS: To determine whether pigment epithelium derived factor (PEDF), a protein that inhibits angiogenesis, is expressed in human choroidal neovascular membranes (CNVMs) and in tissues from an eye with polypoidal choroidal vasculopathy (PCV). In addition, to compare the expression of PEDF with that of vascular endothelial growth factor (VEGF), a known stimulator of angiogenesis, in these tissues. METHODS: CNVMs, associated with age related macular degeneration (AMD), angioid streaks, and PCV, were obtained during surgery. The expression of PEDF and VEGF in the excised subretinal fibrovascular membranes was determined by immunohistochemistry. RESULTS: PEDF and VEGF were strongly expressed in the vascular endothelial cells and retinal pigment epithelial (RPE) cells in the CNVMs where numerous new vessels were prominent (clinically active CNVMs). On the other hand, immunoreactivity for PEDF and VEGF was weak in the new vessels where fibrosis was prominent (clinically quiescent CNVMs). However, the RPE cells were still positive for PEDF and VEGF. The specimens from the eye with PCV also showed strong expression of PEDF and VEGF in the vascular endothelial cells and the RPE cells. CONCLUSION: Because PEDF is an inhibitor of ocular angiogenesis and an inhibitor of ocular cell proliferation, our results suggest that PEDF along with VEGF may modulate the formation of subfoveal fibrovascular membranes.

Aged↗
PubMed2001

Epstein-Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms.

To demonstrate the association of Epstein-Barr virus (EBV) with primary epithelial neoplasms in the south part of Kyushu, Japan, 761 carcinomas consisting of 75 lung, 61 breast, 107 esophagus, 102 colon, 58 pancreas, 45 thyroid, and 313 gastric cancers were examined by EBER-1 in situ hybridization. EBER-1 was detected in 23 cases (7.3%) out of 313 gastric carcinomas, while none of the other carcinomas was positive for EBER-1. Twenty-eight (9.4%) out of 313 gastric carcinomas were differentiated poorly to moderately carcinomas with prominent lymphoid cell infiltration, similar to so-called lymphoepithelioma-like carcinoma, and 19 cases (67.9%) were positive for EBER-1. Although two (2.6%) and 11(10.3%) out of 75 lung and 107 esophagus carcinomas were so-called lymphoepithelioma-like carcinomas, respectively, but EBER-1 was not detected in other epithelial neoplasms that originated from the lung, esophagus, breast, colon, pancreas, and thyroid in the south of Kyushu, Japan. As a result, EBV was associated with only some gastric carcinomas but not with other epithelial neoplasms originating from the lung, esophagus, breast, colon, pancreas, and thyroid in southern Japan.

Adenocarcinoma↗
PubMed2000

In vivo gene transfer into choroidal neovascularization by the HVJ liposome method.

PURPOSE: To evaluate the efficacy of the HVJ liposome method for gene transfer in rats with experimentally induced choroidal neovascularization. METHODS: Plasmid DNA containing the LacZ reporter gene, or fluorescein isothiocyanate (FITC)-labeled double-stranded phosphorothioate oligodeoxynucleotides (S-ODNs), was encapsulated in liposomes. The liposomes were coated with the envelope of inactivated hemagglutinating virus of Japan (HVJ). Intense laser burns were applied to the posterior pole of the retina of pigmented rats to induce choroidal neovascularization. Following photocoagulation, HVJ liposome suspension was injected into the vitreous. On days 3, 7, 14, and 28 after injection, the eyes were removed and fixed. The eyes injected with LacZ gene were reacted with X-gal, frozen, and cut into thin sections. The sections were examined for the expression of the LacZ gene by light microscopy. The enucleated eyes injected with double-stranded S-ODNs were frozen, cut into thin sections, and examined a confocal scanning laser microscope for FITC labeling. Eyes without injection of HVJ liposomes served as controls. RESULTS: Expression of LacZ genes (beta-galactosidase activity), or localization of FITC labeling, was observed mainly in the laser-induced choroidal neovascular tissue from 3 to 28 days after the intravitreal injection of HVJ liposome. CONCLUSIONS: We conclude that the HVJ liposome method achieved effective gene transfer into choroidal neovascular tissue. Thus, this method can be used as a nonviral gene therapy system for the treatment of choroidal neovascularization in vivo.

Animals↗
PubMed1999

Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization.

PURPOSE: Vascular endothelial growth factor (VEGF) is an angiogenic peptide that has been suggested to be important in the pathogenesis of choroidal neovascularization. We investigated the transcription of VEGF and its receptor KDR/flk-1 genes during the development of experimentally induced choroidal neovascularization. METHODS: Rat VEGF or KDR cDNA was inserted in PGEM or pBluescript to prepare antisense or sense riboprobes. Multiple krypton laser burns were applied to the posterior pole of pigmented rat eyes according to a previously described protocol which produces choroidal neovascularization. At intervals of up to 4 weeks after photocoagulation, the eyes were removed and cut into thin sections. The sections were subjected to in situ hybridization with digoxigenin (DIG)-labeled single-strand rat VEGF and KDR cDNA riboprobes. RESULTS: In normal adult rat retinas, VEGF and KDR mRNA expression was mainly observed in the ganglion cell and the inner nuclear layers. During the development of neovascularization, VEGF and KDR mRNAs were detected in retinal pigment epithelial-like cells, fibroblast-like cells and endothelial cells in neovascular lesions. The level of expression was strongest at 1 week after photocoagulation in lasered lesions, and decreased by 4 weeks after photocoagulation. CONCLUSIONS: Our findings demonstrate that expression of VEGF and its receptor KDR may play a role in the formation of experimentally induced choroidal neovascularization. In this study, VEGF and its receptor were co-localized, suggesting that an autocrine and/or paracrine mechanism may be operative.

Animals↗
PubMed1999

Phosphorothioate oligonucleotides induction into experimental choroidal neovascularization by HVJ-liposome system.

PURPOSE: The purpose of this study was to determine whether the inactivated hemagglutinating virus of Japan (HVJ)-liposome method can induce phosphorothioate oligonucleotides effectively into an experimentally-induced choroidal neovascularization of rats. We also examined whether antisense phosphorothioate oligonucleotides against VEGF could be induced into choroidal neovascularization as a therapeutic agent by the HVJ-liposome method. METHODS: The experiments were conducted on a rat model of choroidal neovascularization. FITC-labeled phosphorothioate oligonucleotides were coencapsulated in liposomes. The liposomes were coated with the envelope of inactivated HVJ and injected into the vitreous cavity following photocoagulation of pigmented rat eyes. The eyes were removed following injection, fixed, frozen and cut into thin sections. Induction of oligonucleotides was observed under a laser confocal scanning microscope for fluorescence and the development of choroidal neovascularization was evaluated histopathologically. RESULTS: Phosphorothioate oligonucleotides were effectively induced into ganglion cells and into the cells of the choroidal neovascularization induced by laser photocoagulation. Highly effective induction of oligos was observed 3 to 14 days after intravitreal injection of HVJ-liposomes after which the level decreased. Antisense oligonucleotides against VEGF were induced specifically into cells in the choroidal neovascularization, however neovascularization was still observed. CONCLUSIONS: Phosphorothioate oligonucleotides can be effectively induced into ganglion cells, and specifically into cells in choroidal neovascularization. Although antisense oligonucleotides against VEGF failed to prevent choroidal neovascularization, the HVJ-liposome method provided a highly effective means of inducing antisense oligos for in vivo antisense therapy.

Animals↗
PubMed1994

An experimental model of symptomatic vasospasm induced by oxyhemoglobin in rabbits.

BACKGROUND AND PURPOSE: There are many experimental models for studies of cerebral vasospasm. However, no ideal model has been established thus far to comparatively reproduce the ischemic state of the brain that may occur in patients after subarachnoid hemorrhage. METHODS: In the present study, we attempted to induce severe vasospasm in rabbits by using an oxyhemoglobin-rich blood product prepared from hemolyzed arterial blood and evaluate neurological symptoms, cerebral angiogram, cerebral blood flow, and histology. RESULTS: Clinically significant neurological symptoms were observed in about half of the rabbits. There was no significant correlation between angiographic results of the vasospastic state of the main artery and the severity of neurological symptoms observed. However, the cerebral blood flow was significantly lower than in the control group and significantly correlated with the severity of neurological symptoms. On histological examination, lesions were found in about half of the rabbits. Development of obvious infarction was found more frequently than in other reported models. CONCLUSIONS: These results suggest that this model is appropriate as an experimental model of vasospasm occurring after subarachnoid hemorrhage and is especially useful in that it induces vasospasm intense enough to cause obvious infarction.

Animals↗
PubMed1993

Platelet-activating factor and cerebral vasospasm following subarachnoid hemorrhage.

This study examines whether platelet-activating factor (PAF) is involved in the occurrence of vasospasm after subarachnoid hemorrhage (SAH). A vasospasm model was produced in rabbits, with animals in six experimental groups receiving two subarachnoid injections of autologous arterial blood with the addition of one of the following; saline (Control Group 1), 25% dimethyl sulfoxide (Control Group 2), PAF (1, 2.5, 5, or 10 micrograms), CV6209 (10 or 100 micrograms), BN52021 (10 or 100 micrograms), or anti-PAF immunoglobulin G (IgG, 50 or 500 micrograms). No significant differences were detected between Control Groups 1 and 2 with regard to neurological deterioration and basilar artery constriction after SAH was induced. Administration of PAF together with autologous blood aggravated neurological deficits in a dose-dependent manner (r = 0.724, p < 0.001) and produced basilar artery constriction at two doses each of 2.5 micrograms (p < 0.05), 5 micrograms (p < 0.01), and 10 micrograms (p < 0.01). Neurological deterioration was prevented in rabbits receiving an intracisternal administration of either PAF antagonist CV6209 or BN52021 or anti-PAF IgG (p < 0.01 at a total dose of 20 micrograms and p < 0.05 at a total dose of 200 micrograms CV6209, p < 0.01 at total doses of 20 and 200 micrograms BN52021, and p < 0.01 at total doses of 100 and 1000 micrograms anti-PAF IgG). A reduction in basilar artery constriction was achieved by the injection of anti-PAF IgG (p < 0.05 at total doses of 100 and 1000 micrograms). Histological examination at autopsy on Days 14 to 21 showed mainly ischemic changes in the brain, including selective neuronal necrosis and cerebral infarction. The control and PAF groups showed marked ischemic changes. On the other hand, no ischemic changes were noted in the anti-PAF IgG group, and only 9% of animals in the CV6209 group and 25% in the BN52021 group demonstrated selective neuronal necrosis or infarction. This study thus provides evidence to support the role of PAF in the pathogenesis of vasospasm after SAH.

Animals↗
PubMed1988

[Experimental cerebral vasospasm induced by oxyhemoglobin and the sympathetic nervous system (Part 1): Effect of alpha-adrenergic receptor blockers].

This study was performed as part of a series of investigations into the relation between cerebral vasospasm following subarachnoid hemorrhage and the sympathetic nervous system. We studied the effect of phenoxybenzamine chloride (POB) and prazosin hydrochloride (Prazosin) on the cerebral vasoconstriction in the basilar arteries of cats induced by application of oxyhemoglobin (Oxy-Hb), noradrenaline (Nor) and prostaglandin F2 alpha (PGF2 alpha). Adult cats were anesthetized with intramuscular pentobarbital and maintained on a respirator through a tracheostomy. By the transclival approach, a bone window was formed in the clivus, and the dura was opened, exposing the basilar artery. A cannule was inserted into the subarachnoid space, and through it, Oxy-Hb, Nor and PGF2 alpha were injected. The sequential changes in caliber of the basilar artery were measured using photography. First, we determined the doses of POB and Prazosin necessary for decreasing the vasoconstriction induced by Nor, and 20 mg/kg of POB and 10 mg/kg of Prazosin were found to decrease the vasoconstriction induced by 10(-3) M Nor, statistically. Second, we investigated the effect of 20 mg/kg of POB and 0.5 mg/kg and 10 mg/kg of Prazosin on the cerebral vasoconstriction induced by Oxy-Hb or PGF2 alpha. POB (20 mg/kg) was infused for 2 hours before the application of Oxy-Hb or PGF2 alpha. Prazosin was given intravenously. In the first group, 0.02% Prazosin (0.5 mg/kg) was administered intravenously for 1.5 hours before the application of Oxy-Hb or PGF2 alpha. In the second group, 1.5 hours elapsed between the beginning of Prazosin (10mg/kg) infusion and the application of Oxy-Hb or PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

[Experimental cerebral vasospasm induced by oxyhemoglobin and the sympathetic nervous system (Part 2): An investigation into denervation supersensitivity].

UNLABELLED: The pathological mechanism of cerebral vasospasm following subarachnoid hemorrhage has not been well clarified until now. There have been reports that denervation supersensitivity in cerebral vessels occurring after subarachnoid hemorrhage may possible play a role in the appearance of cerebral vasospasm. On the other hand, we have accepted that oxyhemoglobin (Oxy-Hb) is an important spasmogenic substance. In the present study, we investigated the effect of chemical denervation (reserpine or 6-hydroxydopamine: 6-OHDA) and surgical denervation (bilateral superior cervical ganglionectomy: SCG) on the constrictive sensitivity of cat basilar arteries to noradrenaline (Nor) and oxyhemoglobin (Oxy-Hb) in situ. METHOD: Adult cats were anesthetized with intramuscular pentobarbital and maintained on a respirator through a tracheostomy. By the transclival approach, the basilar artery was exposed. A cannula was then inserted into the subarachnoid space, and through it, Oxy-Hb and Nor were injected. The sequential changes in caliber of the basilar artery were measured using photography. SCG was done 7 days before the application of Nor or Oxy-Hb and 14 days before application of Oxy-Hb. Pretreatment with reserpine was done as follows: 1 mg/kg of reserpine was injected subcutaneously once each day for 2 days. On the following day, the sensitivity of the basilar arteries to Nor or Oxy-Hb was assessed. Pretreatment with 6-OHDA was done as follows: 5 mg of 6-OHDA was dissolved in 1.0 ml of artificial CSF, and then injected into the cisterna magna. Seven days later, Nor or Oxy-Hb was applied. RESULTS: Pretreatment with reserpine tended to increase the vasoconstriction induced by 10(-7)-10(-4) M of Nor and the constriction induced by 10(-3) M of Nor was increased statistically (P less than 0.05). Cisterna magna injection of 6-OHDA tended to increase the vasoconstriction induced by Nor. SGG tended to increase the vasoconstriction induced by 10(-7)-10(-4) M of Nor and at a dose of 10(-3) M of Nor, the constriction of the basilar arteries was increased statistically (P less than 0.05). However, pretreatment with reserpine, 6-OHDA and SCG did not increase the vasoconstriction induced by Oxy-Hb. These results lead us to suggest that denervation supersensitivity does not participate in the vasoconstriction induced by Oxy-Hb.

Animals↗