記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To objectively evaluate surgically induced astigmatism (SIA) after trabeculectomy with mitomycin C and investigate the relationships between SIA and various factors. PATIENTS AND METHODS: This retrospective study included the right eyes of 66 consecutive patients who underwent standard trabeculectomy performed in the superior temporal quadrant for the first time by a single surgeon. Keratometry recordings made before surgery and 3 months after surgery were collected to calculate the SIA in each patient. The arithmetic mean of SIA (M-SIA) and the centroid of SIA (C-SIA) were determined using vector analysis. The relationships between the magnitude of SIA and the following possible related factors were assessed: age, sex, pre-operative corneal astigmatism, pre-operative intraocular pressure (IOP), 3-month postoperative IOP, pre-operative best-corrected visual acuity (BCVA), 3-month postoperative BCVA, the number of total scleral flap sutures (T-SFS), the number of leftover scleral flap sutures without laser suture lysis at 3 months postoperatively (L-SFS), shape of the scleral flap (triangle or trapezoid), and incision type of the conjunctival flap (fornix- or limbal-based). RESULTS: The mean (± standard deviation) M-SIA was 1.00 ± 0.85 D, and the mean C-SIA was 0.34 ± 1.28 D at 104°. The direction of C-SIA showed a trend of corneal steepening to the superior temporal location, in the direction of the scleral flap location. There were significant correlations of the magnitudes of SIA with the number of T-SFS (P = 0.001) and the number of L-SFS (P < 0.001). CONCLUSION: Trabeculectomy induced SIA in the direction of the scleral flap location, and scleral sutures are significantly associated with the SIA. The scleral suture may play a key role in steepening the cornea toward the scleral flap direction in post-trabeculectomy patients.

DOI： 10.2147/OPTH.S389480

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

BACKGROUND: The purpose of this study was to examine changes in the ocular surface before and after phacoemulsification with small incisions and to examine the changes in tear osmolarity. METHODS: This was a prospective, observational study involving 55 eyes of 39 patients (19 male, 20 female patients; average age 72.0±7.3 years) who had cataract surgery at a Nippon Medical School Hospital between December 2013 and June 2018. Compromised tear dynamics were determined by the Schirmer test or the tear break-up time (BUT). An abnormal ocular surface was identified by positive vital staining with fluorescein or lissamine green. Moreover, tear osmolarity (Tosm) and corneal sensitivity were measured. All assessments were done preoperatively and 1 and 4 weeks (P1W and P4W) after the surgery. RESULTS: None of the operations had any complications. Operating time was 17.8±9.3 minutes. BUT was significantly decreased at P1W, and it recovered at P4W. The Schirmer test did not change significantly. The fluorescein staining score (FSS) increased significantly at P1W and recovered at P4W. The Lissamine green score (LSS) did not change significantly. Tear osmolarity increased significantly at P1W and did not recover at P4W. Corneal sensitivity decreased significantly at P1W and recovered at P4W. CONCLUSION: In the present study, there were temporary changes in dry eye-related examinations including tear osmolarity after cataract surgery. In particular, tear osmolarity increased significantly 4 weeks after surgery compared to before surgery, and it showed long-term changes, unlike other factors. After cataract surgery, tear osmolarity, BUT, and FSS increase, resulting in dry eye symptoms. Therefore, it is necessary to pay attention to discomfortable eye symptoms of patients after cataract surgery.

DOI： 10.1272/jnms.jnms.2021_88-405

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

BACKGROUND: The adeno-associated virus (AAV) vector is a promising vector for ocular gene therapy. Surgical internal limiting membrane peeling before AAV vector administration is useful for efficient retinal transduction. However, no report has investigated localization of AAV vectors after administration into a post-vitrectomy eye. This study investigated the effects of vitrectomy surgery on intravitreal-injected AAV vector-mediated gene expression in the anterior segment and examined the presence of neutralizing antibodies (NAbs) in serum before and after AAV vector administration. METHODS: Of six eyes from three female cynomolgus monkeys, four were vitrectomized (Group VIT) and two were non-vitrectomized (Group IV). All eyes were injected with 50 μL of triple-mutated self-complementary AAV2 vector (1.9 × 1013 v.g./mL) encoding green fluorescent protein (GFP). NAbs in the serum were examined before administration and at 2 and 6 weeks after administration. GFP expression was analyzed at 19 weeks after administration. RESULTS: Immunohistological analysis showed no GFP expression in the trabecular meshwork in any eye. The GFP genome copy in two slices of the anterior segment was 2.417 (vector genome copies/diploid genome) in Group VIT and 4.316 (vector genome copies/diploid genome) in group IV. The NAb titer was 1:15.9 (geometric mean) before administration, 1:310.7 at 2 weeks after administration, and 1:669.4 at 6 weeks after administration. CONCLUSION: Previous vitrectomy surgery did not affect gene expression in the anterior segment after intravitreal injection of AAV vectors.

DOI： 10.1272/jnms.jnms.2021_88-203

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

BACKGROUND: Brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of glaucoma. BDNF concentrations reported in previous studies have varied widely, and the concentration of BDNF in aqueous humor is unknown. In this study, BDNF concentrations in the aqueous humor of glaucoma patients and control patients were measured with ELISA kits. METHODS: This prospective, observational study examined BDNF levels in aqueous humor in 62 eyes of 43 patients who underwent cataract surgery or trabeculectomy (11 glaucoma patients and 32 non-glaucoma cataract patients as controls). BDNF concentrations were examined by 4 different enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: The mean ± SD patient age was 72.0 ± 10.1 (range 35 to 87) years. Two of the techniques detected no BDNF in aqueous humor in any samples (n=3 and n=9, respectively); the average value was less than zero. An ultrasensitive ELISA kit did not yield reliable measurements. Finally, in an even more sensitive ELISA (Simoa-HD1), performed by an outside contractor, 25 (54.3%) eyes were below the detection limit, including 20 (55.6%) control and 5 (50%) glaucoma cases. For eyes with detectable BDNF, the overall BDNF concentration was 0.158 pg/mL (n=21): 0.196 pg/mL (n=16) in controls and 0.034 pg/mL (n=5) in glaucoma cases. CONCLUSIONS: BDNF level in aqueous humor varies widely.

DOI： 10.1272/jnms.jnms.2021_88-305

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

BACKGROUND: Epiretinal membrane (ERM) is a disease that affects the vitreoretinal interface and causes metamorphopsia, anorthopia, and decreased visual acuity. In this study, ERM patients who underwent internal limiting membrane (ILM) peeling were classified as those with glaucoma (Group G) and a control group (Group C). Changes in ganglion cell complex (GCC) thickness were compared between these groups to investigate whether such changes had an effect on progression of glaucoma from structural change. METHODS: This was a retrospective, observational study that included 27 eyes of 27 patients. Group C included 22 eyes, and Group G included 5 eyes. Patients underwent ILM peeling, and cataract surgery was combined with vitrectomy for 16 phakic eyes; 2 phakic eyes and 9 aphakic eyes were treated only with vitrectomy. GCC thickness was measured preoperatively and at 2 weeks and 1, 3, and 6 months postoperatively, and these values and the rates of thinning were compared between the two groups. RESULTS: The mean age of patients was 66.7±12.8 years (range 30-84 years). There was no significant difference between groups in the thickness of the GCC or its rate of thinning after ILM peeling. CONCLUSIONS: The present results suggest that this procedure does not cause structural exacerbation of glaucoma in glaucoma patients. Although further studies of the functional effects of ILM peeling are required, the present results suggest that there is no significant difference between the two groups.

DOI： 10.1272/jnms.jnms.2021_88-202

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

Purpose: Maternally inherited diabetes and deafness (MIDD) is caused by a heteroplasmic m.3243A>G mutation in the mitochondrial DNA. The main ocular feature in MIDD is macular dystrophy. The purpose of this study was to identify the phenotypical characteristics of a patient with MIDD by multimodal high-resolution imaging analyses.Methods: A detailed history and ophthalmic examination were performed on a 39-year-old patient with MIDD. Multi-modal imaging included fundus photography, fundus autofluorescence imaging, fluorescein angiography, spectral-domain optical coherence tomography, OCT-angiography, and adaptive optics imaging. The PCR-invader and whole exome sequencing (WES) methods were performed on the DNA of the patient.Results: A 39-year-old woman with sensorineural hearing loss, diabetes mellitus presented with atrophic perifoveal changes and MIDD was suspected. The PCR-invader and WES methods showed that the patient had a m.3243A>G mutation in the mitochondrial DNA with 29% and 16.7% of the heteroplasmy in the peripheral blood, respectively. Morphological analyses revealed that the areas of photoreceptor degeneration and chorioretinal atrophy were present mainly in the perifoveal region. Multifocal ERGs showed that the perifoveal responses were reduced. Goldmann visual field was significant for a cecocentral scotoma in the right eye and an enlarged blind spot in the left eye. The central isopter was constricted bilaterally. The results of high-resolution retinal imaging by AO revealed that the densities of the cone photoreceptor were significantly reduced in the fovea where no obvious atrophy of the RPE and choroid was observed.Conclusions: Our findings indicate that WES analysis can be used to detect the m.3243A>G mutation in the mtDNA. The results of multimodal imaging analyses indicated that the primary dysfunction of the photoreceptors in the fovea might precede the dysfunction of the RPE in patient with MIDD.

DOI： 10.1080/13816810.2021.1881978

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

Cilioretinal artery occlusion (CLRAO) is a rare disease. Here, we report the case of a 70-year-old man with nonarteritic cilioretinal artery occlusion alone. The patient was allergic to fluorescein. Therefore, we followed the retinal circulation with optical coherence tomography angiography (OCTA). OCTA at 40 days postonset showed partial improvement in the retinal circulation.

DOI： 10.1155/2021/8845972

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その他リンク： http://downloads.hindawi.com/journals/criopm/2021/8845972.xml

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe the case of a primary open-angle glaucoma patient with re-elevated nocturnal sitting intraocular pressure (IOP) after restarting medical therapy due to a failing bleb. IOP was markedly higher than diurnal IOP during multiple-drug therapy in both eyes, but it did not increase in the left eye with a functional bleb without medical therapy after trabeculectomy with adjuvant mitomycin. However, nocturnal sitting IOP was re-elevated after restarting multiple-drug therapy due to a failing bleb, while diurnal IOP was maintained at a low level.

DOI： 10.1272/jnms.JNMS.2021_88-521

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Decreased vision and cystoid macular edema (CME) developed in phakic eyes of a patient who underwent laser iridotomy after changing the glaucoma eye drops from carteolol 2% long-acting ophthalmic solution to omidenepag isopropyl 0.002%. CME completely disappeared at approximately 2 months after discontinuation of omidenepag isopropyl in conjunction with the use of bromfenac sodium 0.1%.

DOI： 10.1272/jnms.jnms.2021_88-520

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

PURPOSE: The aim of this study was to measure the serum levels of brain-derived neurotrophic factor (BDNF) in primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients in Japan. METHODS: This was a prospective, observational study that examined serum BDNF levels in 78 patients who underwent cataract surgery or trabeculectomy (27 glaucoma patients and 51 non-glaucoma cataract patients as controls). The patients' age was 68.8 ± 11.1 years (mean ± standard deviation; range 35-86 years). The number of patients with POAG and NTG was 16 and 11, respectively. The diagnosis of POAG was done by intraocular pressure measurement, gonioscopy, optic nerve head change, and the presence of a visual field defect. RESULTS: The serum BDNF concentration was significantly lower in the glaucoma group, including both POAG and NTG, than in the control group (7.2 ± 3.6 ng/mL vs. 12.2 ± 9.3 ng/mL, p=0.004). The serum BDNF concentration was lower in the early phase than in the moderate phases of glaucoma. There was no correlation between the serum BDNF concentration and age. When the NTG and POAG patient groups were compared, the serum BDNF concentration was lower in NTG patients than in POAG patients. No significant correlations were found between glaucoma parameters, including optical coherence tomography and visual field defects, and the serum BDNF concentration. CONCLUSION: This is the first study to have investigated serum BDNF concentrations in glaucoma patients in Japan. Further investigations are needed to evaluate the role of BDNF as a potential biomarker of glaucoma.

DOI： 10.1272/jnms.jnms.2020_87-605

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

PURPOSE: The hexokinase 1 (HK1) gene encodes one of the four human hexokinases that play essential roles in glucose metabolism. Recently, several cases of E847K mutation in the HK1 gene were reported to cause inherited retinal dystrophy. The purpose of this study was to identify the phenotypical characteristics of patients with a recurrent E847K mutation in the HK1 gene. METHODS: Three generations of one family with autosomal dominant retinitis pigmentosa were examined. Whole exome sequencing was performed on the DNA. Fundus imaging by an adaptive optics fundus camera was used to obtain high-resolution photoreceptor images. RESULTS: Fundus examination of the proband showed degeneration of the mid-peripheral retina, and SD-OCT images showed an absence of the ellipsoid zone (EZ) and interdigitation zone (IZ) in the parafovea and more peripherally. SD-OCT images of the mother of the proband showed an absence of the EZ and IZ, and fundus autofluorescence images showed hypo-autofluorescence surrounding the macular region. One daughter of the proband had only mild night blindness, however, the density of the cone photoreceptors was reduced in the parafoveal region. Whole exome sequencing identified a heterozygous variant, E847K, in the HK1 gene. This variant was found to co-segregate with the disease in three family members. CONCLUSIONS: Although the systemic phenotypes were found to be associated with the HK1 mutations, only the E847K mutation can cause a non-syndromic photoreceptor degeneration. Our study strengthened the hypothesis that the amino acid E847 might play a critical role in the maintenance of the morphology and function of the photoreceptors.

DOI： 10.1080/13816810.2020.1810284

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

Capsular stabilization devices were evaluated in a zonular fiber defect model using the slit side view (SSV) system to confirm their utility for capsular stabilization during phacoemulsification. A zonular fiber defect model was made by cutting Zinn’s zonule under observation with a slit lamp microscope in a porcine eye. Phacoemulsification was performed, and the movement of the lens capsule and the depth of the anterior chamber were observed using the SSV in three groups: control group: no surgical instruments used, CE group: a capsule expander was inserted, and CTR group: a capsular tension ring was inserted. In the control group, the equator of the lens was unstable and was easily suctioned to the port of the ultrasound handpiece. The lens capsule was stable in both in the CE and CTR groups. In the CTR group, the equator responsible for the zonular rupture also returned and closed true to its original position. The utility of the capsular stabilization devices in this zonular fiber defect model was confirmed with the SSV system.

DOI： 10.1155/2020/5921965

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その他リンク： http://downloads.hindawi.com/journals/joph/2020/5921965.xml

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Glaucoma is a group of chronic optic neuropathies characterized by the degeneration of retinal ganglion cells (RGCs) and their axons, and they ultimately cause blindness. Because neuroprotection using neurotrophic factors against RGC loss has been proven a beneficial strategy, extensive attempts have been made to perform gene transfer of neurotrophic proteins. This study used the inner retinal injury mouse model to evaluate the neuroprotective effect of tyrosine triple mutated and self-complementary adeno-associated virus (AAV) encoding brain-derived neurotrophic factor (BDNF; tm-scAAV2-BDNF). METHODS: C57BL/6J mice were intravitreally injected with 1 μl of tm-scAAV2-BDNF and its control AAV at a titer of 6.6 E+13 genome copies/ml. Three weeks later, 1 μl of 2 mM N-methyl-D-aspartate (NMDA) was administered in the same way as the viral injection. Six days after the NMDA injection, we assessed the dark-adapted electroretinography (ERG). Mice were sacrificed at one week after the NMDA injection, followed by RNA quantification, protein detection, and histopathological analysis. RESULTS: The RNA expression of BDNF in retinas treated with tm-scAAV2-BDNF was about 300-fold higher than that of its control AAV. Meanwhile, the expression of recombinant BDNF protein increased in retinas treated with tm-scAAV2-BDNF. In addition, histological analysis revealed that tm-scAAV2-BDNF prevented thinning of the inner retina. Furthermore, b-wave amplitudes of the tm-scAAV2-BDNF group were significantly higher than those of the control vector group. Histopathological and electrophysiological evaluations showed that tm-scAAV2-BDNF treatment offered significant protection against NMDA toxicity. CONCLUSIONS: Results showed that tm-scAAV2-BDNF-treated retinas were resistant to NMDA injury, while retinas treated with the control AAV exhibited histopathological and functional changes after the administration of NMDA. These results suggest that tm-scAAV2-BDNF is potentially effective against inner retinal injury, including normal tension glaucoma.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The GUCY2D (guanylate cyclase 2D) gene encodes a photoreceptor guanylate cyclase (GC-E) that is predominantly expressed in the cone outer segments. Mutations in the GUCY2D lead to severe retinal disorders such as autosomal dominant cone-rod dystrophy (adCRD) and autosomal recessive Leber congenital amaurosis type 1. The purpose of this study was to determine the phenotype of a Japanese patient with a probably pathogenic GUCY2D variant. METHODS: Detailed ophthalmic examinations were performed, and whole exome sequencing was performed on the DNA obtained from the patient. The variants identified by exome sequencing and targeted analysis were further confirmed by direct sequencing. RESULTS: A 47-years-old man had atrophic and pigmentary changes in the macula of both eyes. The amplitudes and implicit times of the full-field electroretinograms (ERGs) were within normal limits, however the densities of the multifocal ERGs in the central area were reduced in both eyes. Whole exome sequencing identified heterozygous variant c.2527G>C, p.Glu843Gln in the GUCY2D gene within the mutation hot spot for adCRD. The allelic frequencies of this variant was extremely low and according to ACMG standards and guidelines, the variants were classified as likely pathogenic. CONCLUSIONS: This is the first report on the findings in a patient with a heterozygous variant, c.2527G>C, p.Glu843Gln in the GUCY2D, presenting with mild macular dystrophy without a general reduction of cone function. Our findings expand the spectrum of the clinical phenotypes of GUCY2D-adCRD and help identify the morphological and functional changes caused by defects of dimerization of GC-E in the phototransduction cascade.

DOI： 10.1272/jnms.JNMS.2020_87-207

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To investigate the effects of hydrogen (H2) on Cu, Zn superoxide dismutase (SOD1) activation in a rat model of corneal alkali burn. METHODS: In each rat, one cornea was subjected to alkali exposure. Physiological saline (saline group) or H2-dissolved saline (H2 group) was instilled continuously on the cornea for 5min before and after alkali exposure. Inflammatory cells, neovascularization, and cytoplasmic SOD1 levels were evaluated immunohistochemically in enucleated eyes from both groups. Three-dimensional ultrastructural tissue changes in the eyes were analyzed using low-vacuum scanning electron microscopy. RESULTS: The numbers of both inflammatory and vascular endothelial cells were significantly reduced in the corneas of the H2 group (P<0.01). Furthermore, H2 treatment increased both cytoplasmic SOD1 levels (P<0.01) and activity in corneal epithelial cells (P<0.01). Notably, the SOD1 activity level in the H2 group was approximately 2.5-fold greater than that in the saline group. CONCLUSION: H2 treatment suppresses inflammation and neovascularization in the injured cornea and indirectly suppresses oxidative insult to the cornea by upregulating the SOD1 enzyme protein level and activity.

DOI： 10.18240/ijo.2020.08.01

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

BACKGROUND: In preparation for the 2021 Tokyo Olympic/Paralympic Games, the Japanese government assessed the risks of infectious disease outbreaks and identified necessary preparations. This present study reviewed efforts made during a previous measles epidemic and describes the roles of hospitals. METHODS: This descriptive study investigated the records of 198 children with measles. All children were treated at a general hospital during the period from January 1997 through February 1998. We also examined the actions of pediatricians during and after a measles outbreak in the community. RESULTS: Of the 198 children, 145 (73%) were hospitalized. The measles vaccination rate in the previous year was approximately 75%. Of the patients examined, 53% were younger than 2 years of age; mean age was 2.75 years. Pneumonia and gastroenteritis accounted for 46% and 30% of the complications, respectively. Issues requiring attention included the number of hospital beds located in a negative pressure room or private room with a window, the need for gamma globulin preparations with high measles antibody titers, the necessity of increasing vaccination opportunities, and extension of physician working hours. CONCLUSIONS: Visitors from other countries could cause measles outbreaks in Japan. Measures that might mitigate an outbreak were maintenance of high vaccination rates, ready availability of information on the location of negative pressure hospital rooms, knowledge of the status of the measle outbreak, and flexible medical staffing. There is a risk of measles outbreaks among infants and among those who do not have a measles antibody titer.

DOI： 10.1272/jnms.jnms.2021_88-502

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The GNAT1 gene encodes the alpha-subunit of transducin in rod photoreceptors and is an important part of the phototransduction cascade. Defects in GNAT1 are very rare but have been identified in autosomal dominant and recessive congenital stationary night blindness (CSNB) and autosomal recessive rod-cone dystrophy. The purpose of this study was to determine the phenotype-genotype relationship in a non-consanguineous Japanese family with a GNAT1 mutation.Methods: Detailed ophthalmic examinations were performed on the patients and their family members. Whole exome sequencing (WES) was applied to the DNA obtained from the family members. Sanger sequencing and co-segregation analyses were performed to identify the most likely pathogenic variant.Results: Two female (13- and 11-years) and one male (15-years) patients from a family had night blindness from their childhood. The fundus had a mild golden appearance regardless of the state of light- or dark-adaptation. Electroretinographic (ERG) analyses showed that the scotopic a-wave was extinguished, and the mixed rod-cone responses were severely reduced with an electronegative form in patients. The shapes of the dark-adapted ERGs were similar to those recorded from patients with Oguchi disease. We identified a homozygous in-frame deletion c.818_820delAGA, p.Lys273del in the GNAT1 gene. Variants were verified by Sanger sequencing and co-segregated with the disease in five members of the family.Conclusions: Our findings indicate that a recessive GNAT1 mutation found in this family could be the cause of the golden appearance of the fundus and negative ERGs with reduced a-waves, and nearly absent b-waves in the mixed rod-cone ERGs.

DOI： 10.1080/13816810.2019.1686159

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II-induced polyarthritis and anti-cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H-2) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species-induced injury implicated in RA pathogenesis. We used D1CC mice to analyse chronic lung fibrosis development and evaluate H-2 treatment effects. We injected D1CC mice with type II collagen and supplied them with H-2-rich or control water until analysis. Increased serum surfactant protein D values and lung densities images were observed 10 months after injection. Inflammation was patchy within the perilymphatic stromal area, with increased 8-hydroxy-2MODIFIER LETTER PRIME-deoxyguanosine-positive cell numbers and tumour necrosis factor-alpha, BAX, transforming growth factor-beta, interleukin-6 and soluble collagen levels in the lungs. Inflammatory and fibrotic changes developed diffusely within the perilymphatic stromal area, as observed in humans. H-2 treatment decreased these effects in the lungs. Thus, this model is valuable for studying the effects of H-2 treatment and chronic interstitial pneumonia pathophysiology in humans. H-2 appears to protect against RA-ILD by alleviating oxidative stress.

DOI： 10.1111/jcmm.14603

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jcrs.2019.02.035

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ajo.2019.04.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVE: To characterize the photoreceptors and choroidal morphology of heterozygous female carriers of choroideremia who typically do not have any visual defects but can have severe funduscopic changes. PATIENTS AND METHODS: This was a clinical case series study. Detailed ophthalmic examinations were performed on six female carriers from four families with choroideremia. The subfoveal choroidal thickness (SFCT) was determined by spectral-domain optical coherence tomography (SD-OCT) and the cone photoreceptor density by adaptive optics (AO) retinal imaging. SFCT and cone densities of the carriers were compared to that of normal eyes of healthy subjects. RESULTS: The mean age of the carriers was 42.5 years. Fundus photographs showed diffuse, patchy depigmentation; however, the SFCT was within the normal limits. AO retinal imaging revealed preserved cone densities at temporal eccentricities from 2 to 8 angular degrees. CONCLUSIONS: The findings indicate that despite the presence of distinctive depigmentation of the retinal pigment epithelium in female carriers of choroideremia, their cone photoreceptor densities and SFCT are well-preserved. These observations may account for the good visual acuity and lack of an awareness of visual disturbances. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:76-85.].

DOI： 10.3928/23258160-20190129-03

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/molecules24010114

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記述言語：英語  

DOI： 10.1038/s41598-018-35239-0.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-35239-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2018/5027238

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Netherlands  

Purpose: To the correlation between plasma osmolarity (Posm) and tear osmolarity (Tosm) in patients (54 patients, 88 eyes) who underwent cataract surgery was evaluated. Methods: Before cataract surgery, routine pre-operative biochemical tests were performed, and Posm was determined from blood samples. Also, Tosm was measured using the TearLab system, and objective signs including tear break-up time (BUT), fluorescein staining, lissamine green staining, and Schirmer’s test were evaluated. Dry eye (DE) was diagnosed according to the Japanese criteria for DE. Results: Of the 88 eyes, 4 were diagnosed as definite DE, 70 as probable DE, and 14 as normal. Since the number of definite DE was small, the eyes were divided into two groups: normal group (n = 14) and DE group (n = 74), which included definite DE (n = 4) and probable DE (n = 70). There was no correlation between Posm and Tosm, though Posm (293.32 mOsm/L) was significantly higher than Tosm (288.48 mOsm/L
p &lt
0.001). There was no significant difference in Tosm between the normal group (288.29 mOsm/L) and the DE group (288.51 mOsm/L). No patients had a Tosm higher than 310 mOsm/L even in the DE group. Correlations between Posm/Tosm and each DE sign value were not found. Of 54 patients, 18 were diabetic. Posm was significantly higher in diabetic (295.78 mOsm/L) than in non-diabetic (292.36 mOsm/L
p = 0.014) patients, while there was no significant difference in Tosm between diabetic and non-diabetic patients. Conclusions: The results suggest that Tosm is independent of Posm, and Tosm elevation in DE occurs by some local mechanisms.

DOI： 10.1007/s10792-017-0484-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14260

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1272/jnms.JNMS.2018_85-52

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/ICL.0000000000000438

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CELL PRESS  

The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 pi triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.

DOI： 10.1016/j.ymthe.2016.10.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Purpose: To investigate temperature alterations in the aqueous humor and the corneal endothelium during phacoemulsification, and to evaluate the effect of ophthalmic viscosurgical devices in preventing a temperature rise at the corneal endothelium during phacoemulsification.Methods: Temperatures of the aqueous humor and corneal endothelium were measured using two temperature probes set in the anterior chamber during ultrasound oscillation in porcine eyes, with or without ophthalmic viscosurgical devices.Results: Without an ophthalmic viscosurgical device, temperatures in both the aqueous humor and the corneal endothelium rapidly rose during the ultrasound oscillation, while with an ophthalmic viscosurgical device, the temperature elevation of the corneal endothelium site was suppressed compared with the aqueous humor.Conclusion: Surgeons need to be especially aware of ophthalmic viscosurgical device retention during phacoemulsification, because it can protect the corneal endothelium from heat generated during this procedure.

DOI： 10.3109/02713683.2015.1136420

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

The essential targets of dry eye disease (DED) treatments include both objective signs and subjective symptoms. However, due to the numerous subjective symptoms, it is understandable why little association has been found between the signs and symptoms. Although psychological influences on the subjective symptoms have been reported, little is known about the influence of personality traits. The present study analyzed the relationship between the signs/symptoms of DED and the personality traits of patients using a cross-sectional design. We examined 56 DED patients (mean age; 62.4 +/- 12.9, range 34-85 years) visiting the outpatient clinic of the Department of Ophthalmology at the Nippon Medical School Hospital in Tokyo, Japan. Objective signs evaluated included the Schirmer I test, tear breakup time (BUT), fluorescein and lissamine green staining, and tear osmolality. Subjective symptoms were assessed by the Ocular Surface Disease Index (OSDI) and Dry Eye Related Quality-of-Life Score (DEQS) questionnaires. For personality traits, the Big Five personality traits model analysis was used. Correlations between the objective signs, subjective symptoms, and personality traits were analyzed. A significant correlation was found between the neuroticism in the Big Five Personality Inventory and the symptoms assessed by the DEQS (r = -0.35, p &lt; 0.01), and the OSDI (r = -0.28, p &lt; 0.05). There was no significant correlation observed between the signs and the symptoms, or between the signs and any personality traits. The results of our current study suggest that the personality of the patient, which appears to be the basis of various psychological factors, can have some impact on the subjective symptoms. This may be one of the reasons why there has been little association noted between the signs and symptoms of DED.

DOI： 10.1371/journal.pone.0166838

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

In phacoemulsification, ultrasound induces hydroxyl radical (center dot OH) formation, damaging corneal endothelium. Whether H-2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H-2 was dissolved in a commercial irrigating solution. The effects of H-2 against center dot OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H-2-dissolved solution. The effects of H-2 in phacoemulsification were evaluated in rabbits, comparing H-2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H-2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H-2 group. In conclusion, H-2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage.

DOI： 10.1038/srep31190

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF).
Methods: The tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer.
Results: Intravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were preserved after transient IOP elevation in eyes treated with tm-scAAV2-BDNF but not in the other I/R groups. Significantly reduced glial fibrillary acidic protein (GFAP) immunostaining after I/R injury in the rats that received tm-scAAV2-BDNF indicated reduced retinal stress, and electroretinogram (ERG) analysis confirmed preservation of retinal function in the tm-scAAV2-BDNF group.
Conclusions: These results demonstrate the feasibility and effectiveness of neuroprotective gene therapy using tm-scAAV2-BDNF to protect the inner retina from transiently high intraocular pressure. An in vivo gene therapeutic approach to the clinical management of retinal diseases in conditions such as glaucoma, retinal artery occlusion, hypertensive retinopathy, and diabetic retinopathy thus appears feasible.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Societas Neurologica Japonica  

Here, we present a case of right eyelid drooping in a 79-year-old man. Neurological examination revealed ptosis of the right eye without severe painful eyelid swelling and redness. An ocular motility examination of the right eye revealed upward limitation and downward overshoot. The results of routine blood examinations were within normal limits, and no autoantibodies were detected. Orbital magnetic resonance images revealed mild right eyelid swelling and lacrimal gland enlargement, indicating orbital inflammation. The ocular discharge was positive for Staphylococcus hominis by culture and the patient was diagnosed as having acute dacryoadenitis. Treatment with topical and systemic administration of antibiotics rapidly improved symptoms. Ocular infection is not usually suspected in the absence of local severe painful swelling and redness, and painless acute dacryoadenitis presenting as ophthalmoplegia and ptosis may be misdiagnosed. Orbital inflammation may rapidly progress to orbital cellulitis with treatment delay, which may also lead to aggravation of ophthalmic prognosis. Therefore, neurologists should be aware of the possibility of acute dacryoadenitis occurring without the local severe inflammatory findings mimicking neurological diseases, and acute dacryoadenitis should be considered in patients with ophthalmoplegia even in the absence of severe painful eyelid swelling and redness.

DOI： 10.5692/clinicalneurol.cn-000778

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT, INC  

Hypophosphatasia (HPP) is an inherited skeletal and dental disease caused by loss-of-function mutations in the gene that encodes tissue-nonspecific alkaline phosphatase (TNALP). The major symptoms of severe forms of the disease are bone defects, respiratory insufficiency, and epileptic seizures. In 2015, enzyme replacement therapy (ERT) using recombinant bone-targeted TNALP with deca-aspartate (D-10) motif was approved to treat pediatric HPP patients in Japan, Canada, and Europe. However, the ERT requires repeated subcutaneous administration of the enzyme because of the short half-life in serum. In the present study, we evaluated the feasibility of neonatal ex vivo gene therapy in TNALP knockout (Akp2(-/-)) HPP mice using lentivirally transduced bone marrow cells (BMC) expressing bone-targeted TNALP in which a D-10 sequence was linked to the C-terminus of soluble TNALP (TNALP-D-10). The Akp2(-/-) mice usually die within 20 days because of growth failure, epileptic seizures, and hypomineralization. However, an intravenous transplantation of BMC expressing TNALP-D-10 (ALP-BMC) into neonatal Akp2(-/-) mice prolonged survival of the mice with improved bone mineralization compared with untransduced BMC-transplanted Akp2(-/-) mice. The treated Akp2(-/-) mice were normal in appearance and experienced no seizures during the experimental period. The lentivirally transduced BMC were efficiently engrafted in the recipient mice and supplied TNALP-D-10 continuously at a therapeutic level for at least 3 months. Moreover, TNALP-D-10 overexpression did not affect multilineage reconstitution in the recipient mice. The plasma ALP activity was sustained at high levels in the treated mice, and tissue ALP activity was selectively detected on bone surfaces, not in the kidneys or other organs. No ectopic calcification was observed in the ALP-BMC-treated mice. These results indicate that lentivirally transduced BMC can serve as a reservoir for stem cell-based ERT to rescue the Akp2(-/-) phenotype. Neonatal ex vivo gene therapy thus appears to be a possible treatment option for treating severe HPP.

DOI： 10.1089/hum.2015.078

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Purpose: Because dry eye greatly reduces quality of life, this study aimed to examine rebamipide instillation in patients with dry eye and assess the improvement of signs and symptoms as evaluated with the Ocular Surface Disease Index, which is the most popular index and is highly reliable.
Methods: From June 2013 through January 2014, we examined 50 eyes of 25 patients with dry eye (6 men and 19 woman) at our institution. Dry eye was diagnosed on the basis of the presence of symptoms, tear dynamics, and ocular surface abnormalities according to the Japanese criteria for dry eye. Before being enrolled, all patients underwent ocular surface health assessment, including history interviews, and completed the Ocular Surface Disease Index questionnaire. Patients received 2% rebamipide ophthalmic solution 4 times daily for 4 weeks. Signs and symptoms were analyzed before and 4 weeks after rebamipide administration. Tear dynamics, tear break-up time, and ocular surface abnormalities were measured and compared between before and 4 weeks after rebamipide administration.
Results: Of the 25 patients, 9 had definite dry eye and 16 had probable dry eye. Tear break-up time and the fluorescein staining score significantly improved after 4 weeks. However, no significant change was observed for the Schirmer test I and the lissamine green staining score.
Conclusions: The administration of 2% rebamipide 4 times daily for 4 weeks improves the signs and symptoms of dry eye and improves patients' quality of life.

DOI： 10.1272/jnms.82.229

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

We determined the influence of soft contact lenses (SCLs) on conjunctival sensitivity. A total of 26 volunteers (11 males, 15 females; mean age 28.3 +/- A 4.6 years; range 22-39 years) without dry eye were enrolled in the study. Subjects with a low corneal touch threshold, atopic keratoconjunctivitis, or vernal keratoconjunctivitis were excluded. In 26 participants, 12 were disposable SCL wearers. Touch thresholds were determined using a Cochet-Bonnet esthesiometer with a 0-60 mm nylon monofilament in 5 mm increments. The length (mm) was converted to tension (g/mm(2)). Mean touch sense thresholds in the SCL wearers (n = 12) and non-wearers (n = 14) were 10.7 +/- A 2.57 and 24.6 +/- A 7.3 g/mm(2) in the whole conjunctiva, and 9.07 +/- A 3.02 and 19.2 +/- A 7.8 g/mm(2) in the upper palpebral conjunctiva, respectively. Significant differences were observed in all locations (p &lt; 0.01). The enhanced conjunctival sensitivity associated with SCL use may contribute to the dry eye-like symptoms in SCL users who do not have dry eye.

DOI： 10.1007/s10792-014-9985-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BackgroundOxidative and nitrative processes have an important role in the pathogenesis of glaucomatous neurodegeneration. Oxidative stress occurs when cellular production of reactive oxygen species outweighs the protective capacity of antioxidant defences. Reactive oxygen species are generated as by-products of cellular metabolism, primarily in the mitochondria. Herein, we present a novel investigation of the effects of molecular hydrogen (H-2) on retinal cells exposed to oxidative stress.
MethodsWe cultured adult rat retinal tissues in an organotypic culture system with a nitric oxide donor, S-nitroso-N-acetylpenicillamine, in the presence or absence of H-2. Loss of mitochondrial membrane potential and apoptosis of retinal cells were analysed using a MitoTMRE detection kit and TdT-mediated dUTP nick end labeling (TUNEL) assay, respectively. Tyrosine nitration levels and oxidative stress damage in the retina were evaluated using immunohistochemical staining. Retinal damage was quantified by measuring the numbers of cells in the ganglion cell and inner nuclear layers and the thickness of the retina.
ResultsH(2) suppressed loss of mitochondrial membrane potential and apoptosis in retinal cells. Moreover, H-2 decreased the tyrosine nitration level and suppressed oxidative stress damage in retinal cells. S-nitroso-N-acetylpenicillamine treatment decreased the cell numbers in the ganglion cell layer and inner nuclear layer, but the presence of H-2 inhibited this reduction. These findings suggest that H-2 has a neuroprotective effect against retinal cell oxidative damage, presumably by scavenging peroxynitrite.
ConclusionsH(2) reduces cellular peroxynitrite, a highly toxic reactive nitrogen species. Thus, H-2 may be an effective and novel clinical tool for treating glaucoma and other oxidative stress-related diseases.

DOI： 10.1111/ceo.12525

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: Although tear hyperosmolarity is assumed to play a major role in dry eye disease, correlation between the level of hyperosmolarity and inflammation remains unclear. The purpose of this study was to examine the effect of short-time hyperosmolarity exposure in the production of inflammatory cytokines in corneal epithelial cells in vitro.
Methods: Human corneal epithelial (HCE) cells were cultured under different osmotic conditions [310 (control), and 400-1000 mOsm]. Lactate dehydrogenase (LDH) release after short-term (10 minutes) or long-term (24 hours) hyperosmotic stress exposure was evaluated to determine HCE cell cytotoxicity. Production of inflammatory cytokines, including IL-6, IL-1 beta, IL-8, IL-23, and TGF-beta 1, due to hyperosmotic stress was also measured by enzyme-linked immunosorbent assay and semiquantitative real-time polymerase chain reaction.
Results: After a 24-hour culture, exposures above 700 mOsm caused all HCE cells to die, 500 and 600 mOsm damaged the cells, whereas 400 mOsm caused no morphological changes. However, there was a significant increase in the release of LDH after 24-hour cultures, even in 400 mOsm. In contrast, LDH examination showed that there was no cytotoxicity for the 10-minute exposures, even at above 800 mOsm. The significant increases in IL-6 production and mRNA expression at 700 mOsm during the short-time exposures were both dependent on the osmolarity. Other cytokines such as IL-1 beta, IL-8, IL-23, and TGF-beta 1 were not detected.
Conclusions: Short-time hyperosmolarity exposure may activate IL-6 expression and production in HCE cells without cytotoxicity. These observations suggest that hyperosmolarity could cause inflammation on the ocular surface in dry eye disease.

DOI： 10.1097/ICO.0000000000000256

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: Although tear hyperosmolarity is assumed to play a major role in dry eye disease, correlation between the level of hyperosmolarity and inflammation remains unclear. The purpose of this study was to examine the effect of short-time hyperosmolarity exposure in the production of inflammatory cytokines in corneal epithelial cells in vitro.
Methods: Human corneal epithelial (HCE) cells were cultured under different osmotic conditions [310 (control), and 400-1000 mOsm]. Lactate dehydrogenase (LDH) release after short-term (10 minutes) or long-term (24 hours) hyperosmotic stress exposure was evaluated to determine HCE cell cytotoxicity. Production of inflammatory cytokines, including IL-6, IL-1 beta, IL-8, IL-23, and TGF-beta 1, due to hyperosmotic stress was also measured by enzyme-linked immunosorbent assay and semiquantitative real-time polymerase chain reaction.
Results: After a 24-hour culture, exposures above 700 mOsm caused all HCE cells to die, 500 and 600 mOsm damaged the cells, whereas 400 mOsm caused no morphological changes. However, there was a significant increase in the release of LDH after 24-hour cultures, even in 400 mOsm. In contrast, LDH examination showed that there was no cytotoxicity for the 10-minute exposures, even at above 800 mOsm. The significant increases in IL-6 production and mRNA expression at 700 mOsm during the short-time exposures were both dependent on the osmolarity. Other cytokines such as IL-1 beta, IL-8, IL-23, and TGF-beta 1 were not detected.
Conclusions: Short-time hyperosmolarity exposure may activate IL-6 expression and production in HCE cells without cytotoxicity. These observations suggest that hyperosmolarity could cause inflammation on the ocular surface in dry eye disease.

DOI： 10.1097/ico.0000000000000256

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To evaluate changes in the aqueous humor temperature using 2 phacoemulsification units (Stellaris 28.5 kHz device and Whitestar Signature 40 kHz device).
SETTING: Nippon Medical School, Musashikosugi Hospital, Kawasaki City, Kanagawa, Japan.
DESIGN: Experimental study.
METHODS: Aqueous humor temperatures were measured with a temperature probe set in the anterior chamber during ultrasound (US) oscillation in porcine eyes under 5 conditions.
RESULTS: Continuous longitudinal oscillation caused a rapid rise in aqueous humor temperature, while the pulse and elliptical modes suppressed temperature elevation. Reducing the number of US tip vibrations did not reduce the temperature in the anterior chamber. However, raising the vacuum setting allowed the aspirations to rise to the set value, thereby lowering the temperature in the anterior chamber.
CONCLUSION: Because differences in the phacoemulsification settings can lead to temperature elevations in the anterior chamber, surgeons must carefully monitor these settings to prevent corneal tissue damage. (C) 2014 ASCRS AND ESCRS.

DOI： 10.1016/j.jcrs.2013.08.063

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

siRNA-Purpose: To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated an adeno-associated virus type 8 vector (AAV2/8) encoding an siRNA targeting vascular endothelial growth factor (VEGF), and determined the AAV2/8 vector's ability to inhibit angiogenesis.
Methods: We initially transfected 3T3 cells expressing VEGF with the AAV2/8 plasmid vector psiRNA-VEGF using the H1 promoter and found that VEGF expression was significantly diminished in the transfectants. We next injected 1 l (3 x 10(14) vg/ml) of AAV2/8 vector encoding siRNA targeting VEGF (AAV2/8/SmVEGF-2; n = 12) or control vector encoding green fluorescent protein (GFP) (AAV2/8/GFP; n = 14) into the subretinal space in C57BL/6 mice. One week later, CNV was induced by using a diode laser to make four separate choroidal burns around the optic nerve in each eye. After an additional 2 weeks, the eyes were removed for flat mount analysis of the CNV surface area.
Results: Subretinal delivery of AAV2/8/SmVEGF-2 significantly diminished CNV at the laser lesions, compared to AAV8/GFP (1597.3 +/- 2077.2 versus 5039.5 +/- 4055.9 mu m(2); p&lt; 0.05). Using an enzyme-linked immunosorbent assay, we found that VEGF levels were reduced by approximately half in the AAV2/8/SmVEGF-2 treated eyes.
Conclusions: These results suggest that siRNA-VEGF can be expressed across the retina and that long-term suppression of CNV is possible through the use of stable AAV2/8-mediated siRNA-VEGF expression. In vivo gene therapy may thus be a feasible approach to the clinical management of CNV in conditions such as age-related macular degeneration.

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記述言語：英語   出版者・発行元：The Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.81.59

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background: Intravenous cyclophosphamide (IVCY) pulse therapy has been used for lupus nephritis since the latter half of the 1980s; it has been shown to be effective for lupus nephritis and vasculitis and has become a standard therapy for the diffuse proliferative type of lupus nephritis in adults. IVCY therapy has also come to be used in children. This paper reports the long-term outcomes of IVCY therapy in children.
Methods: Six female patients (age range, 13 to 18 years) with systemic lupus erythematosus (SLE) were enrolled in this retrospective study. Three patients had lupus nephritis (World Health Organization class lib, IVa, IVc), 2 had central nervous system (CNS) lupus, and 1 had neither lupus nephritis nor CNS lupus. The mean pretreatment SLE disease activity index (SLEDAI) score was 18.8 +/- 4.6. Cyclophosphamide (initial dose, 500 mg/m(2)) was administered intravenously each month for 6 months and then given every 3 months for maintenance. Prednisolone was given in dosages ranging from 5 to 60 mg/day, adjusted according to laboratory data and clinical symptoms. Levels of C3, C4, CH50, and creatinine; the SLEDAI score; and the SLE responder index were monitored and evaluated. The SLE responder index was considered to have improved if the SLEDAI score had decreased by 4 points or more after 52 weeks.
Results: Prednisolone doses were reduced in all patients. Because methylprednisolone pulse therapy was administered before IVCY therapy, some patients had low titers of immunoglobin G antibodies against double-stranded DNA at the start of IVCY therapy. All patients had low serum creatinine levels. Proteinuria resolved in 1 of the 3 patients with lupus nephritis. The SLEDAI scores improved after 52 weeks in 5 of 6 patients (mean, 5.2 +/- 2.6). No patients had severe bone marrow suppression or hemorrhagic cystitis during IVCY pulse therapy.
Conclusions: IVCY pulse therapy for SLE in children achieved good long-term outcomes with no serious adverse effects, such as digestive symptoms, bone marrow suppression, infection, and hemorrhagic cystitis. IVCY pulse therapy for children with SLE has recently been approved by the Ministry of Health, Labour and Welfare. Accordingly, this paper might become a guideline for this treatment.

DOI： 10.1272/jnms.80.396

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Membranous nephropathy (MN) is caused by subepithelial deposition of immune complexes in the glomerular basement membrane, with secondary MN arising in association with infection. In secondary MN caused by hepatitis B virus (HBV), seroconversion has been known to occur after the onset of MN, particularly in children. In patients with high serum concentrations of HBV DNA, treatment with interferon-ab or a nucleoside analog has been reported to induce seroconversion and suppress HBV-DNA levels. We treated a 7-year-old boy who presented with proteinuria and liver dysfunction. He had a history of HBV infection since shortly after birth, as his mother was HBV-positive, and he was neither vaccinated nor treated with immunoglobulin at birth. Chronic hepatitis related to HBV was diagnosed following percutaneous needle biopsy of the liver. Percutaneous renal biopsy revealed REV-related glomerulonephritis with diffuse global subepithelial and focal segmental mesangial and subendothelial deposits. Therefore, HBV-associated MN was diagnosed. Treatment with the nucleoside analog lamivudine was started to reduce serum HBV-DNA levels, but lamivudine was discontinued and treatment with entecavir was started at a dosage of 0.5 mg/day after 6 weeks because of possible adverse effects. Tests for HB envelope antibody were positive in week 16 of treatment, and proteinuria had resolved by week 22. Elevated levels of aspartate aminotransferase and alanine aminotransferase were seen with both treatments but were probably attributable to the developing immune response to HBV. In the present case, HBV levels needed to be reduced to: 1) lower elevated serum HBV-DNA titers, which put the patient at high risk of hepatocellular carcinoma; and 2) remove the immune complexes causing MN. Use of nucleoside analogs to suppress the HBV load may facilitate early remission of MN, and entecavir therapy did not cause any serious adverse reactions in this case. Given the advent of lamivudine-resistant HBV, entecavir appears promising for patients with elevated serum levels of HBV DNA.

DOI： 10.1272/jnms.80.387

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Purpose: We recently demonstrated that direct subretinal (SR) injection of adeno-associated virus (AAV) type 8 (AAV8) into photoreceptor cells and retinal pigment epithelium (RPE) is a highly efficient model of gene delivery. The current study compared transduction efficiency and expression patterns associated with various routes of vector administration.
Method: The efficacy of intravitreal (VT), SR and subconjunctival (SC) injections for delivery of AAV8-derived vectors, i.e. those expressing luciferase (Luc) and enhanced green fluorescent protein (GFP) - AAV8/Luc and AAV8/GFP, respectively - were compared in an animal (mouse) model (n = 8 mice/group). Transduction efficiency and expression patterns were examined at post-injection weeks 1 and 2, and months 1, 3, 6 and 12 via in vivo imaging.
Results: One year after AAV injection, AAV8/Luc-treated mice exhibited stable and sustained high expression of vector in the VT and SR groups, but not in the SC group (VT: SR: SC = 3,218: 2,923: 115; 1 x 10(5) photons/s). Histological analysis showed that GFP expression was observed in the inner retina of VT group mice, and in photoreceptor cells and RPE of SR group mice, whereas no GFP expression was noted in the SC group. Electroretinography (ERG) revealed adverse effects following SR delivery.
Conclusions: Results suggest that both SR and VT injections of AAV8 vectors are useful routes for administering ocular gene therapy, and stress the importance of selecting an appropriate administration route, i.e. one that targets specific cells, for treating ocular disorders.

DOI： 10.3109/02713683.2013.779720

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

Cetuximab is a monoclonal antibody that binds to the EGFR, and is used in patients with colorectal cancer. The most common toxicities associated with the use of cetuximab are rash and Hypomagnesemia. Hypomagnesemia is a major adverse event, but it has often been ignored in past studies and its management has not been characterized. The aim of this study was to obtain a better understanding of the overall incidence of hypomagnesemia and to evaluate the usefulness of our original treatment guidelines for hypomagnesemia in patients receiving cetuximab-based therapy. We investigated 15 patients who were treated with cetuximab (with or without combined chemotherapy) between October 2008 and November 2010. Thirteen patients developed hypomagnesemia: 11 patients had Grade 1, one patient had Grade 2, and one patient had severe hypomagnesemia (Grade 3). Grade 1 hypomagnesemia was observed after an average of 7.5±4.8 weeks of treatment. None of the patients developed Grade 2 or higher hypomagnesemia after the implementation of our treatment guidelines. In conclusion, cetuximab treatment is associated with a significant risk of hypomagnesemia. The early monitoring and effective management of hypomagnesemia are important for patients receiving cetuximab-based therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Introduction: A case of mucosa-associated lymphoid tissue (MALT) lymphoma, the most frequent of the various conjunctival lymphoproliferative disorders, in which the initial biopsy was inconclusive but the second biopsy provided a definitive diagnosis, is reported. Case Report: A 26-year-old woman with a 3-month history of bilateral conjunctival swelling was referred by a local physician for suspected MALT lymphoma. A salmon-pink elastic swelling was found to involve both eyes and to extend from the lower palpebral conjunctiva to the bulbar conjunctiva. Tonsillar swelling was also found, and ophthalmologic (left eye) and otolaryngologic biopsies were therefore performed simultaneously under general anesthesia. The otolaryngologic diagnosis was chronic tonsillitis. Light microscope examination of the conjunctival tissue showed proliferation of lymphocytes and small aggregates of small to medium-sized atypical lymphocytes. On immunohistochemical studies, atypical lymphocytes were positive for CD20 and CD79a, but differentiation to plasmacytes was not prominent, and neither Dutcher bodies nor evidence of immunoglobulin light chain restriction was found. The results were not incompatible with MALT lymphoma but were not definitive. A second biopsy of the right eye was therefore performed 3 months later. Staining with hematoxylin and eosin showed proliferation of small lymphocytes and monocytoid B cells and differentiation to plasmacytes. The hyperplastic cells were positive for CD19, CD79a, and CD20, and their cytoplasm were positive for Bcl-2 and slightly positive for Bcl-6. Cells positive for CD38 were noted where differentiation to plasmacytes and immunoglobulin light chain κ restriction was evident on immunohistochemical studies and in situ hybridization. The Ki-67-positivity rate was approximately 5%. The results of paraffin-embedded tissue section fluorescence in situ hybridization were negative for MALT-1 (18q21). A diagnosis of MALT lymphoma was made, and treatment with rituximab was started. Discussion: Few findings lead directly to a definitive diagnosis of MALT lymphoma, and its differential diagnosis from benign lymphoproliferative disorders is difficult. In the present case definitive diagnosis was possible only after a second biopsy. This case suggests repeated biopsy may be necessary when a single biopsy is not definitive.

DOI： 10.1272/jnms.80.475

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pterygium and conjunctivochalasis are common diseases in elderly people and are not uncommonly observed together. However, there have been few reports of the simultaneous treatment of pterygium and conjunctivochalasis. We report such a surgical method and describe the results of two cases. Two patients presented with pterygium accompanied by temporal conjunctivochalasis. We decided to perform simultaneous pterygium excision and free conjunctival autograft transfer using the excess conjunctiva from the conjunctivochalasis surgery. The free graft was obtained from the bulbar conjunctiva from the 6 to 8 o'clock position in the conjunctivochalasis. To reduce the temporal conjunctivochalasis, the conjunctiva was extended and sutured to the perilimbal conjunctiva and episclera at the 6 o'clock position using 8-0 polyglactin suture. Tear meniscus break-up induced by pterygium and by conjunctival laxity was reduced, and the patients' symptoms had been significantly reduced by several days postoperatively.

DOI： 10.1272/jnms.80.74

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Primary Sjogren's syndrome (SS) is a rare autoimmune disease, especially in children. Juvenile primary SS with interstitial nephritis is rare in Japan. We report on a 12-year-old girl in whom salivary gland swelling had recurred from the age of 5 years, SS was diagnosed at the age of 10 years, and interstitial nephritis developed at the age of 12 years. The patient presented with a chief complaint of swelling of both parotid glands. The patient had a history of recurrent parotitis from 5 years of age, with episodes recurring 5 to 6 times a year and resolving within 3 days each time. However, at the age of 11 years, the patient had continuous mild swelling of the parotid glands. Examination on admission showed bilateral nontender parotid gland swelling; mild swelling of the lower extremities. xerostomia, and xerophthalmia but no exanthem. Laboratory findings were as follows: serum protein, 10.1 g/dL; immunoglobulin (Ig) G, 3,828 mg/dL; antinuclear antibodies, 1,280-fold; anti-Ro/SS-A antibody, 512-fold; anti-Ro/SS-B antibody, 4-fold; creatinine, 0.45 mg/dL; blood beta 2-microglobulin, 2.2 mg/L (slightly elevated); and cystatin C, 0.86 mg/L. Urinalysis showed proteinuria and a beta 2-microglobulin concentration of 11,265 mg/L. Thus, this patient had low molecular weight proteinuria. Schirmer's test showed decreased tear secretion (5 mm), and fluorescein staining showed marked bilateral superficial punctate keratitis. A lip biopsy showed infiltration by small round cells (mild to moderate), interstitial fibrosis, loss of salivary gland parenchyma, and atrophy, with no obvious epimyoepithelial islands, leading to a diagnosis of SS. Light microscopic examination of the renal biopsy specimens showed expansion of mononuclear cell infiltration in the renal interstitium. inflammatory cell infiltration of interstitial areas with edema and mild fibrosis, and tubulitis and mononuclear cell infiltration that included many lymphocytes and plasma cells. There were no pathological findings of glomerulonephritis. Small arteries showed no obvious abnormalities. Immunofluorescent staining showed slight, nonspecific deposition of IgM, but no deposition of IgG, complement 1q, 3, or 4. On the basis of the renal biopsy showing nonspecific chronic interstitial nephritis, renal tubular atrophy, and interstitial enlargement, tubulointerstitial nephritis associated with SS was diagnosed. (I Nippon Med Sch 2012; 79: 286-290)

DOI： 10.1272/jnms.79.286

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background: Recent studies have examined the effects of intranasal corticosteroids (INSs) in relieving the ocular symptoms of seasonal allergic rhinoconjunctivitis (SAR) and perennial allergic rhinitis. However, because most of these studies were based on subjective assessments by patients, the associated factors and mechanism of action are unknown.
Methods: A single-center, randomized, double-blind, parallel-group study was carried out in which patients with SAR were randomly assigned to an INS mometasone furoate nasal spray (MFNS) group or to a placebo group and treated once daily for 4 weeks. Substance P concentrations in tears were measured, ocular and nasal symptoms were recorded by patients in an allergy diary, and findings were recorded by an ophthalmologist.
Results: There was no significant difference between treatment groups in the mean change from baseline of substance P concentration in tears after 4 weeks of treatment, but the mean change tended to increase in the placebo group and tended to decrease in the MFNS group (P = 0.089). All ocular and nasal symptom scores, except eye tearing, were significantly lower in the MFNS group than in the placebo group. Furthermore. substance P concentrations were strongly correlated with ocular and nasal symptom scores.
Conclusions: In patients with SAR. INSs tend to decrease the substance P concentration in tears, which is correlated with the severity of ocular and nasal symptoms. (J Nippon Med Sch 2012; 79: 182-189)

DOI： 10.1272/jnms.79.182

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Screening for anemia has been performed in schools in Japan for over 30 years. The long-term effect of the nuclear power plant disaster on the prevalence of anemia in school age children is unknown. This research was performed to evaluate the prevalence of anemia in school age children and to determine grade-level and gender-related reference hemoglobin (Hb) levels prior to the nuclear disaster. Data for this research were obtained from results of screening for anemia obtained by venous blood sampling in schools in 2002. Mean Hb levels were calculated for each grade level (elementary school grades 1-6 and junior high school years 1-3) and according to gender, and the prevalence of anemia was determined. In our research, Tokyo Health Service Association guidelines were used to determine reference Hb levels for anemia. We demonstrated that Hb levels in boys increased with age during childhood and adolescence (from 13.1 +/- 0.7 g/dL in 7 year olds to 14.9 +/- 1.1 g/dL in 15 year olds); in girls, Hb levels peaked at menarche (13.7 +/- 0.8 g/dL in 12 year olds), decreasing slightly thereafter (13.4 +/- 1.1 g/dL in 15 year olds). The prevalence of anemia was 0.26% in elementary school boys, 0.27% in elementary school girls, and 1.21% in junior high school boys. The prevalence of anemia in second- and third-year junior high school girls was lower than that in first-year junior high school girls. Among all junior high school girls, 5.73% had mild anemia. Iron-deficiency anemia is the commonest type of anemia in high school girls, secondary to the relative lack of iron due to menstruation, the growth spurt and exercise. Appropriate dietary therapy and treatment of anemia, together with education about the dietary prevention of anemia, are important to reduce the prevalence of anemia in high school students. When complete blood counts are performed in regions thought to be affected by the Fukushima nuclear power plant disaster, our report can serve as a reference during evaluation of Hb levels. (J Nippon Med Sch 2012; 79: 232-235)

DOI： 10.1272/jnms.79.232

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Problem This study aimed to investigate the regulation of expression, localization and physiological role of the CCL11/ CCR3 axis in mouse ovary during the periovulatory period. Method of study CCL11/ CCR3 expression in the mouse ovary after treatment with pregnant mare serum gonadotropin (PMSG) followed by human chorionic gonadotropin (hCG) 48 hr later was assessed in vivo and in 3-dimensional cultures in vitro. Results Real-time RT-PCR analyses revealed transient CCL11 mRNA upregulation 6 hr after hCG treatment. Immunohistochemical staining of serial ovarian sections demonstrated overlapping expression of CCL11, CCR3 and CD31 endothelial cell marker in the theca-interstitial layer at 10 hr after hCG treatment. In vitro 3-dimensional cultures of periovulatory ovarian tissues demonstrated that treatment with anti-CCL11 neutralizing antibody significantly decreased CD31 transcript. Conclusions Gonadotropin surge leads to transient CCL11/ CCR3 axis upregulation in the ovarian theca-interstitial layer, suggesting that it is involved in periovulatory physiological processes by affecting follicular vessels.

DOI： 10.1111/j.1600-0897.2011.01100.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: To determine whether a mutation in the RP1-like protein 1 (RP1L1) gene is present in a Japanese patient with sporadic occult macular dystrophy (OMD) and to examine the characteristics of focal macular electroretinograms (ERGs) of the patient with genetically identified OMD.
Methods: An individual with OMD underwent detailed ophthalmic clinical evaluations including focal macular ERGs. Mutation screening of all coding regions and flanking intron sequences of the RP1L1 gene were performed with DNA sequencing analysis in this case with OMD.
Results: A new RP1L1 mutation (c. 3596 C&gt;G in exon 4) was identified. The variant c. 3596 C&gt;G in exon 4 resulted in the substitution of cysteine for serine at amino acid position 1199. The serine at position 1199 is well conserved among the RP1L1 family in other species. Four out of five computational assessment tools predicted that this mutation is damaging to the protein function. This mutation was not present in 294 control alleles. The waveform of focal macular ERGs recorded from the patient with OMD had a depolarizing pattern, simulating the ERG waveforms observed after the hyperpolarizing bipolar cell activity is blocked.
Conclusions: We have demonstrated in a Japanese patient the possibility that sporadic OMD may also be caused by an RP1L1 mutation. The waveform of focal macular ERGs elicited from the OMD patient with the RP1L1 mutation showed a depolarizing pattern. This characteristic is the same as reported for the focal macular ERGs of OMD.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：2  

Takahashi H, Kanesaki H, Igarashi T, Kameya S, Yamaki K, Mizota A, Kudo A, Miyagoe-Suzuki Y, Takeda S, Takahashi H, Molecular and cellular neurosciences, 2011, vol. 47, no. 2, pp. 119-130, 2011

DOI： 10.1016/j.mcn.2011.03.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT INC  

To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated a recombinant adeno-associated viral (AAV) vector (type 8) encoding soluble Flt-1 (AAV-sflt-1), and determined its ability to inhibit angiogenesis. When we treated human umbilical vein endothelial cells (HUVECs) with the supernatant of cells transduced with AAV-sflt-1 or AAV-EGFP (control), we found that tube formation was significantly inhibited by the former but not the latter (area: 25,121 +/- 557 vs. 68,628 +/- 1357 pixels [p &lt; 0.01]; length: 4811 +/- 246 vs. 10,894 +/- 297 pixels [p &lt; 0.01]). CNV was induced in C57BL/6 mice by making four separate choroidal burns around the optic nerve in each eye, using a diode laser. Thereafter, 2 ml (5 x 10(11) vector genomes/ml) of AAV-sflt-1 (n = 11) or control AAV-LacZ (n = 12) was injected into the subretinal space, and 2 weeks later the eyes were removed for flatmount analysis of CNV surface area. Notably, subretinal delivery of AAV-sflt-1 significantly diminished CNV at the laser lesions, as compared with AAV-LacZ (555 +/- 304 vs. 1470 +/- 1000 mu m(2); p = 0.007). These results suggest that there was diffusion of the secreted sFlt-1 across the retina and that long-term suppression of CNV is possible through the use of stable rAAV-mediated sflt-1 expression. In vivo gene therapy thus appears to be a feasible approach to the clinical management of CNV in conditions such as age-related macular degeneration.

DOI： 10.1089/hum.2009.153

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：2  

Igarashi T, Takahashi H, Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 2010, vol. 77, no. 2, pp. 66, 2010

DOI： 10.1272/jnms.77.66

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. Retinal ischemia-reperfusion (I/R) injury by transient elevation of intraocular pressure (IOP) is known to induce neuronal damage through the generation of reactive oxygen species. Study results have indicated that molecular hydrogen (H(2)) is an efficient antioxidant gas that selectively reduces the hydroxyl radical (center dot OH) and suppresses oxidative stress-induced injury in several organs. This study was conducted to explore the neuroprotective effect of H(2)-loaded eye drops on retinal I/R injury.
METHODS. Retinal ischemia was induced in rats by raising IOP for 60 minutes. H(2)-loaded eye drops were prepared by dissolving H(2) gas into a saline to saturated level and administered to the ocular surface continuously during the ischemia and/or reperfusion periods. One day after I/R injury, apoptotic cells in the retina were quantified, and oxidative stress was evaluated by markers such as 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine. Seven days after I/R injury, retinal damage was quantified by measuring the thickness of the retina.
RESULTS. When H(2)-loaded eye drops were continuously administered, H(2) concentration in the vitreous body immediately increased and I/R-induced center dot OH level decreased. The drops reduced the number of retinal apoptotic and oxidative stress marker-positive cells and prevented retinal thinning with an accompanying activation of Muller glia, astrocytes, and microglia. The drops improved the recovery of retinal thickness by &gt;70%.
CONCLUSIONS. H(2) has no known toxic effects on the human body. Thus, the results suggest that H(2)-loaded eye drops are a highly useful neuroprotective and antioxidative therapeutic treatment for acute retinal I/R injury. (Invest Ophthalmol Vis Sci. 2010;51:487-492) DOI:10.1167/iovs.09-4089

DOI： 10.1167/iovs.09-4089

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s10384-009-0739-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Synthetic oligodeoxynucleotides (ODN) expressing &apos;suppressive&apos; TTAGGG motifs down-regulate a variety of proinflammatory and T helper type 1 (Th1)-mediated pathological immune responses. The ability of the archetypal suppressive ODN A151 to inhibit ocular inflammation was examined in two murine models: experimental autoimmune uveitis, induced by immunization with a retinal antigen, interphotoreceptor retinoid-binding protein (IRBP) and adoptively transferred ocular inflammation, induced by transferring Th1 cells specific to hen egg lysozyme (HEL) into recipient mice that express HEL in their eyes. A151 treatment suppressed the inflammation in both models. In addition, A151 inhibited IRBP-specific cytokine production and lymphocyte proliferation in mice immunized with IRBP. These findings suggest that suppressive ODN affects both afferent and efferent limbs of the immunopathogenic process and may be of use in the treatment of autoimmune ocular inflammation.

DOI： 10.1111/j.1365-2249.2009.03918.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

The effect of gender on theophylline clearance was investigated retrospectively in 96 Japanese pediatric patients (63 males and 33 females) ranging in age from 0.5 to 8 years and in weight from 6.3 to 36.8 kg. All patients received intravenous constant-rate infusion of aminophylline in the asthmatic acute phase. The theophylline clearances in males and females were 56.2 +/- 5.4 and 50.1 +/- 14.2ml/h/kg for ages 0.5-&lt; 2 years, 58.7 +/- 18.8 and 48.3 +/- 6.5 ml/h/kg for ages 2-&lt; 4 years, and 65.7 +/- 12.0 and 52.1 +/- 16.8 ml/h/kg for ages 4-&lt; 9 years, respectively. At ages from 2 to 8 years, the theophylline clearance was 20%, higher in males than in females (p &lt; 0.05). Our findings suggested that the initial dosage of theophylline should be adjusted according to the gender of pediatric patients and particularly in the case of infants.

DOI： 10.1248/bpb.32.304

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

Amrubicin is a new anticancer drug that has been shown to exert efficacy against small cell lung cancer. The pharmacokinetic parameters of amrubicin have not yet been investigated in hemodialysis patients, although it had been expected that amrubicin might not be cleared by hemodialysis because of its high lipid solubility, high protein binding rate and low urinary excretion rate. We encountered a case of small cell lung cancer on hemodialysis who was treated with amrubicin. We assayed the plasma concentrations of amrubicin and amrubicinol (its active metabolite) and analyzed the pharmacokinetic parameters of the drug in this hemodialysis patient. The results revealed that the pharmacokinetic parameters of the drug in this patient undergoing hemodialysis were similar to those in patients not on hemodialysis. Our results suggest that amrubicin and amrubicinol are cleared by hemodialysis, and that dose adjustment of amrubicin might not be required in hemodialysis patients.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Purpose: To investigate by immunohistochemical observation the effects of amniotic membrane (AM) patching on myofibroblastic differentiation and matrix metalloproteinase (MMP) expression in the corneal stroma after an alkali burn in vivo.
Methods: A corneal alkali burn was made by placing a circular piece of filter paper containing 1N NaOH on the central cornea of rabbits. Burning was done unilaterally in each rabbit. Immediately after the wounding, in the AM group, AM was sutured onto the cornea and removed on day 1. Rabbits with no AM patching were controls. On day 14, corneas were excised and immunohistochemical observation was carried out using antibodies against alpha-smooth muscle actin (alpha-SMA), vimentin, MMP-1, MMP-2, MMP-9, and membrane-type1 (MT1)-MMP. Observation after Masson trichrome staining was also performed.
Results: In the AM group, alpha-SMA positive cells were noticeably fewer, and MMP-2, MMP-9, and MT1-MMP expression was clearly inhibited. Also, collagen fibers were more regularly arranged than in control eyes. The more proximate the cells were to the epithelial side, the fewer alpha-SMA-positive cells were observed in the AM group.
Conclusions: AM patching suppressed myofibroblastic differentiation and MMP expression in the stroma after an alkali burn. An inhibition gradient suggests that AM may release unknown soluble factors possessing some antiscarring capability.

DOI： 10.1007/s10384-006-0389-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Purpose: We studied the contribution made by circulating bone marrow (BM)-derived cells to the newborn and mature retinas of BM-transplanted mice. Methods: Newborn and adult C57BL/6J mice were administered a lethal dose of total-body irradiation, after which pathologic changes to the retinas were periodically assessed. In addition, mice received BM cells from 8-week-old green fluorescent protein (GFP) transgenic mice, and the subsequent differentiation of GFP+ cells was studied. Results: Within 5 hr after irradiation of newborn mice, retinal cells began to die due to apoptosis. By contrast, irradiation of adult mice elicited no histologic changes in the retina. BM cells generally did not differentiate in adult mice, but numerous GFP+ BM cells were integrated into the retinal tissue of newborn mice, where they expressed various cell type-specific markers. Finally, examination of whole retina mounts showed that GFP+ cells also contributed to retinal vascularization. Conclusions: Our findings underscore the importance of careful evaluation of the biological effects of irradiation in models making use of BM transplantation.

DOI： 10.1080/02713680701389333

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To determine the usefulness of the Pentacam corneal volume assay in the assessment of corneal endothelial damage caused by phacoemulsification and aspiration (PEA).
DESIGN: Prospective, comparative, observational case series.
METHODS: PEA was performed in 85 eyes by three surgeons under different conditions. Central cell density (CD) was determined using a specular microscope before and one month after surgery. Pentacam was used before and one day, one week, and one month after surgery to determine 3- and 10,mm corneal volumes.
RESULTS: For all surgeons, no significant differences in the 3-mm corneal volumes were noted between the before and one-month after surgery values. However, 10-mm corneal volumes at one month were significantly higher than preoperative levels. No correlation was noted between the increasing rate of the 10-mm corneal volume and decreasing rate of CD.
CONCLUSIONS: Pentacam-determined corneal volumes may be useful in assessing PEA-caused corneal damage.

DOI： 10.1016/j.ajo.2006.04.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by mutations in the gene encoding the lysosomal enzyme arylsulfatase A (ASA). In MLD, accumulation of the substrate, sulfated glycoprotein, in the central and peripheral nervous systems results in progressive motor and mental deterioration. Neural progenitor cells are thought to be useful for cell replacement therapy and for cell-mediated gene therapy in neurodegenerative diseases. in the present study, we examined the feasibility of ex vivo gene therapy for MLD using neural progenitor cells. Neural progenitor cells (neurospheres) were prepared from the striaturn of E14 embryo MLD knockout mice or GFP transgenic mice and were transduced with the VSV pseudotyped HIV vector carrying the ASA gene (HIV-ASA). For in vivo study, neurospheres from GFP mice were transduced with HIV-ASA and inoculated into the brain parenchyma of adult MLD mice. HIV vector-transduced progenitor cells retained the potential for differentiation into neurons, astrocytes and oligodendrocytes in vitro. Expression of ASA in neurospheres transduced with HIV-ASA was confirmed by spectrophoto metric enzyme assay and Western blotting. In vivo, GFP-positive cells were detectable 1 month after injection. These cells included GFAP- and MAP2-positive cells. Immunohistochemistry using anti-ASA antibody demonstrated localization of ASA in both GFP-positive and -negative cells. Partial clearance of accumulated sulfatide was confirmed in vivo in MLD knockout mice. The present findings suggest that ASA enzyme is released from migrated neurospheres and is able to digest sulfatide in surrounding cells. Our results suggest the potential of genetically engineered neural progenitor cells (neurospheres) for ex vivo therapy in MLD. (c) 2006 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2006.03.116

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To evaluate the incidence of dry eye in rheumatoid arthritis (RA) patients with or without Sjogren syndrome (SS), and to investigate the correlation between dry eye and RA activity.
DESIGN: Prospective case-control study.
METHODS: In 72 RA patients, the severity of dry eye was assessed by the Schirmer test, tear break,up time, rose bengal staining, and fluorescein staining. The RA activity was evaluated by the Lansbury index (LI), which is based on the duration of morning stiffness, erythrocyte sedimentation rate (ESR), grip strength, and joint score.
RESULTS: Ten percent of patients met the Japanese criteria for SS. No difference in dry eye tests or LI was observed between SS patients and non-SS patients. Even in the non,SS group, 90% of patients were diagnosed with probable dry eye. In SS patients, positive correlations were observed between LI and Schirmer test (P = .048), ESR and Schirmer test (P = .035), ESR and rose bengal staining (P = .001), and grip strength and rose bengal staining (P = .047). No such correlations were observed in the non-SS patients.
CONCLUSIONS: Dry eye is common in RA patients, including those without SS. We found that there was a correlation between LI and Schirmer test in RA patients with SS, but no correlation when the entire group was analyzed. Dry eye always should be taken into consideration regardless of the RA activity, because the severity of dry eye is independent of RA activity.

DOI： 10.1016/j.ajo.2005.05.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER HEIDELBERG  

We examined the feasibility of the human immunodeficiency virus (HIV) vector-mediated local expression of angiostatin in the treatment of murine collagen-induced arthritis in a mouse model generated by immunization with bovine type II collagen and Freund&apos;s complete adjuvant. The HIV vector containing the murine angiostatin expression unit (HIV-angiostatin) was injected into right knee joints after arthritis development; the HIV vector containing the enhanced green fluorescein protein (EGFP) marker gene (HIV-EGFP) was injected into the left joints. Quantitative histological evaluation demonstrated that synovial cell hyperplasia and pannus formation were significantly reduced in the right knee joints as determined by this protocol. Suppression of radiographical changes in the ipsilateral paws was also observed. These results indicate that the HIV vector-mediated expression of angiostatin efficiently inhibits the progression of collagen-induced arthritis. Angiostatic gene therapy may provide a new approach to the effective treatment of rheumatoid arthritis.

DOI： 10.1007/s00296-004-0476-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

We examined the feasibility of using adeno-associated virus (AAV)-mediated systemic delivery of endostatin in gene therapy to treat. metastasis of pancreatic cancer. We established an animal model of orthotopic metastatic pancreatic cancer in which the pancreatic cancer cell line PGHAM-1 was inoculated into the pancreas of Syrian golden hamsters. Transplanted cells proliferated rapidly and metastasized to the liver. An AAV vector expressing endostatin (5 x 10(10) particles) was injected intramuscularly into the left quadriceps or intravenously into the portal vein. These routes of vector administration were evaluated by comparing various parameters of tumor development. Intramuscular injection of the vector modestly increased the serum endostatin level. The numbers of metastases and the incidence of hemorrhagic ascites were decreased in the treated animals. In contrast, the serum concentration of endostatin was significantly increased after intraportal injection of the vector. The antitumor effects on all parameters (including the size and microvessel density of primary pancreatic tumors, the sizes and number of liver metastases, and the incidence of hemorrhagic ascites) were significant. These results suggest that systemic delivery of endostatin represents a potentially effective treatment for pancreatic cancer and liver metastases. The route of vector administration influences the efficacy of AAV-mediated endostatin expression. Intraportal injection of the AAV vector appears to tie more effective as an antiangiogenic gene therapy for pancreatic cancer.

DOI： 10.1158/0008-5472.CAN-03-1296

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Purpose: To assess the validity of anterior chamber irrigation with an ozonated solution as prophylaxis against endophthalmitis.
Setting: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan.
Methods: Viability of human corneal endothelium in culture was assessed by the WST-8 assay, lactate dehydrogenase (LDH) release assay, and trypan blue exclusion assay after exposure to a 4 to 40 parts per million (ppm) solution for 10 to 60 seconds. The in vivo effect was observed 1 week after irrigation of a 4 ppm solution in the rabbit anterior chamber by trypan blue exclusion assay. Bactericidal efficacy of the anterior chamber irrigation with the 4 ppm solution was examined by bacterial colony count of the aqueous humor following methicillin-resistant Staphylococcus aureus (MRSA) contaminated intraocular lens implantation in the porcine eye.
Results: The WST-8 assay revealed no significant reduction of viability with 10-second exposure to a 4 ppm solution. Lactate dehydrogenase release and trypan blue exclusion assays similarly demonstrated little damage after 60-second exposure to a 4 ppm solution. In the rabbit cornea 1 week after treatment, damage caused by 30-second exposure to a 4 ppm solution was not significant. The MRSA colony count documented almost complete bactericidal action with 5-second exposure to the 4 ppm solution when no ophthalmic viscosurgical device existed in the anterior chamber.
Conclusion: Limited damage to the corneal endothelium after 10-second exposure and potent bactericidal action with 5-second exposure suggests the validity of anterior chamber irrigation with a 4 ppm ozonated solution as prophylaxis against endophthalmitis. (C) 2004 ASCRS and ESCRS.

DOI： 10.1016/j.jcrs.2004.02.023

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Ischemic retinal diseases, such as diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration, are a major cause of blindness worldwide. Angiostatin is an internal peptide fragment of plasminogen that inhibits endothelial proliferation in vitro and tumor growth in vivo. We now demonstrate that HIV vector encoding angiostatin (HIV-angiostatin) can inhibit retinal neovascularization in a mouse model of proliferative retinopathy. Intravitreal injections of HIV-angiostatin led to stable expression of the angiostatin gene in retinal tissue. Retinal neovascularization was histologically quantitated by a masked protocol. Retinal neovascularization in the eye injected with HIV-angiostatin was reduced in 90% (9/10; P=0.025) of animals, compared with the eye injected with phosphate-buffered saline. Reduction of histologically evident neovascular nuclei per 6-mum section averaged 68%, with maximal inhibitory effects of 87%. Neovascularization was not reduced in the eyes injected with HIV vector encoding enhanced green fluorescent protein. This is the first report that HIV-angiostatin can reduce neovascular cell nuclei in a murine proliferative retinopathy model. These data suggest that the anti-angiogenic activity of angiostatin has therapeutic potential for the treatment of retinal neovascularization.

DOI： 10.1038/sj.gt.3301878

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記述言語：英語  

DOI： 10.3109/s101650200035

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SWETS ZEITLINGER PUBLISHERS  

Purpose. Efficient in vivo gene transfer into corneal epithelial cells and stable transgene expression would have broad clinical applications. We therefore assessed the capacity of adenoviral, adeno-associated viral (AAV) and lentiviral vectors encoding enhanced green fluorescent protein (EGFP) to transduce rat corneal epithelial progenitor cells.
Methods. Superficial cells of the corneal epithelium were shaved, after which 20 m l of the respective vector solutions were inoculated onto the basal cell layer of the limbal epithelium for 30 min.
Results. Three days after transduction, fluorescence microscopic examination revealed the presence of EGFP cells in all corneas, irrespective of the vector used; however, EGFP cells were undetectable in corneas transduced with adenoviral and AAV vectors after 2 and 4 weeks, respectively. By contrast, EGFP cells were still detected among cells transduced with lentiviral vector 6 weeks after transduction. DAPI (4, 6-diamidino-2-phenylindole) staining confirmed that it was the basal layer cells that continued to express EGFP throughout the 6-week period.
Conclusions. The use of a lentiviral vector for in vivo transfer of foreign genes into corneal epithelial stem and transient amplifying cells may represent a new and effective approach to the treatment of corneal disease, as well as to the study of the biology of these stem cells.

DOI： 10.1076/ceyr.24.1.46.5436

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KLUWER ACADEMIC/PLENUM PUBL  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/08916939508995297

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：日本語   出版者・発行元：(株)メディカルドゥ  

網膜色素変性を含む遺伝性網膜変性疾患は,眼科領域の難治性疾患である。現在有効な治療法がなく,遺伝子治療やiPS細胞による網膜再生療法などに期待が集まっている。近年,遺伝性網膜変性疾患に対して,欧米から遺伝子治療の臨床応用の結果が数多く報告されてきた。2017年以降,その安全性と治療効果によりLeber先天盲に対する遺伝子治療薬が認可された。本稿では,使用されるアデノ随伴ウイルス(AAV)ベクターによる治療効果なども含め,網膜色素変性への遺伝子治療の現状と今後の発展予想について紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：アニムス編集委員会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：日本語   出版者・発行元：群馬県小児保健会  

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記述言語：日本語   出版者・発行元：(株)北隆館  

近年、白内障手術は年間150万件と全国で多数の症例がなされ、超音波乳化吸引術の発展に伴い、安全性の高い手術となってきている。しかしながら、角膜内皮障害による水疱性角膜症は、治療法が角膜移植しかなく大きな課題である。我々はさらなる手術の安全性を求めて、水素ガスを用いた新しい超音波乳化吸引術を考案したので紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J06107&link_issn=&doc_id=20210721270010&doc_link_id=%2Fao7gagre%2F2021%2F001004%2F012%2F0460-0466%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao7gagre%2F2021%2F001004%2F012%2F0460-0466%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：眼科臨床紀要会  

目的:東京都ロービジョンケアネットワークは運用開始から3年目を迎えたので今までの実績を報告する。さらに今回リーフレット利用者の意見を反映した改良と一部の改変を行った。方法:3年間の運用を調査した。リーフレットを手にした人から東京都眼科医会に届いた意見の集約後、リーフレットの使用法がわからないとの指摘に対して、視覚障害者の意見を参考に改良を検討した。代表窓口施設の変更についての対応が求められた。結果:3年間の運用実績は308件で、年々増加している。二次元コード「ユニボイス」をリーフレット上へ印刷した。手探りでユニボイスの位置がわかるようリーフレット右下に切り欠き加工を追加した。就労支援の代表窓口施設が日本視覚障害者職能開発センターに変更となった。結論:利用者の意見を反映しながら、リーフレットやネットワークを改良することで、東京都でのロービジョンケアへのアクセスの継続的改善が可能となった。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

緒言:左眼黄斑円孔に対して硝子体手術および眼内レンズ縫着術施行後、露出した縫着糸断端による強膜炎および強膜融解を発症した症例に対して強膜移植が有効であった1例を報告する。症例:80歳、女性。2010年、前医にて左黄斑円孔に対して硝子体手術および眼内レンズ縫着術を施行。2018年11月、左眼耳側の縫着糸断端の露出と周囲の強膜充血を認め抗菌薬点眼で加療するも、2019年2月、強膜融解、豚脂様角膜後面沈着物が認められた。抗菌点眼薬2剤、ステロイド点眼でいったん症状改善したが症状再燃し、強膜移植目的に日本医科大学付属病院眼科を紹介受診した。当科初診時、右眼視力(1.0)、左眼視力(0.4)、右眼眼圧14.5mmHg、左眼眼圧13.5mmHg。8月に融解強膜部位に保存強膜移植を施行した。術後、抗菌薬・ステロイド点眼、およびステロイド内服30mgから漸減投与にシクロスポリン100mg内服を併用、1年後シクロスポリン50mgのみでグラフトは生着良好で経過している。結論:眼内レンズ縫着後に発症した強膜融解に保存強膜移植は有効であった。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01784&link_issn=&doc_id=20220224170020&doc_link_id=%2Fah9atgke%2F2022%2F003902%2F021%2F0235b0238%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah9atgke%2F2022%2F003902%2F021%2F0235b0238%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

記述言語：日本語   出版者・発行元：眼科臨床紀要会  

緒言:癌関連網膜症cancer-related retinopathy(CAR)は急激に進行する視力低下と視野狭窄を特徴とする。今回CARが疑われ、癌の早期治療により進行抑制できた1例を報告する。症例:58歳男性。急な両眼夜盲を自覚したため前医受診し、視野障害を認めたため紹介となった。矯正視力は両眼1.2だが、視野検査で輪状暗点を認め、網膜電図は平坦化し、光干渉断層撮影では中心窩周囲のellipsoid zoneの消失を認めた。同時期に肺小細胞癌が見つかり、初診時の7日後より化学放射線療法が開始された。CARを疑い抗リカバリン抗体を測定したが陰性だった。初診時より6ヵ月で視力、視野の増悪はなかった。考按:網膜色素変性様の症状と肺小細胞癌の罹患からCARを疑ったが、抗網膜抗体は特定できなかった。本例では肺癌の発見が眼症状出現とほぼ同時期であり、早期に化学放射線療法が開始されたため、視機能障害は軽度で保たれたのではないかと考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CELL PRESS  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(株)杏林舎内「IOL&RS」編集事務局  

水素の医療への応用に向けた研究は様々な分野で行われている。筆者らは、眼科分野の虚血再灌流障害モデルであるラット一過性高眼圧緑内障モデルに対し、水素点眼の効用を検討した。また、白内障手術(超音波乳化吸引術)に関する研究では、水素を眼内灌流液に溶解し使用することで、超音波由来のラジカルを軽減し、角膜内皮細胞障害に対する保護効果を示すことを明らかにした。

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：日本緑内障学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本眼科手術学会  

近年、白内障手術は超音波乳化吸引術の発展に伴い、安全性の高い手術となってきているが、それでも角膜内皮障害による水疱性角膜症は大きな課題である。筆者らは、さらなる手術の安全性を求めて、水素ガスを用いた新しい超音波乳化吸引術を考案したので紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

白内障手術は手術機器の発展に伴い、安全性の高い手術となってきているが、それでも角膜内皮障害による水疱性角膜症は今もって大きな問題である。筆者らはさらなる手術の安全性を求めて、水素ガスを用いた新しい超音波乳化吸引術を考案したので紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：生命科学系学会合同年次大会運営事務局  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CELL PRESS  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

眼科分野で最も使用されているアデノ随伴ウイルス(AAV)ベクターを中心に、これまでの遺伝子治療研究の流れと現在の状況について述べた。20年前、遺伝子治療における眼科分野の研究者は非常に数少なかったが、網膜の標的組織が小さく少量のベクターで治療可能なこと、免疫の影響を受けにくい可能性があることやBBB(Blood-brain barrier)と呼ばれる血液-脳関門のような血液-網膜関門が存在するため、眼球内の投与による全身へのベクターの散布が非常に低いことから注目を集め、遺伝子治療分野で最も期待される分野へと成長した。今後、新しいテクニックとベクターの最適化の研究が臨床応用への鍵となるものと思われる。本稿では以下の項目で概説した。1)AAVベクターとその進化[AAV vector serotypes、Self-complementary(sc) AAV Vector、チロシン変異(tm)-scAAVベクター]。2)網膜への遺伝子導入方法。3)霊長類における硝子体投与。

DOI： 10.1272/manms.13.88

CiNii Books

J-GLOBAL

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記述言語：英語   出版者・発行元：(公財)日本眼科学会  

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：MARY ANN LIEBERT, INC  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本緑内障学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：NATURE PUBLISHING GROUP  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

DOI： 10.15036/arerugi.63.605_3

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

目的:開瞼を維持した状態で涙液浸透圧がどのように変化するのかを検討した。対象および方法:Schirmer試験値が正常な健常ボランティア41名(男:女=30:11)、平均年齢34.6±9.9歳を対象に、問診、涙液層破壊時間(BUT)、フルオレセイン染色スコア、リサミングリーン染色スコア、および涙液浸透圧測定を施行した。ついで限界自発開瞼維持時間(自発的に開瞼が維持できる限界時間)を3回測定しその平均限界時間における涙液浸透圧を測定した。結果:41名中、15名がBUT短縮型ドライアイ疑いであった。涙液浸透圧(mOsm/l)は正常群において平時303.68±15.7、開瞼維持後303.26±14.2、BUT短縮群においてそれぞれ301.2±20.5、308.7±15.3と、両群間および開瞼維持前後の有意差を認めなかった。結論:開瞼維持による涙液浸透圧の変化は、正常者のみならずBUT短縮例でも認めなかったことから、蒸発する涙液量に比べメニスカスにおける涙液量全体が十分に多いため、涙液浸透圧変化は起こりにくいと考えられた。(著者抄録)

CiNii Books

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

Web of Science

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：NATURE PUBLISHING GROUP  

Web of Science

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

目的:両眼の汎ぶどう膜炎で発症し,その後強皮症と診断された症例の報告。症例:55歳女性が10日前からの左眼充血と疼痛で受診した。所見:矯正視力は右1.0,左0.5で,左眼に虹彩毛様体炎の所見と乳頭発赤があった。蛍光眼底造影で網膜血管の透過性亢進,光干渉断層計(OCT)で漿液性網膜剥離があった。2ヵ月後に右眼に同様の病変が生じた。次第に手指皮膚の硬化とRaynaud現象が出現し,強皮症と診断された。副腎皮質ステロイドの局所投与で眼所見は10ヵ月後に寛解した。結論:膠原病としての全身症状が顕在化する前に,これと原因的に関連する汎ぶどう膜炎が発症することを本症例は示している。(著者抄録)

DOI： 10.11477/mf.1410104090

CiNii Books

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

DOI： 10.15036/arerugi.60.485_3

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：NATURE PUBLISHING GROUP  

Web of Science

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：眼科臨床医報会  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

超音波検査において、下肢動脈壁拍動下の動態をカラー断層像として観察可能なtissue strain imaging(TSI)を応用開発した。動脈硬化のリスクを有する例の下肢動脈壁では、TSIにより有意にstrain値の低下などが観察された。末梢動脈における本法は、国内外初の試みであり、デバイスの改良により将来、脳・血管系の硬化症病変の病態進行や治療指針の評価として応用可能と思われた。血管超音波検査法のうち、血管の「量」のみならず「質」を診断するTSIは、動脈硬化の研究分野で、今後、強力な画像診断法となり得、動脈硬化の早期診断、治療指針に一役を担うものと期待できる。

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

Web of Science

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

CiNii Books

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-LISS  

Web of Science

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本眼科紀要会  

「眼精疲労」と診断され,シアノコバラミン点眼を処方されている症例のドライアイ頻度を調べた.患者44名(男15名,女29名,平均年齢63±9歳)を対象とした.ドライアイ診断基準により,シルマーI法,綿糸法,tear film break up time(BUT),フルオレセイン染色,及びローズベンガル染色を行った.更に鼻刺激シルマーテストを行い,診断基準との関連を考察した.ドライアイと診断された患者が38名と多く,その内訳は疑い例26名,確定例12名であった.疑い例の多くは,涙液層の質的及び量的異常によるものであった.鼻刺激シルマーテスト異常者の頻度は,正常者,疑い例,確定例において,有意差を認めなかった.以上より,日常臨床において「眼精疲労」を訴える患者に対しては,染色のみならず涙液検査を行い,ドライアイを見逃さないことの重要性が再確認された

CiNii Books

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記述言語：日本語  

目的:開瞼を維持した状態で涙液浸透圧がどのように変化するのかを検討した。対象および方法:Schirmer試験値が正常な健常ボランティア41名(男:女=30:11)、平均年齢34.6±9.9歳を対象に、問診、涙液層破壊時間(BUT)、フルオレセイン染色スコア、リサミングリーン染色スコア、および涙液浸透圧測定を施行した。ついで限界自発開瞼維持時間(自発的に開瞼が維持できる限界時間)を3回測定しその平均限界時間における涙液浸透圧を測定した。結果:41名中、15名がBUT短縮型ドライアイ疑いであった。涙液浸透圧(mOsm/l)は正常群において平時303.68±15.7、開瞼維持後303.26±14.2、BUT短縮群においてそれぞれ301.2±20.5、308.7±15.3と、両群間および開瞼維持前後の有意差を認めなかった。結論:開瞼維持による涙液浸透圧の変化は、正常者のみならずBUT短縮例でも認めなかったことから、蒸発する涙液量に比べメニスカスにおける涙液量全体が十分に多いため、涙液浸透圧変化は起こりにくいと考えられた。(著者抄録)

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記述言語：日本語  

開催地：京都  

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記述言語：日本語  

開催地：名古屋  

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開催地：Seoul, Korea  

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開催地：東京  

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記述言語：日本語  

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開催地：福岡  

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記述言語：日本語  

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開催地：Atlanta,USA  

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開催地：東京  

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記述言語：日本語  

開催地：東京  

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開催地：名古屋  

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記述言語：日本語  

開催地：名古屋  

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開催地：山梨  

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記述言語：日本語  

開催地：東京  

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開催地：岡山  

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開催地：New Orieans, USA  

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記述言語：日本語  

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開催地：Salt lake city, USA  

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開催地：仙台  

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記述言語：日本語  

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開催地：San Francisco, USA  

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開催地：和歌山  

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開催地：Valencia,Spain  

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開催地：大阪  

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開催地：東京  

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開催地：東京  

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開催地：岡山  

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開催地：東京  

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開催地：Florence, Italy  

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開催地：長野  

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開催地：東京  

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開催地：福岡  

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開催地：New Orleans.、USA  

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開催地：福岡  

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記述言語：日本語  

開催地：東京  

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記述言語：日本語  

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開催地：広島  

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記述言語：日本語  

開催地：宮城  

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記述言語：日本語  

開催地：宮城  

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開催地：岡山  

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開催地：Los angels、USA  

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開催地：Baltimore. USA  

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開催地：Washington DC, USA  

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記述言語：英語  

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記述言語：日本語  

眼科分野で最も使用されているアデノ随伴ウイルス(AAV)ベクターを中心に、これまでの遺伝子治療研究の流れと現在の状況について述べた。20年前、遺伝子治療における眼科分野の研究者は非常に数少なかったが、網膜の標的組織が小さく少量のベクターで治療可能なこと、免疫の影響を受けにくい可能性があることやBBB(Blood-brain barrier)と呼ばれる血液-脳関門のような血液-網膜関門が存在するため、眼球内の投与による全身へのベクターの散布が非常に低いことから注目を集め、遺伝子治療分野で最も期待される分野へと成長した。今後、新しいテクニックとベクターの最適化の研究が臨床応用への鍵となるものと思われる。本稿では以下の項目で概説した。1)AAVベクターとその進化[AAV vector serotypes、Self-complementary(sc) AAV Vector、チロシン変異(tm)-scAAVベクター]。2)網膜への遺伝子導入方法。3)霊長類における硝子体投与。

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開催地：長野  

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開催地：長野  

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開催地：長野  

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開催地：London, United kingdom  

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記述言語：日本語  

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開催地：FL, USA  

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開催地：FL, USA  

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記述言語：日本語  

開催地：福岡  

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記述言語：日本語  

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開催地：福岡  

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記述言語：日本語  

開催地：名古屋  

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開催地：仙台  

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開催地：FL, USA  

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開催地：仙台  

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開催地：HI,USA  

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開催地：HI,USA  

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記述言語：日本語  

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記述言語：日本語  

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開催地：Antibes, Alpes-Maritomes, France  

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記述言語：日本語  

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開催地：Antibes, Alpes-Maritomes, France  

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開催地：FL,USA  

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開催地：東京  

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記述言語：日本語  

開催地：大阪  

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開催地：PA,USA  

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記述言語：日本語  

「眼精疲労」と診断され,シアノコバラミン点眼を処方されている症例のドライアイ頻度を調べた.患者44名(男15名,女29名,平均年齢63±9歳)を対象とした.ドライアイ診断基準により,シルマーI法,綿糸法,tear film break up time(BUT),フルオレセイン染色,及びローズベンガル染色を行った.更に鼻刺激シルマーテストを行い,診断基準との関連を考察した.ドライアイと診断された患者が38名と多く,その内訳は疑い例26名,確定例12名であった.疑い例の多くは,涙液層の質的及び量的異常によるものであった.鼻刺激シルマーテスト異常者の頻度は,正常者,疑い例,確定例において,有意差を認めなかった.以上より,日常臨床において「眼精疲労」を訴える患者に対しては,染色のみならず涙液検査を行い,ドライアイを見逃さないことの重要性が再確認された

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開催地：東京  

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開催地：HI, USA  

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開催地：東京  

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開催地：東京  

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開催地：東京  

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開催地：山口  

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開催地：HI,USA  

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開催地：千葉  

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開催地：大阪  

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開催地：愛媛  

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記述言語：日本語  

開催地：仙台  

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開催地：FL, USA  

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開催地：福岡  

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記述言語：日本語  

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記述言語：日本語  

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開催地：仙台  

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開催地：FL,USA  

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記述言語：日本語  

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開催地：Geneva, Switzerland  

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開催地：東京  

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開催地：MA , USA  

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開催地：沖縄  

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開催地：沖縄  

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記述言語：日本語  

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開催地：大阪  

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開催地：福岡  

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