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Degeneration of retinal ganglion cells in hypoxic responses:hypoxia-inducible factor inhibition,a new therapeutic insight

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Neural Regeneration Research 2022年第10期17卷 2230-2231页

作者： Deokho Lee Hiromitsu Kunimi Kazuno Negishi Toshihide Kurihara department of ophthalmology Keio University School of MedicineShinanomachiShinjuku-kuJapan

Degeneration of retinal ganglion cells(RGCs)is one of the hallmarks of common optic neuropathies(Weinreb et al.,2014).Glaucoma,the most common opt ic neuropathy,is characterized by degeneration of *** angle-closure glaucoma is a serious ocular condition caused by a rapid increase in intraocular pressure(IOP)(Emanuel et al.,2014).One of the experimental models which could mimic this condition is a murine model of retinal ischemia/reperfusion(I/R)injury(Johnson and Tomarev,2010).Retinal I/R injury can induce a rapid and transient elevation of IOP,which contributes to the degeneration of *** understanding the pathophysiology of the degeneration of RGCs was considerably attempted,the major contributing pathways have not been yet elucidated(Calkins and Horner,2012).

关键词： degeneration Acute insight

Pemafibrate,a potent selective peroxisome proliferator-activated receptorαmodulator,a promising novel treatment for ischemic retinopathy?

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Neural Regeneration Research 2023年第7期18卷 1495-1496页

作者： UCCAODeokhoLee Yohei Tomita Kazuno Negishi Toshihide Kurihara department of ophthalmology Keio University School of MedicineShinanomachiShinjuku-kuJapan

Ischemic retinopathy is a retinal disease caused by ischemic *** is a common pathologic mechanism in various retinal disorders and diseases such as age-related macular degeneration,diabetic retinopathy,glaucoma,or vascular occlusion(Osborne et al.,2004).Although various murine models have been developed to understand a series of metabolic mechanisms induced by retinal ischemia and further used to test promising therapeutics,effective treatment in ischemic retinopathy has not been clearly *** is associated with the notion that the contributing pathologic metabolic pathways might be enormously complex.

关键词： retinopathy degeneration

An antioxidant resveratrol significantly enhanced replication of hepatitis C virus

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World Journal of Gastroenterology 2010年第2期16卷 184-192页

作者： Mitsuyasu Nakamura Masanori Ikeda Ryota Hokari Nobuyuki Kato Toshifumi Hibi Soichiro Miura department of Internal medicine 2 National Defense Medical Collage3-2 NamikiTokorozawaSaitama 3598513Japan department of Internal medicine School of MedicineKeio University35 ShinanomachiShinjuku-kuTokyo 1608582 Japan department of Internal medicine School of MedicineKeio University35 ShinanomachiShinjuku-kuTokyo 1608582 Japan Masanori Ikeda department of Molecular Biology Okayama University Graduate School of Medicine and Dentistry2-5-1 Shikada-choOkayama 7008558Japan department of Internal medicine School of MedicineKeio University35 ShinanomachiShinjuku-kuTokyo 1608582 Japan Masanori Ikeda

AIM:To elucidate the effect of antioxidants,resveratrol (RVT)and astaxanthin(AXN),on hepatitis C virus(HCV) replication. METHODS:We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system *** is a strong antioxidant and a kind of polyphenol that inhibits replication of various *** is also a strong *** replication of HCV RNA was assessed by the luciferase reporter *** additive effect of antioxidants on antiviral effects of interferon(IFN)and ribavirin(RBV) was ***:This is the first report to investigate the effect of RVT and AXN on HCV *** contrast to other reported viruses,RVT significantly enhanced HCV RNA *** E also enhanced HCV RNA replication as reported previously,although AXN didnot affect *** and RBV significantly reduced HCV RNA replication,but these effects were dose-dependently hampered and attenuated by the addition of *** didnot affect antiviral effects of IFN or RBV. CONCLUSION:These results suggested that RVT is not suitable as an antioxidant therapy for chronic hepatitis C.

关键词： Replicon system Luciferase assay Ribavirin Interferon Polyphenol Astaxanthin

Association between tear film break up time and blink interval in visual display terminal users

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International Journal of ophthalmology(English edition) 2018年第10期11卷 1691-1697页

作者： Miki Uchino Motoko Kawashima Yuichi Uchino Kazuo Tsubota Norihiko Yokoi department of ophthalmology Keio University School of Medicine department of ophthalmology Kyoto Prefectural University School of Medicine

AIM：To investigate the association between tear film break up time（TBUT）and blinking interval in visual display terminal（VDT）***：Nine hundred and thirty VDT users underwent dry eye testing,and functional visual acuity（FVA）*** blinking interval during FVA was compared with *** with longer blinking interval than TBUT were considered as unstable tear *** regression analysis revealed the risk factors for unstable tear ***：Among 930 workers,858 subjects（92.3%）participated in this *** 80% of the subjects were categorized into the unstable tear *** tear group has significantly lower Schirmer values and TBUT（17.5±11.6 vs 21.1±11.5 mm,3.7±2.6 vs 5.7±2.7s,both P〈0.001）.There were no significant differences in epithelial staining or severity of *** regression showed that over 40y was a risk for being unstable tear group[odds ratio（OR）=1.53;95%confidence interval（CI）=1.06-2.20].Contact lens use was protective factor for being in the unstable tear group（OR=0.37;95%CI=0.26-0.53）.CONCLUSION：Subjects with shorter TBUT than blinking interval are prevalent among VDT *** over the age of 40 shows an increased risk for unstable tear film.

关键词： dry eye disease blink interval tear film break up time visual display terminal use

Germline BRCA2 mutation in a case of aggressive prostate cancer accompanied by spinal bulbar muscular atrophy

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Asian Journal of Andrology 2022年第1期24卷 116-118页

作者： Hiroshi Hongo Takeo Kosaka Hideyuki Hayashi Kohei Nakamura Hiroshi Nishihara Shuji Mikami Himisha Beltran Mototsugu Oya department of Urology Keio University School of Medicine35 ShinanomachiShinjuku-kuTokyo 160-8582Japan Genomics Unit Keio Cancer CenterKeio University School of Medicine35 ShinanomachiShinjuku-kuTokyo 160-8582Japan Division of Diagnostic Pathology Keio University Hospital35 ShinanomachiShinjuku-kuTokyo 160-8582Japan department of Medical Oncology Dana-Farber Cancer Institute450 Brookline AvenueBostonMA 02215USA

Dear Editor,Spinal and bulbar muscular atrophy(SBMA)or Kennedy’s disease is a rare X-linked,recessive,lower motor neuron disease caused by a CAG repeat expansion within the first exon of the androgen receptor(AR)*** of the CAG-triplet repeat impacts AR function;therefore,men with SBMA are thought to be at a very low risk of prostate *** previously reported a case of high-risk prostate cancer with SBMA(repeat length 46).

关键词： atrophy muscular cancer

Gender differences in adolescent dry eye disease:a health problem in girls

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International Journal of ophthalmology(English edition) 2018年第2期11卷 301-307页

作者： Masahiko Ayaki Motoko Kawashima Miki Uchino Kazuo Tsubota Kazuno Negishi department of ophthalmology Keio University School of MedicineTokyoJapan.

AIM： To evaluate the signs and symptoms of dry eye disease（DED） in adolescents. METHODS： This was a cross-sectional, case-control study and outpatients aged 10 to 19y were recruited from six eye clinics of various practices and locations in Japan, and 253 non-DED subjects and 70 DED patients were enrolled. Participants were examined for DED-related signs. Patients were also interviewed to ascertain the presence or absence of six common DED-related symptoms： dryness, irritation, pain, eye fatigue, blurring, and photophobia. Main outcome measures were differences in signs and symptoms of dry eye disease between boys and ***： Of the 323 adolescents recruited, 70（21.7%） were diagnosed with DED. Significant differences between the non-DED and DED groups were found for short tear break-up time（BUT; ≤5s; P=0.000） and superficial punctate keratopathy（SPK; staining score ≥3; P=0.000）. Late adolescent girls reported fewer symptoms than late adolescent boys, although their DED-related signs were worse compared to other groups. The prevalence and severity of DED were similar in the Tokyo area compared with suburban and local areas but myopic errors were worse. CONCLUSION： We find that adolescents reported symptoms of DED similar to those found in adults, and the majority have short BUT-type DED. The prevalence and severity of DED in late adolescent girls is comparable with adults. Adolescents with DED are underserved and we believe that DED is a hidden but potentially serious health problem for this age group.

关键词： dry eye disease adolescence gender difference

Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis

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International Journal of ophthalmology(English edition) 2015年第1期8卷 1-10页

作者： Junmi Tanaka Hideo Tanaka Nobuhisa Mizuki Eiichi Nomura Norihiko Ito Naoko Nomura Masayuki Yamane Tomonobu Hida Yoshio Goshima Hiroshi Hatano Hisashi Nakagawa department of ophthalmology and Visual Science Graduate School of MedicineYokohama City University department of ophthalmology Graduate School of MedicineUniversity of Tokyo department of Obstetrics and Gynecology School of MedicineKeio University department of Environmental Immuno-Dermatology Graduate School of MedicineYokohama City University Hatano Eye Clinic 438-1 FujisawaFujisawa Kanagawaken 251-0052Japan Tokushima Eye Clinic 1-2-14 Fujimi-choHigashimurayamaTokyo 189-0024Japan

AIM: To assess the efficacy of topical Semaphorin 3A(SEMA3A) in the treatment of allergic ***: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin(H&E) staining, immunofluor-escence and light microscope photographs. Early phase took the samples in 24 h after instillation and late phase took the samples between 4 to 14 d after the start of treatment. The study use of topical SEMA3A(10 U, 100 U,1000 U) eye drops and subconjunctival injection of SEMA3 A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.· RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3 A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3 A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3 A 1000 U-treated group were significantly lower than low-concentration of SEMA3 A treated groups and non-treated group. SEMA3 A treatment also suppressed T-cell proliferation in vitro and decreased serum total Ig E levels in EAC mice. Moreover, treatment of SEMA3 A suppressed Th2-related cytokines(IL-5, IL-13 and IL-4)and pro-inflammatory cytokines(IFN-γ, IL-17 and TNF-α)release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC ***: SEMA3 A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3 A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.

关键词： Semaphorin 3A experimental allergic conjunctivitis eosinophil infiltration serum total Ig E cytokines instillation subconjunctival administration

Method for Detecting NADPH-Cytochrome P450 Reductase in Liver Microsomal Fractions by Using Native Polyacrylamide Gel Electrophoresis and NADPH-Diaphorase Staining

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American Journal of Analytical Chemistry 2013年第6期4卷 301-305页

作者： Hirokazu Yokoyama Yukishige Okamura Toshifumi Hibi department of Internal medicine School of Medicine Keio University Shinanomachi Shinjukuku Tokyo Japan

By combining native polyacrylamide gel electrophoresis (PAGE) and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining, a simple method for detecting NADPH-cytochrome P450 reductase in tissue samples was established. When rat liver microsomal fractions were examined by this method, several bands with different mobility were visualized. Western blot analysis indicated that the band which appeared in the most anodal position among them represented NADPH-cytochrome P450 reductase. SDS-PAGE/Western blot analysis revealed that the molecular weight of the protein forming the band was around 80 kDa, which was identical to that of rat NADPH-cytochrome P450 reductase. The intensity level of NADPH-diaphorase staining assigned to this enzyme estimated by this method increased four times in microsomal fractions prepared from rat fed ethanol chronically compared to that from controls. When a dilution series of a rat liver microsomal fraction was examined by this method and SDS-PAGE/Western blot analysis, their staining intensities representing this enzyme were significantly correlated with each other. Using the naive PAGE/NADPH-diaphorase staining method, NADPH-cytochrome P450 reductase is detected in rat liver microsomes. This method is beneficial because compared with the conventional SDS-PAGE/Western blot analysis, the quantification of NADPH-cytochrome P450 reductase in tissue samples is allowed to be more easily done.

关键词： NADPH-Cytochrome p450 Reductase Native PAGE NADPH-Diaphorase Staining Chronic Ethanol Consumption

Cloning and expression of a mouse Polycomb group gene, Enx-2

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Cloning and expression of a mouse Polycomb group gene, Enx-2