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Biomedical subjects

Masahiko Usui

Publications and source records attributed to Masahiko Usui.

At least 19 recordsLinked to original sources

Serous retinal detachment in a patient with aplastic anemia associated with parvovirus B19 infection.

BACKGROUND: We report a case of unilateral serous retinal detachment (RD) associated with parvovirus B19 infection. CASE REPORT: A 28-year-old woman had a clinical history of autoimmune hemolytic anemia and pure red cell aplasia associated with parvovirus B19 infection. She demonstrated focal serous RD without retinal exudates. A focal cataract and anterior vitreous cells were also observed. Fluorescein angiography (FA) revealed accumulation of subretinal fluid, but no vascular leakage. After vitrectomy, the retina was re-attached and visual acuity returned to 20/20. IgM antibody to parvovirus and viral DNA were detected by polymerase chain reaction in the vitreous fluid obtained at surgery. CONCLUSION: To our knowledge, this is the first reported case of the presence of anti-viral IgM and viral DNA in vitreous sample. Furthermore, the ocular findings in our patient are definitively different from previously reported cases of parvovirus-associated ocular disorders.

Adult↗

Ciliary body schwannoma successfully treated by local resection.

BACKGROUND: Schwannoma arising from the ciliary body is a rare intraocular neoplasm, and most cases previously reported were diagnosed histopathologically after eyeball enucleation because of a diagnosis of ciliary body melanoma. CASE: A case of ciliary body schwannoma was dissected locally. OBSERVATIONS: A 19-year-old woman was referred to us with a diagnosis of iris cyst. Local resection of the tumor was performed because of deteriorated visual acuity caused by displacement of the lens. In histopathological analysis, the encapsulated tumor showed a proliferation of the spindle cells with no atypia, and in immunohistochemical analysis, tumor cells were positive for S-100 protein; these findings were compatible with schwannoma. Visual acuity improved postoperatively, and no complications or recurrence have been observed in the 4 years since surgery. CONCLUSIONS: Schwannoma should be considered in the differential diagnosis of a ciliary body tumor.

Adult↗

Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats.

AIM: To determine whether intravitreal injection of tacrolimus suppresses ongoing experimental autoimmune uveoretinitis (EAU) in rats. METHODS: Rats were immunised with interphotoreceptor retinoid-binding protein peptide (R14) and given an intravitreal injection of tacrolimus on day 12 after immunisation. Intraocular inflammation was assessed by slit-lamp biomicroscopy and histopathological examination. Interferon gamma and tumour necrosis factor alpha protein levels in the ocular tissues were measured. Gene expression of chemokines was determined in ocular tissues by reverse transcription-polymerase chain reaction. To evaluate the systemic effect of intravitreal injection of tacrolimus, delayed-type hypersensitivity was measured by ear swelling. RESULTS: Clinical and pathological scores showed that ocular inflammation of tacrolimus-treated eyes was markedly less than that of vehicle-treated eyes. The amount of interferon gamma and tumour necrosis factor alpha was considerably inhibited in tacrolimus-treated eyes. The gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES) was markedly reduced in tacrolimus-treated eyes. Delayed-type hypersensitivity responses were not impaired in tacrolimus-treated rats. CONCLUSIONS: Intravitreal injection of tacrolimus was highly effective in suppressing the ongoing process of EAU without any side effects on systemic cellular immunity. This treatment may be useful in the management of patients with severe uveitis.

Animals↗

Possibility of inducing anterior chamber-associated immune deviation by TGF-beta2 treatment of monocytes isolated from Behcet's patients.

Murine macrophages treated with TGF-beta2 are capable of inducing anterior chamber-associated immune deviation (ACAID), and these macrophages are characterized by impaired IL-12 production and CD40 expression, consequently failing to promote Th1 cell differentiation. In this study, we investigated whether human monocytes can also acquire the specific functions by TGF-beta2 treatment, even when the monocytes are isolated from patients with Behcet's disease (BD). Adherent monocytes isolated from peripheral blood mononuclear cells (PBMC) of 16 BD patients and 16 healthy controls, were cultured overnight with or without 5 ng/ml of TGF-beta2. Then, TGF-beta2-treated or untreated adherent cells were co-cultured with allogeneic CD4(+) T cells obtained from healthy subjects. TGF-beta2 treatment inhibited the abilities of adherent monocytes obtained from BD patients to stimulate the proliferation and IFN-gamma production of allogeneic CD4(+) T cells. The reduced IFN-gamma production was also confirmed by IFN-gamma mRNA expression in the co-cultured T cells. IL-12 production and CD40 molecule expression by adherent monocytes obtained from BD patients were strikingly reduced by TGF-beta2 treatment. These results suggest a possibility that adherent monocytes isolated from BD patients may acquire a property to induce ACAID by treatment with TGF-beta2.

Adult↗

Chlamydia psittaci in ocular adnexal lymphoma: Japanese experience.

We searched for the Chlamydia psittaci DNA the touchdown enzyme time release PCR (TETR-PCR) in 23 specimens from 21 patients with ocular adnexal lymphoproliferative disorders, including 12 patients with MALT lymphoma to identify C. psittaci infection. Southern hybridization of the PCR product using the C. psittaci-specific probe failed to detect C. psittaci, although three samples appeared to be positive by ethidium bromide staining. This indicates that technical approach for detecting C. psittaci infection in ocular adnexal lymphoma might be an essential in disclosing this association.

Adult↗

The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis.

ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and plays differential roles in autoimmune diseases. In this study, we examined the role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression was found on infiltrating CD4+ T cells in the region of the retina in EAU-induced mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1 interaction during the effector phase ameliorated the disease, whereas its blockade during the induction phase exhibited no significant effect. Moreover, administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited the expansion and/or effector function of pathogenic T cells, given that proliferative response and IFN-gamma production by lymph node cells were reduced upon restimulation with the antigen peptide in vitro. These results suggest that the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis. We also indicated that ICOS-mediated costimulation plays differential roles in EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease induced in the same manner as EAU.

Adoptive Transfer↗

Association between severity of inflammation in CNS and development of sunset glow fundus in Vogt-Koyanagi-Harada disease.

PURPOSE: To investigate the association between central nervous system (CNS) inflammation at disease onset and the appearance of sunset glow fundus (SGF) in Vogt-Koyanagi-Harada (VKH) disease. DESIGN: Retrospective case series. METHODS: Charts of 102 patients with VKH disease followed from from initial onset were reviewed. The frequency of cerebrospinal fluid (CSF) pleocytosis and the number of cells in the CSF were compared among the patients who eventually developed SGF and the patients who had not developed SGF as of final follow-up. RESULTS: SGF was observed in 69 (67.6%) of 102 patients. The frequency of CSF pleocytosis was 77 (82.7%) of 93 patients examined. The frequency of CSF pleocytosis and the number of cells in CSF were significantly higher in patients who eventually developed SGF (both P = .0029). CONCLUSIONS: Severe inflammatory response in CNS sites at disease onset may influence the development of SGF in VKH disease.

Adolescent↗

Evaluation of the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease.

PURPOSE: To compare the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease. DESIGN: Retrospective comparative interventional case series. METHODS SETTINGS: Nine international uveitis specialty clinics. STUDY POPULATION: Forty-eight patients presenting over a three-year period to a study center with acute Vogt-Koyanagi-Harada disease. INTERVENTION: Initial treatment with corticosteroid either orally (Oral only group) or intravenously followed by an oral taper (IV+Oral group). MAIN OUTCOME MEASURES: Change in visual acuity with treatment; development of ocular complications, including visually significant cataract, choroidal neovascularization, subretinal fibrosis, fundus pigment migration, nummular hypopigmented lesions, and diffuse fundus depigmentation; use of immunosuppressive therapy. RESULTS: The Oral only group comprised 15 patients (31%) and the IV+Oral group 33 patients (69%). Median follow-up was 15 months. There was no difference in duration of follow-up between groups (P = .234). There was no difference in the change in visual acuity between groups, adjusting for initial visual acuity (P = .402). There were no differences in the rates of development of visually significant cataract, fundus pigmentary changes, or in the rate of use of subsequent immunosuppressive therapy between treatment groups. No patients developed choroidal neovascularization or subretinal fibrosis over the study period. CONCLUSIONS: Route of administration of corticosteroid had no detectable effect on change in visual acuity nor on the development of visually significant complications over the study period. Prospective trials are necessary to address speed of resolution and definitively answer outcome questions.

Acute Disease↗

Suppression of fibroblast and bacterial adhesion by MPC coating on acrylic intraocular lenses.

PURPOSE: To investigate cell adhesion to intraocular lens (IOL) surfaces having different properties using bacteria and fibroblasts. SETTING: Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan. METHODS: The polished acrylic IOLs VA60-BB and VA-60-CB (Hoya) were used with no coating or after coating with poly(2-methacryloyloxyethyl phosphocholine-co-n-butyl-methacrylate) (MPC) or methane gas plasma. Each IOL was placed in a culture of Staphylococcus aureus (5 x 10(7) colony forming units [CFU]/mL) or fibroblasts (SUSM-1, 1 x 10(4) cells/mL), and the cells adhering to the IOL surface were counted after the culture. Fibroblast adhesiveness was evaluated by centrifuging post-culture IOLs in test tubes at up to 15,000 rpm and looking at the ICAM-1 mRNA expression in the adhering fibroblasts using real-time polymerase chain reaction. RESULTS: After 1 minute in the bacterial culture, the mean adhering bacteria count was 0.7 x 10(6) CFU in the MPC-coated IOL group and about 2.0 x 106 CFU in the noncoated IOL group (P = 0.03) and the plasma-coated IOL group (P = 0.02). After 96 hours in the fibroblast culture, the adhering fibroblast count was 2.2/mm2 in the MPC-coated IOL group, significantly lower (P = 0.009) than 57.6/mm2 in the noncoated IOL group and 125.8/mm2 in the plasma-coated IOL group. Cell adhesion and ICAM-1 mRNA expression were weak on the MPC-coated IOL, intermediate on the noncoated IOL, and relatively strong on the plasma-coated IOL. CONCLUSION: The MPC-coated IOL surface inhibited bacterial and fibroblast adhesion, which is an initial stage of cell proliferation and expression, suggesting that MPC coating may provide an effective means of reducing the risk for endophthalimitis in IOL implantation.

Acrylic Resins↗

Analysis of retinal findings of acute retinal necrosis using optical coherence tomography.

PURPOSE: To analyze the retinal findings in patients with ARN, optical coherence tomography (OCT) was performed. METHODS: Seven patients (7 eyes) with ARN were studied using OCT. RESULTS: OCT images depicted highly reflective areas in the inner layers of the retina in all seven cases, corresponding with the yellowish-white lesions of the retina in the acute phase. Disorganization of the retinal structure was also observed in these retinal lesions, especially in cases with severe inflammation. Subretinal changes including retinal exudate and/or fluid were observed in only one case. After regression of the yellowish-white lesions in the retina, a significant reduction in retinal thickness was observed on OCT. CONCLUSIONS: OCT permits the detection of full-thickness retinal necrosis in the acute phase and complete absence of retinal structure in the resolution phase, corresponding with the yellowish-white lesions seen in patients with ARN.

Adult↗

Glutamate levels in aqueous humor of patients with retinal artery occlusion.

PURPOSE: We analyzed the levels of glutamate and other amino acids in aqueous humor of patients with retinal artery occlusion (RAO) to determine whether glutamate is associated with retinal ischemia in RAO. METHODS: Aqueous humor samples were obtained from nine RAO patients by paracentesis performed as an emergent therapeutic intervention and from nine cataract patients without other ocular disease who served as controls. Aspartic acid, glutamate, taurine, and alanine concentrations were determined using high-performance liquid chromatography. RESULTS: The glutamate level in aqueous humor of patients with RAO (4.46 +/- 1.62 micromol/L) was significantly higher than that in controls (2.98 +/- 1.12 micromol/L) (P < 0.05). CONCLUSIONS: Elevated glutamate levels in aqueous humor may indicate diffusion of vitreous glutamate released from the damaged retina due to acute retinal ischemia in RAO. An increase in the extracellular glutamate level may play an important role in ischemic retinal damage in RAO.

Aged↗

Induction of eye-derived tolerance does not depend on naturally occurring CD4+CD25+ T regulatory cells.

PURPOSE: Regulatory CD4+ T cells (T regs) arise in the spleens of mice with anterior chamber-associated immune deviation (ACAID), an eye-derived tolerance evoked by injection of antigen into the ocular anterior chamber (AC). The current study was conducted to investigate the possibility that these T regs express CD25 and are derived from natural CD4+CD25+ T cells. METHODS: Naïve T cells from DO11.10 mice were activated in vitro by ovalbumin (OVA)-pulsed, TGFbeta-treated antigen-presenting cells (APCs), and the expression of CD25 assayed by flow cytometry. OVA-specific ACAID T regs were obtained from the spleens of DO11.10 mice with ACAID to OVA. Immunomagnetic enrichment was used to sort out CD4+CD25+, and CD4+CD25- ACAID T cells before they were injected into OVA-immunized mice or examined for mRNA expression of the regulatory T-cell transcription factor Foxp3. In addition, before AC injection of OVA, systemic depletion of CD25+ T cells was performed with injections of anti-IL-2 receptor antibody into the mice. RESULTS: OVA-specific T cells from DO11.10 mice expressed CD25 when exposed to OVA-pulsed, TGFbeta-treated APCs, even when the DO11.10 T cells were depleted of CD25+ cells before their in vitro stimulation. In addition, DH was suppressed in naïve mice that were injected with CD4+CD25+ or CD4+CD25- ACAID T cells. The CD4+CD25+, but not the CD4+CD25-, ACAID T regs expressed Foxp3. Finally, OVA induced ACAID in mice depleted of CD25+ cells. CONCLUSIONS: Some of the CD4+ T regs of ACAID arise from CD25- precursors, and the induction of ACAID is not dependent on the presence of natural CD4+CD25+ T regs.

Adoptive Transfer↗

Alpha-internexin as a corneal autoantigen in spontaneous autoimmune keratitis mouse model.

PURPOSE: The purpose of this study was to identify target antigens of autoimmune keratitis with a disease-prone mouse model. METHODS: BALB/c nude mice grafted with embryonic rat thymi (TG nude mice) develop various organ-localized autoimmune lesions, including keratitis. A hybridoma producing a monoclonal antibody (OT-20), specific for corneal epithelium was established by using spleen cells from this model mouse of keratitis, and the target of OT-20 was identified by immunoblot analysis. Then, using the antigen, T-cell proliferation and cytokine production by TG nude mice with keratitis were examined. RESULTS: Immunoblot analysis revealed alpha-internexin to be the target antigen of OT-20 that specifically recognizes corneal epithelium. Sera from TG nude mice with keratitis reacted with alpha-internexin on Western blot analysis, and the T cells of these mice on stimulation with alpha-internexin exhibited proliferation responses and produced IL-2, IFN-gamma, and TNF-alpha, but not IL-4 or IL-5. CONCLUSIONS: These results suggest that alpha-internexin is one of the corneal antigens associated with keratitis, developing spontaneously in TG-nude mice, with a probable pathogenic role.

Animals↗

Elevated serum levels of CXCL9/monokine induced by interferon-gamma and CXCL10/interferon-gamma-inducible protein-10 in ocular sarcoidosis.

PURPOSE: Sarcoidosis is a chronic multisystem granulomatous disorder characterized by an accumulation of activated CD4+ T cells and monocytes/macrophages in involved organs. Chemokines are required for the extravasation of leukocytes to the inflammation site. This study was undertaken to determine which chemokines are augmented in the serum of patients with active ocular sarcoidosis. METHODS: Seventeen patients with diagnosed ocular sarcoidosis, 28 with suspected ocular sarcoidosis, 16 with Behçet's disease, 17 with Vogt-Koyanagi-Harada disease, and 18 healthy subjects were studied. Serum levels of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 were simultaneously measured by cytometric bead array using flow cytometer. In addition, serum CXCL9 and CXCL10 levels in the patients with diagnosed or suspected ocular sarcoidosis were compared with respect to ocular disease activity, the presence of bilateral hilar lymphadenopathy (BHL), and laboratory data. RESULTS: Serum levels of both CXCL9 and CXCL10 were markedly elevated in the patients with diagnosed or suspected ocular sarcoidosis compared with patients with other types of uveitis and healthy subjects. Although CCL2 and CXCL8 were detected in the serum of all subjects, the levels were extremely low with no significant differences between groups. Elevation of serum CXCL9 and CXCL10 in ocular sarcoidosis correlated significantly with ocular disease activity and ACE (angiotensin converting enzyme) levels and was unrelated to the presence of BHL, erythrocyte sedimentation rate, white blood cell count, serum IgG, or serum lysozyme. CONCLUSIONS: The results demonstrated that serum levels of CXCL9 and CXCL10 were elevated markedly in the patients with ocular sarcoidosis and correlated with ocular disease activity and ACE level.

Adult↗

Expression of costimulatory molecules on human retinoblastoma cells Y-79: functional expression of CD40 and B7H1.

PURPOSE: To examine the expression of various costimulatory molecules on the human retinoblastoma cell line Y-79 and assess the functional roles of selected costimulatory molecules. METHODS: Y-79 cells were incubated in the presence or absence of IFN-gamma, with or without irradiation (100 Gy). Expression of major histocompatibility complex (MHC) class I molecules, MHC class II, CD80, CD86, CD40, CD70, B7H1, B7DC, B7H2, OX40L, and 4-1BBL on Y-79 cells was measured by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. The functional role of CD40-mediated interactions in modifying immune responses to Y-79 was assessed in vitro by using recombinant human CD40 ligand (rhCD40L). The costimulatory effect of B7H1-expressing IFN-gamma-treated Y-79 cells on proliferation of purified T cells was studied in Y-79/T-cell coculture experiments with a blocking anti-B7H1 monoclonal antibody (mAb). RESULTS: CD40 and B7H2 were consistently detected on Y-79 cells by RT-PCR and flow cytometry. Cell surface expression of CD40 was upregulated on stimulation by IFN-gamma alone, radiation alone, and IFN-gamma combined with radiation. B7H1 expression was induced by IFN-gamma stimulation and increased further when irradiated Y-79 cells were stimulated by IFN-gamma. Treatment of Y-79 cells with rhCD40L enhanced cell surface expression of MHC class I and intercellular adhesion molecule (ICAM)-1 and also stimulated monocyte chemotactic protein (MCP)-1 production. Proliferative response of purified CD3+ T cells costimulated with IFN-gamma-stimulated Y-79 was significantly enhanced by the addition of anti-B7H1 mAb. CONCLUSIONS: These results suggest that CD40 expressed on Y-79 plays an important role in augmenting antitumor immunity. In contrast, the expression of B7H1 on IFN-gamma-treated Y-79 cells contributes to the suppression of T cells. The dual effects of CD40 and B7H1 on Y-79 cells may contribute to positive or negative regulation of antitumor immune responses in human retinoblastoma.

Antigens, CD↗

[Case of spontaneous regression of intraocular lymphoma demonstrated by subretinal biopsy].

PURPOSE: To report a case of intraocular lymphoma suspected of spontaneous regression based on ocular fundus findings, subretinal biopsy, and observation of clinical course. CASE: A 64-year-old woman presented at our clinic with multiple yellowish-white patchy lesions in the left fundus and focal atrophy of the retinal pigment epithelium in the right fundus. No inflammatory infiltrates were observed in either eye. Intraocular lymphoma was suspected based on the clinical manifestations including fluorescein angiography and optical coherence tomography. Vitrectomy and subretinal biopsy were subsequently performed for diagnostic purposes. Histological examination showed that the subretinal lesion was composed mostly of necrotic tissue derived from the lymphoid corpuscle and that there was no cellular component except the retinal pigment epithelium. Interleukin-10 in the vitreous humor was low at 9 pg/ml. No serious postoperative complications were observed after surgery and the residual retinal lesions gradually regressed spontaneously. Laboratory data and whole body evaluation including the central nervous system (CNS) showed no remarkable findings for 1 year after surgery. CONCLUSIONS: It is suggested that the present case was an intraocular lymphoma which regressed spontaneously. However, careful follow-up including the possible occurrence of CNS lesions is required in such cases.

Biopsy↗

[Chalcosis bulbi recognized 22 years after trauma].

PURPOSE: To report a case of chalcosis bulbi diagnosed 22 years after accidental entry of a foreign object into the eye. CASE: A 57 year-old woman underwent surgery for vitreous opacity and cataract of unknown cause. During the operation, an intraocular foreign body was found in the vitreous at the pars plana, and was removed. The object was a coated copper wire, 3.5 mm in length and 0.2 mm in thickness. She recalled that such a wire had accidentally entered her eye 22 years previously. Copper particles were detected by copper staining of the anterior lens capsule. RESULT: Fine, sharp metal fragments may penetrate the eye with little resistance. When the injury results in minimal subjective symptoms, the person may not seek examination by an ophthalmologist. In the present case, the foreign body was a fragment of coated copper wire. The exposed metal surface was limited and the copper probably dissolved very slowly. This may account for the lack of significant symptoms. In the Japanese literature, there are many reports of coated copper wire as foreign body in the eye, but few lead to characteristic chalcosis bulbi.

Cataract↗

Treatment of large conjunctival nevus by resection and reconstruction using amniotic membrane.

BACKGROUND: Nevus of the bulbar conjunctiva is a benign pigmented lesion of the ocular surface. Unless a biopsy is required for ruling out malignant melanoma, a nevus is usually excised for cosmetic reasons only. However, with large lesions involving two or more quadrants of the bulbar conjunctiva, a total resection can be difficult. In this report, we present a case of a huge nevus treated by surgical excision and amniotic membrane transplantation for reconstruction of the bulbar conjunctiva. METHODS: A 54-year-old Japanese man was referred to our clinic with suspected malignant tumor of the bulbar conjunctiva in his right eye. A large and diffuse pigmented tumor with numerous small cysts was present mainly on the upper bulbar conjunctiva. Resection of the conjunctival tumor and amniotic membrane transplantation for reconstruction of the bulbar conjunctiva were performed. RESULTS: The histopathological diagnosis was conjunctival nevus. Epithelialization of the bulbar conjunctiva over the amniotic membrane sheet was completed 4 weeks after resection. At 44-month follow-up, there was no recurrence or any postoperative complication. CONCLUSION: Surgical resection combined with reconstruction by amniotic membrane transplantation is effective for the treatment of large conjunctival nevus.

Amnion↗