466 results on '"Sotozono C"'
Search Results
252. "Toward a Bright Future for Corneal Research and Practice in Japan and Abroad," 21st Annual Meeting of the Kyoto Cornea Club, November 27 and 28, 2015.
- Author
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Oshika T, Nishida K, Sotozono C, Saika S, Fukushima A, and Hori Y
- Subjects
- Humans, Japan, Biomedical Research, Cornea
- Published
- 2016
- Full Text
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253. MicroRNA Profiles Qualify Phenotypic Features of Cultured Human Corneal Endothelial Cells.
- Author
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Ueno M, Asada K, Toda M, Hiraga A, Montoya M, Sotozono C, Kinoshita S, and Hamuro J
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- Adolescent, Adult, Aged, Cells, Cultured, Child, Child, Preschool, Endothelium, Corneal pathology, Female, Flow Cytometry, Fuchs' Endothelial Dystrophy metabolism, Fuchs' Endothelial Dystrophy pathology, Humans, Male, MicroRNAs biosynthesis, Microscopy, Phase-Contrast, Middle Aged, Real-Time Polymerase Chain Reaction, Tissue Donors, Young Adult, Endothelium, Corneal metabolism, Fuchs' Endothelial Dystrophy genetics, Gene Expression Profiling methods, Gene Expression Regulation, MicroRNAs genetics, RNA genetics
- Abstract
Purpose: To elucidate a noninvasive method to qualify and identify cultured human corneal endothelial cells (cHCECs) devoid of cell-state transition and adaptable for cell-based therapy., Methods: The variations of cHCECs in their composition of heterogeneous subpopulations (SPs) were verified in relation to their surface cluster-of-differentiation (CD) markers and their morphology. The profiles of microRNA (miRNA) in cultured cells or supernatants were detected by 3D-Gene Human microRNA Chips (Toray Industries, Inc.). The profiles were also analyzed for fresh corneal tissues with distinct endothelial cell densities (ECD) with or without gutatta. To validate the 3D-Gene results, quantitative real-time polymerase chain reaction (PCR) was performed. RNAs were extracted from cHCECs transfected with selected miRNA, and target genes were presumed by PCR array (Qiagen)., Results: Among a variety of morphologically different cHCECs, miRNA expression profiles were distinctively revealed. The one miRNA capable of discriminating CD44- SP from SPs with CD44++∼CD44+++ phenotypes was identified as miR34a. The downregulation of miRNAs in the 378 family paralleled the upregulation of surface CD44 on cHCECs. Interestingly, upregulated miRNAs in the 378 family in corneal endothelium dramatically decreased in the tissues with lower ECD with advanced gutatta, providing new insight on the pathogenesis of Fuchs' endothelial corneal dystrophy., Conclusions: The specified cultured SPs sharing the CD44- surface phenotypes with matured HCECs showed the highest expression of miR-378. Conversely, SPs with upregulated CD44+++ showed a reduction of miR-378. Thus, miRNA in cultured cells may serve as an alternative method to qualify cHCECs.
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- 2016
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254. Measurement of Corneal Endothelial Surface Area Using Anterior Segment Optical Coherence Tomography in Normal Subjects.
- Author
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Kitazawa K, Yokota I, Sotozono C, and Kinoshita S
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- Adult, Age Factors, Aged, Cell Count, Endothelium, Corneal diagnostic imaging, Female, Functional Laterality, Healthy Volunteers, Humans, Male, Middle Aged, Prospective Studies, Sex Factors, Young Adult, Endothelium, Corneal cytology, Tomography, Optical Coherence
- Abstract
Purpose: To calculate the number of corneal endothelial cells (CEC) on the posterior surface of the normal human cornea by measuring specific surface areas through anterior segment optical coherence tomography. The effects of age, sex, and variations between the right and left eyes were also investigated., Methods: This study involved 60 eyes of 30 normal subjects with no history of corneal disease. Subjects were divided into the following groups according to age: group A (20-39 years old), group B (40-59 years old), and group C (60-79 years old). Set areas of the corneal posterior surface were imaged and analyzed using anterior segment optical coherence tomography, and the number of CECs was calculated based on the area measured and a CEC density., Results: The posterior corneal surface area measured within the central circular diameters of 10.2, 8.5, and 7.5 mm was 86.8, 63.8, and 48.4 mm in group A, 86.0, 63.8, and 48.4 mm in group B, and 87.0, 64.2, and 48.6 mm in group C, respectively. The total number of CECs on the posterior surface in the diameters of 10.2, 8.5, and 7.5 mm was 2.3 × 10, 1.7 × 10, and 1.3 × 10, respectively. No clinically relevant differences in the posterior surface were found in relation to age, sex, or variation between right and left eyes., Conclusions: Calculation of the CEC number on the corneal posterior surface is essential for determining the number of cells applied during penetrating keratoplasty, endothelial keratoplasty, or cultivated CEC injection therapy when available.
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- 2016
- Full Text
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255. Cell Homogeneity Indispensable for Regenerative Medicine by Cultured Human Corneal Endothelial Cells.
- Author
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Hamuro J, Toda M, Asada K, Hiraga A, Schlötzer-Schrehardt U, Montoya M, Sotozono C, Ueno M, and Kinoshita S
- Subjects
- Adolescent, Adult, Antigens, CD metabolism, Cell Count, Cell Differentiation, Cell Division, Cells, Cultured, Child, Child, Preschool, Corneal Endothelial Cell Loss metabolism, Corneal Endothelial Cell Loss pathology, Endothelium, Corneal metabolism, Endothelium, Corneal transplantation, Flow Cytometry, Humans, Immunohistochemistry, Infant, Infant, Newborn, Microscopy, Phase-Contrast, Middle Aged, Tissue Donors, Young Adult, Corneal Endothelial Cell Loss surgery, Corneal Transplantation methods, Endothelium, Corneal cytology, Regenerative Medicine methods
- Abstract
Purpose: To identify the subpopulation (SP) among heterogeneous cultured human corneal endothelial cells (cHCECs) devoid of cell-state transition applicable for cell-based therapy., Methods: Subpopulation presence in cHCECs was confirmed via surface CD-marker expression level by flow cytometry. CD markers effective for distinguishing distinct SPs were selected by analyzing those on established cHCECs with a small cell area and high cell density. Contrasting features among three typical cHCEC SPs was confirmed by PCR array for extracellular matrix (ECM). Combined analysis of CD markers was performed to identify the SP (effector cells) applicable for therapy. ZO-1 and Na+/K+ ATPase, CD200, and HLA expression were compared among heterogeneous SPs., Results: Flow cytometry analysis identified the effector cell expressing CD166+CD105-CD44-∼+/-CD26-CD24-, but CD200-, and the presence of other SPs with CD166+ CD105-CD44+++ (CD26 and CD24, either + or -) was confirmed. PCR array revealed three distinct ECM expression profiles. Some SPs expressed ZO-1 and Na+/K+ ATPase at comparable levels with effector cells, while only one SP expressed CD200, but not on effector cells. Human leukocyte antigen expression was most reduced in the effector SP. The proportion of effector cells (E-ratio) inversely paralleled donor age and decreased during prolonged culture passages. The presence of Rho-associated protein kinase (ROCK) inhibitor increased the E-ratio in cHCECs. The average area of effector cells was approximately 200∼220 μm2, and the density of cHCECs exceeded 2500 cells/mm2., Conclusions: A specified cultured effector cell population sharing the surface phenotypes with mature HCECs in corneal tissues may serve as an alternative to donor corneas for the treatment of corneal endothelial dysfunction.
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- 2016
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256. Allogeneic Sensitization and Tolerance Induction After Corneal Endothelial Cell Transplantation in Mice.
- Author
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Yamada J, Ueno M, Toda M, Shinomiya K, Sotozono C, Kinoshita S, and Hamuro J
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- Animals, Anterior Chamber immunology, Corneal Edema pathology, Disease Models, Animal, Endothelium, Corneal cytology, Hypersensitivity, Delayed pathology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Transplantation, Homologous, Cell Transplantation methods, Corneal Edema surgery, Corneal Transplantation methods, Endothelium, Corneal transplantation, Graft Survival immunology, Hypersensitivity, Delayed immunology, Immune Tolerance
- Abstract
Purpose: We evaluated the allogeneic response after corneal endothelial cell transplantation in the anterior chamber (AC) in a new mouse model by examining the acquisition of a delayed-type hypersensitivity (DTH) response, induction of allogeneic AC-associated immune deviation (ACAID), and acquisition of delayed transplantation tolerance., Method: The corneal eyecups from C57BL/6 mice were prepared. The epithelial layer was detached with EDTA solution and treated with trypsin to release mouse-derived primary corneal endothelial cells (mpCECs). The mpCECs (1 × 104 cells) were transplanted into the AC of the eye or subcutaneously (SC) into the neck of BALB/c mice. In the mouse model of endothelial cell transplantation, the endothelial cells in a 2-mm central area of the cornea were eliminated by cryoinjury. The mpCEC transplant model was evaluated by measuring allogeneic cell survival and corneal thickness. The allospecific DTH response and ACAID induction were evaluated 1 week after transplantation. The long-term transplantation tolerance was evaluated by observing a secondary penetrating keratoplasty (PKP) performed on the same donor C57BL/6 mice., Results: The SC injection of mpCECs induced a DTH response, whereas the AC injection induced ACAID. However, eyes inflamed by cryoinjury showed neither the DTH response nor ACAID following AC injection. The mpCECs survived for at least 1 week after injection. Penetrating keratoplasty allografts at 8 weeks after mpCEC transplantation survived indefinitely (100%)., Conclusions: The mpCECs display low allogenicity in the AC and are capable of inducing allogeneic tolerance. Corneal endothelial cell transplantation into the AC may represent a safe technique for allogeneic transplantation.
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- 2016
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257. The Different Binding Properties of Cultured Human Corneal Endothelial Cell Subpopulations to Descemet's Membrane Components.
- Author
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Toda M, Ueno M, Yamada J, Hiraga A, Tanaka H, Schlötzer-Schrehardt U, Sotozono C, Kinoshita S, and Hamuro J
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- Cell Adhesion, Cells, Cultured, Descemet Membrane metabolism, Endothelium, Corneal metabolism, Flow Cytometry, Humans, Immunohistochemistry, Integrin alpha2 biosynthesis, Microscopy, Phase-Contrast, Collagen Type IV metabolism, Descemet Membrane cytology, Endothelium, Corneal cytology, Laminin metabolism
- Abstract
Purpose: To clarify the adherent properties of cultured human corneal endothelial cell (cHCEC) subpopulations (SPs)., Methods: Each SP was prepared by controlling the culture conditions or by using magnetic cell separation, and then confirmed by staining with several cell-surface markers. Binding abilities of HCEC SPs were examined by adding the cells to culture plates immobilized with collagens, laminins, or proteoglycans, and then centrifuging the plates. Adhered cells were then evaluated by phase-contrast microscopy., Results: The cHCECs were bound to laminin-511, laminin-411, and Type-IV collagen in a concentration-dependent manner, yet weakly bound to Perlecan, Agrin, and TSP-1. Comparison of the influence of cell-suspension vehicles on cHCEC attachment showed that cells suspended in Opti-MEM-I or Opeguard-MA were bound to laminin, yet no binding was observed in cells suspended in BSS-Plus. Next, we compared the adherent properties of HCEC SPs. Both the fully differentiated, mature cHCEC SP and the epithelial-to-mesenchymal-transitioned (EMT)-phenotype SP were found to attach to laminin- or collagen-coated plates. Interestingly, the binding properties to laminins differed among those SPs. Although the level of cells adhered to the laminin-411-coated plate was the same among the cHCEC SPs, the fully differentiated, mature cHCEC SP was significantly more tightly bound to laminin-511 than was the EMT-phenotype SP., Conclusions: The findings of this study suggest that the binding ability of cHCECs to major Descemet's membrane components is distinct among cHCEC SPs, and that Opti-MEM-I and Opeguard-MA are useful cell-suspension vehicles for cell-injection therapy.
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- 2016
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258. A Case of Fungal Keratitis Treated Surgically.
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Kitazawa K, Kondo E, Sotozono C, and Kinoshita S
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- Eye Infections, Fungal physiopathology, Female, Humans, Keratitis microbiology, Keratitis physiopathology, Middle Aged, Visual Acuity, Eye Infections, Fungal surgery, Keratitis surgery
- Abstract
Purpose: Here we report a patient who underwent removal of a retrocorneal plaque and anterior chamber irrigation for acute-stage fungal keratitis. Case report: A 56-year-old woman was referred to the Baptist Yamasaki Eye Clinic, Kyoto, Japan due to refractory infectious keratitis. A white plume infiltration from the superficial to deep corneal stroma was present at the central cornea, and a white giant plaque was present on the posterior surface of the cornea. For diagnostic purposes and to reduce inflammation, the retrocorneal plaque was surgically removed and the anterior chamber was irrigated. Findings obtained from the surgically removed plaque revealed many neutrophils coiled with fibrin and filamentous fungus positive to Fungiflora Y staining. At 1-day postoperative, the amount of inflammation and infiltration were drastically decreased and the infection focus became gradually becoming smaller, finally disappearing at 6-weeks postoperative and with no signs of recurrence. Conclusion: The findings of this study show that surgical intervention can be an effective treatment option for cases of fungal keratitis with retrocorneal plaque.
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- 2016
259. Gene Signature-Based Development of ELISA Assays for Reproducible Qualification of Cultured Human Corneal Endothelial Cells.
- Author
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Ueno M, Asada K, Toda M, Schlötzer-Schrehardt U, Nagata K, Montoya M, Sotozono C, Kinoshita S, and Hamuro J
- Subjects
- Adolescent, Adult, Aged, Cells, Cultured, Child, Cytokines biosynthesis, Endothelium, Corneal cytology, Enzyme-Linked Immunosorbent Assay methods, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling methods, Humans, Imaging, Three-Dimensional, Male, Microscopy, Phase-Contrast, Middle Aged, RNA, Messenger biosynthesis, Real-Time Polymerase Chain Reaction, Young Adult, Cytokines genetics, Endothelium, Corneal metabolism, Gene Expression Regulation, RNA, Messenger genetics
- Abstract
Purpose: To develop a method to qualify the function of cultured human corneal endothelial cells (cHCECs) applicable for clinical settings., Methods: The diversified gene and microRNA (miRNA) signatures in HCECs from a variety of tissue donors were confirmed by three-dimensional (3D) gene human miRNA profiling. These were compared with those of more than 20 cHCECs distinct in their cell morphology or culture lots. Candidate genes were selected after quantitative (q)RT-PCR validation, and gene products were assayed by ELISA. After three additional screening steps, final candidate cytokines for qualification were selected., Results: Gene and miRNA signatures among distinct cHCEC lots were greatly diversified compared with those among fresh tissues from different age donors. By comparing more than 20 lots of cultures, 32 candidate genes were assigned to be seemingly linked to distinct cHCEC morphologic features. The validation of candidate genes by qRT-PCR revealed the genes, either upregulated or downregulated, corresponding to morphologic variances in cHCECs (e.g., epithelial-mesenchymal transition or cell senescence). Further adding the ELISA results by Bio-Plex Human Cytokine 27-Plex Panel, 11 candidate cytokines suitable to qualify cHCEC function were selected. In consideration of the presence of these cytokines in the anterior chamber, IL-8, tissue inhibitors of metalloproteinases 1 (TIMP-1), monocyte chemotactic protein-1 (MCP-1), and platelet-derived growth factor-BB (PDGF-BB) were ultimately selected and applied in practice for the qualification of cHCECs actually used in our clinical cell-injection studies., Conclusions: The specified cytokines properly discriminating the functional features of cHCECs indicates a correlation between profiling signatures and cell morphology.
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- 2016
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260. Concomitant Evaluation of a Panel of Exosome Proteins and MiRs for Qualification of Cultured Human Corneal Endothelial Cells.
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Ueno M, Asada K, Toda M, Nagata K, Sotozono C, Kosaka N, Ochiya T, Kinoshita S, and Hamuro J
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- Cells, Cultured, Endothelium, Corneal cytology, Flow Cytometry, Humans, Immunoblotting, MicroRNAs biosynthesis, Microscopy, Phase-Contrast, Phenotype, Real-Time Polymerase Chain Reaction, Endothelium, Corneal metabolism, Exosomes metabolism, MicroRNAs genetics, RNA genetics, Tissue Engineering methods
- Abstract
Purpose: We elucidate a method to use secreted miRNA profiles to qualify cultured human corneal endothelial cells (cHCECs) adaptable for cell-injection therapy., Methods: The variations of cHCECs in their composites of heterogeneous subpopulations (SPs) were verified in relation to their surface cluster-of-differentiation (CD) markers. Integrated analysis of micro RNA (miRNA) profiles in culture supernatants (CS) were investigated by 3D-Gene Human microRNA Chips. To validate 3D-Gene results, quantitative real-time PCR was done from numerous cultures with distinct morphology and SP composition. Exosomes and miRNAs in CS also were analyzed., Results: Secreted miRNA profiles among morphologically-diverse cHCEC SPs proved useful for individual distinction. Candidate miRNAs to discriminate CD44- SPs from those with CD44++ ∼ CD44+++ phenotypes were miRs 221-3p, 1246, 1915-3p, and 4732-5p. The levels of the latter-three miRs decreased dramatically in cHCEC CS without cell-state transition (CST) compared to those of control medium, whereas those from cHCECs with senescence-like CST showed an increase. MicroR184 decreased inversely in parallel with the upregulation of CD44 on cHCECs. CD9+ exosomes were more elevated in cHCEC CS with senescence-like CST than those without CST, indicating the possible import of these extracellular vesicles (EVs) into cHCECs without CST., Conclusions: Cultured HCECs sharing a CD44- phenotype of matured HCECs may be discriminated by measuring the amount of miRNAs or exosome in CS. Thus, miRNA in CS may serve as a tool to qualify cHCECs. Future detailed analysis of cell-to-cell communication via these EVs might open novel pathways for a better understanding of CST in HCEC cultures.
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- 2016
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261. Cultured Human Corneal Endothelial Cell Aneuploidy Dependence on the Presence of Heterogeneous Subpopulations With Distinct Differentiation Phenotypes.
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Hamuro J, Ueno M, Toda M, Sotozono C, Montoya M, and Kinoshita S
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- Adolescent, Adult, Aged, Cell Differentiation, Cell Division, Cells, Cultured, Child, Corneal Endothelial Cell Loss genetics, Corneal Endothelial Cell Loss pathology, Endothelium, Corneal metabolism, Endothelium, Corneal transplantation, Female, Flow Cytometry, Humans, Male, Middle Aged, Phenotype, Tissue Donors, Young Adult, Aneuploidy, Cell Adhesion Molecules metabolism, Corneal Endothelial Cell Loss surgery, Corneal Transplantation methods, Endothelium, Corneal cytology
- Abstract
Purpose: Cultured human corneal endothelial cells (cHCECs) are anticipated to become an alternative to donor corneas for the treatment of corneal endothelial dysfunction. However, cHCECs reportedly tend to exhibit chromosomal abnormality during in vitro cell division, thereby hampering their use in the clinical setting. The purpose of this study was to clarify whether a specified subpopulation (SP) of heterogeneous cHCECs would exhibit aneuploidy, whereas other SPs would not., Methods: The presence of SPs in cHCECs was analyzed on the basis of surface cluster of differentiation (CD) antigen CD166, CD105, CD44, CD26, and CD24 expression levels by flow cytometry. Cytogenetic examination was performed for 23 lots of cHCECs, either as whole-cell preparations (bulk) consisting of mixed SPs or as a semipurified SP by magnetic activated cell sorting (MACS). The HCEC donors ranged from 9 to 69 years of age and the culture passages from primary to fifth passage., Results: Flow cytometry analysis demonstrated the presence of at least three cHCEC SPs. One SP, purified by MACS, with surface expression of CD166+, CD105-, CD44-, CD24-, and CD26- did not show any aneuploidy in 50 cells. However, CD166+, CD44+++, CD24-, and CD26+ cHCEC SPs showed sex chromosome loss in all cells (60 cells), whereas CD166+, CD44+++, CD24+, and CD26- SPs exhibited, albeit partly, trisomy on chromosomes 6, 7, 12, and 20., Conclusions: We found that cHCEC aneuploidy is linked to specified SPs present in cHCECs and that the SP sharing the surface phenotype with mature HCECs in corneal tissues was devoid of the karyotype abnormality.
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- 2016
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262. Metabolic Plasticity in Cell State Homeostasis and Differentiation of Cultured Human Corneal Endothelial Cells.
- Author
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Hamuro J, Ueno M, Asada K, Toda M, Montoya M, Sotozono C, and Kinoshita S
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- Adolescent, Adult, Aged, Biomarkers metabolism, Cell Differentiation, Cells, Cultured, Child, Child, Preschool, Corneal Diseases diagnosis, Electrophoresis, Capillary, Endothelium, Corneal pathology, Female, Flow Cytometry, Humans, Male, Middle Aged, Tandem Mass Spectrometry, Young Adult, Cell Plasticity physiology, Corneal Diseases metabolism, Endothelium, Corneal metabolism, Energy Metabolism physiology, Homeostasis
- Abstract
Purpose: To clarify whether cultured human corneal endothelial cells (cHCECs), heterogeneous in their differentiation state, exhibit distinctive energy metabolism with the aim to develop a reliable method to sort cHCECs applicable for regenerative medicine., Methods: The presence of cHCEC subpopulations (SPs) was verified via surface cluster-of-differentiation (CD) marker expression. Cultured HCEC metabolic extracts or corresponding culture supernatants with distinctive cellular phenotypes in regard to energy-metabolism-related functional markers c-Myc and CD44 were prepared and analyzed via capillary electrophoresis-tandem mass spectrometry. The metabolic requirements of heterogeneous SPs of cHCECs were also investigated., Results: After successfully discriminating SPs, as verified via surface CD markers in terms of their secretory metabolites, we found that the CD44+++ SP with cell-state transition (CST) exhibited disposition for anaerobic glycolysis, whereas the CD44-SP without CST was disposed to mitochondria-dependent oxidative phosphorylation (OXPHOS). These results raised the possibility of establishing effective culture conditions to selectively expand mature cHCECs with a hexagonal cobblestone shape and inclination for mitochondria-dependent OXPHOS., Conclusions: The findings of this study open a pathway for monitoring the disposition of cHCECs via their energy metabolism, thus leading to safe and stable regenerative medicine by use of metabolically defined cHCECs in cell-suspension form.
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- 2016
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263. Stevens-Johnson syndrome: The role of an ophthalmologist.
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Jain R, Sharma N, Basu S, Iyer G, Ueta M, Sotozono C, Kannabiran C, Rathi VM, Gupta N, Kinoshita S, Gomes JA, Chodosh J, and Sangwan VS
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- Humans, Stevens-Johnson Syndrome diagnosis, Corneal Transplantation methods, Dry Eye Syndromes diagnosis, Dry Eye Syndromes etiology, Dry Eye Syndromes surgery, Ophthalmologists, Physician's Role, Stem Cell Transplantation methods, Stevens-Johnson Syndrome complications, Visual Acuity
- Abstract
Stevens-Johnson syndrome (SJS) is an acute blistering disease of the skin and mucous membranes. Acute SJS leads to the acute inflammation of the ocular surface and chronic conjunctivitis. If not properly treated, it causes chronic cicatricial conjunctivitis and cicatricial lid margin abnormalities. Persistent inflammation and ulceration of the ocular surface with cicatricial complications of the lids leads to chronic ocular sequelae, ocular surface damage, and corneal scarring. The destruction of the glands that secrete the tear film leads to a severe form of dry eye that makes the management of chronic SJS difficult. The option that is routinely used for corneal visual rehabilitation, keratoplasty, is best avoided in such cases. We describe the management strategies that are most effective during the acute and chronic stages of SJS. Although treatments for acute SJS involve immunosuppressive and immunomodulatory therapies, amniotic membrane transplantation is also useful. The options for visual rehabilitation in patients with chronic SJS are undergoing radical change. We describe the existing literature regarding the management of SJS and highlight recent advances in the management of this disorder., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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264. Integrin β4 is a major target antigen in pure ocular mucous membrane pemphigoid.
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Li X, Qian H, Sogame R, Hirako Y, Tsuruta D, Ishii N, Koga H, Tsuchisaka A, Jin Z, Tsubota K, Fukumoto A, Sotozono C, Kinoshita S, and Hashimoto T
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- Autoantibodies blood, Autoantigens immunology, Case-Control Studies, Cell Adhesion Molecules immunology, Fluorescent Antibody Technique, Indirect, Hemidesmosomes, Humans, Immunoblotting methods, Non-Fibrillar Collagens immunology, Pemphigoid, Benign Mucous Membrane immunology, Recombinant Proteins immunology, Kalinin, Collagen Type XVII, Immunoglobulin A blood, Immunoglobulin G blood, Integrin beta4 immunology, Pemphigoid, Benign Mucous Membrane blood
- Abstract
Previous studies of ocular mucous membrane pemphigoid (OMMP) have identified several components of the basement membrane zone to be autoantigens, including integrin β4. However, there are no extensive or definitive reported studies that address this, particularly in pure OMMP. To clarify the major autoantigens in pure OMMP. In this study, we examined sera from 43 pure OMMP patients for both IgG and IgA antibodies using newly developed immunoblotting analyses with a hemidesmosome-rich fraction and various recombinant proteins of integrin α6β4, in addition to our routine immune-serological tests. Using a hemidesmosome-rich fraction, sera from patients with pure OMMP demonstrated reactivity of IgG and/or IgA antibodies to integrin β4, BP180 and laminin-332. The reactivity of pure OMMP sera to integrin β4 was further confirmed by immunoblotting using integrin β4 recombinant proteins. Using concentrated supernatant of HaCaT cells, only one serum sample showed positive IgG and IgA reactivity to LAD-1, the ectodomain of BP180. None of the pure OMMP sera reacted with any autoantigens on immunoblotting using normal human epidermal or dermal extracts, or purified human laminin-332. Integrin β4 was considered to be the major and specific autoantigen for pure OMMP. The new methods established in this study are useful for detection of various autoantigens, particularly integrin β4.
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- 2016
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265. Nasal and conjunctival screening prior to refractive surgery: an observational and cross-sectional study.
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Kitazawa K, Sotozono C, Sakamoto M, Sasaki M, Hieda O, Yamasaki T, and Kinoshita S
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- Adult, Corynebacterium isolation & purification, Cross-Sectional Studies, Dermatitis, Atopic complications, Female, Health Personnel, Humans, Japan, Male, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus isolation & purification, Preoperative Care, Propionibacterium acnes isolation & purification, Risk Factors, Staphylococcus epidermidis isolation & purification, Carrier State diagnosis, Carrier State microbiology, Conjunctiva microbiology, Nasal Cavity microbiology, Refractive Surgical Procedures methods
- Abstract
Objectives: To investigate bacterial flora of clinically healthy conjunctiva and nasal cavity among patients prior to refractive surgery, as well as the characteristics of patients with methicillin-resistant Staphylococcus aureus (MRSA) colonisation., Design: Observational and cross-sectional study., Setting: A single-centre study in Japan., Participants: 120 consecutive patients pre-refractive surgery., Primary and Secondary Outcome Measures Methods: Samples were obtained from the right conjunctival sac and the nasal cavity of 120 consecutive patients prior to refractive surgery and were then measured for the levels of the minimum inhibitory concentration (MIC) of antibiotics. Patients were interviewed regarding their occupation, family living situation and any personal history of atopic dermatitis, asthma, smoking or contact lens wear., Results: Propionibacterium acnes (P. acnes) (32.5%) and Staphylococcus epidermidis (4.2%) were detected from the conjunctival sac. S. epidermidis was the most commonly isolated (68.3%) in the nasal cavity. Of the 30 patients (25.0%) with colonisation by S. aureus, 2 patients, both of whom were healthcare workers with atopic dermatitis, were found to be positive for MRSA in the nasal cavity. A history of contact lens wear, asthma or smoking, as well as patient gender and age, was not associated with MRSA colonisation., Conclusions: There were only 2 patients who were colonised with MRSA, both of whom were healthcare workers with atopic dermatitis. P. acnes was predominantly found in the conjunctival sac. Further study is needed to investigate the involvement between nasal and conjunctival flora, and risk factors for infectious complications., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
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- 2016
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266. Acute and Chronic Ophthalmic Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis - A Comprehensive Review and Guide to Therapy. II. Ophthalmic Disease.
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Kohanim S, Palioura S, Saeed HN, Akpek EK, Amescua G, Basu S, Blomquist PH, Bouchard CS, Dart JK, Gai X, Gomes JA, Gregory DG, Iyer G, Jacobs DS, Johnson AJ, Kinoshita S, Mantagos IS, Mehta JS, Perez VL, Pflugfelder SC, Sangwan VS, Sippel KC, Sotozono C, Srinivasan B, Tan DT, Tandon R, Tseng SC, Ueta M, and Chodosh J
- Subjects
- Epidermis, Eye Diseases, Humans, Necrosis, Quality of Life, Skin, Stevens-Johnson Syndrome
- Abstract
Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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267. [Indication and Efficacy of Amniotic Membrane Transplantation Performed under Advanced Medical Healthcare].
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Morikawa K, Sotozono C, Inatomi T, Nakamura T, Yokoi N, Matsuo Y, and Kinoshita S
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- Corneal Ulcer surgery, Glaucoma surgery, Humans, Pterygium surgery, Retrospective Studies, Surveys and Questionnaires, Transplantation, Homologous, Treatment Outcome, Amnion transplantation
- Abstract
Purpose: To survey indications and outcomes of amniotic membrane transplantation (AMT) performed under Advanced Medical Healthcare (AMH) in Japan., Methods: Questionnaires were sent to 21 facilities performing AMT under AMH from 2010-2012. Diagnosis, effectiveness, and final outcomes were surveyed. Moreover, we retrospectively examined the diagnosis, treatment effectiveness, and final outcomes in all AMTs performed under AMH at Kyoto Prefectural University of Medicine (KPUM) from April 2009 through June 2013., Results: Clinical data of 311 eyes that underwent AMT under AMH was obtained. Of those, diagnoses included pterygium (n = 148), corneal ulcer/epithelial defect (n = 60), corneal perforation (n = 28), intractable glaucoma (n = 24), and others (n = 51). The surgical outcome was completely or partially successful in 287 eyes (92.3%). The final outcome was effective in 281 eyes (90.4%). A total of 45 eyes of 37 patients underwent AMT under AMH at KPUM. Of those, diagnoses included pterygium (n = 15), recurrence of pterygium (n = 27), and symblepharon (n = 3). The surgical outcome was completely successful in 98% and partially successful in 2%. The final outcome was effective in all cases., Conclusion: AMT performed under AMH in Japan was most common in eyes with pterygium, and was highly effective in these cases, as well as corneal ulcer/epithelial defect, corneal perforation, and intractable glaucoma.
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- 2016
268. Predictive factors for ocular complications caused by anticancer drug S-1.
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Yamada R, Sotozono C, Nakamura T, Nishida A, Nakanishi S, Hirabatake M, Tsuji A, and Kurimoto Y
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- Adult, Aged, Aged, 80 and over, Conjunctivitis drug therapy, Conjunctivitis epidemiology, Corneal Diseases drug therapy, Corneal Diseases epidemiology, Drug Combinations, Female, Health Knowledge, Attitudes, Practice, Humans, Japan epidemiology, Lacrimal Duct Obstruction drug therapy, Lacrimal Duct Obstruction epidemiology, Male, Middle Aged, Neoplasms drug therapy, Risk Factors, Surveys and Questionnaires, Antimetabolites, Antineoplastic adverse effects, Conjunctivitis chemically induced, Corneal Diseases chemically induced, Lacrimal Duct Obstruction chemically induced, Oxonic Acid adverse effects, Tegafur adverse effects
- Abstract
Purpose: To identify predictive factors for ocular complications caused by the anticancer drug S-1., Methods: A questionnaire was administered to 39 patients who underwent S-1 chemotherapy at Kobe City Medical Center General Hospital, with the aim to determine whether these patients were aware of the ocular complications caused by S-1. Cognition rate was determined. The 26 patients who requested opthalmological examination for further evaluation studied further and classified into two groups-those who had developed corneal epithelial complications, conjunctival injection or chemosis, or lacrimal duct blockages (referred to as the positive group) and those without these findings (referred to as the negative group). Predictive factors, such as age, sex, total administration days, total dose, presence or absence of anticancer drug pretreatment, and single-drug or combination-drug therapy, were investigated and compared between groups., Results: Of the 39 patients who completed the questionnaire, ten were aware of the potential for ocular complications due to S-1 chemotherapy (cognition rate 25.6 %). Of the 26 patients who had requested opthalmological examination and entered into the study, 13 (26 eyes) were classified into the positive group, with corneal complications observed in 15 eyes (57.7 %), conjunctivitis in 26 eyes (100 %), and lacrimal duct blockage in 14 eyes (53.8 %). Cognition rate in the 13 patients in the positive group and the 13 patients in the negative group was 38.5 % (5 patients) and 7.7 % (1 patient), respectively. Patient age was significantly different between the two groups, with the patients in the positive group being significantly older than those in the negative group (mean age ± standard deviation: 71.6 ± 6.8 vs. 63.5 ± 7.3 years, respectively; P = 0.0077, Student's t test). No other significant predictive factors were detected., Conclusion: Older patients were at greater risk of S-1-related ocular complications, but these complications were not associated with total administration days or total dose.
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- 2016
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269. Ocular surface reconstruction using stem cell and tissue engineering.
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Nakamura T, Inatomi T, Sotozono C, Koizumi N, and Kinoshita S
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- Animals, Conjunctiva cytology, Epithelium, Corneal cytology, Humans, Regenerative Medicine, Corneal Diseases therapy, Limbus Corneae cytology, Stem Cell Transplantation, Stem Cells cytology, Tissue Engineering methods
- Abstract
Most human sensory information is gained through eyesight, and integrity of the ocular surface, including cornea and conjunctiva, is known to be indispensable for good vision. It is believed that severe damage to corneal epithelial stem cells results in devastating ocular surface disease, and many researchers and scientists have tried to reconstruct the ocular surface using medical and surgical approaches. Ocular surface reconstruction via regenerative therapy is a newly developed medical field that promises to be the next generation of therapeutic modalities, based on the use of tissue-specific stem cells to generate biological substitutes and improve tissue functions. The accomplishment of these objectives depends on three key factors: stem cells, which have highly proliferative capacities and longevities; the substrates determining the environmental niche; and growth factors that support them appropriately. This manuscript describes the diligent development of ocular surface reconstruction using tissue engineering techniques, both past and present, and discusses and validates their future use for regenerative therapy in this field., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2016
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270. Elevated expression of ABCB5 in ocular surface squamous neoplasia.
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Jongkhajornpong P, Nakamura T, Sotozono C, Nagata M, Inatomi T, and Kinoshita S
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- ATP Binding Cassette Transporter, Subfamily B, Female, Gene Expression Regulation, Neoplastic, Humans, Limbus Corneae metabolism, Male, Neoplastic Stem Cells metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Carcinoma, Squamous Cell metabolism, Eye Neoplasms metabolism, Up-Regulation
- Abstract
ATP-binding cassette subfamily B member 5 (ABCB5) is a new member of the ATP-binding cassette superfamily and has been reported as a novel marker for limbal stem cell (LSC), which is essential for corneal homeostasis. ABCB5 expression has also been discovered in the subpopulation of several cancer cells containing the cancer stem cell (CSC). However, the pathogenetic relationship between LSC and CSC and ABCB5 in the ocular surface squamous neoplasm (OSSN) is still entirely unknown. To improve understanding of the role of ABCB5 in OSSN, we performed immunohistochemistry for ABCB5 in nine OSSN case series. While expression of ABCB5 is restricted to the basal epithelial cell layer in the normal limbus, elevated expressions of ABCB5 were clearly observed in all OSSN, and there was some breadth in the range of intensity of ABCB5 expression. Interestingly, the elevated expression patterns of ABCB5 in OSSN could be classified in three categories: perivascular, marginal and diffuse patterns. Our findings demonstrated for the first time that the expression of ABCB5 was upregulated in OSSN and that elevated expression of ABCB5 may be involved in the pathogenesis of OSSN.
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- 2016
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271. Analysis of Ocular Manifestation and Genetic Association of Allopurinol-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in South Korea.
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Lee HS, Ueta M, Kim MK, Seo KY, Sotozono C, Kinoshita S, and Yoon KC
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- Aged, Asian People ethnology, Conjunctival Diseases drug therapy, Conjunctival Diseases ethnology, Drug Eruptions drug therapy, Drug Eruptions ethnology, Drug Eruptions etiology, Female, Genotype, Genotyping Techniques, Glucocorticoids therapeutic use, Humans, Male, Middle Aged, Polymerase Chain Reaction, Prednisolone therapeutic use, Prospective Studies, Republic of Korea epidemiology, Stevens-Johnson Syndrome drug therapy, Stevens-Johnson Syndrome ethnology, Stevens-Johnson Syndrome etiology, Allopurinol adverse effects, Conjunctival Diseases chemically induced, Conjunctival Diseases genetics, Drug Eruptions genetics, Gout Suppressants adverse effects, HLA Antigens genetics, Stevens-Johnson Syndrome genetics
- Abstract
Purpose: To describe the clinical characteristics and genetic background of allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in South Korea., Methods: This is a prospective, noncomparative case series. Visual acuity, detailed medical history, ocular findings, and systemic manifestations of 5 patients (10 eyes) with allopurinol-induced SJS/TEN were recorded. The acute ocular involvement score and the chronic ocular manifestation score were graded on scales of 0-3 and 0-39, respectively, based on severity. Human leukocyte antigen (HLA) genotyping was also performed during the hospitalization., Results: Three patients were diagnosed with SJS, and 2 with TEN. Mild ocular involvement with only conjunctival hyperemia (acute ocular involvement score ≤ 1) was present in all 10 eyes during the acute stage. Patients were treated with systemic steroids and topical antibiotics, steroids, and preservative-free artificial tears, with rinsing of the ocular surface, in the acute stages of SJS/TEN. In the final follow-up, none of the patients had developed severe chronic ocular complications (chronic ocular manifestation score ≤ 8), including keratinization, corneal conjunctivalization, mucocutaneous junction involvement, or symblepharon. One patient developed bilateral persistent epithelial defects 3 months after the disease onset, which healed after conservative treatment, leaving a bilateral central corneal haze. HLA genotyping showed that 4 of the 5 patients (80%) were positive for HLA-B*58:01., Conclusions: Allopurinol-induced SJS/TEN might not cause serious acute or chronic complications of the ocular surface. In addition, our HLA genotyping results are consistent with previous studies reporting a strong association between HLA-B*58:01 and allopurinol-induced SJS/TEN among Koreans.
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- 2016
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272. [Multicenter Prospective Observational Study of Fungal Keratitis--Current Status of Patients' Background, Clinical Findings, Treatment and Prognosis].
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Inoue Y, Ohashi Y, Suzuki T, Shimomura Y, Fukuda M, Sotozono C, Hatano H, Eguchi H, Araki-Sasaki K, Hoshi S, Sunada A, Asari S, Yaguchi T, Makimura K, Yokokura S, Mochizuki K, Monden Y, and Nejima R
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- Adolescent, Adult, Aged, Aged, 80 and over, Corneal Diseases diagnosis, Eye Infections, Fungal diagnosis, Female, Humans, Japan, Keratitis microbiology, Male, Middle Aged, Ophthalmology methods, Prognosis, Prospective Studies, Visual Acuity drug effects, Visual Acuity immunology, Young Adult, Corneal Diseases drug therapy, Eye Infections, Fungal drug therapy, Keratitis diagnosis, Keratitis therapy
- Abstract
Purpose: To investigate the current status of fungal keratitis in Japan., Methods: The patients with fungal keratitis were examined at 27 facilities in Japan from November 1st 2011 to October 31st 2013, concerning isolates, patient background, clinical findings, treatment and prognosis., Results: Out of 139 cases, 133 were diagnosed as fungal keratitis, of which fungi were isolated from 72 samples of 71 cases (yeast-like fungi 32 strains and filamentous fungi 40 strains). The corrected visual acuity at the first visit of 88 cases (66.2%) was less than 20/200 and 42 cases (31.6%) were involved with deep stromal lesions, indicating high proportion of severe cases in this study. Three months later, 56 cases (42.1%) were still under treatment, and corrected visual acuity of 57 cases (42.9%) was less than 20/200. In cases with yeast-like fungi, there were significantly more cases with past history of corneal diseases, ocular surgery including keratoplasty, and eye drops' use such as steroids than those with filamentous fungi. On the other hand, there were significantly more cases of filamentous fungi, with trauma on the onset and with intervention of previously attending doctors than those with yeast-like fungi. Logistic regression analyses revealed that contact lens wearing was a significant factor of good prognosis, and yeast-like fungi as one of poor outcome compared with no fungal isolation., Conclusion: Although the choice of antifungal drugs has been increasing, fungal keratitis is still severe, refractory and vision-threatening disease.
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- 2016
273. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis--A Comprehensive Review and Guide to Therapy. I. Systemic Disease.
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Kohanim S, Palioura S, Saeed HN, Akpek EK, Amescua G, Basu S, Blomquist PH, Bouchard CS, Dart JK, Gai X, Gomes JA, Gregory DG, Iyer G, Jacobs DS, Johnson AJ, Kinoshita S, Mantagos IS, Mehta JS, Perez VL, Pflugfelder SC, Sangwan VS, Sippel KC, Sotozono C, Srinivasan B, Tan DT, Tandon R, Tseng SC, Ueta M, and Chodosh J
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- Humans, Disease Management, Ophthalmology methods, Practice Guidelines as Topic, Stevens-Johnson Syndrome therapy
- Abstract
The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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274. [Multicenter Prospective Observational Study of Fungal Keratitis--Identification and Susceptibility Test of Fungi].
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Sunada A, Asari S, Inoue Y, Ohashi Y, Suzuki T, Shimomura Y, Fukuda M, Sotozono C, Hatano H, Eguchi H, Araki-Sasaki K, Hoshi S, Yaguchi T, Makimura K, Yokokura S, Mochizuki K, Monden Y, and Nejima R
- Subjects
- Corneal Ulcer diagnosis, Genetic Testing, Humans, Japan, Keratitis microbiology, Prospective Studies, Sensitivity and Specificity, Corneal Ulcer microbiology, Eye Infections, Fungal diagnosis, Eye Infections, Fungal microbiology, Keratitis diagnosis, Mycoses diagnosis
- Abstract
Purpose: To investigate the causative fungi of fungal keratitis in Japan and their drug susceptibility., Methods: Identification and antifungal susceptibility test for 8 drugs (micafungin, amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, miconazole and pimaricin) were performed using isolated fungi from patients with fungal keratitis treated at 27 facilities in Japan between November 1, 2011 and October 31, 2013., Results: Fungal strains were detected in 72 (50.7%) out of 142 samples. The major isolates were Fusarium spp. (18), Candida parapsilosis (12), C. albicans (11) and Alternaria spp. (6), in all, fungi of 31 species were identified by gene analysis. In the yeast-like fungi, susceptibility rates were evident for more than 80% in voriconazole, pimaricin, flucytosine, micafungin, amphotericin B and fluconazole. In filamentous fungi, the susceptibility rate was less than 50% except for PMR (90%). Fusarium spp., which were susceptible to amphotericin B and pimaricin, showed lower susceptibility rates compared with other genera., Conclusions: Although various genera and species of fungi cause fungal keratitis, the obtained drug susceptibility data in this study demonstrates the different susceptibility patterns among the major isolates (Fusarium spp., C. parapsilosis, C. albicans and other groups). This is important evidence useful for fungal keratitis treatment.
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- 2016
275. Diffuse Anterior Retinoblastoma with Sarcoidosis-Like Nodule.
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Kitazawa K, Nagata K, Yamanaka Y, Kuwahara Y, Iehara T, Kinoshita S, and Sotozono C
- Abstract
Background: Retinoblastomas account for 4% of malignancies in children, 1-2% of which are diffuse infiltrating retinoblastomas. Diffuse anterior retinoblastoma is rare and does not involve the retina. Here, we report on a diffuse anterior retinoblastoma with large sarcoidosis-like nodules on the iris that were responsive to anti-inflammatory therapy., Case: We present a 6-year-old girl who had anterior uveitis with white nodules on the iris and posterior surface of the cornea in her right eye. The nodules initially responded well to anti-inflammatory treatment. However, anterior segment optical coherence tomography (AS-OCT) showed that the nodules gradually grew, shrinking the iris. We then collected the aqueous humor for diagnosis. A biopsy revealed clusters of small cells with a high nuclear-to-cytoplasm ratio with partial rosette formation. Therefore, we diagnosed diffuse anterior retinoblastoma without retinal involvement and performed enucleation of the right eye. The histopathology demonstrated undifferentiated cells similar to those seen on the biopsy, and tumor cells invaded the iris stroma, posterior surface of the cornea, ciliary body, and sclera. After the enucleation, she underwent chemotherapy and remains alive., Conclusion: A differential diagnosis of retinoblastoma should be considered when white nodules refractory to anti-inflammatory therapy occur in the eye, even in the absence of obvious retinal masses. AS-OCT findings are useful in assessing retinoblastoma.
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- 2015
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276. [Infection post Excimer Laser Corneal Refractive Surgery].
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Hieda O, Sotozono C, Nakamura T, and Kinoshita S
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- Adult, Astigmatism physiopathology, Female, Humans, Keratomileusis, Laser In Situ adverse effects, Middle Aged, Visual Acuity, Astigmatism surgery, Eye Infections, Bacterial microbiology, Lasers, Excimer adverse effects, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections microbiology
- Abstract
Purpose: To report the cases with severe infection post excimer laser refractive surgery., Methods: This study involved 6 eyes of 4 women (mean age 38 years, range : 27-51 years) who underwent excimer laser corneal refractive surgery., Results: In all 4 cases, the respective primary causative organisms of the infection were quinolone-resistant methicillin-sensitive Staphylococcus aureus, quinolone-resistant methicillin-resistant Staphylococcus aureus, yeast type fungus, and in 1 case, penicillin-resistant Streptococcus pneumoniae. We initiated topical antibiotics or intensive antifungal treatment, yet due to severe inflammation and ophthalmalgia, analgesic drugs were needed. An average hospitalization period was 38.5 days (range : 22-77 days), and the best spectacle-corrected visual acuity was 0.5 or more than 0.5 post discharge., Conclusions: In the treatment of severe corneal infection post refractive surgery, it is important to identify the primary causative organism. If the response to the initial treatment is poor, such patients should immediately be referred to a special clinic to obtain a better visual outcome.
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- 2015
277. [Severe Ocular Infection in Elderly Patients with Dementia: a Case Study].
- Author
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Miyamura Y, Sotozono C, Higashihara H, Hoshi S, and Kinoshita S
- Subjects
- Aged, Aged, 80 and over, Corynebacterium, Eye Infections, Bacterial drug therapy, Female, Gram-Positive Bacterial Infections drug therapy, Humans, Male, Moraxella catarrhalis, Staphylococcal Infections drug therapy, Staphylococcus epidermidis, Dementia complications, Eye Infections, Bacterial complications, Gram-Positive Bacterial Infections complications, Staphylococcal Infections complications
- Abstract
Unlabelled: Purpose : To report 3 cases of severe ocular infection in elderly patients with dementia., Case Reports: Case 1 involved a 75-year-old man who presented after his wife noticed hyperemia and discharge in his right eye. Corneal infection with perforation was found. Wife-administered antibiotics healed the infection within 1 month. Case 2 involved a 97-year-old man who was referred to us after nursing-home staff members noticed redness and discharge in his right eye. Severe corneal infection with hypopyon was found. Following systemic and topical and antibiotics' administration by the nursing-home staff, the infectious keratitis healed within 2 weeks. Case 3 involved an 80-year-old woman referred to us from another clinic due to persistent epithelial defect in her left eye. Since the defect was accompanied by anterior uveitis and vitreous opacity, we suspected bacterial endophthalmitis. Following systemic and topical antibiotics' administration by family members, signs of infection diminished within 3 weeks. In all 3 cases, medical examination was difficult, topical eye-drop instillation by the patients themselves was impossible., Conclusions: In elderly dementia patients, cognizance of infection, medical examination, and treatment are difficult. Support by family members or nursing-home staff is necessary to obtain improved outcomes.
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- 2015
278. Phenotypic Investigation of Regenerated Epithelial Cells After Gonococcal Corneal Perforation: A Clinical, Histological, and Immunohistochemical Study.
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Jongkhajornpong P, Nakamura T, Sotozono C, Inatomi T, and Kinoshita S
- Subjects
- Actins metabolism, Adult, Biomarkers metabolism, Cell Movement physiology, Corneal Perforation metabolism, Corneal Perforation microbiology, Corneal Transplantation, Epithelial Cells cytology, Eye Infections, Bacterial metabolism, Eye Infections, Bacterial microbiology, Gonorrhea metabolism, Gonorrhea microbiology, Humans, Immunohistochemistry, Keratins metabolism, Ki-67 Antigen metabolism, Male, Phenotype, Tight Junction Proteins metabolism, Vimentin metabolism, Wound Healing physiology, Corneal Perforation surgery, Epithelium, Corneal physiology, Eye Infections, Bacterial surgery, Gonorrhea surgery, Neisseria gonorrhoeae isolation & purification, Regeneration physiology
- Abstract
Purpose: To determine the characteristics of regenerated epithelial cells after severe gonococcal infection after corneal perforation., Methods: Pathological tissue was obtained from the cornea at the time of surgery. Hematoxylin and eosin staining and immunohistochemical analysis were performed for cytoskeletal keratins (K12, K13, and K15), basement membrane and junctional markers (laminin 5, ZO-1 and Desmoplakin), and proliferative and mesenchymal markers (Ki67, α-SMA, and vimentin)., Results: A 42-year-old patient with severe gonococcal keratoconjunctivitis rapidly progressed to corneal perforation during administration of intensive topical and systemic antibiotics. After conservative treatment, the perforation healed and 5- × 3-mm corneal ectasia occurred with localized iris attachment. Complete closure of the cornea was confirmed by a negative Seidel test. After lamellar keratoplasty to improve corneal integrity and to prevent secondary glaucoma, the pathological tissue revealed a poorly organized epithelial layer at the regenerated ectatic area. The regenerated epithelial cells clearly expressed K12, ZO-1, and Desmoplakin with underlying laminin 5 (+) basement membrane. K15 and Ki67 expressions were observed predominantly at the limbal area but not in the regenerated area. α-SMA and vimentin were sporadically expressed in the underlying connective tissue., Conclusions: We speculate that the process of epithelial wound healing at the site of corneal perforation was responsible for migration of the surrounding epithelial cells. Although the regenerated cells expressed several cytokeratins and junctional markers, they remained disorganized and fragile.
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- 2015
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279. Drugs causing severe ocular surface involvements in Japanese patients with Stevens-Johnson syndrome/toxic epidermal necrolysis.
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Kaniwa N, Ueta M, Nakamura R, Okamoto-Uchida Y, Sugiyama E, Maekawa K, Takahashi Y, Furuya H, Yagami A, Matsukura S, Ikezawa Z, Matsunaga K, Sotozono C, Aihara M, Kinoshita S, and Saito Y
- Subjects
- Humans, Severity of Illness Index, Eye pathology, Stevens-Johnson Syndrome diagnosis, Stevens-Johnson Syndrome etiology
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- 2015
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280. Predictive Factors Associated With Acute Ocular Involvement in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.
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Sotozono C, Ueta M, Nakatani E, Kitami A, Watanabe H, Sueki H, Iijima M, Aihara M, Ikezawa Z, Aihara Y, Kano Y, Shiohara T, Tohyama M, Shirakata Y, Kaneda H, Fukushima M, Kinoshita S, and Hashimoto K
- Subjects
- Acute Disease, Eye Diseases diagnosis, Eye Diseases etiology, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Prognosis, Retrospective Studies, Stevens-Johnson Syndrome diagnosis, Conjunctiva pathology, Cornea pathology, Eye Diseases epidemiology, Risk Assessment methods, Sclera pathology, Stevens-Johnson Syndrome complications
- Abstract
Purpose: To suggest an objective score for grading the acute ocular severity of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to determine predictive factors for severe acute ocular involvement such as ocular surface epithelial defect and/or pseudomembrane formation., Design: Retrospective cohort study., Methods: The medical records of SJS (n = 87) and TEN (n = 48) patients between 2005 and 2007 were reviewed. An acute ocular severity score was determined on a scale from 0 to 3 (none, mild, severe, and very severe) according to the existence of hyperemia, corneal or conjunctival epithelial defect, and pseudomembrane formation. The associations between the severe acute ocular involvement and factors such as patient age, exposed drugs, systemic severity, and the prevalence of ocular sequelae were examined., Results: The number of cases with score grade 0, 1, 2, and 3 was 19 (21.8%), 31 (35.6%), 22 (25.3%), and 15 (17.2%) in 87 SJS cases and 12 (25.0%), 11 (22.9%), 17 (35.4%), and 8 (16.7%) in 48 TEN cases. Multivariate logistic regression analysis revealed that patient age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; P = .007) and nonsteroidal anti-inflammatory drugs NSAIDs or cold remedies (OR, 2.58; 95% CI, 1.26-5.29; P = .010) were predictive factors for severe acute ocular involvement. The prevalence of visual disturbance and eye dryness increased according to the increase of acute ocular severity (P = .001 and P = .007 in SJS; P = .007 and P = .014 in TEN, respectively)., Conclusions: At the onset of SJS/TEN, strict attention should be paid to ocular involvement in young patients and in patients exposed to NSAIDs or cold remedies., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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281. HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens-Johnson syndrome with severe ocular complications.
- Author
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Ueta M, Tokunaga K, Sotozono C, Sawai H, Yoon KC, Kum Kim M, Yul Seo K, Joo CK, Tashiro K, and Kinoshita S
- Abstract
We previously reported that PTGER3 (prostaglandin E receptor 3 (subtype EP3)) single-nucleotide polymorphisms (SNPs) were associated with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with severe ocular complications (SOC). We also documented that approximately 80% of our SJS/TEN patients had taken cold medicines within several days before disease onset, and we thus designated them cold medicine-related SJS/TEN (CM-SJS/TEN) patients. Moreover, we reported that HLA-A*02:06 with TLR3 polymorphisms exerted more than additive effects in SJS/TEN with SOC. In this study, we focused on CM-SJS/TEN with SOC and analyzed the association with PTGER3 SNPs and an interactive effect between PTGER3 SNPs and HLA-A*02:06 in not only the Japanese but also the Korean population. In the Japanese population, PTGER3 SNP rs1327464 was most significantly associated with CM-SJS/TEN with SOC (G versus A; odds ratio (OR)=0.232, P=7.92×10(-10)), and we found an interaction with additive effects between HLA-A*02:06 and the high-risk genotypes PTGER3 rs1327464 GA or AA (OR=10.8, P=2.56×10(-7)). We also found a significant association between Korean CM-SJS/TEN with SOC and PTGER3 SNP rs1327464 (GG versus GA+AA, OR=0.246, P=0.00101), and we detected an additive effect between HLA-A*02:06 and the high-risk genotypes PTGER3 rs1327464 GA or AA (OR=14.2, P=5.58×10(-6)).
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- 2015
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282. IKZF1, a new susceptibility gene for cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis with severe mucosal involvement.
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Ueta M, Sawai H, Sotozono C, Hitomi Y, Kaniwa N, Kim MK, Seo KY, Yoon KC, Joo CK, Kannabiran C, Wakamatsu TH, Sangwan V, Rathi V, Basu S, Ozeki T, Mushiroda T, Sugiyama E, Maekawa K, Nakamura R, Aihara M, Matsunaga K, Sekine A, Gomes JÁ, Hamuro J, Saito Y, Kubo M, Kinoshita S, and Tokunaga K
- Subjects
- Adolescent, Adult, Aged, Alternative Splicing, Asian People, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-A Antigens immunology, Humans, Ikaros Transcription Factor immunology, Male, Middle Aged, Mouth Mucosa pathology, Odds Ratio, Polymorphism, Single Nucleotide, Protein Isoforms genetics, Protein Isoforms immunology, Stevens-Johnson Syndrome ethnology, Stevens-Johnson Syndrome etiology, Stevens-Johnson Syndrome pathology, White People, Anti-Inflammatory Agents, Non-Steroidal adverse effects, HLA-A Antigens genetics, Ikaros Transcription Factor genetics, Mouth Mucosa drug effects, Multi-Ingredient Cold, Flu, and Allergy Medications adverse effects, Stevens-Johnson Syndrome genetics
- Abstract
Background: Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface, oral cavity, and genitals. These reactions are very rare but are often associated with inciting drugs, infectious agents, or both., Objective: We sought to identify susceptibility loci for cold medicine-related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement (SMI)., Methods: A genome-wide association study was performed in 808 Japanese subjects (117 patients with CM-SJS/TEN with SMI and 691 healthy control subjects), and subsequent replication studies were performed in 204 other Japanese subjects (16 cases and 188 control subjects), 117 Korean subjects (27 cases and 90 control subjects), 76 Indian subjects (20 cases and 56 control subjects), and 174 Brazilian subjects (39 cases and 135 control subjects)., Results: In addition to the most significant susceptibility region, HLA-A, we identified IKZF1, which encodes Ikaros, as a novel susceptibility gene (meta-analysis, rs4917014 [G vs. T]; odds ratio, 0.5; P = 8.5 × 10(-11)). Furthermore, quantitative ratios of the IKZF1 alternative splicing isoforms Ik1 and Ik2 were significantly associated with rs4917014 genotypes., Conclusion: We identified IKZF1 as a susceptibility gene for CM-SJS/TEN with SMI not only in Japanese subjects but also in Korean and Indian subjects and showed that the Ik2/Ik1 ratio might be influenced by IKZF1 single nucleotide polymorphisms, which were significantly associated with susceptibility to CM-SJS/TEN with SMI., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2015
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283. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR).
- Author
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Kano Y, Tohyama M, Aihara M, Matsukura S, Watanabe H, Sueki H, Iijima M, Morita E, Niihara H, Asada H, Kabashima K, Azukizawa H, Hashizume H, Nagao K, Takahashi H, Abe R, Sotozono C, Kurosawa M, Aoyama Y, Chu CY, Chung WH, and Shiohara T
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Drug Hypersensitivity Syndrome epidemiology, Eosinophilia complications, Eosinophilia epidemiology, Female, Follow-Up Studies, Humans, Japan epidemiology, Male, Middle Aged, Taiwan epidemiology, Young Adult, Diabetes Mellitus, Type 1 epidemiology, Drug Hypersensitivity Syndrome complications, Infections epidemiology, Thyroid Diseases epidemiology
- Abstract
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction caused by specific drug. It is characterized by visceral organ involvement and reactivation of various human herpesviruses. Although sporadic reports have documented certain conditions that appear after the resolution of DIHS/DRESS, little information is available on sequelae after resolution of DIHS/DRESS in a large patient population. The Asian Research Committee on Severe Cutaneous Adverse Reactions, comprised of doctors from Japan and Taiwan, conducted a survey on sequelae and deterioration of the underlying disease in patients with DIHS/DRESS. This was achieved by directly interviewing patients who had been followed-up by experts or through a questionnaire mailed to patients. Questions were asked about new onset cardiovascular disease, collagen disease or autoimmune disease, gastrointestinal disease, renal disease, respiratory disease, neoplasms, and other diseases such as herpes zoster and diabetes mellitus, as well as deterioration of the underlying disease. A total of 145 patients were analyzed in this study. The following newly developed diseases after recovery from DIHS/DRESS were observed: Graves' disease (n = 2), Hashimoto's disease (n = 3), painless thyroiditis (n = 2), fulminant type 1 diabetes mellitus (n = 5), and infectious diseases (n = 7). Several DIHS/DRESS patients with pre-existing renal dysfunction required lifelong hemodialysis. DIHS/DRESS is a condition that increases the risk of new onset of disease. Long-term observation of DIHS/DRESS can provide an opportunity to investigate substantial diseases from onset to the full-blown stage. Patients with DIHS/DRESS require careful long-term follow-up., (© 2015 Japanese Dermatological Association.)
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- 2015
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284. The role of systemic immunomodulatory treatment and prognostic factors on chronic ocular complications in Stevens-Johnson syndrome.
- Author
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Kim DH, Yoon KC, Seo KY, Lee HS, Yoon SC, Sotozono C, Ueta M, and Kim MK
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- Adolescent, Adult, Aged, Biological Dressings, Child, Child, Preschool, Chronic Disease, Corneal Diseases physiopathology, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prognosis, Pulse Therapy, Drug, Retrospective Studies, Stevens-Johnson Syndrome physiopathology, Visual Acuity physiology, Corneal Diseases drug therapy, Glucocorticoids therapeutic use, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors therapeutic use, Immunomodulation, Prednisolone therapeutic use, Stevens-Johnson Syndrome drug therapy
- Abstract
Purpose: To compare the effect of early systemic immunomodulatory treatment and to identify prognostic factors of chronic ocular complications in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients., Design: Retrospective, comparative, multicenter study., Participants: Forty-three patients admitted to 1 of 3 University Hospitals (Seoul National University Hospital, Chonnam National University Hospital, and Yonsei University Hospital) with a diagnosis of SJS or TEN who were followed up for at least 6 months in Korea., Methods: Patients were divided into 5 groups according to systemic immunomodulatory treatment received: systemic steroids (S), intravenous immunoglobulin (IVIG), combined S plus IVIG, systemic pulse steroids (PS), and supportive care only (C). Best-corrected visual acuity (BCVA) and chronic ocular surface complications score (COCS; range, 0-15) at final follow-up were compared among the 5 groups. Prognostic factors at onset (age, gender, causative drugs, initial visual acuities, acute ocular involvement score [range, 0-3], acute systemic involvement score [range, 0-16], systemic steroid dose, IVIG dose, and amniotic membrane transplantation [AMT]) were analyzed to predict final BCVA or COCS using logistic regression or linear regression analysis., Main Outcome Measures: Best-corrected visual acuity and COCS at final follow-up., Results: The mean age and follow-up period of the patients was 30.5±21.0 years and 29.1±30.4 months, respectively. The acute systemic involvement score in the IVIG, S plus IVIG, and PS groups was significantly higher than that in the S and C groups (P < 0.001). However, final BCVA and COCS were not significantly different between groups, even after statistical adjustment. High COCS (≥8 points) was associated with female gender (P = 0.012) and AMT at the acute stage (P = 0.040). High acute ocular and systemic involvement scores were associated with worse COCS (P < 0.001), and COCS showed good correlation with final BCVA (R(2) = 0.7101; P < 0.0001)., Conclusions: There were no therapeutic benefits of systemic immunomodulatory treatments in final visual outcome and COCS in SJS and TEN patients. Female gender and acute ocular and systemic involvement scores may be prognostic factors predicting chronic ocular complications., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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285. Clinical study of autologous cultivated oral mucosal epithelial transplantation for severe ocular surface disorders.
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Sotozono C, Inatomi T, Nakamura T, Koizumi N, Hamuro J, and Kinoshita S
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- Humans, Transplantation, Autologous, Cell Transplantation, Eye Diseases therapy, Mouth Mucosa cytology
- Published
- 2015
286. Development of a simple genotyping method for the HLA-A*31:01-tagging SNP in Japanese.
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Maekawa K, Nakamura R, Kaniwa N, Mizusawa S, Kitamoto A, Kitamoto T, Ukaji M, Matsuzawa Y, Sugiyama E, Uchida Y, Kurose K, Ueta M, Sotozono C, Ikeda H, Yagami A, Matsukura S, Kinoshita S, Muramatsu M, Ikezawa Z, Sekine A, Furuya H, Takahashi Y, Matsunaga K, Aihara M, and Saito Y
- Subjects
- Anticonvulsants adverse effects, Carbamazepine adverse effects, DNA genetics, Gene Frequency, Genetic Markers, Genotype, Humans, Japan, Linkage Disequilibrium, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide, Stevens-Johnson Syndrome epidemiology, Treatment Outcome, Asian People genetics, HLA-A Antigens genetics, Stevens-Johnson Syndrome genetics
- Abstract
Aim: To construct a simple, low-cost typing method for the surrogate marker of HLA-A*31:01, a risk factor for carbamazepine (CBZ) related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)., Materials & Methods: DNAs from Japanese SJS/TEN patients were used for genotyping and developing the assay., Results: HLA-A*31:01 was confirmed to be significantly associated with definite/probable cases of CBZ-related SJS/TEN (p = 0.0040). Three single nucleotide polymorphisms, rs1150738, rs3869066 and rs259945, were in absolute linkage disequilibrium with HLA-A*31:01 in 210 Japanese SJS/TEN patients. Robust genotyping of rs3869066 in ZNRD1-AS1 was developed using polymerase chain reaction-restriction fragment length polymorphism assays., Conclusion: Single nucleotide polymorphism genotyping is less time consuming and cheaper than conventional HLA typing, and would be useful for identifying Japanese patients at risk of CBZ-related SJS/TEN.
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- 2015
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287. [Ultrasound biomicroscopy in infants with congenital corneal opacity and its correlations with clinical diagnosis and intraocular pressure].
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Yoshikawa H, Ikeda Y, Sotozono C, Mori K, Ueno M, and Kinoshita S
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- Child, Preschool, Corneal Opacity congenital, Female, Humans, Infant, Male, Ultrasonography, Corneal Opacity diagnostic imaging, Corneal Opacity physiopathology, Intraocular Pressure
- Abstract
Purpose: Ultrasound biomicroscopy (UBM) can be used to investigate the appearance of the anterior chamber in infants with congenital corneal opacity. This study investigated the association between the UBM-obtained clinical imaging of anterior chamber morphology and the clinical diagnosis in infants with congenital corneal opacity., Subjects and Methods: This study involved 19 eyes of 10 consecutive infants with congenital corneal opacity, 13 eyes with Peters anomaly (PA, 7 cases) and 6 eye with sclerocornea (SC, 3 cases), recruited at the Kyoto Prefectural University of Medicine, Kyoto, Japan between September 2001 and January 2009. In each subject eye, UBM findings were compared with the clinical diagnosis based on slit-lamp findings and intraocular pressure (IOP)., Results: UBM findings revealed partial angle closure in 10 PA eyes and in 5 SC eyes, absence of Descemet's membrane in 13 eyes and 6 eyes, and funicular fiber from the iris in 12 eyes and 6 eyes. All 6 eyes with SC showed normal IOP, while 9 eyes with PA were diagnosed as glaucoma., Conclusion: Similarities in UBM appearance were observed between PA and SC. PA had a higher incidence of glaucoma; however, there was no relation between IOP and the UBM images.
- Published
- 2015
288. Tear exchangeable limbal rigid contact lens for ocular sequelae resulting from Stevens-Johnson syndrome or toxic epidermal necrolysis.
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Sotozono C, Yamauchi N, Maeda S, and Kinoshita S
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- Adult, Aged, Corneal Diseases physiopathology, Equipment Design, Female, Follow-Up Studies, Humans, Male, Middle Aged, Quality of Life, Retrospective Studies, Stevens-Johnson Syndrome physiopathology, Surveys and Questionnaires, Time Factors, Visual Acuity, Contact Lenses, Corneal Diseases therapy, Limbus Corneae pathology, Stevens-Johnson Syndrome therapy, Tears physiology
- Abstract
Purpose: To evaluate the therapeutic benefits of tear-exchangeable, limbal, rigid contact lenses (limbal CLs) in patients with Stevens-Johnson syndrome- or toxic epidermal necrolysis-associated ocular sequelae., Design: Noncomparative, retrospective, interventional case series., Methods: We enrolled 53 eyes of 42 patients (mean age, 51.8 ± 13.9 years; mean follow-up, 25.7 ± 15.7 months) with Stevens-Johnson syndrome- or toxic epidermal necrolysis-associated ocular sequelae and divided them into 3 groups according to the best-corrected visual acuity (BCVA) before limbal CL fitting: (1) BCVA worse than 20/2000 (11 eyes), (2) BCVA ranging from 20/200 to 20/2000 (31 eyes), and (3) BCVA of 20/200 or better (11 eyes). The BCVA and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite score before fitting and after 3 months of limbal CL use were evaluated. The change in BCVA (in logarithm of the minimal angle of resolution [logMAR] units) and 25-item National Eye Institute Visual Function Questionnaire composite score change were compared among the 3 groups., Results: Best-corrected visual acuity improved from 1.61 to 0.86 logMAR at 3 months after fitting CL use. Improvement in BCVA in groups 1, 2, and 3 was 0.95 logMAR, 0.82 logMAR, and 0.37 logMAR, respectively. The mean 25-item National Eye Institute Visual Function Questionnaire composite score for the 11 subscales improved from 37.6 ± 16.0 to 58.4 ± 17.4 (P = .000001). All 11 subscores, except that for driving ability, improved significantly. The general vision subscore improved most in group 3, yet the general health subscore improved most in group 1. No serious adverse events attributable to limbal CL use occurred., Conclusions: The tear-exchangeable limbal CL is safe and effective for the improvement of vision and quality of life in Stevens-Johnson syndrome or toxic epidermal necrolysis patients with severe ocular sequelae., (Copyright © 2014 Elsevier Inc. All rights reserved.)
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- 2014
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289. Downregulation of IL-8, ECP, and total IgE in the tears of patients with atopic keratoconjunctivitis treated with rebamipide eyedrops.
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Ueta M, Shoji J, Sotozono C, and Kinoshita S
- Abstract
Rebamipide eyedrops are approved in Japan for the treatment of dry eye disease. Some patients with allergic conjunctival diseases also manifest dry eye. Earlier we reported that rebamipide suppressed polyI:C-induced inflammatory cytokines in human conjunctival epithelial cells. In the current study we examined the effect of rebamipide eyedrops on the level of interleukin-8 (IL-8), eosinophil cationic protein (ECP), and total IgE on the ocular surface. We prescribed rebamipide eyedrops to patients with atopic keratoconjunctivitis (AKC) who presented with dry eye (6 eyes in 4 AKC patients) and measured the IL-8, ECP, and total IgE levels in their tears before- and 2, and 4-6 weeks after the start of rebamipide treatment. To measure the IL-8 and total IgE levels in their tears we used BD™ CBA Flex sets; ECP measurements were with ELISA. The level of IL-8, ECP, and total IgE in the tears of AKC patients was reduced significantly 4-6 weeks after the start of rebamipide treatment. We also recorded subjective symptoms associated with AKC, e.g. itching, foreign body sensation, and eye mucus discharge, by using a patient questionnaire. Their subjective symptoms associated with AKC were also significantly ameliorated at 2 and 4-6 weeks. Our observations suggest that the anti-inflammatory effects of rebamipide eyedrops help to combat human ocular surface inflammation and that they may be a new effective therapy in patients with AKC.
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- 2014
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290. Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity.
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Sotozono C, Inatomi T, Nakamura T, Koizumi N, Yokoi N, Ueta M, Matsuyama K, Kaneda H, Fukushima M, and Kinoshita S
- Subjects
- Acute Disease, Adult, Aged, Aged, 80 and over, Burns, Chemical pathology, Cell Transplantation, Cells, Cultured, Child, Corneal Injuries pathology, Eye Burns pathology, Female, Humans, Male, Middle Aged, Pemphigoid, Benign Mucous Membrane pathology, Re-Epithelialization, Stevens-Johnson Syndrome pathology, Visual Acuity, Burns, Chemical surgery, Corneal Injuries surgery, Epithelial Cells transplantation, Eye Burns chemically induced, Mouth Mucosa cytology, Pemphigoid, Benign Mucous Membrane surgery, Stevens-Johnson Syndrome surgery
- Abstract
Purpose: To assess the clinical efficacy of cultivated oral mucosal epithelial transplantation (COMET) for the treatment of persistent epithelial defect (PED)., Methods: We treated 10 eyes of nine patients with PED (Stevens-Johnson syndrome: three eyes; thermal/chemical injury: five eyes; ocular cicatricial pemphigoid: two eyes) with COMET at Kyoto Prefectural University of Medicine, Kyoto, Japan from 2002 to 2008., Results: Preoperatively, PED existed on over more than 50% of the corneal surface in seven eyes. Severe ocular surface inflammation with fibrovascular tissue surrounded the PED in all 10 eyes. At 24-weeks postoperative, PED had improved in all cases except 1 in which the patient was unable to return to the hospital (95% CI, 55.5-99.7; Wilcoxon signed-rank test, p = 0.0078). The preoperative median of logarithmic minimum angle of resolution was 1.85 (range 0.15-2.70), and 1.85, 1.85, and 1.52 at the 4th, 12th, and 24th postoperative week, respectively. The mean total preoperative ocular surface grading score was 7.0 (range 4-17). At 4 and 12 weeks postoperative, the total ocular surface grading score had improved significantly (p = 0.0020, p = 0.0078), and at 24 weeks postoperative, it was 3.0 (range 2-12, p = 0.0234). During the follow-up period (median 23.3 months, range 5.6-39.7 months), no recurrence of PED was observed in any eye, and long-term ocular surface stability was obtained., Conclusion: COMET enabled complete epithelialization of PED and stabilization of the ocular surface in patients with severe ocular surface disease, thus preventing end-stage cicatrization and vision loss at a later stage., (© 2014 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)
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- 2014
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291. Trans-ethnic study confirmed independent associations of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.
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Ueta M, Kannabiran C, Wakamatsu TH, Kim MK, Yoon KC, Seo KY, Joo CK, Sangwan V, Rathi V, Basu S, Shamaila A, Lee HS, Yoon S, Sotozono C, Gomes JÁ, Tokunaga K, and Kinoshita S
- Subjects
- Adolescent, Adult, Alleles, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Brazil, Child, Dry Eye Syndromes ethnology, Dry Eye Syndromes etiology, Dry Eye Syndromes immunology, Epithelium, Corneal immunology, Epithelium, Corneal pathology, Ethnicity, Female, Gene Frequency, HLA-A2 Antigen immunology, HLA-B44 Antigen immunology, Humans, India, Male, Middle Aged, Multi-Ingredient Cold, Flu, and Allergy Medications adverse effects, Republic of Korea, Retinal Pigment Epithelium immunology, Retinal Pigment Epithelium pathology, Risk Factors, Stevens-Johnson Syndrome ethnology, Stevens-Johnson Syndrome etiology, Stevens-Johnson Syndrome immunology, Trichiasis ethnology, Trichiasis etiology, Trichiasis immunology, Dry Eye Syndromes genetics, HLA-A2 Antigen genetics, HLA-B44 Antigen genetics, Stevens-Johnson Syndrome genetics, Trichiasis genetics
- Abstract
Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs and multi-ingredient cold medications are reported to be important inciting drugs. Recently, we reported that cold medicine related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement including severe ocular surface complications (SOC) is associated with HLA-A*02:06 and HLA-B*44:03 in the Japanese. In this study, to determine whether HLA-B*44:03 is a common risk factor for CM-SJS/TEN with SOC in different ethnic groups we used samples from Indian, Brazilian, and Korean patients with CM-SJS/TEN with SOC, and investigated the association between CM-SJS/TEN with SOC and HLA-B*44:03 and/or HLA-A*02:06. We found that HLA-B*44:03 was significantly associated with CM-SJS/TEN with SOC in the Indian and Brazilian but not the Korean population, and that HLA-A*02:06 might be weakly associated in the Korean- but not the Indian and Brazilian population.
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- 2014
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292. Upregulation of Toll-like receptor 5 expression in the conjunctival epithelium of various human ocular surface diseases.
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Yamada K, Ueta M, Sotozono C, Yokoi N, Inatomi T, and Kinoshita S
- Subjects
- Case-Control Studies, Conjunctiva abnormalities, Epithelium metabolism, Eye Burns metabolism, Humans, Immunohistochemistry, Pemphigoid, Benign Mucous Membrane metabolism, Pterygium metabolism, Stevens-Johnson Syndrome metabolism, Up-Regulation, Conjunctiva metabolism, Conjunctival Diseases metabolism, Toll-Like Receptor 5 metabolism
- Abstract
Aims: To examine the expression of Toll-like receptor (TLR) 5 in the conjunctival epithelium of patients with severe ocular surface diseases., Methods: Immunohistochemical study of TLR5 was performed on conjunctival tissues obtained from patients undergoing surgical reconstruction of the ocular surface to treat Stevens-Johnson syndrome (SJS) (n=4), ocular cicatricial pemphigoid (OCP) (n=3), chemical eye burn (n=3), and pterygium (n=2), and on nearly normal conjunctival tissues obtained during surgery for four cases of conjunctivochalasis as a control., Results: TLR5 protein was consistently and abundantly expressed in the conjunctival epithelium and detected only at the basal and wing cells. However, in the conjunctival epithelium obtained from the patients with SJS, OCP and chemical eye burns, the TLR5 protein was detected at not only the basal and wing cells but also at the superficial cells. TLR5 protein detected in the pterygium patients mirrored that detected in the controls., Conclusions: Although TLR5 was normally present on the basal and wing cells of conjunctival epithelium with spatially selective presence, it was expressed on not only the basal and wing cells but also the superficial cells in the conjunctival epithelium of patients with SJS, OCP or chemical eye burns, suggesting that TLR5 might be upregulated in the conjunctival epithelium of these diseases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
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- 2014
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293. Independent strong association of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe mucosal involvement.
- Author
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Ueta M, Kaniwa N, Sotozono C, Tokunaga K, Saito Y, Sawai H, Miyadera H, Sugiyama E, Maekawa K, Nakamura R, Nagato M, Aihara M, Matsunaga K, Takahashi Y, Furuya H, Muramatsu M, Ikezawa Z, and Kinoshita S
- Subjects
- Acetaminophen adverse effects, Adolescent, Adult, Aged, Case-Control Studies, Child, Female, Humans, Male, Middle Aged, Stevens-Johnson Syndrome complications, Vision Disorders etiology, Young Adult, Anti-Inflammatory Agents, Non-Steroidal adverse effects, HLA-A Antigens genetics, HLA-B Antigens genetics, Mucous Membrane pathology, Stevens-Johnson Syndrome etiology, Stevens-Johnson Syndrome pathology
- Abstract
Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs (NSAIDs) and multi-ingredient cold medications are reported to be important inciting drugs. We used two sample sets of Japanese patients to investigate the association between HLA genotypes and cold medicine-related SJS/TEN (CM-SJS/TEN), including acetaminophen-related SJS/TEN (AR-SJS/TEN) with severe mucosal involvement such as severe ocular surface complications (SOC). HLA-A*02:06 was strongly associated with CM-SJS/TEN with SOC and AR-SJS/TEN with SOC. HLA-B*44:03 was also detected as an independent risk allele for CM-, including AR-SJS/TEN with SOC. Analyses using data obtained from CM-SJS/TEN patients without SOC and patients with CM-unrelated SJS/TEN with SOC suggested that these two susceptibility alleles are involved in the development of only CM-SJS/TEN with SOC patients.
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- 2014
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294. LRIG1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia.
- Author
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Nagata M, Nakamura T, Sotozono C, Inatomi T, Yokoi N, and Kinoshita S
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Carcinoma, Squamous Cell pathology, Cell Transformation, Neoplastic pathology, Down-Regulation, ErbB Receptors biosynthesis, Eye Neoplasms pathology, Female, Humans, Keratins biosynthesis, Male, Middle Aged, Biomarkers, Tumor biosynthesis, Carcinoma, Squamous Cell metabolism, Cell Transformation, Neoplastic metabolism, Eye Neoplasms metabolism, Eye Proteins biosynthesis, Gene Expression Regulation, Neoplastic, Membrane Glycoproteins biosynthesis, Neoplasm Proteins biosynthesis
- Abstract
The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.
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- 2014
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295. Usefulness of a new therapy using rebamipide eyedrops in patients with VKC/AKC refractory to conventional anti-allergic treatments.
- Author
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Ueta M, Sotozono C, Koga A, Yokoi N, and Kinoshita S
- Subjects
- Adolescent, Adult, Alanine administration & dosage, Child, Conjunctivitis, Allergic diagnosis, Female, Humans, Male, Middle Aged, Ophthalmic Solutions, Treatment Outcome, Young Adult, Alanine analogs & derivatives, Anti-Allergic Agents administration & dosage, Conjunctivitis, Allergic drug therapy, Quinolones administration & dosage
- Abstract
Background: Rebamipide, a gastroprotective drug, has been reported to suppress gastric mucosal inflammation. In Japan, rebamipide eyedrops have recently been approved for the treatment of dry eye disease. Some patients with allergic conjunctival diseases such as vernal keratoconjunctivitis (VKC) or atopic keratoconjunctivitis (AKC) manifest dry eye with decreased tear break-up time only. We report patients with VKC/AKC refractory to anti-allergic treatments who responded to the combination of rebamipide eyedrops and conventional anti-allergic treatments with anti-allergic- and/or immunosuppressive/steroid eyedrops., Methods: Four patients with allergic conjunctival diseases with giant papillae (VKC or AKC) instilled rebamipide eyedrops three or four times a day for varying periods. All had dry eye with decreased tear break-up time. We evaluated changes in the size of their giant papillae using Image J software., Results: We observed attenuation of the giant papillae in all 4 patients. In 2 patients with severe disease, whose giant papillae had become larger despite the administration of tacrolimus and steroids, the addition of rebamipide contributed to their attenuation. In 2 patients with mild disease, the giant papillae had become larger or remained the same size despite the administration of anti-allergy drugs; the addition of rebamipide eyedrops also resulted in the attenuation of their giant papillae., Conclusions: Our findings suggest that rebamipide eyedrops might attenuate giant papillae in patients with allergic conjunctival diseases and that these eyedrops may be useful for the treatment of not only dry eye but also of allergic conjunctival diseases.
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- 2014
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296. Folliculitis in clinically "quiet" chronic Stevens-Johnson syndrome.
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Watanabe A, Sotozono C, Ueta M, Shinomiya K, Kinoshita S, Kakizaki H, and Selva D
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers metabolism, Child, Chronic Disease, Female, Folliculitis diagnosis, Folliculitis metabolism, Hair Follicle metabolism, Hair Follicle pathology, Humans, Infant, Male, Conjunctivitis complications, Folliculitis etiology, Stevens-Johnson Syndrome complications
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- 2014
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297. Clinical outcomes in descemet stripping automated endothelial keratoplasty with internationally shipped precut donor corneas.
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Nakagawa H, Inatomi T, Hieda O, Sotozono C, Yokoi N, Iliakis B, Miller TD, Ulrickson C, and Kinoshita S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cell Count, Corneal Diseases physiopathology, Eye Banks, Female, Graft Survival physiology, Humans, Japan, Male, Middle Aged, Postoperative Complications, Retrospective Studies, Tissue Donors, Treatment Outcome, United States, Visual Acuity physiology, Young Adult, Corneal Diseases surgery, Corneal Endothelial Cell Loss diagnosis, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal pathology, Internationality, Tissue and Organ Procurement methods
- Abstract
Purpose: To report the endothelial cell loss and clinical outcomes in Descemet stripping automated endothelial keratoplasty (DSAEK) with internationally shipped, precut donor corneas., Design: Retrospective analysis of a noncomparative case series., Methods: The setting was a single hospital. The clinical results of 134 eyes of 128 patients who underwent DSAEK in Kyoto, Japan, with internationally shipped precut donor corneas from Portland, Oregon, or Seattle, Washington, were evaluated. In addition, 40 precut donor corneas from Seattle were evaluated in respect to the postprecut international shipment-related loss of corneal endothelial cell density (ECD). Observation procedures were noncontact specular microscopy. The main outcome measures were the evaluation of international shipment-related ECD loss, postoperative ECD, visual recovery, and complications., Results: The mean postprecut ECD loss in 40 donor corneas during international shipment was 2.3%. The mean elapsed time from cut to surgery was 63.2 ± 31.1 hours. At 6, 12, 24, and 36 months postoperatively, the mean ECD of the internationally shipped donor corneas was 2038, 1933, 1670, and 1431 cells/mm(2), respectively. The mean ECD loss at 6, 12, 24, 36 months after DSAEK was 30%, 34%, 44%, and 51%, respectively. Preoperative logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity was 1.40 ± 0.55, and at 12 months after DSAEK was 0.22 ± 0.19. Complications included graft dislocation in 12 eyes (8.9%) and graft rejection in 3 eyes (2.2%)., Conclusions: The present study shows that the outcomes of DSAEK with internationally shipped precut donor corneas were acceptable and that the additional endothelial cell loss associated with international shipment was minimal and did not affect the clinical results., (Copyright © 2014 Elsevier Inc. All rights reserved.)
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- 2014
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298. [Postcataract endophthalmitis caused by Enterococcus faecalis].
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Suzuki T, Todokoro D, Kobayakawa S, Sotozono C, Eguchi S, Miyata K, Miyajima HB, Ike Y, and Ohashi Y
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- Aged, Aged, 80 and over, Humans, Middle Aged, Postoperative Complications, Retrospective Studies, Cataract Extraction, Endophthalmitis etiology, Enterococcus faecalis, Gram-Positive Bacterial Infections etiology
- Abstract
Purpose: Enterococcus faecalis is a major endophthalmitis-causing pathogen and often causes significant visual impairment. We investigated the clinical background, treatment and the visual outcome of patients with E. faecalis endophthalmitis after cataract surgery., Methods: We retrospectively conducted a postal survey directed mainly at the members of Japanese Society of Cataract and Refractive Surgery, and collected data on 30 eyes of 30 patients with E. faecalis endophthalmitis., Results: The mean age of the patients was 73.5 years, and 10 cases had diabetes mellitus. The average time between cataract surgery and diagnosis of endophthalmitis was 4.8 days, and in 16 cases the disease developed 2 days after surgery. Final visual acuity was better than 40/200 in 13 eyes and 20/200 to no light perception in 15 eyes., Conclusions: E. faecalis caused acute-onset endophthalmitis. The visual outcome of the patients can be divided into good and poor groups.
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- 2014
299. Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects.
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Kaniwa N, Sugiyama E, Saito Y, Kurose K, Maekawa K, Hasegawa R, Furuya H, Ikeda H, Takahashi Y, Muramatsu M, Tohkin M, Ozeki T, Mushiroda T, Kubo M, Kamatani N, Abe M, Yagami A, Ueta M, Sotozono C, Kinoshita S, Ikezawa Z, Matsunaga K, and Aihara M
- Subjects
- Adolescent, Adult, Aged, Biomarkers, Child, Child, Preschool, Female, Genotype, Humans, Male, Middle Aged, Anticonvulsants adverse effects, Asian People genetics, Drug-Related Side Effects and Adverse Reactions genetics, HLA-DRB1 Chains genetics, Stevens-Johnson Syndrome genetics
- Abstract
Aim: This preliminary study investigated genomic biomarkers for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), related to three antiepileptic drugs, zonisamide, phenobarbital and phenytoin., Patients & Methods: HLA class I and HLA-DRB1 loci were genotyped for Japanese patients with zonisamide-, phenobarbital- or phenytoin-induced SJS/TEN (n = 12, 8 and 9, respectively) and for healthy Japanese volunteers (n = 2878)., Results: Carrier frequencies of HLA-A*02:07 in patients with zonisamide-induced SJS/TEN and in the general Japanese population were 41.7 and 6.81%, respectively. Carrier frequencies of HLA-B*51:01 in patients with phenobarbital- and phenytoin-induced SJS/TEN and in controls were 75.0, 55.6 and 15.2%, respectively. HLA-A*02:07 and HLA-B*51:01, in a dominant model, were significantly associated with zonisamide- and phenobarbital-induced SJS/TEN, respectively (Pc = 0.0176 and 0.0042, respectively)., Conclusion: Our data suggest that HLA-A*02:07 and HLA-B*51:01 are potential biomarkers for zonisamide- and phenobarbital-induced SJS/TEN, respectively, in Japanese individuals.
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- 2013
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300. Rebamipide suppresses PolyI:C-stimulated cytokine production in human conjunctival epithelial cells.
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Ueta M, Sotozono C, Yokoi N, and Kinoshita S
- Subjects
- Alanine pharmacology, Animals, Antioxidants pharmacology, Conjunctiva metabolism, Conjunctivitis, Allergic pathology, Cytokines genetics, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Epithelial Cells cytology, Humans, Inflammation genetics, Inflammation metabolism, Interferon Inducers pharmacology, Mice, Mice, Inbred BALB C, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Alanine analogs & derivatives, Conjunctiva drug effects, Conjunctivitis, Allergic prevention & control, Cytokines metabolism, Epithelial Cells drug effects, Inflammation prevention & control, Poly I-C pharmacology, Quinolones pharmacology
- Abstract
Purpose: We previously documented that ocular surface epithelial cells could regulate ocular surface inflammation and suggested that, while Toll-like receptor 3 upregulates, EP3, one of the prostaglandin E2 receptors, downregulates ocular surface inflammation. Others reported that rebamipide, a gastroprotective drug, could not only increase the gastric mucus production, but also suppressed gastric mucosal inflammation and that it was dominantly distributed in mucosal tissues. The eyedrop form of rebamipide, approved in Japan for use in the treatment of dry eye diseases, upregulates mucin secretion and production, thereby suppressing superficial punctate keratopathy on the ocular surface of patients with this disease. In the current study, we investigated whether rebamipide has anti- inflammatory effects on the ocular surface., Methods: To examine the effects of rebamipide on polyI:C-induced cytokine expression by primary human conjunctival epithelial cells, we used enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction assay. We studied the effects of rebamipide on ocular surface inflammation in our murine experimental allergic conjunctivitis (EAC) model., Results: Rebamipide could suppress polyI:C-induced cytokine production and the expression of mRNAs for CXCL10, CXCL11, RANTES, MCP-1, and IL-6 in human conjunctival epithelial cells. In our EAC model, the topical administration of rebamipide suppressed conjunctival allergic eosinophil infiltration., Conclusions: The topical application of rebamipide on the ocular surface might suppress ocular surface inflammation by suppressing the production of cytokines by ocular surface epithelial cells.
- Published
- 2013
- Full Text
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