H Obata

Jichi Medical University, Tochigi, Tochigi-ken, Japan

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Publications (46)76.01 Total impact

  • Neurology 08/2011; 77(7):676. · 8.25 Impact Factor
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    ABSTRACT: ST2 gene products that are members of IL-1 receptor family are expressed in various cells such as growth-stimulated fibroblasts and Th2 helper T-cells, and recently, IL-33, which belongs to IL-1 family, was identified as the ligand for ST2L, the receptor type product of the ST2 gene. Subsequently, IL-33 and ST2L have been reported to be involved in Th2 immunity and inflammation, however, their functions on non-immunological cells are still obscure. Among non-immunological adhesive cells, vascular endothelial cells were reported to express both ST2 gene products and IL-33, therefore, we investigated the expression manner of the ST2 gene in vascular endothelial cells and the effect of IL-33 on endothelial cells. ST2 gene was expressed in each of the vascular endothelial cell types tested, and the expression was growth-dependent and down-regulated when the cells were differentiated to form vascular structures on the extracellular membrane matrix. IL-33 scarcely affected the growth and tube formation of the endothelial cells, but induced IL-6 and IL-8 secretion from endothelial cells with the rapid activation of extracellular signal-regulated kinase (ERK) 1/2, so IL-33 is supposed to involve in inflammatory reaction of vascular endothelial cells through its receptor, ST2L.
    Molecular and Cellular Biochemistry 09/2009; 335(1-2):75-81. · 2.33 Impact Factor
  • Hiroto Obata
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    ABSTRACT: The lachrymal gland is an appendage of the ocular surface that secretes tear fluid consisting of water, proteins, and electrolytes, which helps to maintain the cells of the ocular surface. The lachrymal gland and ocular surface form a mucosal immune system, and both are affected by environmental factors. The quality and quantity of tear fluid decreases with age, and dry eye is one of most common problems in elderly patients visiting ophthalmologists. The lachrymal gland is innervated by the autonomic nervous system and the secretory function is very complicated. Few previous studies have examined the aging mechanisms of the lachrymal gland. Histopathological studies of the human lachrymal gland have demonstrated that acinar atrophy, periacinar fibrosis, and periductal fibrosis increase with age. Animal studies have shown that morphological changes, reduced lachrymal secretion of protein, decreased density of innervation, and increased number of inflammatory cells in the lachrymal glands occur with aging. Generally, inflammation and neural dysfunction might be involved in the pathogenesis of age-related lachrymal gland dysfunction, but the mechanisms linking lachrymal gland dysfunction with aging remain unclear. Keywordslachrymal gland–aging–dry eye–tear fluid–secretion–atrophy–fibrosis–inflammation–neural dysfunction
    05/2008: pages 305-318;
  • Hiroto Obata, Tadahiko Tsuru
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    ABSTRACT: To review corneal wound healing with special reference to the function of the Bowman layer and Descemet membrane. Corneal specimens were obtained from keratoplasties, including regrafted cases. Recipient corneal buttons were evaluated histopathologically with attention to 5 layers of corneal structure: 3 cellular layers consisting of epithelial cells, keratocytes, and endothelial cells and 2 acellular layers consisting of the Bowman layer and Descemet membrane. Subepithelial fibrosis was found in advanced bullous keratopathy. The possible source of subepithelial fibrosis was either conjunctival stroma or corneal stroma through disruption of the Bowman layer. Subepithelial fibrosis was observed in the area of the Bowman layer disruption at the host-graft junction in regrafted cases. The Bowman layer was disrupted in eyes with not only keratoconus but also corneal dystrophy such as macular dystrophy and gelatinous drop-like dystrophy. Newly formed, thin Descemet membrane was found in keratoconic eyes of patients with acute hydrops. Retrocorneal membranes were observed in eyes with advanced bullous keratopathy and graft failure. Abnormal wound healing of Descemet membrane such as override and separation was found in the host-graft interface of regrafted eyes, causing stromal overgrowth. The Bowman layer and Descemet membrane seem to serve as barriers to separate 3 cellular layers of epithelium, stroma, and endothelium. Disruption of the Bowman layer forms a new epithelial-stromal interaction and may cause cellular proliferative response. Separation of Descemet membrane can provide the trigger for emanating stromal tissue from the wound edge.
    Cornea 11/2007; 26(9 Suppl 1):S82-9. · 1.75 Impact Factor
  • Hiroto Obata
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    ABSTRACT: To review the anatomy and histopathologic changes of the human main lacrimal gland. Samples of lacrimal gland including palpebral lobes and orbital lobes were taken in autopsies, and the relationship between histopathologic changes and age and sex, as well as histopathologic differences between palpebral and orbital lobes of the lacrimal gland, were studied using light microscopy. Various histopathologic changes were observed in the human main lacrimal gland as follows: acinar atrophy; periacinar fibrosis; periductal fibrosis; interlobular ductal dilatation; interlobular ductal proliferation; lymphocytic infiltration; and fatty infiltration. Several histopathologic differences exist between the palpebral and orbital lobes. There were statistically significant correlations between age and diffuse fibrosis, diffuse atrophy, and periductal fibrosis in the orbital lobes of women. Diffuse fibrosis and diffuse atrophy in orbital lobes were more frequently observed in women than in men. It is speculated that periductal fibrosis is related to a decrease of tear flow with age and that interlobular ductal dilatation in palpebral lobes may be caused by stenosis of the excretory duct in conjunctival fornix. However, the mechanisms of these histopathologic changes in the human main lacrimal gland are not yet clear.
    Cornea 01/2007; 25(10 Suppl 1):S82-9. · 1.75 Impact Factor
  • Hiroto Obata, Taeko Inoki, Tadahiko Tsuru
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    ABSTRACT: Diagnosis of Salzmann's nodular degeneration is based on clinical findings, as histopathologic findings in nodules are nonspecific on routine examination. This study demonstrates that presence of oxytalan fibers (ie, elastic system fibers) in lesions of Salzmann's nodular degeneration under light and electron microscopy allows definitive diagnosis. A 55-year-old woman noticed white nodular lesions on both corneas. Excised lesion tissues were examined under light microscopy with special staining and transmission electron microscopy. Nodular lesions comprised hyalinized connective tissue showing nonspecific findings on routine histologic examination. However, oxidized aldehyde fuchsin staining yielded positive results in lesions, indicating the presence of oxytalan fibers. Transmission electron microscopy identified bundles of microfibrils in lesions, confirming the presence of oxytalan fibers. Light microscopic examination by oxidized aldehyde fuchsin staining should be performed when diagnosing Salzmann's nodular degeneration.
    Cornea 07/2006; 25(5):586-9. · 1.75 Impact Factor
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    ABSTRACT: To describe a technique for the prevention of spontaneous loss of lacrimal punctal plugs. Interventional case series. Four consecutive patients (10 puncta in seven eyes) with severe dry eyes who experienced repeated spontaneous plug loss underwent punctal occlusion by suturing plugs with 10-0 polypropylene sutures. All punctal plugs were fitted to lacrimal puncta by anchoring the sutures. Plug retention rate was 80% at 6 months after the procedure. Suturing punctal plugs is effective in the production of long-term punctal closure in patients with repeated spontaneous plug loss.
    American Journal of Ophthalmology 04/2006; 141(3):567-9. · 4.02 Impact Factor
  • Hiroto Obata, Kana Mori, Tadahiko Tsuru
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    ABSTRACT: We report the first case of subconjunctival mucosa-associated lymphoid tissue (MALT) lymphoma arising in Tenon's capsule (fascia bulbi). A 75-year-old woman presented with painless swelling of the superior bulbar conjunctiva in her left eye. During the biopsy of the bulbar lymphoid lesion, it was noticed that the conjunctiva was movable and that the lesion was located in the subconjunctiva. The tissues were studied by conventional light microscopy, immunohistochemistry, flow cytometry, and gene rearrangement analysis. Histopathological examination revealed that a diffuse lymphoid infiltrate consisting of small-sized lymphoid cells was present in Tenon's capsule but not in the substantia propria of the conjunctiva. Immunohistochemical and flow cytometric studies documented tumor cells of B-lymphocyte lineage. Molecular analysis demonstrated positive immunoglobulin heavy chain gene rearrangement. The final diagnosis was subconjunctival MALT lymphoma arising in Tenon's capsule. Ophthalmologists and pathologists need to distinguish the subconjunctival lymphoma that arises in Tenon's capsule from the conjunctival lymphoma in the substantia propria during diagnosis of epibulbar lymphoid tumors.
    Albrecht von Graæes Archiv für Ophthalmologie 02/2006; 244(1):118-21. · 1.93 Impact Factor
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    ABSTRACT: To examine the incidence of benign and malignant eyelid lesions and conjunctival tumors. One-hundred-and twenty-eight cases (131 eyes) which were treated during the period from January 1990 to February 2004 were histopathologically diagnosed for eyelid or conjunctival tumors (87 cases of eyelid tumors and 41 cases of conjunctival tumors) in retrospective evaluations. The incidence of benign or malignant lesions, the pathological classification, age, sex, and clinical diagnostic accuracy were all investigated. Sixty-four (73%) of the tumors were found to be benign eyelid tumors. The common benign eyelid tumors were 14 nevocellular nevi, 9 seborrheic keratosis, 7 epidermoid cysts, and 6 papillomas. Twenty-four (27%) eyelid tumors were malignant. These included 9 basal cell carcinomas, 9 sebaceous gland carcinomas, 4 malignant lymphomas, and 2 metastatic tumors. Thirty-four (79%) conjunctival tumors were benign, and the common benign conjunctival tumors were 9 nevocellular nevi and 7 papillomas. Nine (21%) conjunctival tumors were malignant, comprising 7 malignant lymphomas and 2 squamous cell carcinomas. The mean ages of malignant eyelid and conjunctival tumor patients were significantly older than those of benign tumor patients. Clinical accuracy in predicting basal cell carcinoma and sebaceous gland carcinoma was 11.1% and 44.4%, respectively. Approximately 70 approximately 80% of all eyelid and conjunctival tumors are benign. Clinicians should suspect that the lesions are malignant when seeing elderly patients with eyelid or conjunctival tumors. Excised eyelid lesions should be submitted for histopathologic confirmation because there are some cases where clinical diagnosis does not match pathological diagnosis.
    Nippon Ganka Gakkai zasshi 10/2005; 109(9):573-9.
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    Acta Ophthalmologica Scandinavica 11/2004; 82(5):632-3. · 1.85 Impact Factor
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    Acta Ophthalmologica Scandinavica 06/2003; 77(2):151 - 156. · 1.85 Impact Factor
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    ABSTRACT: Acute dacryoadenitis is an uncommon disease. We present what we believe to be the first reported case of herpes zoster ophthalmicus with the onset of acute dacryoadenitis. A 30-year-old man complained of severe ocular pain and hyperemia in his right eye. Magnetic resonance imaging (MRI) demonstrated enlargement of the right lacrimal gland and acute dacryoadenitis was diagnosed. Two days after treatment with systemic antibiotics he developed iridocyclitis and skin lesions confined to the first division of the trigeminal nerve; therefore, herpes zoster ophthalmicus was diagnosed. Treatment with acyclovir immediately resolved the ocular pain and swelling of the upper eyelid. MRI conducted in the 4 months after the initial examination showed there was no longer enlargement of the right lacrimal gland. Clinicians should be aware that varicella-zoster virus may cause acute dacryoadenitis.
    Japanese Journal of Ophthalmology 01/2003; 47(1):107-9. · 1.27 Impact Factor
  • Hiroto Obata
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    ABSTRACT: To investigate histopathologic changes in human meibomian gland. Human meibomian gland samples were obtained at autopsy from 50 men and 33 women aged from 17 to 87 years with a mean age (+/- SD) of 61 +/- 13 years. Pieces of tarsal plate measuring 3 x 3 mm including meibomian glands were excised from the center of both upper eyelids, then fixed and embedded in paraffin. Sections 4-microm thick were stained with hematoxylin and eosin and periodic acid-Schiff. Light microscopy was used to observe any histopathologic changes. The following histopathologic changes were observed: (1) cystic dilatation of acini and/or ducts, (2) atrophy of acini, (3) basement membrane thickening of acini, (4) granulation tissue, and (5) lipogranulomatous inflammation. Various histopathologic changes were observed in the human meibomian gland. Hyperkeratinization of ductal epithelium and atrophy of acinar cells may cause meibomian gland dysfunction.
    Cornea 11/2002; 21(7 Suppl):S70-4. · 1.75 Impact Factor
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    British Journal of Ophthalmology 08/2002; 86(7):827. · 2.73 Impact Factor
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    ABSTRACT: To investigate the effect of anti-inflammatory agents on conjunctival inflammation and corneal haze formation after excimer laser keratectomy. Department of Ophthalmology, University of Tokyo Faculty of Medicine, Tokyo, Japan. After excimer laser keratectomy was performed in 21 rabbits (42 eyes), saline, betamethasone 0.1%, or diclofenac 0.1% was topically applied 6 times a day for 4 weeks and then 3 times a day for 8 weeks. The degree of conjunctival inflammation was determined 1, 2, 3, and 7 days after the keratectomy. The degree of corneal haze was quantitatively measured using a digital analyzer before and once a week after the keratectomy. The expression of type IV collagen in the corneas at baseline and 4 and 12 weeks after the keratectomy was examined immunohistochemically. Compared with saline, betamethasone and diclofenac significantly decreased early-phase conjunctival inflammation. Betamethasone significantly inhibited corneal haze formation compared with saline at 3 to 5 and 8 to 12 weeks. Diclofenac did not inhibit corneal haze formation significantly. Although betamethasone tended to be more effective in inhibiting corneal haze formation and deposition of type IV collagen than diclofenac, there was no statistical difference between the 2 anti-inflammatory agents. Topically applied betamethasone effectively suppressed corneal haze formation after excimer laser keratectomy. Diclofenac was not statistically effective in inhibiting corneal haze formation.
    Journal of Cataract and Refractive Surgery 04/2000; 26(3):426-31. · 2.53 Impact Factor
  • Transplantation Proceedings 10/1999; 31(6):2673-4. · 0.95 Impact Factor
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    ABSTRACT: Transforming growth factor-beta (TGF-beta) superfamily consists of many multifunctional cytokines including TGF-beta, activins, and bone morphogenetic proteins (BMPs). Previous reports show that these factors are expressed in ocular tissue, and exert their effects through type I and type II serine/threonine type receptors. The purpose of this study is to observe the expression of these receptor families in normal rat eyes as the first step in investigating the functions of TGF-beta superfamily members in ocular tissue. The expression of receptors was examined immunohistochemically in one eye each of 6 Lewis rats. The type I receptors examined were the TGF-beta type I receptor (TbetaR-I), activin type I receptor (ActR-I), activin type IB receptor (ActR-IB), bone BMP type IA receptor (BMPR-IA), BMP type IB receptor (BMPR-IB), and activin receptor-like kinase-1 (ALK-1). The type II receptors examined were TGF-beta type II receptor (TbetaR-II), activin type II receptor (ActR-II), and BMP type II receptor (BMPR-II). All 6 type I receptors, ActR-II and the alternative spliced long version of BMPR-II were expressed in the following cells: corneal and conjunctival epithelium, corneal keratocytes, corneal endothelium, epithelium of iris and ciliary body, epithelium of lens, sensory retina excluding the outer segments of photoreceptors, retinal pigment epithelium (RPE), and vascular cells. TbetaR-II and the short version of BMPR-II (truncated form) were expressed in the outer segments of the photoreceptors in addition to the above. The results of staining were similar in all the sections examined. The cornea, ciliary body, iris, lens, retinal cells, RPE and vascular cells expressed the receptors for TGF-beta superfamily at protein level.
    Acta Ophthalmologica Scandinavica 05/1999; 77(2):151-6. · 1.85 Impact Factor
  • Experimental Eye Research 05/1999; 68(4):513-9. · 3.03 Impact Factor
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    ABSTRACT: To ascertain the role played by the transforming growth factor (TGF)-beta superfamily in retinal development by determining the changes in the expression patterns of their receptors during development of the normal rat retina. The expression of type I and type II receptors of the TGF-beta superfamily was observed at the protein level in rat eyes at embryonic age 17 days (E17), at birth (P0), at postnatal days 3, 6, 9, and at 11 weeks (P3, P6, P9, and adult, respectively). Activin type I receptor and BMP type IB receptor were first detected in P6 and P3 retinas, respectively, at the protein level, and activin type II receptor was first detected in the P0 retina. The other receptors (TGF-beta type I and II receptors, activin type IB receptor, BMP types IA and II receptors) were detected at E17. The period from P0 to P9 corresponded to the period of dynamic changes in the rat retinal development. The results suggest that the expression of TGF-beta superfamily is regulated along with retinal development and may be related to retinal development.
    Japanese Journal of Ophthalmology 01/1999; 43(4):290-4. · 1.27 Impact Factor
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    ABSTRACT: Transforming growth factor beta (TGF-beta) regulates extracellular matrix deposition, cell proliferation, and migration, and is expressed in cornea. TGF-beta is thought to be involved in the corneal wound healing process. The central corneal area (3 mm in diameter) of Lewis rats was ablated using PTK mode excimer laser and the wound healing process was observed at 12 and 24 h and 2, 5, 10, and 30 days after treatment. The expression of TGF-beta 1, -beta 2 and -beta 3, TGF-beta type I and type II receptors, alpha 3, alpha 5, beta 4 integrin subunits, laminin and fibronectin was studied immunohistochemically. Antibody neutralizing TGF-beta 1, -beta 2 and -beta 3 was administered intraperitoneally, 50 micrograms daily, for 5 days after the laser treatment to investigate the effects of TGF-beta function blockade. At the leading edge of the regenerating epithelium, no TGF-beta type I and type II receptors and beta 4 integrin subunits were expressed after 24 h. Regenerating epithelium covered the ablated area after 2 days. An abnormal fibrotic layer was formed in the subepithelial area. This layer contained round-shaped cells in the stroma in the early stage (2-5 days after laser ablation) and spindle-shaped fibroblast-like keratocytes after 10 days. Laminin and fibronectin expression increased in the fibrotic layer. The increased stromal cells expressed TGF-beta isoforms and TGF-beta receptors. Neutralizing TGF-beta inhibited the stromal cell increase in the laser ablated area after 5 days. TGF-beta may be involved in epithelial cell migration and stromal cell reaction during the corneal wound healing process after excimer laser ablation in rat models.
    Albrecht von Graæes Archiv für Ophthalmologie 12/1998; 236(11):834-43. · 1.93 Impact Factor

Publication Stats

709 Citations
76.01 Total Impact Points


  • 2002–2007
    • Jichi Medical University
      • Department of Ophthalmology
      Tochigi, Tochigi-ken, Japan
  • 2003
    • Tokyo Medical University
      • Department of Ophthalmology
      Edo, Tōkyō, Japan
  • 1993–2000
    • The University of Tokyo
      • • Faculty & Graduate School of Medicine
      • • Department of Neuroscience
      • • Department of Pathology
      Tokyo, Tokyo-to, Japan
  • 1998
    • State University of New York
      New York City, New York, United States