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1.  Histone Acetylation Level and Histone Acetyltransferase/Deacetylase Activity in Ejaculated Sperm from Normozoospermic Men 
Yonsei Medical Journal  2014;55(5):1333-1340.
The aim of this work was to evaluate nuclear histone acetylation level and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in ejaculated sperm and their relevance to conventional sperm parameters.
Materials and Methods
Thirty-three normozoospermic men were included in this study. Semen samples were processed by swim-up and then immunostained by six acetylation antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our preliminary study verified the expression of HAT/HDAC1 in mature human sperm. From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by commercially available kits. Nuclear DNA integrity was also measured by TUNEL assay.
The levels of six acetylation marks were not related with conventional sperm parameters including sperm DNA fragmentation index (DFI) as well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative relationship with HDAC activity (r=-0.51, p<0.01). Strict morphology was negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity) (r=-0.53, p<0.01).
Our works demonstrated a significant relationship of acetylation-associated enzyme activity and strict morphology or sperm DFI.
PMCID: PMC4108820  PMID: 25048493
Acetylation; acetyltransferase; deacetylase; histone; sperm
2.  Anti-Müllerian Hormone Levels in the Follicular Fluid of the Preovulatory Follicle: A Predictor for Oocyte Fertilization and Quality of Embryo 
Journal of Korean Medical Science  2014;29(9):1266-1270.
This prospective study investigated the relationship between anti-Müllerian hormone (AMH) level in the follicular fluid (FF) and the quality of the oocyte and embryo. A total of 65 FF samples from 54 women were included in this study. FF was collected from the largest preovulatory follicle sized≥20 mm of mean diameter from each ovary. Samples were divided into 3 groups according to the FF AMH levels: below the 33th percentile (low group, FF AMH<2.1 ng/mL, n=21), between the 33th and the 67th percentile (intermediate group, FF AMH=2.1-3.6 ng/mL, n=22), and above the 67th percentile (high group, FF AMH>3.6 ng/mL, n=22). The quality of the ensuing oocytes and embryos was evaluated by fertilization rate and embryo score. FF AMH levels correlated positively with the matched embryo score on day 3 after fertilization (r=0.331, P=0.015). The normal fertilization rate was significantly lower in the low group than in the intermediate group (61.9% vs. 95.5% vs. 77.3%, respectively, P=0.028). Our results suggest that the FF AMH level could be a predictor of the ensuing oocyte and embryo quality.
Graphical Abstract
PMCID: PMC4168181  PMID: 25246746
Anti-Müllerian Hormone; Follicular Fluid; Oocyte Competence; Embryo Quality; In Vitro Fertilization
3.  Dose-dependent embryotrophic effect of recombinant granulocyte-macrophage colony-stimulating factor and brain-derived neurotrophic factor in culture medium for mouse preimplantation embryo 
Obstetrics & Gynecology Science  2014;57(5):373-378.
To evaluate the dose effect of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) or brain-derived neurotrophic factor (BDNF) in culture medium on the development of in vitro fertilized mouse embryos.
Mature oocytes were retrieved from superovulated female BDF1 mice and inseminated by sperm from male BDF1 mice. On day 1, two-cell stage embryos were divided and cultured until day 5 in the embryo maintenance medium supplemented with 0, 1, 2, 5, or 10 ng/mL of rmGM-CSF or supplemented with 0, 5, 10, or 20 ng/mL of BDNF. Blastocyst formation rate and their cell numbers were assessed.
The blastocyst formation rate and the total cell count in blastocyst was similar in all the rmGM-CSF treatment groups when compared with the control. However, the blastocyst formation rate and the total cell count was significantly higher in the group supplemented with 10 ng/mL of BDNF compared with the control (63.9%, 45.8±11.5 vs. 52.3%, 38.0±6.8; P<0.05, respectively).
Supplementation of 10 ng/mL of BDNF enhanced the developmental potential of mouse preimplantation embryos, but supplementation of rmGM-CSF did not.
PMCID: PMC4175597  PMID: 25264527
Brain-derived neurotrophic factor; Culture medium; Embryotrophic effects; Granulocyte-macrophage colony-stimulating factor
4.  Actinomyces-like organisms in cervical smears: the association with intrauterine device and pelvic inflammatory diseases 
Obstetrics & Gynecology Science  2014;57(5):393-396.
To investigate the incidence of actinomyces-like organisms in routine cervical smears of Korean women and to evaluate its association with the development of pelvic inflammatory disease (PID) in these women.
The results of cervical smears between 2011 and 2012 at a single university hospital were searched. If positive for actinomyces-like organisms, the medical record of the patient was searched and development of PID was followed. If the data were not available in the medical record, the patient was contacted by telephone.
The incidence of actinomyces-like organisms in cervical smears was 0.26% (52/20,390). Forty-two women (80.8%) were intrauterine device (IUD) users: the copper-IUD in 25 women and the levonorgestrel-releasing intrauterine system in 13 women (type unknown in 4 women). The majority (71.4%, 30/42) of the IUD users maintained the IUD. Prophylactic antibiotics were prescribed to 12 women. Two continuous IUD users were later diagnosed with PID, but these cases were not pelvic actinomycosis.
It would be a reasonable option to choose the expectant management for asymptomatic women who incidentally showed actinomyces-like organisms in their cervical smear.
PMCID: PMC4175600  PMID: 25264530
Actinomyces-like organism; Intrauterine devices; Vaginal smears
5.  Mitochondrial DNA Copy Number in Peripheral Blood Is Independently Associated with Visceral Fat Accumulation in Healthy Young Adults 
Aims. Visceral obesity is associated with an increased risk of cardiometabolic diseases and it is important to identify the underlying mechanisms. There is growing evidence that mitochondrial dysfunction is associated with metabolic disturbances related to visceral obesity. In addition, maintaining mitochondrial DNA (mtDNA) copy number is important for preserving mitochondrial function. Therefore, we investigated the relationship between mtDNA copy number and visceral fat in healthy young adults. Methods. A total of 94 healthy young subjects were studied. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. mtDNA copy number was measured in peripheral leukocytes using real-time polymerase chain reaction (PCR) methods. Results. The mtDNA copy number correlated with BMI (r = −0.22, P = 0.04), waist circumference (r = −0.23, P = 0.03), visceral fat area (r = −0.28, P = -0.01), HDL-cholesterol levels (r = 0.25, P = 0.02), and hs-CRP (r = 0.32, P = 0.02) after adjusting for age and sex. Both stepwise and nonstepwise multiple regression analyses confirmed that visceral fat area was independently associated with mtDNA copy number (β = -0.33, P < 0.01, β = 0.32, and P = 0.03, resp.). Conclusions. An independent association between mtDNA content and visceral adiposity was identified. These data suggest that mtDNA copy number is a potential predictive marker for metabolic disturbances. Further studies are required to understand the causality and clinical significance of our findings.
PMCID: PMC3953665  PMID: 24707289
6.  MR Findings of the Osteofibrous Dysplasia 
Korean Journal of Radiology  2014;15(1):114-122.
The aim of this study was to describe MR findings of osteofibrous dysplasia.
Materials and Methods
MR images of 24 pathologically proven osteofibrous dysplasia cases were retrospectively analyzed for a signal intensity of the lesion, presence of intralesional fat signal, internal hypointense band, multilocular appearance, cortical expansion, intramedullary extension, cystic area, cortical breakage and extraosseous extension, abnormal signal from the adjacent bone marrow and soft tissue and patterns of contrast enhancement.
All cases of osteofibrous dysplasia exhibited intermediate signal intensity on T1-weighted images. On T2-weighted images, 20 and 4 cases exhibited heterogeneously intermediate and high signal intensity, respectively. Intralesional fat was identified in 12% of the cases. Internal low-signal bands and multilocular appearance were observed in 91%. Cortical expansion was present in 58%. Intramedullary extension was present in all cases, and an entire intramedullary replacement was observed in 33%. Cortical breakage (n = 3) and extraosseous mass formation (n = 1) were observed in cases with pathologic fractures only. A cystic area was observed in one case. Among 21 cases without a pathologic fracture, abnormal signal intensity in the surrounding bone marrow and adjacent soft tissue was observed in 43% and 48%, respectively. All cases exhibited diffuse contrast enhancement.
Osteofibrous dysplasia exhibited diverse imaging features ranging from lesions confined to the cortex to more aggressive lesions with complete intramedullary involvement or perilesional marrow edema.
PMCID: PMC3909842  PMID: 24497800
Osteofibrous dysplasia; Bone neoplasms; Magnetic resonance imaging
7.  Up-Regulation of Cyclooxygenase 2 and Matrix Metalloproteinases-2 and -9 in Cutaneous Squamous Cell Carcinoma: Active Role of Inflammation and Tissue Remodeling in Carcinogenesis 
Annals of Dermatology  2013;25(2):145-151.
Tissue inflammation and remodeling have been extensively studied in various tumors in relation with their invasiveness and metastasis.
The purpose of this study was to investigate the change in tissue inflammation and remodeling markers in cutaneous squamous cell carcinoma (SCC).
Expression levels of cyclooxygenase-2 (COX-2) as an inflammatory marker and matrix metalloproteinases-2 and -9 (MMPs 2/9) as remodeling markers were studied in mouse and human SCCs. Western blot analysis and RT-PCR for COX-2 and MMPs 2/9 were performed with skin samples from SCC patients and chronic ultraviolet B (UVB)-induced SCC from hairless mice.
mRNA and protein levels of COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in mouse SCCs, which were induced by chronic UVB irradiation. Consistently, COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in human SCCs.
COX-2 and MMPs 2/9 are up-regulated in well-differentiated cutanous SCC. Our findings indicate that inflammatory and tissue remodeling processes are actively induced during carcinogenesis of cutaneous SCC.
PMCID: PMC3662905  PMID: 23717003
Cyclooxygenase 2; MMP-2; MMP-9; SCC
9.  Empty follicle syndrome 
Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved after an apparently adequate ovarian response to stimulation and meticulous follicular aspiration. EFS can be classified into 'genuine' and 'false' types according to hCG levels. It is a rare condition of obscure etiology. The existence of genuine EFS has been questioned and is still controversial. The limitation around EFS is that the definition of EFS is obscure. Management of patients with EFS is a challenge to physicians. No single treatment is known to be universally effective. However, patients should be adequately informed regarding the importance of correct hCG administration because improper hCG administration is a common and preventable cause of EFS. EFS is a syndrome that deserves additional study because such investigation could lead to a further understanding of ovarian biology and infertility.
PMCID: PMC3548070  PMID: 23346522
Infertility; Ovarian stimulation; Retrieval; Oocyte; Chorionic gonadotropin
10.  Complete Genome Sequence of Bacteriophage phiAS7, a T7-Like Virus That Infects Aeromonas salmonicida subsp. salmonicida 
Journal of Virology  2012;86(5):2894-2895.
To date, a number of Myoviridae bacteriophages that infect Aeromonadaceae have been identified and characterized. However, the genome sequences of Aeromonas phages that not belong to the Myoviridae have not been investigated yet. Herein, we report the complete genome sequence of Aeromonas phage phiAS7, which belongs to the Podoviridae and infects Aeromonas salmonicida subsp. salmonicida.
PMCID: PMC3302256  PMID: 22328699
11.  In vitro growth of mouse preantral follicles: effect of animal age and stem cell factor/insulin-like growth factor supplementation 
To determine whether animal age impacts in vitro preantral follicle growth. Effects of hCG, stem cell factor (SCF), and/or insulin-like growth factor (IGF) supplementation in growth medium were also investigated.
Intact preantral follicles were mechanically isolated from fresh ovaries of BDF1 mice and cultured in growth medium for 9 to 11 days. Surviving follicles with antrum formation were transferred to maturation medium for 14 to 18 hours. Follicle survival, antrum formation, and retrieval of metaphase II (MII) oocytes were compared among three age categories (4-5, 7-8, and 10-11 week-old). By using 7- to 8-week-old mice, preantral follicles were cultured in growth medium supplemented with hCG (0, 5, or 10 mIU/mL), SCF (50 ng/mL), IGF-1 (50 ng/mL), and SCF+IGF-1.
Seven- to eight-week-old mice showed a higher follicle survival and antrum formation and produced more MII oocytes compared to other groups. In the 7- to 8-week-old mice, supplementation of 5 mIU/mL hCG significantly enhanced the antrum formation but the percentage of MII oocytes was similar to that of the control. Supplementation of SCF+IGF-1 did not enhance follicle survival or antrum formation but the percentage of MII oocytes increased modestly (39.1%) than in the control (28.6%, statistically not significant).
Seven- to eight-week-old mice showed better outcomes in growth of preantral follicles in vitro than 4- to 5- or 10- to 11-week-old mice. Supplementation of hCG enhanced antrum formation and supplementation of SCF+IGF-1 yielded more mature oocytes; hence, these should be considered in the growth of preantral follicles in vitro.
PMCID: PMC3479233  PMID: 23106041
Ovarian follicle; Oocyte; Age groups; Stem cell factor; Insulin-like growth factor
12.  Serum Ferritin Is Differentially Associated with Anti-oxidative Status and Insulin Resistance in Healthy Obese and Non-obese Women 
Korean Journal of Family Medicine  2012;33(4):205-210.
Ferritin is known to be associated with insulin resistance (IR) and oxidative stress; however, recent studies have shown that there is an association between ferritin and anti-oxidative status. To date, the biphasic response of ferritin to oxidative stress has not been fully evaluated. Thus, we investigated the association between ferritin and IR and anti-oxidative status in obese and non-obese women.
We evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) and total anti-oxidant status (TAS) in a total of 111 healthy women between the ages of 32 and 68 years.
In all of the study subjects, ferritin levels were positively correlated with age (r = 0.38, P < 0.001), body mass index (r = 0.24, P = 0.01), TAS (r = 0.38, P < 0.001) and HOMA-IR (r = 0.20, P = 0.04). In the subgroup analysis, ferritin levels were correlated with age (r = 0.39, P < 0.001) and TAS (r = 0.43, P < 0.001) in the non-obese group and with insulin (r = 0.50, P = 0.02) and HOMA-IR (r = 0.52, P = 0.01) levels in the obese group. On stepwise multiple linear regression analysis, ferritin was found to be independently associated with TAS (B = 177.16, P < 0.0001) in the non-obese group and independently associated with HOMA-IR (B = 30.36, P = 0.01) in the obese group.
Our findings suggest ferritin is associated with IR in obese women and with anti-oxidative status in non-obese women. Further studies are warranted to elucidate the precise role of ferritin in obesity.
PMCID: PMC3418339  PMID: 22916322
Ferritins; Obesity; Oxidative Stress
13.  Serum biomarkers for predicting pregnancy outcome in women undergoing IVF: human chorionic gonadotropin, progesterone, and inhibin A level at 11 days post-ET 
This study was performed to assess the prognostic value of serum hCG, progesterone, and inhibin A levels measured at 11 days post-ET for predicting pregnancy outcome in women participating in IVF.
Between May 2005 and April 2008, sera were obtained from 70 infertile women who underwent IVF-ET at 11 days post-ET and stored. HCG, progesterone, and inhibin A levels were measured by commercial enzyme-linked immunosorbent assay kits. The predictive accuracy of hCG, progesterone, and inhibin A levels for establishment of intrauterine pregnancy and ongoing pregnancy was calculated by receiver-operating characteristic curve analysis.
For the prediction of intrauterine and ongoing pregnancy, serum hCG was better than progesterone and inhibin A. The predictive performance of progesterone and inhibin A was similar. The serum progesterone and inhibin A levels were significantly correlated each other (r=0.915, p=0.010).
A single measurement of the serum hCG level is sufficient to predict pregnancy outcome in IVF-ET patients.
PMCID: PMC3341449  PMID: 22563548
Chorionic gonadotropin; Progesterone; Inhibins; In vitro fertilization; Embryo transfer; Outcomes, pregnancy
14.  A Clinical Study of Cutaneous Adverse Reactions to Nonionic Contrast Media in Korea 
Annals of Dermatology  2012;24(1):22-25.
The use of intravenous contrast media (CM) has increased for the diagnosis of several diseases. The newly developed low osmolar nonionic contrast agents cause significantly decreased adverse reactions than the higher osmolar ones. However, adverse reactions may still occur, ranging in severity from minor side effects to severe complications. However, there have been few reports about cutaneous adverse reactions (CARs) to nonionic monomer CM.
The purpose of this study was to evaluate clinical features of CAR to intravenous nonionic monomer CM.
A total 47,338 examinees underwent intravenous iodinated contrast-enhanced computed tomography scan using nonionic monomer CM. Among the adverse reactions to the CM, we divided them into cutaneous or noncutaneous and immediate (<1 hr) or late (≥1 hr) adverse reactions.
Adverse reactions were noted in 62 cases out of the total 47,338 cases; 50 cases (80.7%) were categorized CARs. Among them, there were 24 male and 26 female patients. There was no significant difference between the sexes, and CARs occurred in all age groups. The highest occurrence was in the age range of 50~59 years. CARs included urticaria (78%), angioedema (10%), maculopapular rash (8%), erythema (2%), and pruritus without rash (2%). Immediate reactions were 92% (46 cases), while late reactions were 8% (4 cases).
CARs to nonionic monomer CM accounted for most of the adverse reactions (80.7%) and urticaria was the most common.
PMCID: PMC3283846  PMID: 22363151
Contrast media; CT; Cutaneous adverse reaction
15.  Molecular characterization of tetracycline- and quinolone-resistant Aeromonas salmonicida isolated in Korea 
Journal of Veterinary Science  2011;12(1):41-48.
The antibiotic resistance of 16 Aeromonas (A.) salmonicida strains isolated from diseased fish and environmental samples in Korea from 2006 to 2009 were investigated in this study. Tetracycline or quinolone resistance was observed in eight and 16 of the isolates, respectively, based on the measured minimal inhibitory concentrations. Among the tetracycline-resistant strains, seven of the isolates harbored tetA gene and one isolate harbored tetE gene. Additionally, quinolone-resistance determining regions (QRDRs) consisting of the gyrA and parC genes were amplified and sequenced. Among the quinolone-resistant A. salmonicida strains, 15 harbored point mutations in the gyrA codon 83 which were responsible for the corresponding amino acid substitutions of Ser83→Arg83 or Ser83→Asn83. We detected no point mutations in other QRDRs, such as gyrA codons 87 and 92, and parC codons 80 and 84. Genetic similarity was assessed via pulsed-field gel electrophoresis, and the results indicated high clonality among the Korean antibiotic-resistant strains of A. salmonicida.
PMCID: PMC3053466  PMID: 21368562
Aeromonas salmonicida; minimal inhibitory concentration; pulsed-field gel electrophoresis; quinolone-resistance determining region; tetracycline-resistance
16.  Lateral Decubitus Positioning Stereotactic Vacuum-Assisted Breast Biopsy with True Lateral Mammography 
Journal of Breast Cancer  2011;14(1):64-68.
Stereotactic vacuum-assisted breast biopsy (VAB) has been used to evaluate microcalcifications or non-palpable breast lesions on mammography. Although stereotactic VAB is usually performed in a prone or upright position, an expensive prone table is necessary and vasovagal reactions often occur during the procedure. For these reasons, the lateral decubitus position can be applied for stereotactic VAB, and true lateral mammography can be used to detect the lesion. We report on 15 cases of lateral decubitus positioning for stereotactic VAB with true lateral mammography for non-palpable breast lesions or microcalcifications. The mean procedure time was approximately 30.1 minutes, and no complications occurred during the procedures. Fourteen cases had benign breast lesions and one case had a ductal carcinoma in situ. The lateral decubitus stereotactic VAB with true lateral mammography can be applied for microcalcifications or non-palpable breast lesions and helps to minimize anxiety and vasovagal reactions in patients.
PMCID: PMC3148512  PMID: 21847397
Stereotactic techniques; Breast biopsy; Lateral positioning; Mammography
17.  Sequence and structure of Brassica rapa chromosome A3 
Genome Biology  2010;11(9):R94.
The species Brassica rapa includes important vegetable and oil crops. It also serves as an excellent model system to study polyploidy-related genome evolution because of its paleohexaploid ancestry and its close evolutionary relationships with Arabidopsis thaliana and other Brassica species with larger genomes. Therefore, its genome sequence will be used to accelerate both basic research on genome evolution and applied research across the cultivated Brassica species.
We have determined and analyzed the sequence of B. rapa chromosome A3. We obtained 31.9 Mb of sequences, organized into nine contigs, which incorporated 348 overlapping BAC clones. Annotation revealed 7,058 protein-coding genes, with an average gene density of 4.6 kb per gene. Analysis of chromosome collinearity with the A. thaliana genome identified conserved synteny blocks encompassing the whole of the B. rapa chromosome A3 and sections of four A. thaliana chromosomes. The frequency of tandem duplication of genes differed between the conserved genome segments in B. rapa and A. thaliana, indicating differential rates of occurrence/retention of such duplicate copies of genes. Analysis of 'ancestral karyotype' genome building blocks enabled the development of a hypothetical model for the derivation of the B. rapa chromosome A3.
We report the near-complete chromosome sequence from a dicotyledonous crop species. This provides an example of the complexity of genome evolution following polyploidy. The high degree of contiguity afforded by the clone-by-clone approach provides a benchmark for the performance of whole genome shotgun approaches presently being applied in B. rapa and other species with complex genomes.
PMCID: PMC2965386  PMID: 20875114
18.  A Case of Complication after Matridex® Injection 
Annals of Dermatology  2010;22(1):81-84.
Matridex® is an injectable skin filler that's composed of a mixture of cross linked hyaluronic acid and dextranomer particles, and it was recently developed for soft tissue augmentation. To the best of our knowledge, there have been few previous reports on complications associated with Matridex. We report here on a delayed inflammatory reaction to an injection of Matridex in the glabellar fold, and this developed five weeks after the injection and it lasted more than a year. The patient was treated with oral doxycycline and intralesional injection of triamcinolone acetonide; this resulted in almost complete resolution of the lesion. The patient should be informed of the potential complications with the use of injectable fillers before treatment, for it could lead to undesirable aesthetic consequences.
PMCID: PMC2883406  PMID: 20548890
Complication; Delayed inflammatory reaction; Filler; Matridex
19.  Necrotizing Fasciitis versus Pyomyositis: Discrimination with Using MR Imaging 
Korean Journal of Radiology  2009;10(2):121-128.
We wanted to evaluate the MR findings for differentiating between necrotizing fasciitis (NF) and pyomyositis (PM).
Materials and Methods
The MR images of 19 patients with surgically confirmed NF (n = 11) and pathologically confirmed PM (n = 8) were retrospectively reviewed with regard to the presence or absence of any MRI finding criteria that could differentiate between them.
The patients with NF had a significantly greater prevalence of the following MR findings (p < 0.05): a peripheral band-like hyperintense signal in muscles on fat-suppressed T2-weighted images (73% of the patients with NF vs. 0% of the patients with PM), peripheral band-like contrast enhancement (CE) of muscles (82% vs. 0%, respectively) and thin smooth enhancement of the deep fascia (82% vs. 13%, respectively). The patients with PM had a significantly greater prevalence of the following MRI findings (p < 0.05): a diffuse hyperintense signal in muscles on fat-suppressed T2-weighted images (27% of the patients with NF vs. 100% in the patients with PM), diffuse CE of muscles (18% vs. 100%, respectively), thick irregular enhancement of the deep fascia (0% vs. 75%, respectively) and intramuscular abscess (0% vs. 88%, respectively). For all patients with NF and PM, the superficial fascia and muscle showed hyperintense signals on T2-weighted images and CE was seen on fat-suppressed CE T1-weighted images. The subcutaneous tissue and deep fascia showed hyperintense signals on T2-weighted images and CE was seen in all the patients with NF and in seven (88%) of the eight patients with PM, respectively.
MR imaging is helpful for differentiating between NF and PM.
PMCID: PMC2651441  PMID: 19270857
Soft tissue; Infection; Necrotizing fasciitis; Pyomyositis, MR
20.  Multiple Sclerosis and Peripheral Multifocal Demyelinating Neuropathies Occurring in a Same Patient 
The co-occurrence of multiple sclerosis and peripheral demyelinating neuropathy is rare. It has been disputed whether these are pathologically related or coincidental findings. We report a 36-year-old woman who presented with diplopia, right facial palsy and left-sided weakness. Brain magnetic resonance imaging showed a lesion indicative of central demyelinating disease. Nerve conduction studies revealed peripheral multifocal demyelinating neuropathies. We suggest that the central and the peripheral lesions may be continua of a demyelinating process.
PMCID: PMC2686880  PMID: 19513326
Multiple sclerosis; Demyelinating neuropathy; Conduction block
21.  Identification of Enteroviruses by Using Monoclonal Antibodies against a Putative Common Epitope 
Journal of Clinical Microbiology  2003;41(7):3028-3034.
A common epitope region of enteroviruses was identified by sequence-independent single-primer amplification (SISPA), followed by immunoscreening of 11 cDNA libraries from two Korean enterovirus isolates (echoviruses 7 and 30) and a coxsackievirus B3 (ATCC-VR 30). The putative common epitope region was localized in the N terminus of VP1 when the displayed recombinant proteins from the phages were chased by the convalescent-phase sera. The genomic region encoding the common epitope region was amplified and then expressed by using the vector pGEX-5X-1. The antigenicity of the expressed recombinant protein was identified by Western blotting with guinea pig antisera for six different serotypes of enteroviruses. After successive immunization of mice with the recombinant common epitope protein, splenocytes were extracted and hybridized with P3X63-Ag8-653 cells. A total of 24 hybridomas that produced monoclonal antibodies (MAbs) against the putative common epitope of enteroviruses were selected. Four of these were immunoglobulin G1 isotypes with a kappa light chain. These MAbs recognized 15 Korean endemic serotypes and prototypes of enteroviruses in an indirect immunofluorescence assay. These results suggest that the expressed protein might be a useful antigen for producing group common antibodies and that the use of the MAbs against the putative common epitope of enteroviruses might be a valuable diagnostic tool for rapidly identifying a broad range of enteroviruses.
PMCID: PMC165318  PMID: 12843038
22.  Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery 
The Journal of Cell Biology  2014;206(4):493-507.
Phosphorylated RPA recruits repair factors to stalled forks, thereby enhancing fork integrity during replication stress.
Phosphorylation of replication protein A (RPA) by Cdk2 and the checkpoint kinase ATR (ATM and Rad3 related) during replication fork stalling stabilizes the replisome, but how these modifications safeguard the fork is not understood. To address this question, we used single-molecule fiber analysis in cells expressing a phosphorylation-defective RPA2 subunit or lacking phosphatase activity toward RPA2. Deregulation of RPA phosphorylation reduced synthesis at forks both during replication stress and recovery from stress. The ability of phosphorylated RPA to stimulate fork recovery is mediated through the PALB2 tumor suppressor protein. RPA phosphorylation increased localization of PALB2 and BRCA2 to RPA-bound nuclear foci in cells experiencing replication stress. Phosphorylated RPA also stimulated recruitment of PALB2 to single-strand deoxyribonucleic acid (DNA) in a cell-free system. Expression of mutant RPA2 or loss of PALB2 expression led to significant DNA damage after replication stress, a defect accentuated by poly-ADP (adenosine diphosphate) ribose polymerase inhibitors. These data demonstrate that phosphorylated RPA recruits repair factors to stalled forks, thereby enhancing fork integrity during replication stress.
PMCID: PMC4137056  PMID: 25113031
23.  A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2 
Human Molecular Genetics  2013;23(4):1108-1119.
Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10−14) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10−7). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10−165), ADIPOQ (P = 1.8 × 10−22), PEPD (P = 3.6 × 10−12), CMIP (P = 2.1 × 10−10), ZNF664 (P = 2.3 × 10−7) and GPR109A (P = 7.4 × 10−6). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10−7). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10−4), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10−4) and body mass index (BMI)-adjusted waist–hip ratio (P = 9.8 × 10−3). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.
PMCID: PMC3900106  PMID: 24105470
24.  Genome-wide SNP identification and QTL mapping for black rot resistance in cabbage 
BMC Plant Biology  2015;15:32.
Black rot is a destructive bacterial disease causing large yield and quality losses in Brassica oleracea. To detect quantitative trait loci (QTL) for black rot resistance, we performed whole-genome resequencing of two cabbage parental lines and genome-wide SNP identification using the recently published B. oleracea genome sequences as reference.
Approximately 11.5 Gb of sequencing data was produced from each parental line. Reference genome-guided mapping and SNP calling revealed 674,521 SNPs between the two cabbage lines, with an average of one SNP per 662.5 bp. Among 167 dCAPS markers derived from candidate SNPs, 117 (70.1%) were validated as bona fide SNPs showing polymorphism between the parental lines. We then improved the resolution of a previous genetic map by adding 103 markers including 87 SNP-based dCAPS markers. The new map composed of 368 markers and covers 1467.3 cM with an average interval of 3.88 cM between adjacent markers. We evaluated black rot resistance in the mapping population in three independent inoculation tests using F2:3 progenies and identified one major QTL and three minor QTLs.
We report successful utilization of whole-genome resequencing for large-scale SNP identification and development of molecular markers for genetic map construction. In addition, we identified novel QTLs for black rot resistance. The high-density genetic map will promote QTL analysis for other important agricultural traits and marker-assisted breeding of B. oleracea.
Electronic supplementary material
The online version of this article (doi:10.1186/s12870-015-0424-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4323122  PMID: 25644124
Cabbage; Whole-genome resequencing; Genetic linkage map; Black rot; QTL
25.  A Candidate Single Nucleotide Polymorphism in the 3′ Untranslated Region of Stearoyl-CoA Desaturase Gene for Fatness Quality and the Gene Expression in Berkshire Pigs 
Fatness qualities in pigs measured by the amount of fat deposition and composition of fatty acids (FAs) in pork have considerable effect on current breeding goals. The stearoyl-CoA desaturase (SCD) gene plays a crucial role in the conversion of saturated FAs into monounsaturated FAs (MUFAs), and hence, is among the candidate genes responsible for pig fatness traits. Here, we identified a single nucleotide polymorphism (SNP, c.*2041T>C) in the 3′ untranslated region by direct sequencing focused on coding and regulatory regions of porcine SCD. According to the association analysis using a hundred of Berkshire pigs, the SNP was significantly associated with FA composition (MUFAs and polyunsaturated FAs [PUFAs]), polyunsaturated to saturated (P:S) FA ratio, n-6:n-3 FA ratio, and extent of fat deposition such as intramuscular fat and marbling (p<0.05). In addition, the SNP showed a significant effect on the SCD mRNA expression levels (p = 0.041). Based on our results, we suggest that the SCD c.*2041T>C SNP plays a role in the gene regulation and affects the fatness qualities in Berkshire pigs.
PMCID: PMC4283158  PMID: 25557809
Stearoyl-CoA Desaturase [SCD]; Polymorphism; Gene Expression; Fatness Quality; Berkshire

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