Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.
Animals ; Aorta ; Biomarkers ; Cause of Death ; Cell Adhesion ; Connective Tissue ; Cytoskeleton ; Dilatation ; Elastic Tissue ; Gene Expression ; Gene Expression Profiling ; Gene Ontology ; Humans ; Marfan Syndrome* ; Mice* ; Myofibrils ; Transcriptome*

PURPOSE: A Trans-Illuminated Powered Phlebectomy (TIPP) is accepted as a useful surgical procedure for varicose vein, but requires hospitalization and general or spinal anesthesia. To show the feasibility of outpatient TIPP under local anesthesia, we established an outpatient fast track protocol of TIPP, and showed the results. METHOD: We performed outpatient department-based TIPP, under local anesthesia with a 2% lidocaine subcutaneous injection and the tumescent method. Using the visual analogue pain scale and a questionnaire, the compliance of the patient were examined. RESULT: Between August 2001 and January 2005, 252 limbs of 238 patients underwent operations using our protocol. Mean age of the patients was 59 years, with a male:female of 185:53. The mean operation time and number of incisions were 30.6 minutes and 4.6, respectively. There were 7 wound problems (2.78%) and 5 redo TIPP (1.98%) due to a recurrence. 58 questionnaires were completed and collected from the patients. The mean visual analogue pain scale score was 5.7. Of the 58 patients that completed the questionnaires, 6 (10%) replied that the procedure was intolerable and that they would not have again. Whereas, the other 52 patients (90%) said the procedure was tolerable, and would have again, if necessary. CONCLUSION: Outpatient TIPP, under local anesthesia, might be a relatively safe and feasible method to establish a fast track protocol for varicose veins.
Anesthesia, Local* ; Anesthesia, Spinal ; Compliance ; Extremities ; Hospitalization ; Humans ; Injections, Subcutaneous ; Lidocaine ; Outpatients* ; Pain Measurement ; Surveys and Questionnaires ; Recurrence ; Varicose Veins* ; Wounds and Injuries

BACKGROUND AND OBJECTIVES: In our previous study, we found that the gene transfer of a potent derivative of cartilage oligomeric matrix protein Angiopoietin-1 (COMP-Ang-1) substantially prevented hypertension, microvascular rarefaction, and target organ damage in spontaneously hypertensive rats (SHRs). The purpose of the present study was to examine the role of nitric oxide (NO) in the therapeutic effects observed after COMP-Ang-1 gene transfer. MATERIALS AND METHODS: To exclude the NO-mediated effects in COMP-Ang-1 gene therapy, the SHRs were treated with an NO synthase (NOS) inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) before the electrophoretic gene transfer. RESULTS: The pretreatment with L-NAME induced a severe and sustained increase in systolic blood pressure (BP) in a LacZ plasmid transferred control SHR. However, the electrophoretic transfer of a COMP-Ang-1 plasmid instead of LacZ plasmid in L-NAME-pretreated SHRs substantially blocked the development of hypertension without any significant difference in comparison with L-NAME-untreated COMP-Ang-1 plasmid transferred groups. In addition, the COMP-Ang-1 plasmid transfer substantially attenuated microvascular rarefaction and arteriole remodeling in the heart and kidney, which might account for the mild histological alterations observed in the COMP-Ang-1 plasmid transferred group, in contrast to the severe fibrosis and necrosis seen in the LacZ plasmid controls. CONCLUSION: These therapeutic outcomes of COMP-Ang-1 gene transfer even in NOS inhibited SHRs suggested that the antihypertensive effect of COMP-Ang-1 was not merely secondary to NO-mediated vasorelaxation, but it may be associated with its ability to protect the vascular endothelium probably via an NO-independent mechanism which serves to attenuate microvascular rarefaction and target organ damage, and also to prevent hypertension by reducing peripheral vascular resistance.
Angiopoietin-1 ; Arterioles ; Blood Pressure ; Cartilage ; Endothelium ; Endothelium, Vascular ; Extracellular Matrix Proteins ; Fibrosis ; Genetic Therapy ; Glycoproteins ; Heart ; Hypertension ; Kidney ; Necrosis ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Plasmids ; Rats, Inbred SHR ; Vascular Resistance ; Vasodilation

BACKGROUND: This study quantitatively and qualitatively analyzed the characteristics and trends of papers published in the Journal of the Korean Geriatrics Society. METHODS: Original articles, case reports, review articles published from 2006 to 2013 were retrospectively examined. All of the article research topics, paper-specific corresponding author's affiliations and number of authors were investigated. Original articles were separated and grouped according to research designs. Using the Korean Citation Index, impact factor of this journal was examined and compared with four related journals. RESULTS: Of the 276 articles analyzed, 159 (57.6%) were original articles, 145 (91.2%) were analytic studies, and 36 (22.6%) were experimental studies. The proportion of original articles accounted for about 60% until 2007 but decreased to 41.0% in 2013. By clinical study topics, 37 studies (13.4%) addressed the understanding of geriatric diseases and 45 studies (16.3%) were focused on nervous system diseases. The median number of authors for the 276 studies was 6. Internal medicine accounted for the largest proportion of corresponding author's affiliation (109 studies, 39.5%) studies. Impact factor of the journal increased from 0.05 (4th position) in 2009 to 0.48 (3rd position) in 2011. CONCLUSION: Articles published in the Journal of the Korean Geriatrics Society increasingly included experimental studies based on evidence-centered medicine, with the proportion of original articles decreasing. The impact factor increased annually along with the journal ranking, compared with other journals. Journal of the Korean Geriatrics Society is judged to be qualitatively improving.
Bibliometrics* ; Geriatrics* ; Internal Medicine ; Nervous System Diseases ; Publications ; Research Design ; Retrospective Studies

We examined the precision, accuracy, and capability of detecting changes of Dual-Energy X-ray Absorptiometry (DXA) for the measurements of total-body weight (TBW), total-body fat weight (TBFW), and total-body lean weight (TBLW) in an 8-week follow-up study of rats. Twenty male rats (4-week) were divided into 2 diet groups. For 8 weeks, we measured body composition (TBW, TBFW, TBLW) by DXA and TBW by an electronic scale once a week. In week 8, we measured body composition 5 times by DXA and TBFW by dissecting experiment (EXP) of euthanized rats (12-week). Total-body fat ratio (TBFR) was defined as TBFW/(TBFW+TBLW). The precision of DXA was evaluated by measuring the coefficient of variation (CV) and accuracy was evaluated by comparing DXA-derived data with EXP data. The capability of detecting changes of DXA in follow-up study was verified by analyzing the trend of DXA-derived values over the 8 weeks. For TBW, TBFW, TBLW of DXA, CVs were 0.02 ± 0.01, 0.10 ± 0.05, 0.03 ± 0.02 and errors were − 6.996 ± 3.429 (r = 0.999), + 14.729 ± 3.663 (r = 0.982), − 21.725 ± 4.223 (r = 0.991), respectively. Prediction models were [EXP TBW = − 31.767 + 1.085 (DXA TBW), R2 = 0.998, root mean square error (RMSE) = 1.842] and [EXP TBFR = − 0.056 + 1.177 (DXA TBFR), R2 = 0.948, RMSE = 0.007]. Over 8 weeks, DXA TBW and DXA TBLW steadily increased, DXA TBFW steadily increased followed by saturation or declination, difference of DXA TBFW between 2 diet groups steadily increased. In conclusion, our study verified that DXA (iNSiGHT VET DXA, OsteoSys, Korea) is accurate and precise enough to measure body composition of rats. Additionally, we confirmed the possibility that DXA could be used for the long-term follow-up studies.
Absorptiometry, Photon ; Animals ; Body Composition ; Diet ; Diet, High-Fat ; Follow-Up Studies ; Humans ; Male ; Obesity ; Rats

Cyclophosphamide is alkylating agent used in the treatment of various solid tumors. Mucosal irritation by acrolein, the metabolite of cyclophosphamide, is believed to cause various symptoms of cystitis. The thiol compound, sodium 2-mercaptoethane sulfonate (Mesna), has been found to inactivate acrolein. We present an unusual case of a 64-year-old woman, who was treated as chronic cystitis. Her symptoms did not improve, so she was treated with Mesna under the assumption of cyclophosphamide induced cystitis; her symptoms then improved.
Acrolein ; Cyclophosphamide* ; Cystitis* ; Female ; Humans ; Mesna* ; Middle Aged ; Sodium

BACKGROUND: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that is characterized by invasive synovial hyperplasia, leading to progressive joint destruction. Recent studies have described that RA is caused by virus, bacteria or outside material. Approximately 2 to 20% of RA cases are reported to be associated with infected hepatitis C virus (HCV). However, the mechanisms underlying virus-induced RA are still unknown. Moreover, few molecular studies have addressed the inflammatory aspects of HCV-associated autoimmune RA. In this study, we aimed to determine whether or not another HCV core protein transactivates the IL-8 gene expression, prototypic chemokine, in synovial cell. METHODS: To establish the HCV core expressing stable synovial cell line, pCI-neo-core, a plasmid encoding HCV core protein, were transfected to HIG-82 cell line that is an established cell line from rabbit periaricular soft tissue. We examined the morphological changes and cell cycle distribution of HIG-82 cells with expression of HCV core protein by inverted microscopy and flow cytometry analysis, respectively. Also, we determined the mRNA levels of Interleukin (IL)-6 and IL-8 related to the inflammation by RT-PCR and then analyzed regulation of IL-8 expression by the NF-kB pathway. RESULTS: Our study showed no significant differences in morphology and cell cycle between HIG-82 control cell line and HIG-82 expressing HCV core protein. However, expression of HCV core protein induces the IL-8 mRNA expression in HIG-82 core cells via activated NF-kB pathway. CONCLUSION: These results suggest that HCV core protein can lead to enhanced IL-8 expression. Such a pro-inflammatory role may contribute to the etiologic pathogenesis in RA patients with HCV infection.
Arthritis, Rheumatoid ; Bacteria ; Cell Cycle ; Cell Line ; Flow Cytometry ; Gene Expression ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Hyperplasia ; Inflammation ; Interleukin-8* ; Interleukins ; Joints ; Microscopy ; NF-kappa B ; Plasmids ; RNA, Messenger

PURPOSE: Adiponectin and resistin are potent regulators of glucose homeostasis and energy metabolism. In this study, we aimed to determine (1) the role of gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) on the plasma levels of adiponectin and resistin in cord blood, and (2) the association of the hormones with anthropometric parameters at birth. METHODS: This study investigated 80 pregnant women at 26-41 weeks of gestation, including 46 healthy pregnant woman as controls; 14 women with GDM; and 20 women with PIH, and 80 newborn infants (36 male, and 44 female). The following anthropometric measurements were obtained: maternal weight, length, body mass index (BMI), neonatal birth weight, neonatal length, and ponderal index. Cord blood samples were obtained from 80 neonates at the time of delivery. Plasma adiponectin levels (RIA) and resistin levels (ELISA) were measured. RESULTS: Adiponectin levels were significantly lower in the fullterm group with GDM and fullterm group with PIH than the control group. Plasma resistin levels were significantly lower in the preterm and the fullterm groups with PIH than in the control group, and significantly higher in the fullterm group with GDM than in the PIH group. Similarly, adiponection was significantly lower in large for gestational age (LGA) infants than appropriate gestational age (AGA) and small for gestational age (SGA) infants, and resistin was significantly higher in LGA infants than in SGA infants. Adiponectin levels were negatively correlated with ponderal index, maternal HbA1c, and maternal body mass index (BMI). Plasma resistin levels were positively correlated with birth weight and maternal BMI. CONCLUSION: Alteration of adiponectin and resistin levels in cord blood of fetuses of women with GDM and PIH may influence the development of metabolic disorders at all stages of development.
Adiponectin ; Birth Weight ; Body Mass Index ; Diabetes, Gestational ; Energy Metabolism ; Female ; Fetal Blood ; Fetus ; Gestational Age ; Glucose ; Homeostasis ; Humans ; Hypertension, Pregnancy-Induced ; Infant ; Infant, Newborn ; Male ; Parturition ; Plasma ; Pregnancy ; Pregnancy Complications ; Pregnant Women ; Resistin

PURPOSE: Adiponectin and resistin are potent regulators of glucose homeostasis and energy metabolism. In this study, we aimed to determine (1) the role of gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) on the plasma levels of adiponectin and resistin in cord blood, and (2) the association of the hormones with anthropometric parameters at birth. METHODS: This study investigated 80 pregnant women at 26-41 weeks of gestation, including 46 healthy pregnant woman as controls; 14 women with GDM; and 20 women with PIH, and 80 newborn infants (36 male, and 44 female). The following anthropometric measurements were obtained: maternal weight, length, body mass index (BMI), neonatal birth weight, neonatal length, and ponderal index. Cord blood samples were obtained from 80 neonates at the time of delivery. Plasma adiponectin levels (RIA) and resistin levels (ELISA) were measured. RESULTS: Adiponectin levels were significantly lower in the fullterm group with GDM and fullterm group with PIH than the control group. Plasma resistin levels were significantly lower in the preterm and the fullterm groups with PIH than in the control group, and significantly higher in the fullterm group with GDM than in the PIH group. Similarly, adiponection was significantly lower in large for gestational age (LGA) infants than appropriate gestational age (AGA) and small for gestational age (SGA) infants, and resistin was significantly higher in LGA infants than in SGA infants. Adiponectin levels were negatively correlated with ponderal index, maternal HbA1c, and maternal body mass index (BMI). Plasma resistin levels were positively correlated with birth weight and maternal BMI. CONCLUSION: Alteration of adiponectin and resistin levels in cord blood of fetuses of women with GDM and PIH may influence the development of metabolic disorders at all stages of development.
Adiponectin ; Birth Weight ; Body Mass Index ; Diabetes, Gestational ; Energy Metabolism ; Female ; Fetal Blood ; Fetus ; Gestational Age ; Glucose ; Homeostasis ; Humans ; Hypertension, Pregnancy-Induced ; Infant ; Infant, Newborn ; Male ; Parturition ; Plasma ; Pregnancy ; Pregnancy Complications ; Pregnant Women ; Resistin

Purpose: With an increase in the aging population, the number of patients with degenerative spinal diseases undergoing surgery has risen, as has the incidence of postoperative delirium. This study aimed to investigate the risk factors affecting postoperative delirium in older adults who had undergone spine surgery and to identify the associated biomarkers. Methods: This study is a prospective study. Data of 100 patients aged ≥ 70 years who underwent spinal surgery were analyzed. Demographic data, medical history, clinical characteristics, cognitive function, depression symptoms, functional status, frailty, and nutritional status were investigated to identify the risk factors for delirium. The Confusion Assessment Method, Delirium Rating Scale-R-98, and Nursing Delirium Scale were also used for diagnosing deliri-um. To discover the biomarkers, urine extracellular vesicles (EVs) were analyzed for tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1),neurofilament light, and glial fibrillary acidic protein using digital immunoassay technology. Results: Nine patients were excluded, and data obtained from the remaining 91 were analyzed. Among them, 18 (19.8%) developed delirium. Differences were observed between partici-pants with and without delirium in the contexts of a history of mental disorder and use of benzodiazepines (p = .005 and p = .026, respectively). Tau and UCH-L1—concentrations of urine EVs—were comparatively higher in participants with severe delirium than that in partici-pants without delirium (p = .002 and p = .001, respectively). Conclusion These findings can assist clinicians in accurately identifying the risk factors before surgery, classifying high-risk patients, and predicting and detecting delirium in older patients. Moreover, urine EV analysis revealed that postoperative delirium following spinal surgery is most likely associated with brain damage.