Morphological characterization of subretinal hyper-reflective material in posterior uveitis using swept-source optical coherence tomography and optical coherence tomography angiography

Purpose: To analyze the structural features of subretinal hyper-reflective material (SHRM) in posterior uveitis using swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (SS-OCTA). Methods: In this observational study, subjects with quiescent posterior uveitis and the presence of SHRM on SS-OCT were subjected to SS-OCTA to identify the presence of an intrinsic choroidal neovascular (CNV) network. OCT features were compared for SHRM harboring CNV (vascular SHRM) with those without CNV network (avascular SHRM) to identify clinical signs pointing toward the presence of CNVM inside SHRM. Results: Forty-two eyes of 33 subjects (18 males; mean age: 29.52 ± 12.56 years) were evaluated. Two-thirds (28/42) of eyes having SHRM on SS-OCT harbored intrinsic neovascular network (vascular SHRM). Increased reflectivity of SHRM (P < 0.001) and increased transmission of OCT signal underlying SHRM (P = 0.03) were suggestive of the absence of CNVM. The presence of intra/subretinal fluid (P = 0.08) and pitchfork sign (P = 0.017) were important markers of vascular SHRM. Conclusion: SHRM is an important OCT finding in eyes with posterior uveitis. Meticulous assessment of SHRM characteristics on SS-OCT can aid in identifying the underlying intrinsic neovascular network.

Effect of Artesunate on Experimental Choroidal Neovascularization and Expression of HIF-1α and VEGF / 中国实验方剂学杂志

Objective:To observe the effects of artesunate （ART） on experimental choroidal neovascularization （CNV） and the expression of related proteins， and to explore the underlying mechanism. Method:Eighty BN rats were randomly divided into five groups： a normal group， a model group， a conbercept group， and low- （10.08 mg·kg^-1·d^-1） and high-dose （20.16 mg·kg^-1·d^-1） ART groups， with 16 rats in each group. A CNV model was established with 532 nm laser in rats of the groups except for the normal group. The rats in each group were treated with corresponding drugs by gavage for 14 days. The normal group， the model group， and the conbercept group received 1% CMC-Na solution at the same volume， while the conbercept group received an intravitreal injection （5 μL） once. On days 7 and 14， fundus fluorescein angiography （FFA） was used to evaluate the fluorescein leakage （gray value） of CNV. Hematoxylin-eosin （HE） staining was adopted to observe the histopathological changes of CNV. Western blot was employed to detect the protein expression levels of hypoxia-inducible factor-1<italic>α</italic> （HIF-1<italic>α</italic>） and vascular endothelial growth factor （VEGF） in the retina and choroid. Result:FFA results showed that compared with the normal group， other groups showed increased gray value on days 7 and 14 （<italic>P</italic><0.01）. On day 7， the gray value of the high-dose ART group and the conbercept group decreased compared with that in the model group （<italic>P</italic><0.01）. On day 14， the gray value of the ART groups and the conbercept group decreased in varying degrees compared with that in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. HE results showed that compared with the normal group， the model group showed increased thickness of CNV on days 7 and 14 （<italic>P</italic><0.01）. Compared with the model group， the ART groups and the conbercept group displayed decreased thickness of CNV （<italic>P</italic><0.01）. Western blot results revealed that the expression of HIF-1<italic>α</italic> and VEGF in the model group increased in varying degrees on the days 7 and 14 compared with that in the normal group （<italic>P</italic><0.05， <italic>P</italic><0.01）， while compared with the model group， the ART groups and the conbercept group showed decreased expression （<italic>P</italic><0.01）. Conclusion:ART can inhibit experimental CNV by down-regulating the expression of HIF-1<italic>α</italic> and VEGF in the early stage of experimental CNV formation.

Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely

Genetic and genomics in congenital heart disease: a clinical review / Genética e genômica na cardiopatia congênita: uma revisão clínica

Abstract Objective: Discuss evidence referring to the genetic role in congenital heart diseases, whether chromosomic alterations or monogenic diseases. Data source: LILACS, PubMed, MEDLINE, SciELO, Google Scholar, and references of the articles found. Review articles, case reports, book chapters, master's theses, and doctoral dissertations were included. Summary of findings: Congenital heart diseases are among the most common type of birth defects, afflicting up to 1% of the liveborn. Traditionally, the etiology was defined as a multifactorial model, with both genetic and external contribution, and the genetic role was less recognized. Recently, however, as the natural evolution and epidemiology of congenital heart diseases change, the identification of genetic factors has an expanding significance in the clinical and surgical management of syndromic or non-syndromic heart defects, providing tools for the understanding of heart development. Conclusions: Concrete knowledge of congenital heart disease etiology and recognition of the genetic alterations may be helpful in the bedside management, defining prognosis and anticipating complications.

Resumo Objetivo: Discutir as evidências referentes ao papel genético em cardiopatias congênitas, sejam alterações cromossômicas ou doenças monogênicas. Fonte de dados: Lilacs, PubMed, Medline, SciELO, Google Scholar e referências dos artigos encontrados. Artigos de revisão, relatos de casos, capítulos de livros, dissertações de mestrado e teses de doutorado foram incluídos. Síntese dos dados: As cardiopatias congênitas estão entre os tipos mais comuns de defeitos congênitos, afetando até 1% dos nascidos vivos. Tradicionalmente, a etiologia era definida como um modelo multifatorial, com contribuição tanto genética quanto externa, sendo o papel genético menos reconhecido. Recentemente, no entanto, à medida que a evolução natural e a epidemiologia das cardiopatias congênitas mudaram, a identificação de fatores genéticos tem adquirido importância crescente no tratamento clínico e cirúrgico de defeitos cardíacos sindrômicos e não-sindrômicos, fornecendo ferramentas para a compreensão do desenvolvimento do coração. Conclusões: O conhecimento concreto da etiologia das cardiopatias congênitas e o reconhecimento das alterações genéticas podem ser úteis no tratamento à beira do leito, definindo o prognóstico e antecipando as complicações.

Genómica de los trastornos del desarrollo neurológico / Genomics of neurodevelopmental disorders

Introduction: Neurodevelopmental disorders (NDD) are featured by a delay in the acquisition of motor functions, cognitive abilities and speech, or combined deficits in these areas with the onset before the age of 5 years. Genetic causes account for approximately a half of all NDD cases. Objective: to describe alterations of the genome implied in neurodevelopmental disorders and some aspects of their genetic counseling. Methods: Bibliographic search in Medline, Pubmed, Scielo, LILACS and Cochrane, emphasizing in the last five years, the relationship between the various genetic factors that may be involved in neurodevelopmental disorders. Results: Multiple genetic factors are involved in neurodevelopmental disorders, from gross ones such as chromosomal aneuploidies to more subtle ones such as variations in the number of copies in the genome. Special emphasis is placed on microdeletion-micro duplication syndromes as a relatively frequent cause of NDDs and their probable mechanisms of formation are explained. Final Considerations: Genetic aberrations are found in at least 30-50 percent of children with NDD. Conventional karyotyping allows the detection of chromosomal aberrations encompassing more than 5-7 Mb, which represent 5-10 percent of causative genome rearrangements in NDD. Molecular karyotyping (e.g. SNP array/array CGH) can significantly improve the yield in patients with NDD and congenital malformations(AU)

Introducción: Los trastornos del neurodesarrollo están caracterizados por retardo en la adquisición de las funciones motoras, habilidades cognitivas para el habla o el déficit combinado en estas áreas; se presenta en niños menores de 5 años de edad. Las causas genéticas están implicadas en más de la mitad de los pacientes con estos trastornos Objetivo: Examinar las alteraciones del genoma implicados en los trastornos del neurodesarrollo y algunos aspectos de su asesoramiento genético. Métodos: Búsqueda bibliográfica en Medline, Pubmed, Scielo, LILACS y Cochrane con énfasis en los últimos cinco años, acerca de la relación entre los variados factores genéticos que pueden estar involucrados en los trastornos del neurodesarrollo. Resultados: Los factores genéticos involucrados pueden ser groseros como las aneuploidías cromosómicas hasta los más sutiles como las variaciones en el número de copias en el genoma. Se describen los síndromes de microdeleción-micro duplicación como una causa relativamente frecuente de los trastornos del neurodesarrollo y se explican sus probables mecanismos de formación. Se relacionan las aneuploidías cromosómicas y las variaciones en el número de copia como causas de estos trastornos. Consideraciones finales . Las aberraciones genéticas se encuentran en 30-50 por ciento de los niños con trastornos del neurodesarrollo. El cariotipo convencional permite la detección de aberraciones cromosómicas que abarcan más de 5-7 Mb, lo que representa 5-10 por ciento de los reordenamientos genómicos causales en estos trastornos. El cariotipo molecular (por ejemplo, una matriz de SNP/ CGH de matriz) puede mejorar significativamente la certeza del diagnóstico en pacientes con trastornos del neurodesarrollo y malformaciones congénitas(AU)

A review on the Variable copies of C-C motif Chemokine Ligand 3 Like 1 (CCL3L1) Gene among Different Populations and Current Methods for Quantification

@#C-C motif Chemokine Ligand 3 Like 1 (CCL3L1) is characterized as a gene with copy number variable (CNV) and clustered at the segmental duplication on chromosome 17q12. CCL3L1 is responsible for the production of macrophage inflammatory protein (MIP) 1α that plays an important function in the immune system and host defense. Various copies range of CCL3L1 have been reported and associated with the diseases in different populations. Thus, this review aimed to summarise the distribution of CCL3L1 copy number from different populations according to the geographical region and highlighted the lacking of data from Malaysian population, which is one of the multi-ethnic countries due to the impacts of CCL3L1 copies on various diseases. Besides, we also outlined the methodologies available for the copy number typing. In overall, this review could provide significant information on the role of CCL3L1 copies in disease association and as well as providing evidence on the population diversity

Expression and function of MCP-1 and its receptor in wAMD model mouse / 临床与实验病理学杂志

Purpose To detect the expression and the function of MCP-1 and its receptor CCR2 in wet agerelated macular degenerative (wAMD) model mouse retina. Methods C57BL/6J mouse were enrolled into the study. Model mouse of wAMD was induced with laser. Frozen sections were prepared for histopathological tests. Immunofluorescence study for MCP-1 and CCR2 was carried out. Co-expression study for CCR2/ CDllb or CCR2/CD68 was carried out. Total protein and total mRNA from the eyes of both wAMD and wild type mouse were extracted. The expression of mRNA and protein of MCP-1 and CCR2 in the eyes were determined by reverse transcription-poly-merase chain reaction (RT-PCR) and Western blots test, respectively. Results In wild type mouse, both MCP-1 and its receptor CCR2 were not detected in the retina. However in wAMD mouse, an obvious up-regulated MCP-1 and CCR2 expression was seen in the retinal pigment epithelium (RPE) cells accompanied with the increased expression of their mRNA and protein. The co-expression study showed that CCR2 co-ex-pressed with CDllb, but not with CD68. Conclusion MCP-1 and its receptor CCR2 may play a role in the wAMD through stimulation of microglia.

Recurrent benign copy number variants & issues in interpretation of variants of unknown significance identified by cytogenetic microarray in Indian patients with intellectual disability.

Background & objectives: Cytogenetic microarray (CMA) is now recommended as a first-tier clinical diagnostic test in cases with idiopathic intellectual disability and/or developmental delay (ID/DD). Along with clinically relevant variants, CMA platforms also identify variants of unknown significance (VUS). This study was done to look for utility and various issues in interpretation of copy number variants (CNVs) in Indian patients with ID/DD. Methods: The CMA was performed in 86 Indian patients with idiopathic ID/DD with or without dysmorphic features. CNV was reported if copy number gain was >400 kb in size and copy number loss was > 200 kb in size. Results: Pathogenic CNVs were found in 18 of 86 (20.9%) patients. One large (14 Mb size) de novo heterozygous copy number gain was found in one patient. VUS (total 31) were present in 17 of 86 (19.7%) patients. Five novel recurrent benign CNVs were also present in our patients. Interpretation & conclusions: Our findings highlight the difficulties in interpretation of CNVs identified by CMA. More Indian data on VUS and recurrent benign CNVs will be helpful in the interpretation of CMA in patients with ID/DD.

A GO analysis of gene expression on the inhibitory effect of endostatin on mouse choroidal neovascularization / 西安交通大学学报(医学版)

Objective To study the gene expression on the inhibitory effect of endostatin on choroidal neovascularization in C57BL/6J mice and the mechanisms.Methods Photocoagulation using 532 nm diode laser was performed to establish a CNV model in mice’s eye.The mice were randomly divided into three groups:blank group (model group);endostatin group (experimental group),in which endostatin of 0.01 mg/2μL was given intravitreally;and saline group (control group),which received intravitreal injection of 2μL of 0.9 g/L saline.Four samples selected respectively from experimental group and control group were used to complete the gene expression profiling analysis.By comparing the differences of gene expression between the two groups,we selected the genes with expression difference ≥ 1.5 times and P ≤ 0.05. Results CD105 marking showed that choroidal neovascularization was significantly lower in endostatin group than in control group.The gene expression analysis showed that 1 1 6 genes were up-regulated and 1 0 6 genes were down-regulated in endostatin group compared with control group.GO analysis indicated that endostatin could inhibit cell activity and growth,but did not initiate the activity of the immune system,and even suppress it.Conclusion Endostatin can inhibit the activity and locomotion of endothelial cells and synergically inhibits the immune system,thus suppressing choroidal neovascular-ization.

The study of sustain attention of CNV in patients with subcortical ischemic vascular cognitive impairment / 中国神经精神疾病杂志

Objective To investigate the characteristics of contingent negative variation(CNV) in patients with subcortical ischemic vascular cognitive impairment (SIVCI) and their relationship with continuous performance task (CPT) to establish a neuroelectrophysiological index of attention impairment in earlier period of Vascular Cognitive Impair-ment. Methods CNV was assessed in 45 SIVCI patients [30 patients with subcortical ischemic vascular cognitive impair-ment no dementia (SIVCIND ) and 15 patients with subcortical ischemic vascular dementia (SIVD )] and 15 normal con-trol (NC) by using a EB-Neuro ERP Instrument. Results ①CNV in SIVCI group were less regular compared with nor-mal control;CNV in SIVCIND group had decreased Expectancy Wave (EW) amplitudes (9.98± 4.10μV vs. 16.13±2.75μV) and EW areas (14848.10 ± 3199.16 μV · ms vs 20058.87 ± 1025.95 μV · ms) compared with normal control (P0.05);②Pearson correlation\Spearman rank correlation analysis revealed that there were significant, positive correlations between EW latency and CPT Reacting time(R=0.748, P0.05)、EW amplitude(R=-0.191,P>0.05)and there were significant, negative correlations between EW area and CPT Reacting time(R=-0.718,P<0.01)、CPT missing rate(R=-0.829 ,P<0.01), EW amplitude and CPT Reacting time(R=-0.616, P<0.01). Conclusion SIVCI patients in early stage have attention deficits in sustained attention and CNV EW ar-ea may be a good neuroelectrophysiological index for sustained attention impairment .

Enhancing production of ergosterol in Pichia pastoris GS115 by over-expression of 3-hydroxy-3-methylglutaryl CoA reductase from Glycyrrhiza uralensis

The rate-limiting enzyme in the mevalonic acid (MVA) pathway which can lead to triterpenoid saponin glycyrrhizic acid (GA) is 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR). In order to reveal the effect of copy number variation in the HMGR gene on the MVA pathway, the HMGR gene from Glycyrrhiza uralensis Fisch. (GuHMGR) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy numbers of the GuHMGR gene were obtained and the content of ergosterol was analyzed by HPLC. The results showed that all the recombinant P. pastoris strains contained more ergosterol than the negative control and the strains with 8 and 44 copies contained significantly more ergosterol than the other strains. However, as the copy number increased, the content of ergosterol showed an increasing-decreasing-increasing pattern. This study provides a rationale for increasing the content of GA through over-expressing the GuHMGR gene in cultivars of G. uralensis.

Genome-Wide Analysis of DNA Copy Number Changes in Liver Steatosis.

Aims: Liver steatosis is the most common benign form of non-alcoholic fatty liver disease. It might be a risk factor for hepatocellular carcinoma, either (i) by causing fibrosis, which highly predisposes to hepatoma, or (ii) by being an early precursor of carcinoma, although it is usually considered not to be pre-neoplastic. We investigated the genomic profile of liver samples from patients with fatty liver disease. Study Design & Methodology: Copy number variation was investigated by array-CGH, using the Human Genome 244K catalogue array (Agilent Technologies), and changes validated by quantitative polymerase chain reaction analysis. Results: The analysis of liver biopsies from 17 patients, 10 of whom had histological diagnosis of non-alcoholic fatty liver disease, showed differences in the type of variants in patients with steatosis compared to those without steatosis at several chromosome bands, including 3q29, 6p2, 11q11 and 22q11. Conclusion: The genomic copy number changes we have demonstrated suggest that genomic structural variations may be associated with the pathogenesis or the evolution of steatosis.

Predictive Factors for Visual Outcome after Treatment for Myopic Choroidal Neovascularization

PURPOSE: To determine predictive factors associated with visual outcome after treatment for myopic choroidal neovascularization (mCNV). METHODS: Medical records of the patients who underwent photodynamic therapy (PDT), intravitreal anti-vascular endothelial growth factor (Anti-VEGF) injection, or combination therapy of PDT and Anti-VEGF for myopic CNV, and followed up for more than a year, were reviewed retrospectively. Multiple linear regression analyses were performed to evaluate the predictive factors significantly associated with the visual outcome at 1 year after the treatment. RESULTS: Mean best-corrected visual acuity (BCVA) of 45 eyes of 45 patients showed statistically significant improvement 1 year after the treatment with a mean of 3.5 line improvement (p < 0.01, Wilcoxon signed rank test). Age, 1-month BCVA after treatment and treatment type appeared to be associated with the 1-year visual outcome after treatment for mCNV (p = 0.033, p < 0.001, and p = 0.044, respectively, multivariate linear regression analysis). CONCLUSIONS: Younger age (less than 40 years), better 1-month BCVA after treatment, intravitreal Anti-VEGF monotherapy were associated with improved visual outcome after treatment for mCNV. In particular, 1-month BCVA after treatment is a useful indicator to predict therapeutic response after treatment for mCNV.

La etiología de la esquizofrenia / The etiology of schizophrenia

Las investigaciones realizadas en los últimos años iniciaron una nueva era de conocimiento de los factores de riesgo de la esquizofrenia. Por otra parte, los métodos de estudio del genoma completo han revolucionado el campo del mapeado genético de la esquizofrenia. Estudios genéticos recientes sugieren que la variación genética rara y la variación genética común tienen una función importante en la arquitectura genética de la esquizofrenia, que el modelo poligénico es correcto, e indican una superposición de los factores genéticos que confieren susceptibilidad a la esquizofrenia y otros trastornos psiquiátricos, como el trastorno bipolar y el autismo (pleotropía). Los programas de resecuenciación del genoma completo permitirán una disección más profunda de la genética molecular de la enfermedad. Uno de los desafíos importantes de la psiquiatría genética es la traducción de las asociaciones estadísticas detectadas en estudios de genoma completo en una mejor comprensión fisiopatológica de la esquizofrenia.

Research conducted in recent years represents a new dawn of knowledge for the risk factors of schizophrenia, and genome-wide approaches have revolutionized the field of genetic mapping of schizophrenia. The aggregate genetic data increasingly support a combination of rare and common genetic variation in schizophrenia, a major role for polygenic inheritance, and a genetic overlap (pleiotropy) of schizophrenia and other psychiatric disorders, such as bipolar disorder and autism. A main challenge for the field is the translation of established genetic associations into a better pathophysiological understanding of schizophrenia. The current and upcoming resequencing programs - both exomes (all exons) and full genomes - and genome-wide transcriptional analyses will allow a more thorough dissection of the molecular genetics of the disorder.

Photodynamic Therapy of Choroidal Neovascularization in Age-Related Macular Degeneration with Verteporfin: An Analysis of 10 Years of Clinical Results

PURPOSE: To analyze the long-term results of photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). METHODS: The clinical data of patients treated with photodynamic therapy for exudative age-related macular degeneration between April 2000 and December 2000 were analyzed. Patients were followed-up for at least 10 years after PDT. RESULTS: Twenty-nine eyes of 29 patients were enrolled. Mean visual acuity on the logarithm of the minimum angle of resolution (log MAR) scale was 0.78 +/- 0.34 at baseline, 1.01 +/- 0.42 at 60 months, and 1.02 +/- 0.41 at 120 months. Predominantly classic, minimally classic, and occult without classic choroidal neovascularization was noted in 51.7%, 17.2%, and 31.1% of patients, respectively. Visual acuity was improved by 1 or more lines in 27.6% of patients and was unchanged in 20.7% of patients, while 51.7% of patients had lost 1 or more lines of visual acuity by 120 months. Baseline visual acuity and age were associated with the final visual prognosis (p < 0.05). Four patients developed neovascular AMD in the contralateral eye. CONCLUSIONS: PDT is safe and effective for neovascular AMD. However, AMD can recur at any time and thus patients should be followed-up for a long period of time.

Effect of Combining Multiple CNV Defining Algorithms on the Reliability of CNV Calls from SNP Genotyping Data

In addition to single-nucleotide polymorphisms (SNP), copy number variation (CNV) is a major component of human genetic diversity. Among many whole-genome analysis platforms, SNP arrays have been commonly used for genomewide CNV discovery. Recently, a number of CNV defining algorithms from SNP genotyping data have been developed; however, due to the fundamental limitation of SNP genotyping data for the measurement of signal intensity, there are still concerns regarding the possibility of false discovery or low sensitivity for detecting CNVs. In this study, we aimed to verify the effect of combining multiple CNV calling algorithms and set up the most reliable pipeline for CNV calling with Affymetrix Genomewide SNP 5.0 data. For this purpose, we selected the 3 most commonly used algorithms for CNV segmentation from SNP genotyping data, PennCNV, QuantiSNP; and BirdSuite. After defining the CNV loci using the 3 different algorithms, we assessed how many of them overlapped with each other, and we also validated the CNVs by genomic quantitative PCR. Through this analysis, we proposed that for reliable CNV-based genomewide association study using SNP array data, CNV calls must be performed with at least 3 different algorithms and that the CNVs consistently called from more than 2 algorithms must be used for association analysis, because they are more reliable than the CNVs called from a single algorithm. Our result will be helpful to set up the CNV analysis protocols for Affymetrix Genomewide SNP 5.0 genotyping data.

Sequence Analysis and Expression of ORF5 in Korean Isolate of Porcine Reproductive and Respiratory Syndrome Virus

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of reproductive failure and respiratory disorders in pigs. The viral genome consists of eight overlapping open reading frames (ORFs). ORF5 encodes one of the major glycoproteins and is known as an immunologically important structural protein associated with virus neutralization. The ORF5 gene of the Korean PRRSV isolate, CNV-1, was amplified by reverse transcription-polymerase chain reaction (RT-PCR), cloned and sequenced. The nucleotide and amino acid sequences of CNV-1 ORF5 shared 91% and 83% identity, respectively, with the American isolate (VR2332 strain) and 57% and 49% identity with the European isolate. For the expression and easy purification of ORF5, the cDNA containing the complete ORF5 sequence fused in-frame with sequence encoding glutathione S-transferase (GST) was cloned into a baculovirus transfer vector and transfected into Sf9 cells. The GST-ORF5 fusion protein produced in Sf9 cells was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Sequencing results confirmed that the recombinant baculovirus from Sf9 cells contains the complete ORF5 gene. Further studies in this direction will address whether ORF5 can be a good candidate for a subunit vaccine against PRRSV in Korea.

A Genome-Wide Study of Moyamoya-Type Cerebrovascular Disease in the Korean Population

OBJECTIVE: Structural genetic variation, including copy-number variation (CNV), constitutes a substantial fraction of total genetic variability, and the importance of structural variants in modulating susceptibility is increasingly being recognized. CNV can change biological function and contribute to pathophysiological conditions of human disease. Its relationship with common, complex human disease in particular is not fully understood. Here, we searched the human genome to identify copy number variants that predispose to moya-moya type cerebrovascular disease. METHODS: We retrospectively analyzed patients who had unilateral or bilateral steno-occlusive lesions at the cerebral artery from March, 2007, to September, 2009. For the 20 subjects, including patients with moyamoya type pathologies and three normal healthy controls, we divided the subjects into 4 groups : typical moyamoya (n=6), unilateral moyamoya (n=9), progression unilateral to typical moyamoya (n=2) and non-moyamoya (n=3). Fragmented DNA was hybridized on Human610Quad v1.0 DNA analysis BeadChips (Illumina). Data analysis was performed with GenomeStudio v2009.1, Genotyping 1.1.9, cnvPartition_v2.3.4 software. Overall call rates were more than 99.8%. RESULTS: In total, 1258 CNVs were identified across the whole genome. The average number of CNV was 45.55 per subject (CNV region was 45.4). The gain/loss of CNV was 52/249, having 4.7 fold higher frequencies in loss calls. The total CNV size was 904,657,868, and average size was 993,038. The largest portion of CNVs (613 calls) were 1M-10M in length. Interestingly, significant association between unilateral moyamoya disease (MMD) and progression of unilateral to typical moyamoya was observed. CONCLUSION: Significant association between unilateral MMD and progression of unilateral to typical moyamoya was observed. The finding was confirmed again with clustering analysis. These data demonstrate that certain CNV associate with moyamoya-type cerebrovascular disease.

The Effect of Triple Therapy on Patients with Subretinal Hemorrhage Accompanied by Choroidal Neovascularization

PURPOSE: To presents the effect of triple therapy including C3F8 gas injection, intravitreal anti-VEGF injection and photodynamic therapy on patients with subretinal hemorrhage accompanied by choroidal neovascularization. METHODS: Twelve eyes of 12 patients suffering from subretinal hemorrhage accompanied by choroidal neovascularization with onset of the symptom within a week prior to three-day prone positioning after C3F8 gas injection were included in the present study. Next, intravitreal anti-VEGF injection and photodynamic therapy was performed. Then, within two months, intravitreal bevacizumab or ranibizumab injection was performed. RESULTS: After stabilization of the submacular hemorrhagic lesion, ten eyes of ten patients showed improved visual acuity, one eye showed no improvement, and decreased visual acuity developed in one patient. LogMAR visual acuity improved after the initial treatment from 1.05 +/- 0.43 to 0.74 +/- 0.58 and 0.53 +/- 0.51 at three and six months, respectively. The improvement was considered to be clinically significant. CONCLUSIONS: An appropriate regimen for treating broad submacular hemorrhage accompanied by choroidal neovascularization has not been established. The authors of the patients had obtained positive results from C3F8 gas injection, intravitreal anti-VEGF injection and photodynamic therapy. In the future, additional studies should be conducted.