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Biomedical subjects

H Inomata

Publications and source records attributed to H Inomata.

At least 19 recordsLinked to original sources
PubMed2003

Separation of cashew (Anacardium occidentale L.) nut shell liquid with supercritical carbon dioxide.

Cashew nut shell liquid (CNSL) represents the largest readily available bioresource of alkenyl phenolic compounds. In this work, separation of CNSL from the pericarp of the cashew nut with supercritical carbon dioxide was studied. In the initial extractions with CO(2) at 40-60 degrees C and at pressures from 14.7 to 29.4 MPa, low yields were obtained. However, when the extractions were performed with one or more intermediate depressurization steps, the yield of CNSL increased to as high as 94%. Most of the oil did not separate from the shell during the depressurization step, but was obtained during the subsequent repressurization. The CNSL extract had a clear light brownish pink color and exhibited no evidence of polymerization or degradation. The pressure profile extraction method proposed in this work increases the possible CNSL extraction yields and greatly reduces the amount of CO(2) required for CNSL separation.

Anacardium↗
PubMed2001

Control of methanol oxidation by ionic behavior in supercritical water.

In supercritical water the rate of methanol oxidation was controlled by ionic behavior as follows: the oxidation rate of methanol decreased with increasing proton and hydroxide ion concentration, possibly due to stabilization of the reactant, while that of CO was suppressed by added protons and enhanced by added hydroxide ions.

Journal Article↗
PubMed2001

Tissue factor increases in the aqueous humor of proliferative diabetic retinopathy.

BACKGROUND: Tissue factor (TF) is a cellular initiator of the coagulation cascade and is upregulated by the major factors of diabetic angiopathy, TF might thus be one of the key molecules in diabetic retinopathy (DR). PURPOSE: To measure TF in diabetic eyes and evaluate its possible role in DR. METHODS: TF concentration in the aqueous humor of the eyes in 44 patients with diabetes and 35 age-matched control patients was evaluated by ELISA. The concentration of TF in aqueous humor (AH) was compared with the grade of DR. The concentration of TF in AH was also compared with duration of diabetes, renal function, and blood glucose control. The serum TF concentration in each group was also compared. The correlation between the serum TF and aqueous TF in each patient was analyzed. The effect of vascular endothelial growth factor (VEGF) on the TF activity of cultured bovine retinal endothelial cells was evaluated. RESULTS: The mean TF concentration in AH was higher in patients with active proliferative DR (244.5 pg/ml) than in either those with non-proliferative DR (132.4 pg/ml, P<0.05) or the control patients (114.9 pg/ml, P<0.01). The serum TF concentration in active proliferative DR patients (348.3 pg/ml) was significantly higher than in either non-proliferative DR patients, (235.9 pg/ml, P<0.01) or in the controls (223.5 pg/ml, P<0.01). However, the TF concentration of AH was not significantly correlated to that of the serum in each patient. The TF concentration in AH closely correlated with the grade of DR and protein concentration. VEGF increased the biological activity of TF in vitro. CONCLUSION: The origin of TF in AH, however, is still not clearly understood. Nonetheless, TF in AH directly reflects the severity of ocular diabetic change, and the present results indicate that TF indeed plays some role in the progression of DR.

Adult↗
PubMed2001

Depigmented atrophic lesions in sunset glow fundi of Vogt-Koyanagi-Harada disease.

PURPOSE: Although the depigmented, small, round to oval lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are considered to represent Dalén-Fuchs nodules, there is no histopathologic evidence to support such a consideration. An attempt is made herein to clarify the nature of the atrophic lesions and distinguish them from Dalén-Fuchs nodules seen in eyes with Vogt-Koyanagi-Harada disease. METHODS: Eyes from five individuals with clinical diagnoses of Vogt-Koyanagi-Harada disease were subjected to histopathologic examination. The retinal pigment epithelial changes from early active to convalescent and late chronic recurrent stages were evaluated. Particular attention was paid to Dalén-Fuchs nodules, depigmented lesions in the sunset glow fundi, and hyperpigmentation of the chronic recurrent stage. RESULTS: Eyes of two individuals, one in the active stage of Vogt-Koyanagi-Harada disease and the other in the convalescent stage, showed the presence of Dalén-Fuchs nodules. The depigmented small retinal pigment epithelial lesions were seen in two individuals, both of whom exhibited the sunset glow fundus of the convalescent stage. The retinal pigment epithelial lesions represented damage or disappearance of retinal pigment epithelial cells, and the sunset glow fundus appearance was from the loss of choroidal melanocytes. The heavy pigmentation seen in fundi with the chronic recurrent stage was the result of the proliferation of retinal pigment epithelial cells. CONCLUSION: The Dalén-Fuchs nodule is a specific histologic change observed at the level of retinal pigment epithelium in patients with Vogt-Koyanagi-Harada disease. There is no histologic confirmation that the depigmented small atrophic lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are Dalén-Fuchs nodules. The depigmented lesions represent localized damage or disappearance of retinal pigment epithelial cells.

Adult↗
PubMed2001

Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo.

Apoptosis-inducing factor (AIF) is a novel mediator in apoptosis. AIF is a flavoprotein that is normally confined to the mitochondrial intermembrane space, yet translocates to the nucleus in several in vitro models of apoptosis. To investigate the role of AIF in the apoptotic process in vivo, we induced retinal detachment (RD) by subretinal injection of sodium hyaluronate, either in Brown Norway rats or in C3H mice. Apoptotic DNA fragmentation, as determined by terminal nick-end labeling, was most prominent 3 days after RD. The subcellular localization of AIF was examined by immunohistochemistry and immunoelectron microscopy. In normal photoreceptor cells, AIF was present in the mitochondrion-rich inner segment. However, AIF was found in the nucleus after RD. Photoreceptor apoptosis developed similarly in C3H control mice, and in mice bearing the gld or lpr mutations, indicating that cell death occurs independently from the CD95/CD95 ligand system. Both the mitochondrio-nuclear transition of AIF localization and the nuclear DNA fragmentation were inhibited by subretinal application of brain-derived neurotrophic factor. To our knowledge, this is the first description of AIF relocalization occurring in a clinically relevant, in vivo model of apoptosis.

Animals↗
PubMed2000

Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration.

Accumulating evidence has shown the importance of vascular endothelial growth factor (VEGF) in chorioretinal angiogenesis. However, whether or not VEGF is indeed critical for the pathogenesis of subretinal neovascularization (SRN) in adulthood, which is a serious complication of age-related macular degeneration, has to be further investigated. We constructed an adenovirus expressing an entire ectodomain of the human VEGF receptor/flt-1 fused to Fc portion of human IgG (Adflt-ExR): this soluble receptor is secreted from Adflt-ExR-transfected cells. We studied the effect of Adflt-ExR on the formation of experimental SRN. Experimental SRN was induced by intense photocoagulation on the retina in pigmented rats and Adflt-ExR was injected into the femoral muscle. The formation of SRN assessed by fluorescein angiography was more significantly inhibited for 7 days in the Adflt-ExR-treated rats than in the control rats who received either an adenovirus vector encoding LacZ gene or balanced salt solution (BSS). The serum concentration of this soluble receptor increased for 7 days and thereafter gradually decreased. An immunohistochemical study disclosed the fibroblast cell proliferation and inflammatory cell infiltration to be reduced in the photocoagulation spot of Adflt-ExR-treated rats. VEGF plays a crucial role in the formation of SRN and VEGF soluble receptor gene transfection can inhibit SRN. This method will contribute to future gene therapy for age-related macular degeneration.

Adenoviridae↗
PubMed2000

Blockade of TGF-beta by in vivo gene transfer of a soluble TGF-beta type II receptor in the muscle inhibits corneal opacification, edema and angiogenesis.

Accumulating evidence suggests the involvement of TGF-beta in the process of corneal opacity, which is one of the serious causes of visual loss. However, whether TGF-beta is indeed critical for the pathogenesis remains unknown. We constructed an adenovirus expressing an entire ectodomain of the human type II TGF-beta receptor fused to Fc portion of human IgG (AdTbeta-ExR): this soluble receptor is secreted from AdTbeta-ExR-infected cells, binds to TGF-beta and inhibits TGF-beta signaling. When AdTbeta-ExR was injected into the femoral muscle of Balb/c mice, a high level of the soluble receptor protein (2.0-3.5 x 10(3) pM) was detectable in the serum and in the ocular fluid for at least 10 days. In the mice subjected to corneal injury with silver nitrate and to intramuscular injection with either saline or a control adenovirus expressing beta-galactosidase (AdLacZ), corneal opacification composed of extracellular matrix (ECM) accumulation, of infiltration of neutrophils and monocytes/macrophages, and of angiogenesis were all induced. In contrast, they were markedly reduced in the mice injected with AdTbeta-ExR. Immunohistochemical analysis revealed that TGF-beta, fibronectin, macrophage chemoattractant protein-1, and vascular endothelial growth factor were densely stained in the edge of wounded cornea, but they were scarcely present in the injured-cornea of AdTbeta-ExR-treated mice. Our results demonstrate that TGF-beta indeed plays a critical role in the process of cornea opacification, and that adenovirus-mediated expression of a soluble TGF-beta receptor can be therapeutically useful.

Adenoviridae↗
PubMed2000

High prevalence of antineutrophil cytoplasmic antibody positivity in childhood onset Graves' disease treated with propylthiouracil.

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and nephritis were recently reported in about 30 patients with hyperthyroidism. The objective of this study was to clarify the prevalence of ANCA and the relationship between ANCA and thyroid antibodies in children with Graves' disease. Titers of myeloperoxidase (MPO)-ANCA in sera of 51 patients with childhood onset Graves' disease (16 before treatment, 25 and 10 treated with PTU and methimazole, respectively) were measured by enzyme-linked immunosolvent assay. Antithyroglobulin antibodies (TGAbs) and antithyroperoxidase antibodies (TPOAbs) were also measured by RIA in 25 PTU-treated patients. No patients had clinical manifestations of vasculitis and nephritis. MPO-ANCA was positive in 6.7% of patients before treatment and in 64.0% of those treated with PTU and in none of those treated with methimazole. MPO-ANCA had a significantly positive correlation with TGAbs (P < 0.05) and no significant correlation with TPOAbs. These findings show the high prevalence of the MPO-ANCA positivity in PTU-treated childhood onset Graves' disease, suggesting that PTU may not be preferred as the first line for the treatment of children with Graves' disease. The significant correlation between MPO-ANCA and TGAbs indicates that the severity of Graves' disease may be a factor responsible for the MPO-ANCA positivity. The cross-reactivity between MPO-ANCA and TPOAbs may not play a role in the high prevalence of MPO-ANCA in the patients exposed to PTU.

Adolescent↗
PubMed2000

[A case of ring 14 chromosome with ocular manifestations].

BACKGROUND: Ring 14 chromosome has been reported to be associated with mental retardation, craniofacial dysmorphology, and epilepsy. Flecked and/or pigmented retina are also ocular manifestations of this disease. CASE: A 29-year-old female suffered from seizures and developmental and growth delay. Narrow palpebral fissura, broad flat nose, large auricula, high arched palate, and short neck were present. Chromosomal analysis disclosed her ring 14 chromosome (p 11.2 q 32.3). Ophthalmologically, cortical cataract, refractive error (right--3.00 D, left--1.50 D), and yellow-white flecks in the macula and yellow-white spots in the mid-peripheral retina in both eyes were present. CONCLUSIONS: To date, ophthalmic changes concomitant to a breakpoint at 14 q 32.2 have been reported. We report a case of ring 14 chromosome with breakpoint at 14 q 32.3 which showed yellow flecks in the macula and mid-peripheral retina.

Adult↗
PubMed2000

Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental eyelid malignant melanoma.

PURPOSE: To determine the effect of adenovirus-mediated gene transfer of a soluble receptor of vascular endothelial growth factor (VEGF) on the growth of experimental eyelid malignant melanoma. METHODS: An adenovirus vector encoding a soluble VEGF receptor/flt-1 (Adflt-ExR) was constructed. The bovine retinal endothelial cells (ECs) were incubated in a culture medium of 293E1 cells infected by means of an adenovirus vector or uninfected (control), which contained human recombinant VEGF, and the [3H]thymidine uptake was tested. The experimental eyelid malignant melanoma was induced by the injection of B16 melanoma cells (4 x 10(6) cells) into the right upper eyelid of BALB/c nu/nu mice, and the size of the tumor was recorded for 3 weeks after tumor cell injection. The effect of Adflt-ExR was examined in three ways. Model 1: B16 cells were infected by Adflt-ExR beforehand (at a multiplicity of infection [MOI] of 10) and injected into the eyelid. Model 2: Adflt-ExR was injected into pre-established B16 cell-induced eyelid malignant melanoma. Model 3: Adflt-ExR was injected into the femoral muscle of mice before B16 cell injection into the eyelid, and the remote effect was evaluated. An adenovirus vector bearing the LacZ gene (AdLacZ) or phosphate-buffered saline was used as a control. The amount of VEGF and the flt-ExR protein was measured by sandwich enzyme-linked immunosorbent assay (ELISA). Vascularization was evaluated by counting the number and the size of the vessels. RESULTS: The supernatant of Adflt-ExR-transfected cells clearly inhibited VEGF-induced bovine retinal EC proliferation in vitro. In models 1 and 2, the tumor growth in Adflt-ExR-treated mice was significantly lower than that of controls (P < 0.05). In model 3, no significant difference was found (P = 0.14). The molar ratio of VEGF/flt-ExR protein was clearly low in the tumors of Adflt-ExR-treated mice in models 1 and 2 (P < 0.01) but not in model 3 (P > 0.05). In vessel density, the tumors in Adflt-ExR-treated mice had fewer vessels than tumors in control animals in models 1 and 2 (P < 0.05). CONCLUSIONS: Adenovirus-mediated gene transfer of a soluble form of VEGF receptor (flt-1) gene inhibited the growth of the experimental eyelid malignant melanoma. This method may be useful as an antiangiogenic therapy for eyelid malignant melanoma.

Adenoviridae↗
PubMed1999

Target gene transfer of tissue plasminogen activator to cornea by electric pulse inhibits intracameral fibrin formation and corneal cloudiness.

Intracameral fibrin formation, a complication of ocular inflammation and intraocular operations, sometimes results in glaucoma and/or corneal damage leading to permanent visual loss. We transferred a therapeutic gene to the corneal endothelium in order to use it as a therapeutic organ. A plasmid encoding tissue plasminogen activator (tPA) was injected into the anterior chamber of rats and electric pulses (EPs) were given subsequently, which transferred a plasmid gene to a highly selected area of corneal endothelium with no inflammation. The biologically active tPA was clearly present for 4 days after treatment. Fibrin formation induced by YAG laser-generated bleeding in the anterior chamber decreased significantly more in treated eyes than in control eyes. Corneal opacity was significantly lower in treated eyes than in control eyes and histological damage was not apparent in the treated eyes. This genetic modification allows us to use the corneal endothelium to treat various ocular diseases and could be a new and effective type of pharmacologic gene therapy.

Animals↗
PubMed1999

Histopathological changes in iridocorneal angle of inherited glaucoma in rabbits.

BACKGROUND: We examined morphologically the angular region of eyes affected by inherited glaucoma in rabbits genetically developed by crossbreeding in order to investigate the etiologic changes in the iridocorneal angle and to establish whether this strain of rabbit is a suitable animal model of goniodysgenetic glaucoma in humans. METHODS: The angular regions of both normal and glaucomatous eyes from four rabbits having unilateral inherited glaucoma were observed with light and electron microscopy. RESULTS: In the glaucomatous eyes angular region, the aqueous plexus corresponding to Schlemm's canal in humans was open and located far peripherally to the peripheral margin of the anterior chamber angle, although the plexus of one glaucomatous eye was poorly developed with a small lumen. In the angular meshwork, which corresponds to the trabecular meshwork in humans, a thick abnormal tissue with round cells embedded in the extracellular matrix was located just beneath the plexus. A large amount of extracellular matrix of basal lamina-like material was observed in the thick tissue. In the normal eyes, the angular region consisted of well-developed trabecular sheets with neither a thick tissue nor accumulations of extracellular matrix in the angular meshwork. CONCLUSION: The findings observed in the glaucomatous eyes are much the same as those observed in goniodysgenetic glaucoma in humans, suggesting that this strain of inherited glaucoma rabbits is a suitable animal model of goniodysgenetic glaucoma in humans. The present study also supports the hypothesis that the presence of a thick subcanalicular tissue due to maldevelopment of the iridocorneal angle is one of the main causes of this type of glaucoma.

Animals↗
PubMed1999

The effect of tranilast on experimental proliferative vitreoretinopathy.

BACKGROUND: Tranilast has been clinically used for various allergic diseases. Recently, it has also been found to inhibit excessive scarring in wound healing processes. In this study, we examined the effects of tranilast on the treatment for experimental proliferative vitreoretinopathy (PVR). METHODS: Cultured rabbit conjunctival fibroblasts were injected intravitreously (50000 cells/eye) into the rabbit vitreous to induce experimental PVR. Immediately after that, tranilast (0.5-5 mg/ml, 0.1 ml/eye) was injected into the vitreous. Injection of vehicle solution was used as a negative control. PVR was clinically evaluated by masked observers using ophthalmoscopy and graded into six stages: 0 (no PVR) to 5 (severe PVR). The amount of transforming growth factor beta1 (TGF-beta1) in the vitreous was measured by ELISA method. Functional and morphological changes induced by 5 mg/ml tranilast were sought by electroretinography, light microscopy, and electron microscopy on day 28. RESULTS: The average stage of PVR in the eyes treated with tranilast (1 or 5 mg/ml) was significantly lower than that in the control group on days 14 and 28. There was no difference between the eyes treated with low-dose tranilast (0.5 mg/ml) and the control group. The amount of TGF-beta1 in the vitreous of tranilast-treated eyes was significantly lower than in the control group. The morphological and functional studies did not show any deleterious effect of tranilast on the retinal function and morphology. CONCLUSION: Tranilast effectively inhibits the progression of PVR without showing apparent toxicity of the eye. This agent has therapeutic value for PVR.

Animals↗
PubMed1999

The comparative benefits of glaucoma filtering surgery with an electric-pulse targeted drug delivery system demonstrated in an animal model.

PURPOSE: To evaluate the safety and effectiveness of glaucoma filtering surgery performed with the adjunctive use of bleomycin administered in conjunction with electric pulses (EP). DESIGN: Experimental study in rabbits. CONTROLS AND METHODS: Trabeculectomies were performed on pigmented rabbits (2 to 2.5 kg) using the following adjunctive treatments: 5 microM of topical bleomycin and EP (5V, 50 msec, 8 pulses) (group A: B+E+, n=15); bleomycin but no EP (group B: B+E-, n=15); 5 ,uM mitomycin C (MMC) and EP (group C: M+E+, n= 10); MMC but no EP (group D: M+E-, n=10); EP alone (group E: E+, n=10); and no adjunctive treatment (group F: E-, negative control, n=10). MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured regularly for 60 days after the operation. Bleb formation and the condition of the conjunctiva, cornea, and retina were also regularly evaluated. Histologic studies were performed by light microscopy, and retinal functions were evaluated by electroretinography. RESULTS: Postoperative IOP was significantly lower than the preoperative level in all the animals until day 7. However, in groups E and F (the negative control) it returned to the preoperative level after day 7, and in groups B, C, and D after 15 days. The IOP of group A remained lower even on day 40. The average amount IOP was lowered or increased on day 20 was -6.4 mmHg (P < 0.05) in group A; -0.2 mmHg in group B; +1.2 mmHg in group C; and -3.25 mmHg in group D. The survival rate of the filtering blebs on day 20 was significantly higher in group A than in the other groups. Clinical and histologic studies uncovered no pathologic findings in any intra- or paraocular tissues. Electroretinographic evaluation of retinal function in group A showed no apparent change over the 60 days of the study. CONCLUSION: Glaucoma filtering surgery in rabbits with the adjunctive use of bleomycin in conjunction with EP significantly lowered IOP for up to 40 days without clinically, morphologically, or functionally harming intraocular tissues.

Animals↗
PubMed1999

Induction of macrophage inflammatory protein-1alpha and vascular endothelial growth factor during inflammatory neovascularization in the mouse cornea.

We predicted that the appearance of macrophages in inflammatory areas is necessary for angiogenic responses in various inflammatory diseases. Using a mouse inflammatory corneal model in which model mouse corneas were cauterized with silver nitrate, we examined the infiltration of macrophages immunohistochemically and the total area of neovascularization quantitively. The expression of macrophage inflammatory protein-1alpha (MIP-1alpha) and vascular endothelial growth factor (VEGF) levels were also examined. A day after cauterization, short capillaries began to develop into the corneal stroma, and after 4 or 5 days the neovascularization became maximal and then began to regress. The number of macrophages within the cauterized cornea increased to a maximum at day 3 and began to decrease at day 5. The number of infiltrated macrophages reached maximum at day 3. Both MIP-1alpha and VEGF protein levels increased markedly immediately after the chemical cauterization, and production of MIP-1alpha (85.8 pg/4 corneas) and VEGF (206.5 pg/4 corneas) was maximal at 1 day and 0.5 day after cauterization, respectively. MIP-1alpha and VEGF mRNA levels also increased at 0.5 day after cauterization. In situ hybridization showed that MIP-1alpha was localized in corneal epithelial cells, and VEGF was localized in corneal epithelial cells and infiltrating inflammatory cells. MIP-1alpha and VEGF may have an important role in recruiting macrophages and neovascularization.

Journal Article↗