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ABSTRACT: Abstract Purpose: To analyze the incidence of and risk factors for newly developed or increased macular hemorrhage after intravitreal ranibizumab injection (IVR) for neovascular age-related macular degeneration (AMD). Methods: We performed a retrospective chart review of 220 subjects (220 eyes) from 5 hospitals who received IVRs for neovascular AMD between 1 June 2009 and 30 June 2010. Systemic conditions (age, sex, presence of diabetes, hypertension, cardiovascular disease, smoking, and use of anticoagulation agent) and presence of hemorrhage at the initial exam were evaluated. The primary study outcome was the incidence of newly developed or increased macular hemorrhage during the 1-month postinjection period. Results: The incidence of newly developed or increased macular hemorrhage including vitreous hemorrhage was 8% (18/220). Presence of diabetes was found to be a risk factor for macular hemorrhage [odds ratios (OR): 2.16, 95% confidence intervals (CI): 1.07-8.13]. When subjects had both diabetes and hypertension, the risk of macular hemorrhage after injection increased 4.8-fold (OR: 4.84, CI: 1.24-18.85). Conclusion: The systemic condition of subjects was found to be an important risk factor for newly developed or increased macular hemorrhage after IVR for neovascular AMD. More consideration should be given to the statuses of diabetes and hypertension in subjects who receive ranibizumab for neovascular AMD.
Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 03/2013; · 1.46 Impact Factor
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ABSTRACT: Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER). In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L) in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.
BioMed research international. 01/2013; 2013:948181.
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Tae-Joon Cho,
Kyung-Eun Lee,
Sook-Kyung Lee, Su Jeong Song,
Kyung Jin Kim,
Daehyun Jeon,
Gene Lee,
Ha-Neui Kim,
Hye Ran Lee,
Hye-Hyun Eom,
Zang Hee Lee,
Ok-Hwa Kim,
Woong-Yang Park,
Sung Sup Park,
Shiro Ikegawa,
Won Joon Yoo,
In Ho Choi,
Jung-Wook Kim
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ABSTRACT: Osteogenesis imperfecta (OI) is a heterogenous group of genetic disorders of bone fragility. OI type V is an autosomal-dominant disease characterized by calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation; the causative mutation involved in this disease has not been discovered yet. Using linkage analysis in a four-generation family and whole-exome sequencing, we identified a heterozygous mutation of c.-14C>T in the 5'-untranslated region of a gene encoding interferon-induced transmembrane protein 5 (IFITM5). It completely cosegregated with the disease in three families and occurred de novo in five simplex individuals. Transfection of wild-type and mutant IFITM5 constructs revealed that the mutation added five amino acids (Met-Ala-Leu-Glu-Pro) to the N terminus of IFITM5. Given that IFITM5 expression and protein localization is restricted to the skeletal tissue and IFITM5 involvement in bone formation, we conclude that this recurrent mutation would have a specific effect on IFITM5 function and thus cause OI type V.
The American Journal of Human Genetics 08/2012; 91(2):343-8. · 10.60 Impact Factor
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ABSTRACT: To describe the association between retinal vessel caliber and risk factors for branch retinal vein occlusion (BRVO).
We included 10,890 participants who underwent a health checkup at Kangbuk Samsung Hospital between January 2006 and December 2006. BRVO was diagnosed from retinal photographs taken for both eyes. Retinal vascular caliber measurements were performed using a computer-assisted program. Risk factors were assessed based on a patient-answered questionnaire and laboratory investigations. Logistic regression analyses were performed to identify potential risk factors for BRVO.
The overall prevalence of BRVO was 0.8%. Among all BRVO patients, the mean central retinal artery equivalent (CRAE) was 142.59 µm (±14.63 µm), and the mean central retinal vein equivalent (CRVE) was 203.46 µm (±18.84 µm). The mean CRAE and CRVE of the control eyes were 148.15 µm (± 15.89 µm) and 211.12 µm (±18.54 µm), respectively. There were significant differences in mean CRAE and CRVE between the control group and the BRVO group (P < 0.05). Arterial hypertension was an important risk factor for BRVO (OR: 1.02 (1.01-1.03).
Eyes with BRVO had narrow CRAE and CRVE when compared with age- and gender-matched normal eyes. Generalized attenuation of retinal vessel caliber may be characteristic of eyes with BRVO. Emphasis on blood pressure control is needed for the prevention of BRVO.
Current eye research 02/2012; 37(4):334-8. · 1.51 Impact Factor
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Sang Hyun Cho,
Figen Seymen,
Kyung-Eun Lee,
Sook-Kyung Lee,
Young-Sun Kweon,
Kyung Jin Kim,
Seung-Eun Jung, Su Jeong Song,
Mine Yildirim,
Merve Bayram,
Elif Bahar Tuna,
Koray Gencay,
Jung-Wook Kim
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ABSTRACT: Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects without any other nonoral symptoms. Recently, a disease-causing nonsense mutation (c.406C>T) in a novel gene, FAM20A, was identified in a large consanguineous family affected by AI with gingival hyperplasia. We performed mutational analyses on nine AI families with similar phenotypes and identified three homozygous mutations (c.34_35delCT, c.813-2A>G, c.1175_1179delGGCTC) in three families and a compound heterozygous mutation (c.[590-2A>G] + [c.826C>T]) in one family. An in vitro splicing assay with a minigene confirmed the mutations located in the splicing acceptor site caused the deletion of exons 3 and 6, respectively. Taking into consideration the locations of the nonsense and frameshift mutations, the mutant transcripts are most likely degraded by nonsense-mediated mRNA degradation and it results in a loss of the FAM20A protein. This study confirms the importance of the FAM20A protein in enamel biomineralization as well as tooth eruption.
Human Mutation 01/2012; 33(1):91-4. · 5.69 Impact Factor
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Kyung-Chul Yoon,
Gui-Hyeong Mun,
Sang-Duck Kim,
Seung-Hyun Kim,
Chan Yun Kim,
Ki Ho Park,
Young Jeung Park,
Seung-Hee Baek, Su Jeong Song,
Jae Pil Shin,
Suk-Woo Yang,
Seung-Young Yu,
Jong Soo Lee,
Key Hwan Lim,
Hye-Jin Park,
Eun-Young Pyo,
Ji-Eun Yang,
Young-Taek Kim,
Kyung-Won Oh,
Se Woong Kang
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ABSTRACT: The aim of this study is to report on preliminary data regarding the prevalence of major eye diseases in Korea.
We obtained data from the Korea National Health and Nutrition Examination Survey, a nation-wide cross-sectional survey and examinations of the non-institutionalized civilian population in South Korea (n = 14,606), conducted from July 2008 to December 2009. Field survey teams included an ophthalmologist, nurses, and interviewers, traveled with a mobile examination unit and performed interviews and ophthalmologic examinations.
The prevalence of visual impairment, myopia, hyperopia and astigmatism in participants over 5 years of age was 0.4 ± 0.1%, 53.7 ± 0.6%, 10.7 ± 0.4%, and 58.0 ± 0.6%, respectively. The prevalence of strabismus and blepharoptosis in participants over 3 years of age was 1.5 ± 0.1% and 11.0 ± 0.8%, respectively. In participants over 40 years of age, the prevalence of cataract, pterygium, early and late age-related macular degeneration, diabetic retinopathy and glaucoma was 40.2 ± 1.3%, 8.9 ± 0.5%, 5.1 ± 0.3%, 0.5 ± 0.1%, 13.4 ± 1.5%, and 2.1 ± 0.2%, respectively.
This is the first nation-wide epidemiologic study conducted in South Korea for assessment of the prevalence of eye diseases by both the Korean Ophthalmologic Society and the Korea Center for Disease Control and Prevention. This study will provide preliminary information for use in further investigation, prevention, and management of eye diseases in Korea.
Korean Journal of Ophthalmology 12/2011; 25(6):421-33.
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ABSTRACT: Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders with regard to genetic aetiology and clinical phenotype and affects tooth enamel with no other non-oral syndromic conditions. X-linked AI is caused by mutations in the amelogenin (AMELX) gene, the only AI candidate gene located on the X chromosome. To date, 15 mutations in the AMELX gene have been found to cause AI. We identified a proband with generalized hypoplastic enamel and unusual multiple crown resorption in premolars and molars. Pedigree analysis suggested an X-linked hereditary pattern. We performed mutational analysis for the AMELX gene based on the candidate gene approach. Sequencing analysis revealed a novel mutation in exon 6 (g.4090delC, c.517delC, p.Pro173LeufsX16). This frameshift mutation produces a premature stop codon within exon 6 and is predicted to replace 33 amino acids at the C-terminus with 15 novel amino acids if the mutant mRNA escapes the nonsense-mediated decay system. Although crown resorptions occur frequently in patients with the hypoplastic type of A1, an association with the AMELX mutation has not been previously reported. We believe that these findings will broaden our understanding of the clinical phenotype and pathogenesis of X-linked AI.
European Journal Of Oral Sciences 12/2011; 119 Suppl 1:324-8. · 1.88 Impact Factor
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ABSTRACT: To evaluate the prevalence of and risk factors for diabetic retinopathy (DR) in Koreans with type II diabetes.
Subjects (400 male, 296 female) aged 30-65 years (mean 55.3 years) with hyperglycaemia (fasting plasma glucose ≥7.0 mmol/ml) or known diabetes (mean±SD duration 6.36±5.73 years) were enrolled in the Seoul Metro-City Diabetes Prevention Program (SMC-DPP) from September 2008 to September 2009. The severity of DR was diagnosed by grading fundus photographs taken from five standard fields per eye and categorised following the Early Treatment of Diabetic Retinopathy Study grading protocol. All participants underwent routine clinical and laboratory examinations to evaluate risk factors for DR. ResulTS: The overall prevalence of any type of DR was 18.7%. Logistic regression analyses showed that the following factors were significantly associated with DR after adjustment for age and gender, duration of diabetes, serum glycated haemoglobin A1c (HbA1c), mean arterial pressure, serum total cholesterol and serum triglycerides: duration of diabetes (OR 1.14, 95% CI 1.10 to 1.18, for 1 year increase), HbA1c (OR 1.49, 95% CI 1.20 to 1.85, for 1% increase), serum concentration of insulin (OR 0.87, 95% CI 0.81 to 0.94, for 1 μIU/ml increase), homoeostasis model assessment of insulin resistance (OR 0.06, 95% CI 0.01 to 0.29, for 10 unit increase), and presence of macroalbuminuria (OR 5.14, 95% CI 1.45 to 18.20, albumin to creatinine ratio >300 mg/g).
In addition to traditional risk factors, insulin resistance was associated with an increased risk of DR in Koreans with type 2 diabetes.
The British journal of ophthalmology 07/2011; 96(2):151-5. · 2.92 Impact Factor
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ABSTRACT: To report 6-month outcomes of a prospective, randomized study comparing the efficacy and safety between low-fluence photodynamic therapy (PDT) and intravitreal injections of ranibizumab in the treatment of chronic central serous chorioretinopathy.
Prospective, randomized, single-center pilot study.
Sixteen eyes with chronic central serous chorioretinopathy were randomized to receive either low-fluence PDT or intravitreal injections of ranibizumab: 8 eyes in the low-fluence PDT group and 8 in the ranibizumab group. Rescue treatment was considered if subretinal fluid was sustained after completion of primary treatment: low-fluence PDT for the ranibizumab group and ranibizumab injection for the low-fluence PDT group. Main outcome measures were excess foveal thickness, resolution of subretinal fluid, choroidal perfusion on indocyanine green angiography, and best-corrected visual acuity.
At 3 months, the mean excess foveal thickness was reduced from 74.1 ± 56.0 μm to -35.4 ± 44.5 μm in the low-fluence PDT group (P = .017) and from 26.3 ± 50.6 μm to -23.1 ± 56.5 μm in the ranibizumab group (P = .058). After a single session of PDT, 6 eyes (75%) in the low-fluence PDT group achieved complete resolution of subretinal fluid and reduction of choroidal hyperpermeability, whereas 2 (25%) eyes in the ranibizumab group achieved this after consecutive ranibizumab injections. Four eyes (50%) in the ranibizumab group underwent additional low-fluence PDT and accomplished complete resolution. At 3 months, significant improvement of best-corrected visual acuity was not demonstrated in the low-fluence PDT group (P = .075), whereas it was observed in the ranibizumab group (P = .012). However, the tendency toward improvement of best-corrected visual acuity was not maintained.
In terms of anatomic outcomes, the effect of ranibizumab injections was not promising compared with that of low-fluence PDT.
American journal of ophthalmology 07/2011; 152(5):784-92.e2. · 3.83 Impact Factor
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ABSTRACT: To characterize retinal changes in areas of commotio retinae using spectral-domain optical coherence tomography.
In this retrospective observational case series, we included 14 eyes of 14 patients who had experienced blunt ocular trauma and underwent spectral-domain optical coherence tomography and fundus photography evaluation on the same day. The retinal thickness and volume of eyes with commotio retinae were compared with those of eyes without it. Normal untraumatized fellow eyes served as control. Fundus images obtained by spectral-domain optical coherence tomography were compared with fundus photographs. The retinal tissue reflectivities indicated by the images were compared across each lesion.
There were 7 eyes with commotio retinae involving the macula and 7 eyes without it. Macular thickness and volume were not different between eyes with and without commotio retinae involving the macula. Photoreceptor outer segment reflectivity corresponding to the area of retinal opacity was increased with characteristic features and recovered with the disappearance of retinal opacity over time.
Lesions exhibiting retinal opacity characteristic of commotio retinae corresponded to hyperreflective outer segment lesions without the increase in retinal thickness on spectral-domain optical coherence tomography.
Retina (Philadelphia, Pa.) 06/2011; 31(10):2044-9. · 2.93 Impact Factor
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ABSTRACT: We report a rare case of multicentric Castleman's disease that presented with ophthalmic involvement, along with a review of the literature. A 63-year-old male presented with decreased visual acuity in both eyes. Both eyes had serous elevations of the retinas with shifting subretinal fluid and annular choroidal detachment. No retinal breaks were found. Laboratory tests revealed pancytopenia, hypergammaglobulinemia, and an increased erythrocyte sedimentation rate. Chest and abdominal computed tomographies showed multiple lymphadenopathies in the mediastinum, abdomen, and in both inguinal areas. Histological examination of the inguinal lymph node biopsy was consistent with Castleman's disease. After combination chemotherapy, the serous elevations of both retinas and the annular choroidal detachments of both eyes disappeared. Ophthalmic involvement in Castleman's disease is very rare, and to the authors' knowledge, this is the first report of ophthalmic involvement of Castleman's disease in Korea.
Korean Journal of Ophthalmology 06/2010; 24(3):182-5.
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ABSTRACT: To determine the prevalence of age-related macular degeneration (AMD) in Asian populations and to compare this with prevalence in white populations.
A clear understanding of AMD prevalence in Asians is essential to meet future demands for eye health care.
We searched published literature reporting AMD prevalence in Asian populations. We limited studies examined to those using standardized grading systems (either the Wisconsin Age-Related Maculopathy Grading System or the international classification proposed by the International ARM Epidemiological Study Group). We used metaanalytical methods to calculate age-specific pooled prevalence of AMD using inverse-variance weighting in a random effect model. We also calculated pooled estimates of age-standardized prevalence. A metaregression model was used to examine gender differences and differences between Asian and white populations.
We identified 9 studies reporting AMD prevalence from 4 Asian populations. Pooled prevalence estimates of early and late AMD in Asian populations aged 40 to 79 years were 6.8% (95% confidence interval [CI], 4.6%-8.9%) and 0.56% (95% CI, 0.30%-0.81%), respectively; corresponding prevalence estimates in white populations were 8.8% (95% CI, 3.8%-13.8%) and 0.59% (95% CI, 0.35%-0.84%), respectively. Reliable prevalence estimates of AMD in Asian persons aged > or =80 years were not available owing to small subject numbers in this age category.
Among persons aged 40 to 79 years, the age-specific prevalence of late AMD in Asians was comparable with that reported from white populations, but early AMD signs were less common among Asians. Further studies in Asian populations are warranted to investigate whether certain specific AMD phenotypes or subtypes, such as polypoidal choroidal vasculopathy, are more common.
Ophthalmology 05/2010; 117(5):921-7. · 5.45 Impact Factor
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ABSTRACT: It was the aim of this study to evaluate the effects of YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, one of the hypoxia-inducible factor 1 (HIF-1) inhibitors, on laser-induced choroidal neovascularization (CNV) in rats.
Thirty female Brown Norway rats underwent laser photocoagulation to induce CNV. Twenty of them (treatment group) were treated with a single intravitreal injection of 5 microg YC-1, and the remaining 10 (control) were sham-treated with a single intravitreal injection of 2.5 mg/ml dimethyl sulfoxide 2 weeks after laser photocoagulation. The expression of HIF-1alpha and vascular endothelial growth factor (VEGF) in CNV was evaluated by immunofluorescence staining. Fluorescein angiography was performed 2 weeks before and 2 weeks after single intravitreal YC-1 (5 microg) and dimethyl sulfoxide (2.5 mg/ml) injection, grading fluorescein leakage from 0 to 3. The size of the CNV was measured on histologic sections.
Both HIF-1alpha and VEGF were expressed in CNV lesions in the control group 4 weeks after laser photocoagulation, whereas the expressions of HIF-1alpha and VEGF were not observed in the intravitreally YC-1-treated group. The mean fluorescein leakage score decreased from 2.56 +/- 0.49 to 0.79 +/- 0.71 in the intravitreally YC-1-injected group and from 2.62 +/- 0.49 to 1.58 +/- 0.60 in the control group. Sixty-eight (71.6%) out of 95 CNV lesions of intravitreally YC-1-treated eyes (71.4%) and 12 (21.8%) out of 55 lesions in DMSO-treated eyes showed a decreased fluorescein leakage score of 2 or more. The mean difference of fluorescein leakage scores between the intravitreally YC-1-treated group and the control group was significant (p = 0.004). The mean thickness of the CNV lesions in the intravitreally YC-1-treated group (27.30 +/- 6.47 microm) was smaller than that of the control group (64.36 +/- 8.26 microm, p < 0.001). There was no ocular inflammation, retina hemorrhage or systemic toxicity induced by YC-1 treatment.
These results suggest that YC-1 inhibits the HIF-1 expression after photocoagulation and suppresses the development of laser-induced CNV formation.
Ophthalmic Research 01/2008; 40(1):35-40. · 1.56 Impact Factor
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ABSTRACT: To evaluate the efficacy of vitrectomy for persistent diabetic macular edema after laser photocoagulation or intravitreal triamcinolone injections and to determine the demographic and ocular factors that influence functional and anatomical outcomes.
We retrospectively evaluated 55 eyes (51 patients) that had persistent diffuse macular edema after laser photocoagulation or intravitreal triamcinolone injections. We compared preoperative and postoperative best corrected visual acuity and macular thickness by Optical Coherence Tomography and investigated factors including patient's age, presence of vitreomacular traction, grade of diabetic retinopathy, and intraoperative internal limiting membrane removal that may influence the surgical results.
The mean preoperative BCVA (log MAR) was 0.91+/-0.40 (0.8-1.2). The BCVA improved to 0.72+/-0.39 (0.3-1.2). The mean preoperative macular thickness was 440+/-130 (202-805) micrometer and the mean macular thickness decreased to 306+/-97 (136-580) micrometer postoperatively. The eyes showed statistically significant improvement in BCVA and central macular thickness (p<0.001). Preoperative better BCVA was associated with an improved postoperative visual acuity. (p=0.04). No other covariates were found to be statistically significant factors for prognosis of postoperative BCVA.
In eyes with persistent diabetic macular edema after laser or IVTA injections, vitrectomy was effective for decreasing macular thickness and improvement of vision. The visual improvement after vitrectomy was associated with the preoperative better BCVA.
Korean Journal of Ophthalmology 09/2007; 21(3):146-50.
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ABSTRACT: To investigate the degree of implicit time delay in aretinopathic hexagons according to the grading of diabetic retinopathy and factors that affect the mfERG responses of aretinopathic areas.
MfERG was recorded using the RETIscan system (Roland consult, Brandenbrug, Germany) in 40 eyes of 20 nondiabetic controls, 32 eyes of 16 diabetic patients without retinopathy, and 96 eyes of 48 diabetic patients with nonproliferative diabetic retinopathy (NPDR). Hexagons are divided into retinopathic and aretinopathic hexagons, which were selected using fundus photographs and fluorescence angiography. Relative amplitude and implicit time delay were compared between patient groups and controls.
The mean implicit time delay in aretinopathic hexagons was significantly different between each subject group and correlated with the retinopathy severity of the whole retina, as well as in retinopathic hexagons. In all three NPDR groups, implicit time was significantly more delayed in retinopathic hexagons compared to aretinopathic hexagons. Relative amplitude was significantly decreased only in the severe NPDR group in both retinopathic and aretinopathic hexagons. The duration of diabetes and glycemic control status did not correlate with the local mfERG responses.
Local mfERG showed considerable implicit time delays in clinically normal retinal areas that correlated significantly with the severity of diabetic retinopathy of the whole retina.
Ophthalmic Research 02/2007; 39(5):282-8. · 1.56 Impact Factor
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ABSTRACT: To evaluate the efficacy of arteriovenous (AV) sheathotomy with internal limiting membrane peeling for persistent or recurrent macular edema after intravitreal triamcinolone injection and/or laser photocoagulation in branch retinal vein occlusion.
Twenty-two eyes with branch retinal vein occlusion (BRVO) with recurrent macular edema underwent vitrectomy with AV sheathotomy and internal limiting membrane peeling. All eyes had previous intravitreal triamcinolone injection and/or laser photocoagulation for macular edema. The best corrected visual acuity (BCVA), fluorescein angiography and optical coherence tomography (OCT) before and after surgery were compared.
The mean preoperative BCVA (log MAR) were 0.79 +/- 0.29 and postoperative BCVA (log MAR) at 3 months was 0.57 +/- 0.33. And improvement of visual acuity > or = 2 lines was observed in 10 eyes (45%). The mean preoperative fovea thickness measured by OCT was 595.22 +/- 76.83 microm (510-737 microm) and postoperative fovea thickness was 217.60 +/- 47.33 microm (164-285 microm).
Vitrectomy with AV sheathotomy can be one treatment option for the patients with recurrent macular edema in BRVO.
Korean Journal of Ophthalmology 01/2007; 20(4):210-4.
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ABSTRACT: The protein RAS association domain family protein 1A (RASSF1A), which is encoded by a gene that is frequently silenced in many types of sporadic tumor, functions in mitosis as a regulator of the anaphase-promoting complex (APC). With the use of a yeast two-hybrid screen, we identified a human protein, previously designated C19ORF5, that interacts with RASSF1A. This protein, here redesignated RASSF1A-binding protein 1 (RABP1), contains two microtubule-associated protein domains, and its association with RASSF1A was confirmed in mammalian cells by immunoprecipitation and immunofluorescence analyses. RABP1 was found to be localized to the centrosome throughout the cell cycle in a manner dependent on its microtubule-associated protein domains. Ectopic expression of RABP1 induced both stabilization of mitotic cyclins and mitotic arrest at prometaphase in a RASSF1A-dependent manner. It also increased the extent of association between RASSF1A and Cdc20. Conversely depletion of RABP1 by RNA interference prevented both the localization of RASSF1A to the spindle poles as well as its binding to Cdc20, resulting in premature destruction of mitotic cyclins and acceleration of mitotic progression. These findings indicate that RABP1 is required for the recruitment of RASSF1A to the spindle poles and for its inhibition of APC-Cdc20 activity during mitosis.
Journal of Biological Chemistry 03/2005; 280(5):3920-7. · 4.77 Impact Factor
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Min Sup Song, Su Jeong Song,
Nagi G Ayad,
Jin Sook Chang,
Joo Hyun Lee,
Hyun Kyung Hong,
Ho Lee,
Naeyun Choi,
Jhingook Kim,
Hojoong Kim,
Jin Woo Kim,
Eui-Ju Choi,
Marc W Kirschner,
Dae-Sik Lim
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ABSTRACT: The tumour suppressor gene RASSF1A is frequently silenced in lung cancer and other sporadic tumours as a result of hypermethylation of a CpG island in its promoter. However, the precise mechanism by which RASSF1A functions in cell cycle regulation and tumour suppression has remained unknown. Here we show that RASSF1A regulates the stability of mitotic cyclins and the timing of mitotic progression. RASSF1A localizes to microtubules during interphase and to centrosomes and the spindle during mitosis. The overexpression of RASSF1A induced stabilization of mitotic cyclins and mitotic arrest at prometaphase. RASSF1A interacts with Cdc20, an activator of the anaphase-promoting complex (APC), resulting in the inhibition of APC activity. Although RASSF1A does not contribute to either the Mad2-dependent spindle assembly checkpoint or the function of Emi1 (ref. 1), depletion of RASSF1A by RNA interference accelerated the mitotic cyclin degradation and mitotic progression as a result of premature APC activation. It also caused a cell division defect characterized by centrosome abnormalities and multipolar spindles. These findings implicate RASSF1A in the regulation of both APC-Cdc20 activity and mitotic progression.
Nature Cell Biology 03/2004; 6(2):129-37. · 19.49 Impact Factor
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ABSTRACT: To identify the prevalence, risk factors, and subtypes of age-related macular degeneration (AMD) in a screened South Korean population.
A total of 10,890 participants (aged 50-92) who underwent a health check-up at Kangbuk Samsung Hospital from January to December 2006 were included. Fundus photographs and systemic risk factors were assessed. Subtype frequencies of neovascular AMD were recorded according to angiograms. AMD was defined in accord with the international classification and grading system. Logistic regression analyses were performed to identify risk factors for AMD.
The mean age of the 10,890 participants was 57.2 +/- 6.3 years (50-92 years), and 56.2% were men. The age-gender-adjusted prevalence of early AMD was 5.07%. Multiple logistic regression analysis showed that age (OR per 10-year increment, 2.22) and high blood pressure (adjusted OR: 1.35) were independent risk factors for early AMD. The age-gender-adjusted prevalence of late AMD was 0.34%. Only age was significantly associated with late AMD. Of 9 exudative AMD patients who received fluorescein angiography or indocyanine green angiography, 6 eyes (66.7%) showed choroidal neovascularization, 2 eyes (22.2%) had polypoidal choroidal vasculopathy (PCV), and 1 eye (11.1%) had retinal angiomatous proliferation.
In this study, the prevalence of early AMD was similar to other studies though the prevalence of late AMD was low. High blood pressure as well as age was a risk factor of early AMD. South Koreans may have a higher prevalence of PCV than white populations. These findings provide preliminary information for further investigation of AMD in South Koreans.
Ophthalmic epidemiology 16(5):304-10. · 1.93 Impact Factor
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Japanese Journal of Ophthalmology 52(4):342-4. · 0.92 Impact Factor
