Publications by authors named "Jina Park"

51 Publications

CORO7 functions as a scaffold protein for the core kinase complex assembly of the Hippo pathway.

J Biol Chem 2020 Nov 23;296:100040. Epub 2020 Nov 23.

School of Biological Sciences, Seoul National University, Seoul, Republic of Korea; Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea. Electronic address:

The Hippo pathway controls organ size and tissue homeostasis through the regulation of cell proliferation and apoptosis. However, the exact molecular mechanisms underpinning Hippo pathway regulation are not fully understood. Here, we identify a new component of the Hippo pathway: coronin 7 (CORO7), a coronin protein family member that is involved in organization of the actin cytoskeleton. pod1, the Drosophila ortholog of CORO7, genetically interacts with key Hippo pathway genes in Drosophila. In mammalian cells, CORO7 is required for the activation of the Hippo pathway in response to cell-cell contact, serum deprivation, and cytoskeleton damage. CORO7 forms a complex with the core components of the pathway and functions as a scaffold for the Hippo core kinase complex. Collectively, these results demonstrate that CORO7 is a key scaffold controlling the Hippo pathway via modulating protein-protein interactions.
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http://dx.doi.org/10.1074/jbc.RA120.013297DOI Listing
November 2020

CORO7 functions as a scaffold protein for the core kinase complex assembly of the Hippo pathway.

J Biol Chem 2020 Nov 8. Epub 2020 Nov 8.

School of Biological Sciences, Seoul National University, Republic of Korea.

The Hippo pathway controls organ size and tissue homeostasis through the regulation of cell proliferation and apoptosis. However, the exact molecular mechanisms underpinning Hippo pathway regulation is not fully understood. Here, we identify a new component of the Hippo pathway: CORO7, a coronin protein family member that is involved in organization of the actin cytoskeleton. pod1, the Drosophila orthologue of CORO7, genetically interacts with key Hippo pathway genes in Drosophila. In mammalian cells, CORO7 is required for the activation of the Hippo pathway in response to cell-cell contact, serum deprivation, and cytoskeleton damage. CORO7 forms a complex with the core components of the pathway and functions as a scaffold for the Hippo core kinase complex. Collectively, these results demonstrate that CORO7 is a key scaffold controlling the Hippo pathway via modulating protein-protein interactions.
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http://dx.doi.org/10.1074/jbc.RA120.013297DOI Listing
November 2020

Socioeconomic dependency and kidney transplantation accessibility and outcomes: a nationwide observational cohort study in South Korea.

J Nephrol 2021 02 13;34(1):211-219. Epub 2020 Oct 13.

Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: Socioeconomic status is an important determinant for patients' accessibility to, and prognosis of, kidney transplantation. However, the association between socioeconomic dependency and kidney transplantation accessibility or prognosis after kidney transplantation remains unclear.

Methods: In this nationwide cohort study, based on the claims database of South Korea, we included 12,889 kidney transplant recipients from 2007 to 2015 and stratified them according to health insurance categories that reflect socioeconomic dependency: workplace-independent (employed, N = 3257), workplace-dependent (dependent to the workplace-independent, N = 3661), community-representative (heads of the household but self-employed or unemployed, N = 2479), community-member (N = 1618), aided-representative (heads of household receiving medical aid from the government, N = 1580), and aided-member (N = 294). The incidence of kidney transplantation was calculated to evaluate its accessibility. The risk of graft failure was assessed using the Cox regression analysis, adjusted for clinicodemographic variables, including financial status.

Results: End-stage kidney disease patients who were employed (workplace-independent group) had the highest incidence proportion of kidney transplantation. The dependent groups' prognoses were worse than those of their independent counterparts [workplace-dependent versus workplace-independent, HR 1.26 (1.11-1.43) and community-dependent versus community-independent, HR 1.46 (1.23-1.74)], although no difference was observed between the aided subgroups [aided-dependent versus aided-independent, adjusted HR 1.16 (0.90-1.50)].

Conclusion: Disparities in kidney transplantation accessibility were present in South Korea according to socioeconomic dependency; these differences may have an impact on prognosis.
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http://dx.doi.org/10.1007/s40620-020-00876-0DOI Listing
February 2021

Functional Voice and Swallowing Outcome Analysis After Thyroid Lobectomy: Transoral Endoscopic Vestibular Versus Open Approach.

World J Surg 2020 Dec 11;44(12):4127-4135. Epub 2020 Aug 11.

Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.

Background: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a scarless remote-access thyroidectomy technique. This study compared subjective and objective voice outcomes and swallowing outcomes of patients who underwent thyroid lobectomy using the TOETVA versus conventional open thyroidectomy (OT).

Methods: In addition to questionnaires, acoustic and aerodynamic analyses were performed to compare subjective and objective voice outcomes of the two groups. Swallowing outcome analyses were conducted using Swallowing Impairment Index-6 (SIS-6) scores. Assessments were performed preoperatively and 3 and 6 months after surgery. Propensity score matching was performed to compare the outcomes of the two groups.

Results: One hundred and two patients were included in this study (52 TOETVA and 50 OT). Excluding two patients who had vocal cord palsy and open conversion in the TOETVA group, 100 patients completed 3-month postoperative surveys. There were no significant differences between the groups in VAS, GRBAS, or VHI-10 scores at the preoperative and 3- and 6-month assessments. For both groups, there were no significant changes in acoustic or aerodynamic parameters during the 3-6-month postoperative period. The TOETVA group had lower SIS-6 scores at the postoperative 6-month assessment, but the SIS-6 scores after 12 months were similar between groups before and after propensity score matching.

Conclusions: Following TOETVA lobectomy, there were no significant changes in voice outcomes 3 and 6 months after surgery, and the outcomes were comparable with those of OT. The TOETVA group also had swallowing outcomes that were comparable with the OT group.
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http://dx.doi.org/10.1007/s00268-020-05731-8DOI Listing
December 2020

Life-history features and oceanography drive phylogeographic patterns of the chiton cf. (Lischke, 1873) in the northwestern Pacific.

PeerJ 2020 8;8:e8794. Epub 2020 Apr 8.

Division of EcoScience, Ewha Womans University, Seoul, Republic of Korea.

Chitons are a group of marine mollusks (class Polyplacophora) characterized by having eight articulating shell plates on their dorsal body surface. They represent suitable materials for studying the spatiotemporal processes that underlie population differentiation and speciation in ocean environments. Here we performed population genetic analyses on the northwestern Pacific chiton cf. (Lischke, 1873) using two mitochondrial gene fragments (COI and 16S) from 180 individuals sampled from 11 populations among the coastal waters of Korea, Japan, and China. The phylogenetic network uncovered a reticulated relationship with several sub-haplogroups for all cf. haplotypes. SAMOVA analyses suggested the best grouping occurred at three groups (Φ = 0.151,  < 0.0001), which geographically corresponds to hydrographic discontinuity among the coastal regions of Korea, Japan, and China. The assumed limited dispersal ability of cf. , coupled with northeasterly flowing, trifurcate warm currents, might have contributed to the genetic differentiation among the three groups. Meanwhile, a high level of within-group genetic homogeneity was detected, indicating extensive coastal currents might facilitate gene flow among the populations within each group. Bayesian skyline plots demonstrated significant population expansion after the Last Glacial Period (110-25 thousand years ago) for all studied populations except the Japan group. Together these results suggest that the present-day phylogeographic patterns of cf. are strongly affected by the interplay of historical and/or contemporary oceanography and species-specific life-history features.
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http://dx.doi.org/10.7717/peerj.8794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359822PMC
April 2020

Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction.

Ann Neurol 2020 09 27;88(3):526-543. Epub 2020 Jul 27.

Department of Neuroscience, College of Medicine, Korea University.

Objective: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2 ) mice to understand their neurobehavioral phenotypes and the underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2 mice and specified a neuronal function mediating its efficacy.

Methods: We performed behavioral analyses of Cyfip2 mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses of Cyfip2 prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with virus injections.

Results: Adult Cyfip2 mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adult Cyfip2 PFC that was restricted to layer 5 (L5) neurons. Consistently, adult Cyfip2 mice showed increased seizure susceptibility and auditory steady-state responses from the cortical electroencephalographic recordings. Among the identified prefrontal defects, lithium selectively normalized the hyperexcitability of Cyfip2 L5 neurons. RNA sequencing revealed reduced expression of potassium channel genes in the adult Cyfip2 PFC. Virus-mediated reduction of CYFIP2 in the PFC was sufficient to induce L5 hyperexcitability and lithium-responsive abnormal behavior.

Interpretation: These results suggest that L5-specific prefrontal dysfunction, especially hyperexcitability, underlies both the pathophysiology and the lithium-mediated amelioration of neurobehavioral phenotypes in adult Cyfip2 mice, which can be implicated in CYFIP2-associated brain disorders. ANN NEUROL 2020;88:526-543.
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http://dx.doi.org/10.1002/ana.25827DOI Listing
September 2020

Disparity in Accessibility to and Prognosis of Kidney Transplantation According to Economic Inequality in South Korea: A Widening Gap After Expansion of Insurance Coverage.

Transplantation 2021 02;105(2):404-412

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Nationwide studies on the effects of wealth inequality on kidney transplantation are rare, particularly in a country with an expanded National Health Insurance Service and in Asian countries.

Methods: In this nationwide, population-based cohort study, we reviewed the national claims database of Korea in which details of nationwide health insurance are provided. From 2007 to 2015, 9 annual cohorts of end-stage renal disease patients were included. The annual financial statuses were collected and stratified into 5 subgroups in each year: the aided group in which insurance fee was waived and the 4 other groups divided by quartiles of their medical insurance fee. Time trends of incidence proportion of kidney transplantation among end-stage renal disease patients in each year were initially assessed. The risk of graft failure, both including death-censored graft failure and death with a functioning graft, was analyzed as a prognostic outcome within the transplant recipients.

Results: Significant disparity in the accessibility of kidney transplantation was present, and it was further widening, particularly from 2009 in which the National Health Insurance Service started to cover desensitized kidney transplantation. Desensitized or preemptive transplantation was less common in the poorest group who were more frequently receiving transplantation after 5 years of dialysis in the latter years. The prognosis of kidney transplantation was significantly worse in the poorer people, and this disparity also worsened during the study period.

Conclusions: Prominent disparity regarding accessibility to and prognosis of kidney transplantation was observed in Korea according to wealth inequality, and this disparity was worsening.
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http://dx.doi.org/10.1097/TP.0000000000003256DOI Listing
February 2021

Clinical Utility of Quantitative CT Analysis for Fissure Completeness in Bronchoscopic Lung Volume Reduction: Comparison between CT and Chartis™.

Korean J Radiol 2019 07;20(7):1216-1225

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: The absence of collateral ventilation (CV) is crucial for effective bronchoscopic lung volume reduction (BLVR) with an endobronchial valve. Here, we assessed whether CT can predict the Chartis™ results.

Materials And Methods: This study included 69 patients (mean age: 70.9 ± 6.6 years; 66 [95.7%] males) who had undergone CT to assess BLVR eligibility. The Chartis™ system (Pulmonox Inc.) was used to check CV. Experienced thoracic radiologists independently determined the completeness of fissures on volumetric CT images.

Results: The comparison between the visual and quantitative analyses revealed that 5% defect criterion showed good agreement. The Chartis™ assessment was performed for 129 lobes; 11 (19.6%) of 56 lobes with complete fissures on CT showed positive CV, while this rate was significantly higher (40 of 49 lobes, i.e., 81.6%) for lobes with incomplete fissures. The size of the fissure defect did not affect the rate of CV. Of the patients who underwent BLVR, 22 of 24 patients (91.7%) with complete fissures and three of four patients with incomplete fissures (75%) achieved target lobe volume reduction (TLVR).

Conclusion: The quantitative analysis of fissure shows that incomplete fissures increased the probability of CV on Chartis™, while the defect size did not affect the overall rates. TLVR could be achieved even in some patients with relatively large fissure defect, if they showed negative CV on Chartis™.
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http://dx.doi.org/10.3348/kjr.2018.0724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609435PMC
July 2019

Inositol polyphosphate multikinase deficiency leads to aberrant induction of synaptotagmin-2 in the forebrain.

Mol Brain 2019 06 20;12(1):58. Epub 2019 Jun 20.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea.

Inositol polyphosphate multikinase (IPMK), the key enzyme responsible for the synthesis of higher inositol polyphosphates and phosphatidylinositol 3, 4, 5-trisphosphate, is known to mediate various biological events, such as cellular growth and metabolism. Conditional deletion of IPMK in excitatory neurons of the mouse postnatal forebrain results in enhanced extinction of fear memory accompanied by activation of p85 S6 kinase 1 signaling in the amygdala; it also facilitates hippocampal long-term potentiation. However, the molecular changes triggered by IPMK deletion in the brain have not been fully elucidated. In the present study, we investigated gene expression changes in the hippocampal region of IPMK conditional knockout (cKO) mice by performing genome-wide transcriptome analyses. Here we show that expression of synaptotagmin 2 (Syt2), a synaptic vesicle protein essential for Ca-dependent neurotransmitter release, is robustly upregulated in the forebrain of IPMK mice. Compared to wild-type mice, in which weak Syt2 expression was detected in the forebrain, IPMK mice showed marked increases in both Syt2 mRNA and protein expression in the hippocampus as well as the amygdala. Collectively, our results suggest a physiological role for IPMK in regulating expression of Syt2, providing a potential underlying molecular mechanism to explain IPMK-mediated neural functions.
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http://dx.doi.org/10.1186/s13041-019-0480-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584979PMC
June 2019

Laser asymmetric ablation method to improve corneal shape.

Lasers Med Sci 2019 Dec 22;34(9):1763-1779. Epub 2019 Mar 22.

ShapeVision Co., Hwaseong City, Republic of Korea.

This study aims to assess whether central-symmetric corneal thickness reduces off-centered corneal shift caused by intraocular pressure (IOP). In this retrospective study, 122 healthy eyes of 62 presbyopic patients, mostly myopic, were divided into two groups. Two distinct asymmetric corneal ablations were applied in peripheral presbyopia correction to produce central-symmetric corneal thickness, which reduces the off-centered corneal shift by utilizing intraocular pressure. The first method used a 90° angled combination in group 1 and the second method used a 45° angled combination in group 2. Target refraction was spherical equivalent of - 1D. Self-developed image processing algorithm analyzed the change in thickness and the posterior cone, and obtained two factors: central symmetry (f) and visual axis deviation (d), from each eye's pre and postoperative maps of Orbscan II. UDVA and UNVA were also analyzed. In both groups, mean SE was about - 1D and there was no significant difference in UDVA. UNVA was better in group 2 than group 1. Only in group 2, corneal thickness and posterior cone became central-symmetric and the posterior corneal apex point relocated towards the visual axis. The p values were 0.03, 0.04, and 0.03, respectively. This is the first study to control corneal shape by utilizing the interaction between intraocular pressure and corneal thickness. Only group 2 was applied with asymmetric corneal ablation created by the 45° angled combination of semi-cylindrical ablation patterns, and intraocular pressure contributed significantly to reduce the off-centered corneal shift and reshaped the posterior corneal cone to the center.
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http://dx.doi.org/10.1007/s10103-019-02770-zDOI Listing
December 2019

Reliable measurements of physiologic ankle syndesmosis widening using dynamic 3D ultrasonography: a preliminary study.

Ultrasonography 2019 Jul 14;38(3):236-245. Epub 2018 Nov 14.

Department of Radiology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.

Purpose: The purpose of this study was to present a technique for measuring physiologic distal tibiofibular syndesmosis widening using 3-dimensional ultrasonography (3D-US) with an evaluation of its reliability, and to determine whether there were differences in the measurements between different dynamic stress tests.

Methods: We retrospectively evaluated 3D-US of 20 subjects with normal ankle syndesmosis. 3D-US was performed in neutral (N), dorsiflexion with external rotation (DFER), and weightbearing standing (WB) positions at the anterior inferior tibiofibular ligament level in both ankles for comparison. Using 3D-US volume data, axial images were reconstructed at the level of the lateral prominence of the anterior tibial tubercle to ensure consistent measurements of the tibiofibular clear space (TFCS) by two radiologists.

Results: There was a wide range of TFCS values among the subjects (N, 1.2 to 4.2 mm; DFER, 2.3 to 4.8 mm; WB, 1.7 to 4.6 mm). When both ankles of each subject were evaluated, the side-toside differences were less than 1 mm in all positions, with high intraclass correlation coefficient (ICC) values between both ankles (ICC, 0.85 to 0.93). The inter-rater agreement for all TFCS measurements between the two radiologists was excellent (ICC, 0.81 to 0.96). In comparisons between the two dynamic stress tests, the TFCS was significantly wider in the DFER position than in the WB position (DFER vs. WB, 3.3 mm vs. 2.9 mm; P<0.001).

Conclusion: Using 3D-US, we were able to consistently evaluate the TFCS with good reliability. In a comparison of the two dynamic tests, there was more significant widening of the TFCS in the DFER position than in the WB position.
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http://dx.doi.org/10.14366/usg.18056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595131PMC
July 2019

Mapping the research trends on the biological effects of radiation less than 100 mSv: a bibliometric analysis for 30 years publication.

Int J Radiat Biol 2019 05 27;95(5):527-536. Epub 2019 Feb 27.

a Laboratory of Low Dose Risk Assessment , National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences , Seoul , Korea.

Purpose: The purpose of this study is to evaluate the global scientific publication of biological research of low dose radiation for the past 30 years and provide the insights into the characteristics of research activities and major topics regarding biological effects of low dose radiation exposure.

Materials And Methods: We bibliometrically investigated the biological research publication of radiation exposure less than 100 mSv. References published from 1987 to 2016 were achieved from the Scopus database and filtered by several criteria such as publication types, research fields, and radiation dose range.

Results: Total 753 references were assembled for the bibliometric analysis on the biological studies of radiation effect less than 100 mSv. It provided fundamental knowledge of research, including production tendency, contribution, impact journals, and major research themes. Based on the keyword analysis, we found that specific topics on the biological response to radiation exposure have been changed from the examination of low dose radiation-induced phenomena to the investigation of how to induce a physiological response. In addition, featured articles showed the various views on the biological effects of radiation less than 100 mSv in 30 years publication, depending on radiation doses and types.

Conclusions: Continuous studies in large programs of low dose radiation led to the increment of research achievements in accordance with societal needs in radiation safety regulation for health protection. Our findings can surely help radiation researchers to gain insights and penetration in low dose risk research for radiation protection, and establish a further research direction.
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http://dx.doi.org/10.1080/09553002.2019.1552373DOI Listing
May 2019

Inositol polyphosphate multikinase mediates extinction of fear memory.

Proc Natl Acad Sci U S A 2019 02 28;116(7):2707-2712. Epub 2019 Jan 28.

The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

Inositol polyphosphate multikinase (IPMK), the key enzyme for the biosynthesis of higher inositol polyphosphates and phosphatidylinositol 3,4,5trisphosphate, also acts as a versatile signaling player in regulating tissue growth and metabolism. To elucidate neurobehavioral functions of IPMK, we generated mice in which IPMK was deleted from the excitatory neurons of the postnatal forebrain. These mice showed no deficits in either novel object recognition or spatial memory. IPMK conditional knockout mice formed cued fear memory normally but displayed enhanced fear extinction. Signaling analyses revealed dysregulated expression of neural genes accompanied by selective activation of the mechanistic target of rapamycin (mTOR) regulatory enzyme p85 S6 kinase 1 (S6K1) in the amygdala following fear extinction. The IPMK mutants also manifested facilitated hippocampal long-term potentiation. These findings establish a signaling action of IPMK that mediates fear extinction.
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http://dx.doi.org/10.1073/pnas.1812771116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377498PMC
February 2019

Anterior capsular abnormality: another important MRI finding for the diagnosis of adhesive capsulitis of the shoulder.

Skeletal Radiol 2019 Apr 11;48(4):543-552. Epub 2018 Sep 11.

Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, Republic of Korea.

Objective: To evaluate the usefulness of anterior capsular abnormality, thickening, and abnormal signal intensity on MRI for the diagnosis of adhesive capsulitis of the shoulder.

Materials And Methods: This retrospective study included 29 patients with adhesive capsulitis and 20 controls. Clinical criteria with significant restricted passive motion was used for the diagnosis of adhesive capsulitis. The anterior capsular thickness and signal intensity were evaluated on the thickest portion of anterior glenohumeral joint capsule, located deep to the subscapularis muscle. In addition, the previously known MR findings of adhesive capsulitis, such as humeral and glenoid capsular thickness in axillary recess, maximal axillary capsular thickness, and coracohumeral ligament thickness, were measured. The presence of humeral and glenoid capsular abnormal hyperintensity in axillary recess, abnormal hyperintensity, and obliteration of the subcoracoid fat triangle were also evaluated.

Results: All MRI findings significantly differed between adhesive capsulitis and controls. Among MR findings, multivariable analysis showed that anterior capsular thickness, maximal axillary capsular thickness, and anterior capsular abnormal hyperintensity were variables that could differentiate adhesive capsulitis from the control group, with odds ratios of 7.97, 17.75, and 12.41, respectively (p < 0.05). In ROC analysis, the anterior capsular thickness showed high diagnostic performances with an AUC of 0.897. The cut-off value of anterior capsular thickness at 3.5 mm showed excellent diagnostic accuracy, with sensitivity of 68.97% and specificity of 100%.

Conclusions: Anterior capsular abnormality, thickening, and abnormal hyperintensity can be used for the diagnosis of adhesive capsulitis of shoulder, in addition to previously known abnormal MRI findings.
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http://dx.doi.org/10.1007/s00256-018-3064-8DOI Listing
April 2019

Time-Lapse Live-Cell Imaging Reveals Dual Function of Oseg4, WDR35, in Ciliary Protein Trafficking.

Mol Cells 2018 Jul 9;41(7):676-683. Epub 2018 Jul 9.

Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Seoul 03722, Korea.

Cilia are highly specialized antennae-like organelles that extend from the cell surface and act as cell signaling hubs. Intraflagellar transport (IFT) is a specialized form of intracellular protein trafficking that is required for the assembly and maintenance of cilia. Because cilia are so important, mutations in several IFT components lead to human disease. Thus, clarifying the molecular functions of the IFT proteins is a high priority in cilia biology. Live imaging in various species and cellular preparations has proven to be an important technique in both the discovery of IFT and the mechanisms by which it functions. Live imaging of cilia, however, has not yet been reported. Here, we have visualized the movement of IFT in cilia using time-lapse live imaging for the first time. We found that NOMPB-GFP (IFT88) moves according to distinct parameters depending on the ciliary segment. NOMPB-GFP moves at a similar speed in proximal and distal cilia toward the tip (~0.45 μm/s). As it returns to the ciliary base, however, NOMPB-GFP moves at ~0.12 μm/s in distal cilia, accelerating to ~0.70 μm/s in proximal cilia. Furthermore, while live imaging NOMPB-GFP, we observed one of the IFT proteins required for retrograde movement, Oseg4 (WDR35), is also required for anterograde movement in distal cilia. We anticipate our time-lapse live imaging analysis technique in cilia will be a good starting point for a more sophisticated analysis of IFT and its molecular mechanisms.
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http://dx.doi.org/10.14348/molcells.2018.0179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078859PMC
July 2018

Proactive strategy for long-term biological research aimed at low-dose radiation risk in Korea.

Int J Radiat Biol 2018 07 19;94(7):685-693. Epub 2018 Jun 19.

a Laboratory of Low Dose Risk Assessment , National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences , Seoul , Republic of Korea.

Purpose: Since the 2011 Fukushima nuclear power plant accident, Korean radiation experts have agreed that reliable data on health risks of low-dose radiation (LDR) are needed to ease the anxiety of lay people. The intent of this study was to devise a sustainable biological program suited for the research environment in Korea and aimed at the health effects of radiation exposures <100 millisieverts (mSv). To address pressing public concerns over LDR risk, we investigated the current understanding of LDR effects by analyzing the previous reports of international authorities for radiation protection and research publications that appeared after the Chernobyl accident. A research program appropriate for societal and scientific inclinations of Korea was then devised based on input from Korean radiation scientists.

Conclusions: After review by our advisory committee, program priorities were set, calling for an agenda that focused on dose-response relationships in carcinogenesis, health span responses to lifestyle variations, and systemic metabolic changes. Our long-term biological research program may contribute scientific evidence to reduce the uncertainties of LDR health risks and help stakeholders formulate policies for radiation protection.
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http://dx.doi.org/10.1080/09553002.2018.1478163DOI Listing
July 2018

Epithelial cell shape change of Drosophila as a biomonitoring model for the dose assessment of environmental radiation.

Ecotoxicol Environ Saf 2018 Aug 6;157:292-299. Epub 2018 Apr 6.

Laboratory of Low Dose Risk Assessment, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul, Korea. Electronic address:

Inevitable exposure to ionizing radiation from natural and human-made sources has been increasing over time. After nuclear disasters, such as the Fukushima accident, the public concerns on health risk of radiation exposure because of radioactive contamination of the environment have increased. However, it is very difficult to assess the biological effects of exposure caused by environmental radiation. A reliable and rapid bioassay to monitor the physiological effects of radiation exposure is therefore needed. Here, we quantitatively analyzed the changes in cell shape in Drosophila epidermis after irradiation as a model for biomonitoring of radiation. Interestingly, the number of irregularly shaped epithelial cells was increased by irradiation in a dose-dependent manner. A dose-response curve constructed with the obtained data suggests that the measurement of the number of irregular shaped cell in the epidermis is useful for the assessment of radiation dose. In addition, a comparison of the variation in the different samples and the data scored by different observers showed that our evaluation for cellular morphology was highly reliable and accurate and would, therefore, have immense practical application. Overall, our study suggests that detection of morphological changes in the epithelial cells is one of the efficient ways to quantify the levels of exposure to radioactive radiation from the environment.
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http://dx.doi.org/10.1016/j.ecoenv.2018.03.093DOI Listing
August 2018

Dynamic ultrasonography of the shoulder.

Ultrasonography 2018 Jul 26;37(3):190-199. Epub 2017 Aug 26.

Department of Radiology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.

Ultrasonography (US) is a useful diagnostic method that can be easily applied to identify the cause of shoulder pain. Its low cost, excellent diagnostic accuracy, and capability for dynamic evaluation are also advantages. To assess all possible causes of shoulder pain, it is better to follow a standardized protocol and to perform a comprehensive evaluation of the shoulder than to conduct a focused examination. Moreover, a proper dynamic study can enhance the diagnostic quality of US, especially when the pathology is not revealed by a static evaluation. The purpose of this article is to review the common indications for dynamic US of the shoulder, and to present the basic techniques and characteristic US findings.
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http://dx.doi.org/10.14366/usg.17055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044221PMC
July 2018

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

Ann Pediatr Endocrinol Metab 2017 Mar 31;22(1):27-35. Epub 2017 Mar 31.

Department of Pediatrics, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.

Purpose: Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP.

Methods: Patient group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment.

Results: No statistical difference in BMI -score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all <0.001). In normal-weight subjects in the patient group, BMI -score was significantly increased during GnRHa treatment (-0.1±0.7 vs. 0.1±0.8, <0.001), whereas HOMA-IR and QUICKI exhibited no differences. In overweight subjects in the patient group; BMI -score and HOMA-IR were not significantly different, whereas QUICKI was significantly decreased during GnRHa treatment (0.35±0.03 vs. 0.33±0.02, =0.044).

Conclusion: Girls with CPP exhibited increased insulin resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI -scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI -scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.
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http://dx.doi.org/10.6065/apem.2017.22.1.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401819PMC
March 2017

Digital tomosynthesis as a new diagnostic tool for evaluation of spine damage in patients with ankylosing spondylitis.

Rheumatol Int 2017 Feb 8;37(2):207-212. Epub 2016 Dec 8.

Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 133-792, Republic of Korea.

We aimed to compare digital tomosynthesis (DTS) with radiographs for the assessment of spinal bone damage in patients with ankylosing spondylitis (AS). The study comprised 68 patients with AS who underwent both DTS and radiographs of the cervical and lumbar spine on the same day. Spinal bone damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and the presence of facet joint damage. The Wilcoxon signed-rank test and McNemar's test were used to compare spinal bone damage between the two modalities. In 68 AS patients with mean 4.5 years of disease duration, the mean mSASSS was 11.7 ± 11.3 with radiographs and 13.1 ± 11.5 with DTS (p = 0.001). A grade 1 (erosion, sclerosis, or squaring) score in the mSASSS system was higher with DTS than with radiographs (p = 0.001), but grade 2 (syndesmophyte) and grade 3 (bridge) scores (p > 0.005 each) were not. In particular, the grade 1 score was higher with DTS than with radiographs at the cervicothoracic (p < 0.001) and thoracolumbar (p = 0.003) junctions. With regard to facet joint damage, erosion/sclerosis of facet joints was better depicted by DTS than by radiographs in the cervical (54.4 vs. 22.1%, p < 0.001) and lumbar spine (72.1 vs. 11.8%, p < 0.001). DTS depicted more subtle damage of spinal vertebrae in patients with AS than radiographs did. Moreover, erosion/sclerosis of facet joints was better detected with DTS than with radiographs.
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http://dx.doi.org/10.1007/s00296-016-3627-8DOI Listing
February 2017

Radial head button holing: a cause of irreducible anterior radial head dislocation.

Skeletal Radiol 2016 Oct 8;45(10):1449-52. Epub 2016 Aug 8.

Department of Orthopedic Surgery, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.

"Buttonholing" of the radial head through the anterior joint capsule is a known cause of irreducible anterior radial head dislocation associated with Monteggia injuries in pediatric patients. To the best of our knowledge, no report has described an injury consisting of buttonholing of the radial head through the annular ligament and a simultaneous radial head fracture in an adolescent. In the present case, the radiographic findings were a radial head fracture with anterior dislocation and lack of the anterior fat pad sign. Magnetic resonance imaging (MRI) clearly demonstrated anterior dislocation of the fractured radial head through the torn annular ligament. The anterior joint capsule and proximal portion of the annular ligament were interposed between the radial head and capitellum, preventing closed reduction of the radial head. Familiarity with this condition and imaging findings will aid clinicians to make a proper diagnosis and fast decision to perform an open reduction.
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http://dx.doi.org/10.1007/s00256-016-2451-2DOI Listing
October 2016

Muscle Involvement in Polyarteritis Nodosa: Report of Eight Cases With Characteristic Contrast Enhancement Pattern on MRI.

AJR Am J Roentgenol 2016 Feb;206(2):378-84

1 Department of Radiology, Seoul National University College of Medicine, 101 Daehak-ro Jongno-gu, Seoul 110-744, Korea.

Objective: The purpose of this study is to describe MRI findings of muscle involvement in patients with polyarteritis nodosa (PAN), with an emphasis on the contrast enhancement characteristics.

Materials And Methods: MRI studies of eight patients with PAN were retrospectively reviewed (four male and four female patients; mean age at presentation, 34.3 years; age range, 7-64 years). MR images were evaluated focusing on the following features: affected structures (muscle, fascia, or periosteum), lesion signal intensity and characteristics on T1-and T2-weighted images, and contrast enhancement patterns.

Results: Seven patients had lower leg involvement, and one had thigh involvement. In the seven patients with lower leg involvement, the main lesions were within the muscles, whereas in one patient with thigh involvement, the investing fascia was mainly involved. In the seven patients with predominantly muscle involvement, T2-weighted images showed either diffuse (n = 3) or patchy (n = 4) hyperintensity of the affected muscles. On contrast-enhanced images, small fluffy enhancing lesions centered on vessels (i.e., the "cotton-wool appearance") were noted within the affected muscles in six patients. In the one patient with mainly fascial lesions, the investing fascia showed diffuse enhancement. Periosteal enhancement was found along the tibial cortex in 50% (4/8) of our patients.

Conclusion: PAN should be considered a differential diagnosis in cases where MR images show patchy or diffuse muscle signal changes. Muscle involvement in PAN may show fluffy enhancing lesions centered on vessels on contrast-enhanced images and may accompany fascial or periosteal enhancement.
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http://dx.doi.org/10.2214/AJR.15.14774DOI Listing
February 2016

Ciliary Phosphoinositide Regulates Ciliary Protein Trafficking in Drosophila.

Cell Rep 2015 Dec;13(12):2808-16

Department of Oral Biology, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. Electronic address:

Cilia are highly specialized antennae-like cellular organelles. Inositol polyphosphate 5-phosphatase E (INPP5E) converts PI(4,5)P2 into PI4P and is required for proper ciliary function. Although Inpp5e mutations are associated with ciliopathies in humans and mice, the precise molecular role INPP5E plays in cilia remains unclear. Here, we report that Drosophila INPP5E (dINPP5E) regulates ciliary protein trafficking by controlling the phosphoinositide composition of ciliary membranes. Mutations in dInpp5e lead to hearing deficits due to the mislocalization of dTULP and mechanotransduction channels, Inactive and NOMPC, in chordotonal cilia. Both loss of dINPP5E and ectopic expression of the phosphatidylinositol-4-phosphate 5-kinase Skittles increase PI(4,5)P2 levels in the ciliary base. The fact that Skittles expression phenocopies the dInpp5e mutants confirms a central role for PI(4,5)P2 in the regulation of dTULP, Inactive, and NOMPC localization. These data suggest that the spatial localization and levels of PI(4,5)P2 in ciliary membranes are important regulators of ciliary trafficking and function.
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http://dx.doi.org/10.1016/j.celrep.2015.12.009DOI Listing
December 2015

IPMK: A versatile regulator of nuclear signaling events.

Adv Biol Regul 2016 05 2;61:25-32. Epub 2015 Dec 2.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address:

Inositol-derived metabolites (e.g., phosphoinositides and inositol polyphosphates) are key second messengers that are essential for controlling a wide range of cellular events. Inositol polyphosphate multikinase (IPMK) exhibits complex catalytic activities that eventually yield water-soluble inositol polyphosphates (e.g., IP4 and IP5) and lipid-bound phosphatidylinositol 3,4,5-trisphosphate. A series of recent studies have suggested that IPMK may be a multifunctional regulator in the nucleus of mammalian cells. In this review, we highlight the novel modes of action of IPMK in transcriptional and epigenetic regulation, and discuss its roles in physiology and disease.
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http://dx.doi.org/10.1016/j.jbior.2015.11.005DOI Listing
May 2016

Femoral Trochlear Groove Morphometry Assessed on Oblique Coronal MR Images.

AJR Am J Roentgenol 2015 Dec;205(6):1260-8

1 All authors: Department of Radiology, Seoul National University College of Medicine, 101 Daehak-ro Jongno-gu, Seoul 110-744, Korea.

Objective: The objective of our study as to assess several indexes relevant to patellofemoral instability (PFI) associated with femoral trochlear dysplasia as measured on oblique coronal MR images at three standardized reference levels.

Materials And Methods: A total of 30 knee MRI examinations were selected as the study group of PFI patients. Sixty knee MRI examinations were included as a control group. MRI protocols included sagittal T2-weighted, axial proton density-weighted, and oblique coronal T2-weighted imaging. On a midline sagittal image, the following three levels of the femoral trochlear groove cartilage were determined: level 1 (one-fourth level of the trochlear groove in the midsagittal plane), level 2 (one-half level of the trochlear groove in the midsagittal plane), and level 3 (three-fourths level of the trochlear groove in the midsagittal plane). Three-level axial and oblique coronal images were selected using the sagittal image as a scout. Femoral trochlear indexes including the sulcus angle, sulcus depth, facet length, and trochlear groove area were measured on the axial and oblique coronal images.

Results: Most indexes showed significant differences between the PFI and control groups in the axial and oblique coronal planes at all three levels (p < 0.05). Almost all indexes measured on the oblique coronal plane images were significantly different from those measured on the axial plane images (p < 0.05). Oblique coronal images showed little variability in the sulcus angle among the three levels in contrast to a marked decrease in the angle from the proximal to distal level on axial images.

Conclusion: Femoral trochlear indexes measured on oblique coronal knee MR images can be used to assess femoral trochlear dysplasia. Oblique coronal images showed less morphologic distortion of the distal femoral trochlear groove than axial images.
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http://dx.doi.org/10.2214/AJR.15.14398DOI Listing
December 2015

Comparison of the effects of Korean mindfulness-based stress reduction, walking, and patient education in diabetes mellitus.

Nurs Health Sci 2015 Dec 14;17(4):516-25. Epub 2015 Aug 14.

College of Nursing, Pusan National University, Yangsan, Korea.

The purpose of this study was to compare the effects of Korean mindfulness-based stress reduction (K-MBSR), walking, and patient education regarding diabetes mellitus (DM) on stress response, glycemic control, and vascular inflammation in patients with diabetes mellitus. A cluster randomized trial including 56 adults with diabetes mellitus (K-MBSR group = 21, walking group = 18, patient education group = 17) was conducted between 13 July and 14 September 2012. The questionnaire included the Diabetes Distress Scale and Perceived Stress Response Inventory. Fasting blood samples were used to measure levels of cortisol, blood glucose, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). There were no statistically significant differences between the effects of K-MBSR, walking, and patient education on stress, glycemic control, or vascular inflammation. However, in the K-MBSR and walking groups, significant reductions in the levels of serum cortisol and PAI-1 were observed. A significant reduction in psychological responses to stress was observed in the walking and patient education groups. Longitudinal studies could provide better insight into the impact of K-MBSR, walking, and patient education on health outcomes in adults with diabetes mellitus.
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http://dx.doi.org/10.1111/nhs.12229DOI Listing
December 2015

Assessment of the Postoperative Appearance of the Rotator Cuff Tendon Using Serial Sonography After Arthroscopic Repair of a Rotator Cuff Tear.

J Ultrasound Med 2015 Jul;34(7):1183-90

Departments of Radiology (H.J.Y., J.-Y.C., S.H.H., Y.K., J.P.) and Orthopedic Surgery (S.H.K.), Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea; and Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea (H.S.K.).

Objectives: The purpose of this study was to evaluate serial changes in sonographic findings of a rotator cuff tendon after rotator cuff repair.

Methods: Sixty-five arthroscopically repaired rotator cuff tears (43 full-thickness tears and 22 partial-thickness tears) were retrospectively included in this study. Serial sonographic examinations were performed at 5 weeks, 3 months, and 6 months after surgery. The sonographic findings of the repaired tendon were assessed for a recurrent tear, tendon thickness, morphologic tendon characteristics, vascularity, and bursitis at each time point.

Results: Four recurrent tears occurred within 3 months of surgery. The postoperative tendon thickness decreased from 5 weeks to 6 months after surgery (P = .001). There were significant changes in the morphologic tendon characteristics, including the echo texture, fibrillar pattern, and surface irregularity of the repaired tendon, from 5 weeks to 6 months after surgery (P < .001). Additionally, subacromial-subdeltoid bursitis and the vascularity of the repaired tendon decreased postoperatively over time.

Conclusions: Serial sonography after arthroscopic rotator cuff repair was useful for monitoring the postoperative changes in a repaired tendon. The morphologic appearance of the repaired tendon and peritendinous soft tissue changes improved over time and nearly normalized within 6 months of surgery.
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http://dx.doi.org/10.7863/ultra.34.7.1183DOI Listing
July 2015

Monitoring change in refractive index of cytosol of animal cells on affinity surface under osmotic stimulus for label-free measurement of viability.

Biosens Bioelectron 2015 Feb 6;64:241-6. Epub 2014 Sep 6.

Nanobiotechnology Major, Korea University of Science and Technology, 52 Eoeun-Dong, Yuseong-Gu, Daejeon 305-333, Republic of Korea; Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-Dong, Yuseong-Gu, Daejeon 305-333, Republic of Korea. Electronic address:

We demonstrated that a metal-clad waveguide (MCW)-based biosensor can be applied to label-free measurements of viability of adherent animal cells with osmotic stimulation in real time. After Chinese hamster ovary (CHO) and human embryonic kidney cell 293 (HEK293) cells were attached to a Concanavalin A (Con A)-modified sensor surface, the magnitudes of cell responses to non-isotonic stimulation were compared between live and dead cells. The live cells exhibited a change in the refractive index (RI) of the cytosol caused by a redistribution of water through the cell membrane, which was induced by the osmotic stimulus, but the dead cells did not. Moreover, the normalized change in the RI measured via the MCW sensor was linearly proportional to the viability of attached cells and the resolution in monitoring cell viability was about 0.079%. Therefore, the viability of attached animal cells can be measured without labels by observing the relative differences in the RI of cytosol in isotonic and non-isotonic buffers.
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http://dx.doi.org/10.1016/j.bios.2014.09.007DOI Listing
February 2015

Corpus callosum diffusion tensor imaging and volume measures are associated with disease severity in pediatric Niemann-Pick disease type C1.

Pediatr Neurol 2014 Nov 28;51(5):669-674.e5. Epub 2014 Jul 28.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Background: Niemann-Pick disease type C1 is a neurodegenerative lysosomal storage disorder. Without a highly effective treatment, biomarkers of severity would be beneficial for prognostication and testing new interventions. Diffusion tensor imaging has shown microstructural abnormalities in adults with Niemann-Pick disease type C1. This is the first study to apply diffusion tensor imaging and volume analysis to evaluate the corpus callosum in a pediatric and adolescent population of patients with Niemann-Pick disease type C1. We hypothesized that the callosal fractional anisotropy, volume, and cross-sectional area will negatively correlate with NPC severity score.

Methods: Thirty-nine individuals with Niemann-Pick disease type C1 aged 1-21.9 years (mean = 11.1; S.D. = 6.1), and each received one magnetic resonance imaging examination. Severity score were obtained by examination and clinical observation. An atlas-based automated approach was used to measure fractional anisotropy, cross-sectional area, and volume. For comparative analysis and validation of this atlas-based approach, one midsagittal image was chosen and the corpus callosum manually traced to obtain cross-sectional area. Statistical analyses were applied to study the relationships between imaging and clinical severity.

Results: For patients with Niemann-Pick disease type C1, lower corpus callosum fractional anisotropy, volume, and cross-sectional area significantly correlate with higher severity score. Severity subdomain analysis revealed ambulation, speech, seizures, and incontinence have the strongest relationships with callosal measures. Comparison of atlas-based processing and manual tracing techniques demonstrated validity for the automated method.

Conclusions: For individuals with Niemann-Pick disease type C1, the corpus callosum measures correlate with clinical severity. These findings reveal promise for the discovery of new imaging biomarkers for this disorder.
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http://dx.doi.org/10.1016/j.pediatrneurol.2014.07.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696056PMC
November 2014

Nodular fasciitis mimicking soft tissue metastasis on 18F-FDG PET/CT during surveillance.

Clin Nucl Med 2015 Feb;40(2):172-4

From the Departments of *Nuclear Medicine, †Radiology, and ‡Pathology, Hanyang University Hospital, Seoul, Korea.

Nodular fasciitis (NF) is a common benign soft tissue tumor. However, F-FDG PET/CT findings of NF are limited. Two cases of NF are described that mimic soft tissue metastasis on F-FDG PET/CT during surveillance. F-FDG PET/CT is well documented in the surveillance of malignancy and increasing worldwide. There are growing chances of encountering FDG-avid nonmalignant soft tissue lesion. Nodular fasciitis could be considered as possible diagnosis on F-FDG PET/CT if a solitary well- circumscribed ovoid hypermetabolic soft tissue lesion is located in a muscle, intermuscular space, or adjacent tendon, especially in patients with a clinically low probability of tumor recurrence or metastasis.
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http://dx.doi.org/10.1097/RLU.0000000000000559DOI Listing
February 2015