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1.
Invest Ophthalmol Vis Sci ; 60(12): 3696-3707, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31487370

RESUMO

Purpose: We assess if α retinal ganglion cells (αRGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma. Methods: Two microliters of N-methyl-D-aspartate (NMDA; 1 mM) or PBS were injected intraocularly 7 days before sacrifice. Immunohistochemical analyses of the retina were performed using antibodies against RNA-binding protein with multiple splicing (RBPMS), osteopontin, and melanopsin. Immunohistochemical analyses also were performed in adult mice with glutamate/aspartate transporter (GLAST) deletion (GLAST knockout [KO] mice), a mouse model of normal tension glaucoma. Results: NMDA-induced loss of RBPMS-positive total RGCs was 58.4% ± 0.4% compared to PBS-treated controls, whereas the loss of osteopontin-positive αRGCs was 5.0% ± 0.6% and that of melanopsin-positive ipRGCs was 7.6% ± 1.6%. In GLAST KO mice, the loss of total RGCs was 48.4% ± 0.9% compared to wild-type mice, whereas the loss of αRGCs and ipRGCs was 3.9% ± 0.4% and 9.3% ± 0.5%, respectively. The distribution of survived total RGCs, αRGCs, and ipRGCs was similar regardless of the location of the retina. Conclusions: These results suggest that αRGC and ipRGC are highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.

2.
Ophthalmology ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31257036

RESUMO

PURPOSE: To present phenotypic features of 22 patients with S-antigen (SAG) mutations. DESIGN: Retrospective cohort study. PARTICIPANTS: Twenty-one Japanese patients from 16 families with a homozygous c.924delA mutation and 1 patient with a homozygous c.636delT mutation in the SAG gene. METHODS: Clinical records on symptoms; best-corrected visual acuity; and Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), OCT, and electroretinography results were reviewed. MAIN OUTCOME MEASURES: Best-corrected visual acuity, Goldmann perimetry results, imaging findings, and electroretinography results. RESULTS: Ten patients had Oguchi disease and 12 had retinitis pigmentosa (RP) with mean follow-up periods of 13.8 and 10.2 years, respectively. Retinitis pigmentosa patients were older (mean age, 56.0 years) than those with Oguchi disease (mean age, 22.1 years; P < 0.001) at the initial visit. Night blindness noted in childhood was the most common initial symptom for both Oguchi disease (80.0%) and RP (91.7%) patients. Best-corrected visual acuity in the logarithm of the minimum angle of resolution (logMAR) was well preserved in Oguchi disease patients (mean, 0.02 logMAR in both eyes) but reduced in most RP patients (mean, 1.32 logMAR [right eye] and 1.35 logMAR [left eye]). Similarly, the visual field in the retinal area was preserved in Oguchi disease patients (mean, 677 mm2 right eye and 667 mm2 left eye) and reduced in RP patients (mean, 369 mm2 right eye and 294 mm2 left eye). Fundus images revealed a characteristic golden sheen with no retinal degeneration in Oguchi disease patients, excluding 2 with macular degeneration detected by FAF, OCT, or both and 1 with mild retinal degeneration confirmed by OCT and fluorescein angiography. Pigmentary retinal degeneration most evident posteriorly was observed in RP patients, accompanied by a characteristic golden sheen in 12 of 14 patients undergoing ultra-widefield fundus imaging. OCT showed disrupted macular structure, and FAF revealed variable hypofluorescence. Electroretinography identified absent rod responses in both diseases, along with relative preservation of cone responses in Oguchi disease patients. Three patients showed progressive loss of the golden sheen based on fundus images, including 1 who demonstrated RP 26 years after the initial diagnosis of Oguchi disease. CONCLUSIONS: Retinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP.

3.
Nat Commun ; 10(1): 2884, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253780

RESUMO

Hereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e., a 3.5-fold enrichment; p-value = 9.2 × 10-5). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation in trans with the Alu insertion, but might also associate with disease in combination with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance.


Assuntos
Ciliopatias/genética , Proteínas do Olho/genética , Predisposição Genética para Doença , Doenças Retinianas/genética , Elementos Alu/genética , Grupo com Ancestrais do Continente Asiático/genética , Genômica , Humanos , Japão , Mutação , Linhagem
4.
Transpl Infect Dis ; 21(4): e13123, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165536

RESUMO

PURPOSE: This study investigated the donor characteristics of methicillin-resistant Staphylococcus aureus (MRSA) contamination in storage medium before transfer of corneas to preservation medium for corneal transplantation, in order to identify donor characteristic risk factors for MRSA contamination. METHODS: This retrospective, cross-sectional study was performed using Juntendo Eye Bank records for all corneal transplantation procedures. Storage medium (EP-II® ) cultures for right eyes were included for the period between July 2008 and December 2017. The following donor characteristics were collected: age, sex, cause of death, history of cataract surgery, death-to-enucleation interval, death-to-preservation interval, and endothelial cell density (ECD). Donor characteristics were compared between MRSA and non-MRSA contamination groups. Odds ratios (ORs) for donor-related risk factors for MRSA contamination were determined using logistic regression. RESULTS: In total, 370 storage medium samples were examined; 222 were positive for bacterial cultures (60.0%) and 36 were MRSA-positive (9.7%). Donor age was significantly higher in the MRSA contamination group than in the non-MRSA contamination group (86.1 ± 9.5 years vs 75.9 ± 15.9 years, P < 0.001). Univariate logistic regression analysis showed that MRSA contamination risk factors were older age (OR = 1.07; 95% confidence interval [95% CI]: 1.03-1.11) and decreased ECD (OR = 0.9993; 95% CI: 0.9986-0.9992). The fully adjusted OR for every year of age as a risk factor for MRSA contamination was 1.07 (95% CI: 1.03-1.11). CONCLUSIONS: Aging was a risk factor for MRSA contamination in storage medium. Careful pre-banking assessment of elderly donor corneas is needed to prevent intractable postoperative MRSA infection.

5.
BMJ Open ; 9(6): e028656, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31203249

RESUMO

OBJECTIVES: To investigate the impact of standardisation of the perioperative protocol based on the Joint Commission International (JCI) accreditation guidelines for operating time in cataract surgery. DESIGN: Retrospective observational study. SETTING: Single centre in Japan. PARTICIPANTS: Between March 2014 and June 2016, 3127 patients underwent cataract surgery under topical anaesthesia including 2581 and 546 patients before and after JCI accreditation, respectively. PRIMARY AND SECONDARY OUTCOMES: We compared three time periods, comprising the preprocedure/surgery time (pre-PT), PT and post-PT, and total PT (TPT) of cataract surgery between patients before and after JCI accreditation, by regression analysis adjusted for age, sex and cataract surgery-associated confounders. RESULTS: The main outcomes were pre-PT, PT, post-PT and TPT. Pre-PT (19.8±10.5 vs 13.9±8.5 min, p<0.001) and post-PT (3.5±4.6 vs 2.6±2.1 min, p<0.001) significantly decreased after JCI accreditation, while PT did not significantly change (16.8±6.7 vs 16.2±6.3 min, p=0.065). Consequently, TPT decreased on average by 7.3 min per person after JCI accreditation (40.1±13.4 vs 32.8±10.9 min, p<0.001). After adjusting for confounders, pre-PT (ß=-5.82 min, 95% CI -6.75 to -4.88), PT (ß=-0.76 min, 95% CI -1.34 to -1.71), post-PT (ß=-0.85 min, 95% CI -1.24 to -0.45) and TPT (ß=-7.43 min, 95% CI -8.61 to -6.24) were significantly shortened after JCI accreditation. CONCLUSION: Perioperative protocol standardisation, based on JCI accreditation, shortened TPT in cataract surgery under local anaesthesia.

6.
J Med Genet ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31213501

RESUMO

BACKGROUND: The genetic profile of retinitis pigmentosa (RP) in East Asian populations has not been well characterised. Therefore, we conducted a large-scale sequencing study to investigate the genes and variants causing RP in a Japanese population. METHODS: A total of 1209 Japanese patients diagnosed with typical RP were enrolled. We performed deep resequencing of 83 known causative genes of RP using next-generation sequencing. We defined pathogenic variants as those that were putatively deleterious or registered as pathogenic in the Human Gene Mutation Database or ClinVar database and had a minor allele frequency in any ethnic population of ≤0.5% for recessive genes or ≤0.01% for dominant genes as determined using population-based databases. RESULTS: We successfully sequenced 1204 patients with RP and determined 200 pathogenic variants in 38 genes as the cause of RP in 356 patients (29.6%). Variants in six genes (EYS, USH2A, RP1L1, RHO, RP1 and RPGR) caused RP in 65.4% (233/356) of those patients. Among autosomal recessive genes, two known founder variants in EYS [p.(Ser1653fs) and p.(Tyr2935*)] and four East Asian-specific variants [p.(Gly2752Arg) in USH2A, p.(Arg658*) in RP1L1, p.(Gly2186Glu) in EYS and p.(Ile535Asn) in PDE6B] and p.(Cys934Trp) in USH2A were found in ≥10 patients. Among autosomal dominant genes, four pathogenic variants [p.(Pro347Leu) in RHO, p.(Arg872fs) in RP1, p.(Arg41Trp) in CRX and p.(Gly381fs) in PRPF31] were found in ≥4 patients, while these variants were unreported or extremely rare in both East Asian and non-East Asian population-based databases. CONCLUSIONS: East Asian-specific variants in causative genes were the major causes of RP in the Japanese population.

7.
Chem Pharm Bull (Tokyo) ; 67(4): 327-332, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930436

RESUMO

Δ9-Fatty acid desaturase (Δ9-desaturase) is a rate-limiting enzyme of unsaturated fatty acid biosynthesis in animal cells and specifically introduces a cis-double bond at the Δ9-position of acyl-CoA. Since the chemical structure of fatty acids determines the physicochemical properties of cellular membrane and modulates a broad range of cellular functions, double bond introduction into a fatty acid by Δ9-desaturase should be specifically carried out. Reported crystal structures of stearoyl-CoA desaturase (SCD)1, one of the most studied Δ9-desaturases, have revealed the mechanism underlying the determination of substrate preference, as well as the position (Δ9) and conformation (cis) of double bond introduction. The crystal structures of SCD1 have also provided insights into the function of other Δ9-desaturases, including Drosophila homologs. Moreover, the amino-terminal sequences of Δ9-desaturases are shown to have unique roles in protein degradation. In this review, we introduce recent advances in the understanding of the function and regulation of Δ9-desaturase from the standpoint of protein structure.


Assuntos
Ácidos Graxos Dessaturases/química , Sequência de Aminoácidos , Animais , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/biossíntese , Humanos , Estrutura Terciária de Proteína , Alinhamento de Sequência , Estearoil-CoA Dessaturase/química , Estearoil-CoA Dessaturase/metabolismo , Especificidade por Substrato
8.
Curr Eye Res ; 44(8): 921-924, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30892956

RESUMO

Purpose: Venting slits are widely used as an effective method to avoid the high intraocular pressure (IOP) phase immediately after the implantation of non-valved glaucoma drainage devices. However, there have been no detailed reports comparing the types of needles used and the numbers of slits made. In this study we investigated the effects of different needle types and the number of venting slits. Methods: IOP was measured using a Keyence NR-600 transducer connected to the limbus of a pig eye with a 27G needle. A microsyringe pump was also connected to the corneal limbus using a 27 G needle to make a continuous perfusion system at the rate of 200 µl/hr. The silicone tube of a Baerveldt glaucoma drainage implant (BG101-350) was ligated near the plate and then implanted in the anterior chamber of the pig eye. The tube was covered with scleral tissue of another pig eye after 1 or 3 venting slits were created in the middle of the outer diameter using different types of needles (7-0 Vicryl®, 7-0 PDSⅡ®, 5-0 PDSⅡ®, 3-0 PDS Plus®). IOP measurement was started from 50 mmHg and then we monitored the chronological changes of IOP for 15 minutes. Results: The IOPs at 15 minutes after continuous perfusion with the venting slits made using 7-0 Vicryl needles were 29.0 ± 2.5 mmHg (1 slit) and 23.1 ± 8.3 mmHg (3 slits). The IOPs were 23.1 ± 3.1 mmHg and 23.5 ± 4.7 mmHg with 7-0 PDS needles (1 slit and 3 slits, respectively), 21.8 ± 2.2 mmHg and 20.8 ± 4.3 mmHg with 5-0 PDS needles (1 slit and 3 slits, respectively), and with 3-0 PDS needles they were 12.2 ± 3.0 mmHg for one slit and 13.2 ± 3.5 mmHg for 3 slits. Conclusions: Usage of a round (PDS) needles produces more predictable IOP than a spatulated (Vicryl) needle.

9.
Orthopedics ; 42(3): e339-e342, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30810756

RESUMO

Isolated tears of the brachialis muscle are rare and often take on the clinical appearance of other pathology, such as a distal biceps brachii tendon tear or an intramuscular tumor, thus making diagnosis especially difficult. The authors describe the case of a 31-year-old competitive male weight lifter who was found to have a full-thickness tear of the brachialis tendon at its distal ulnar attachment after performing a 40.8-kg biceps curl. The authors describe the differential diagnosis, radiographic findings, and methods used that led to the diagnosis and also provide a comprehensive review of the literature on brachialis muscle injuries. The patient decided to proceed with conservative management consisting of a period of rest and physical therapy. At 10 months after the injury, the patient went back to weightlifting and biceps curls. He had progressed to full strength and had returned to all weightlifting activities at final follow-up. Isolated full-thickness brachialis muscle ruptures can be treated successfully with conservative management, including rest and physical therapy. [Orthopedics. 2019; 42(3):e339-e342.].


Assuntos
Ruptura/terapia , Traumatismos dos Tendões/terapia , Extremidade Superior/lesões , Levantamento de Peso/lesões , Adulto , Atletas , Tratamento Conservador , Humanos , Masculino , Modalidades de Fisioterapia , Descanso , Volta ao Esporte
10.
Chem Res Toxicol ; 32(4): 638-644, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30735032

RESUMO

Benzyl isothiocyanate (BITC), a dietary isothiocyanate (ITC) derived from cruciferous vegetables, has anticancer properties. It is believed that the ITC moiety (-N═C═S) that reacts predominantly with thiol compounds plays a central role in triggering the activities resulting from these properties. Recent studies have demonstrated that ITCs also covalently modify amino moieties in a protein. In this study, we examined the chemical reaction between BITC and the aminophospholipid, phosphatidylethanolamine (PE), in the cell membrane or lipoprotein particle. To detect the BITC-modified PE, the bond between ethanolamine (EA) and phosphatidic acid in PE was cleaved using phospholipase D to form the BITC-EA adduct, which was then measured. BITC-EA was detected from the BITC-treated unilamellar liposome and low-density lipoprotein even with only a few micromoles of BITC treatment, suggesting that BITC might react with not only a thiol/amino group of a protein but also an amino moiety of an aminophospholipid. Moreover, after incorporating BITC-PE included in the liposomes into the cultured cells or after direct exposure of BITC to the cells, free BITC-EA was excreted and accumulated in the medium in a time-dependent manner. It indicates that an intracellular enzyme catalyzes the cleavage of BITC-PE to produce BITC-EA. Because the ITC-amine adduct is stable, the ITC-EA adduct could be a promising indicator of ITC exposure in vivo.

11.
Jpn J Ophthalmol ; 63(2): 215-220, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30796548

RESUMO

PURPOSE: To investigate the proteolytic effect of mast cell tryptase on eotaxin-1/CCL11, eotaxin-2/CCL24 and eotaxin-3/CCL26 produced by conjunctival fibroblasts. STUDY DESIGN: Experimental. METHODS: The production of eotaxin-1, -2 and -3 by conjunctival fibroblasts stimulated both with and without IL-4/IL-13 or/and TGF-ß1 was assessed by ELISA. The proteolytic activity of tryptase on eotaxins derived from conjunctival fibroblasts and recombinant eotaxins was also estimated by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). RESULTS: Conjunctival fibroblasts produced eotaxin-1 and -3, but not eotaxin-2. Stimulation with IL-4/IL-13 and TGF-ß1 synergistically increased eotaxin-1 and -3 production. Tryptase reduced the immunoreactivity of eotaxin-1 and -3 but not of eotaxin-2, due to the proteolysis of these eotaxins but not the inhibition of their m-RNA expression. CONCLUSION: Mast cell tryptase may exercise proteolytic activity on eotaxin-1 and -3 produced by conjunctival fibroblasts, resulting in partial suppression of the ability of eotaxin-1 and -3 to accumulate eosinophils in the conjunctiva. Eotaxin-2 in the tears may be a suitable biomarker of severity of allergic conjunctival disease.


Assuntos
Quimiocina CCL11/biossíntese , Quimiocina CCL24/biossíntese , Quimiocina CCL26/biossíntese , Túnica Conjuntiva/patologia , Conjuntivite Alérgica/metabolismo , Triptases/metabolismo , Células Cultivadas , Quimiocina CCL11/genética , Quimiocina CCL24/genética , Quimiocina CCL26/genética , Túnica Conjuntiva/metabolismo , Conjuntivite Alérgica/genética , Conjuntivite Alérgica/patologia , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Mastócitos/metabolismo , Mastócitos/patologia , Proteólise , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Jpn J Ophthalmol ; 63(1): 46-55, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30535821

RESUMO

PURPOSE: To report genetic mutational analysis and in vivo histology of Meesmann corneal dystrophy. STUDY DESIGN: Prospective, case control study. METHODS: Six patients from three independent families with clinically diagnosed Meesmann corneal dystrophy were enrolled in this study. Slit-lamp biomicroscopy with fluorescein vital staining, anterior segment optical coherence tomography (AS-OCT), and in vivo laser confocal microscopy (IVCM) were performed on selected patients. Mutational screening for the keratin genes KRT3 and KRT12 was performed in all six patients and selected unaffected family members. RESULTS: Slit-lamp biomicroscopy revealed numerous intraepithelial microcysts in all affected individuals. AS-OCT revealed hyperreflectivity and high corneal epithelial layer thickness (mean, 64.8µm) in all individuals tested (3/3). By using IVCM, multiple epithelial microcysts and hyperreflective materials (6/6), subepithelial nerve abnormalities (6/6), tiny punctate hyperreflective material (6/6), and needle-like hyperreflective materials (4/6) were observed in the corneal stromal layer. A heterozygous genetic mutation in the KRT12 gene (c.394 C>G, p.L132V) was identified in all six patients. No pathological mutation was observed in the KRT3 gene. CONCLUSION: We identified a heterozygous genetic mutation (c.394 C>G, p.L132V) in the KRT12 gene in six Japanese patients with inherited Meesmann corneal dystrophy. This is the first study to confirm this genetic mutation in Japanese Meesmann corneal dystrophy patients. This mutation has been independently reported in an American Meesmann corneal dystrophy patient, confirming its pathogenicity. AS-OCT and IVCM proved to be useful tools for observing corneal epithelial layer pathology in this dystrophy. Furthermore, IVCM reveals corneal stromal layer pathological changes not previously reported in this dystrophy.


Assuntos
Distrofia Corneana Epitelial Juvenil de Meesmann/genética , DNA/genética , Epitélio Anterior/patologia , Queratina-12/genética , Mutação , Adulto , Idoso , Estudos de Casos e Controles , Distrofia Corneana Epitelial Juvenil de Meesmann/metabolismo , Distrofia Corneana Epitelial Juvenil de Meesmann/patologia , Análise Mutacional de DNA , Éxons , Feminino , Heterozigoto , Humanos , Queratina-12/metabolismo , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Estudos Prospectivos , Tomografia de Coerência Óptica
14.
FASEB J ; : fj201801805R, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383446

RESUMO

Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (Th2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting Th2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of Th2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6-derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet-fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.-Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary omega-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.

16.
Cell Death Dis ; 9(9): 891, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30166529

RESUMO

Leber congenital amaurosis (LCA) is a severe, genetically heterogeneous dystrophy of the retina and mutations in the nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene is one of causal factors of LCA. NMNAT1 is a nuclear enzyme essential for nicotinamide adenine dinucleotide (NAD) biosynthesis pathways, but the mechanisms underlying the LCA pathology and whether NMNAT1 has a role in normal retinal development remain unclear. Thus, we examined the roles of Nmnat1 in retinal development via short hairpin (sh)-RNA-mediated downregulation. Retinal explants expressing sh-Nmnat1 showed large numbers of apoptotic retinal progenitor cells in the inner half of the neuroblastic layer. Decreased intracellular NAD content was observed and the addition of NAD to the culture medium attenuated sh-Nmnat1-induced apoptosis. Of the nuclear Sirtuin (Sirt) family, the expression of sh-Sirt1 and sh-Sirt6 resulted in a phenotype similar to that of sh-Nmnat1. Sirt proteins are histone deacetylases and the expression of sh-Nmnat1 increased the levels of acetylated histones H3 and H4 in the retina. Expression of sh-Nmnat1 resulted in significantly increased expression of Noxa and Fas, two pro-apoptotic genes. Acetylation of the genomic 5'-untranslated regions of Noxa and Fas loci was upregulated by sh-Nmnat1 expression. The co-expression of sh-Fas with sh-Nmnat1 reduced the number of apoptotic cells induced by sh-Nmnat1 expression alone. Taken together, our data suggested that the increased expression of Noxa and Fas explains, at least in part, the phenotype associated with sh-Nmnat1 in the retina. Taken together, these findings demonstrate the importance of the NAD biosynthesis pathway in normal development of the retina.

17.
Sci Rep ; 8(1): 13443, 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30194447

RESUMO

The prevalence of dry eye disease (DED) is increasing worldwide, and its diagnosis often needs dedicated reagents and machines. We investigated the usefulness of maximum blink interval (MBI) (the length of time that participants could keep their eyes open) in screening for DED. This cross-sectional study included 292 patients (194 with DED and 98 without DED) recruited between September 2016 and September 2017. We compared the MBI between patients with and without DED; examined correlations between MBI and other clinical features of DED, including subjective symptoms (Dry Eye-Related Quality-of-Life Score), tear film breakup time (TFBUT), cornea fluorescence score (CFS), and Schirmer test I value; and determined the optimal cutoff value of MBI to suspect DED using a receiver operating characteristic (ROC) analysis. The MBI was significantly shortened in DED group compared to the non-DED group (10.0 ± 9.1 vs. 24.3 ± 38.2 seconds, p < 0.001). TFBUT was strongly positively correlated with MBI (r = 0.464), whereas CFS was negatively correlated with MBI (r = -0.273). The area under the ROC curve was 0.677, and the optimal MBI cutoff value was 12.4 seconds, providing a sensitivity of 82.5% and specificity of 51.0% to suspect DED. In conclusion, MBI may be a simple, useful test for screening DED.

18.
Sci Rep ; 8(1): 12032, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30104680

RESUMO

To evaluate the association between vision-related quality of life (QoL), physical inactivity, and locomotor dysfunction in subjects with visual impairment.This cross-sectional study included 215 visually impaired subjects recruited from six ophthalmology departments in Japan. The physical inactivity and locomotor dysfunction associated with their visual impairment was investigated. The physical activity level was assessed using the short form of the International Physical Activity Questionnaire and classified as high, moderate, or low. Locomotor function was evaluated with the Geriatric Locomotive Function Scale. Vision-related QoL was evaluated using the 25-item National Eye Institute Visual Function Questionnaire. Background data, including for age, sex, best-corrected visual acuity for each eye, causative eye diseases, systemic comorbidities, and body mass index, were also collected.The average patient age was 69.6 (range, 20-93 years; standard deviation, 14.5 years) and 118 patients (54.9%) were men. Multivariate analysis showed that vision-related QoL and best-corrected visual acuity in the worse eye were significantly associated with physical inactivity and that vision-related QoL, female sex, age, and presence of systemic comorbidity were significantly associated with locomotor dysfunction. Vision-related quality of life is associated with physical inactivity and locomotor dysfunction.

19.
BMC Musculoskelet Disord ; 19(1): 296, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30115059

RESUMO

BACKGROUND: To use Magnetic Resonance Imaging (MRI) to characterize the severity, location, prevalence, and demographics of shoulder injuries in athletes at the Rio de Janeiro 2016 Summer Olympic Games. METHODS: This was a retrospective analysis of all routine shoulder MRIs obtained from the Olympic Village Polyclinic during the Rio 2016 Summer Olympics. Imaging was performed on 1.5 T and 3 T MRI, and interpretation was centrally performed by a board-certified musculoskeletal radiologist. Images were assessed for tendon, muscle, bone, bursal, joint capsule, labral, and chondral abnormality. RESULTS: A total of 11,274 athletes participated in the Games, of which 55 (5%) were referred for a routine shoulder MRI. Fifty-three (96%) had at least two abnormal findings. Seven (13%) had evidence of an acute or chronic anterior shoulder dislocation. Forty-nine (89%) had a rotator cuff partial tear and / or tendinosis. Subacromial / subdeltoid bursitis was present in 29 (40%). Thirty (55%) had a tear of the superior labrum anterior posterior (SLAP). CONCLUSION: Our study demonstrated a high prevalence of both acute and chronic shoulder injuries in the Olympic athletes receiving shoulder MRI. The high rates of bursal, rotator cuff, and labral pathology found in these patients implies that some degree of glenohumeral instability and impingement is occurring, likely due to fatigue and overuse of the dynamic stabilizers. Future studies are needed to better evaluate sport-specific trends of injury.

20.
AJR Am J Roentgenol ; 211(4): 880-886, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30063380

RESUMO

OBJECTIVE: The purpose of this article is to describe knee abnormalities and the occurrence of MRI-detected sports-related knee abnormalities by evaluating MRI examinations performed during the Rio de Janeiro Olympic Games held in August 2016. CONCLUSION: There were 11,274 athletes at the Rio 2016 Olympic Games, and 113 of them underwent at least one knee MRI in the Olympic Village. Cartilage abnormalities, followed by meniscal tears and ligament sprains, were the most frequent abnormalities.

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