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1.  Engineering microscale cellular niches for three-dimensional multicellular co-cultures 
Lab on a chip  2009;9(12):1740-1748.
Summary
Modeling the in vivo microenvironment typically involves placing cells in a three-dimensional (3D) extracellular matrix (ECM) in physiologically relevant context with respect to other cells. The mechanical and chemical features of 3D microenvironments play important roles in tissue engineering, tumor growth and metastasis, and in defining stem cell niches, and it is increasingly recognized that cells behave much differently when surrounded by a 3D ECM than when anchored to a 2D substrate. To create microenvironments that more closely mimic in vivo settings, here we describe a novel microfluidic device that allows multiple discrete constructs of 3D cell-laden hydrogels to be patterned in a sequence of simple steps. The microfluidic platform allows for real time imaging of the interactions between multiple cell types exposed to both autocrine and paracrine signaling molecules, all within a 3D ECM environment. Detailed modeling determined that surface tension, hydrophobic interactions, and spatial geometry were important factors in containing the gels within distinct separate channels during the filling process. This allowed us to pattern multiple gel types side-by-side and pattern 3D gels spatially with tight dimensional control. Cells embedded in gels could be patterned by culturing MDA-MB-231 metastatic breast cancer cells and RAW 264.1 macrophage cells within distinct collagen type I and Matrigel ECM environments, respectively. Over a 7 day culture experiment, RAW cells invaded into neighboring gels containing MDA-MB-231 cells, but not into gels lacking cells. These studies demonstrate the versatility and potential of this new microfluidic platform to engineer 3D microscale architectures to investigate cell-cell and cell-matrix interactions.
doi:10.1039/b818401a
PMCID: PMC3758562  PMID: 19495458
2.  Acute myeloid leukaemia presenting as faecal incontinence 
BMJ Case Reports  2009;2009:bcr12.2008.1397.
Epidural sacral nerve compression as an initial feature of leukaemia is a rare complication. The findings in a 16-year-old boy who presented to an emergency department with symptoms of faecal incontinence are reported herein. Radiological imaging demonstrated soft tissue masses in the sacral epidural space. The diagnosis of acute myeloid leukaemia was confirmed on bone marrow aspirate. The characteristics and management of extramedullary leukaemia are discussed.
doi:10.1136/bcr.12.2008.1397
PMCID: PMC3028031  PMID: 21686339
3.  Multidimensional classification of hippocampal shape features discriminates Alzheimer's disease and mild cognitive impairment from normal aging 
NeuroImage  2009;47(4):1476-1486.
We describe a new method to automatically discriminate between patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and elderly controls, based on multidimensional classification of hippocampal shape features. This approach uses spherical harmonics (SPHARM) coefficients to model the shape of the hippocampi, which are segmented from magnetic resonance images (MRI) using a fully automatic method that we previously developed. SPHARM coefficients are used as features in a classification procedure based on support vector machines (SVM). The most relevant features for classification are selected using a bagging strategy. We evaluate the accuracy of our method in a group of 23 patients with AD (10 males, 13 females, age±standard-deviation (SD)=73±6 years, mini-mental score (MMS)=24.4±2.8), 23 patients with amnestic MCI (10 males, 13 females, age±SD=74±8 years, MMS=27.3±1.4) and 25 elderly healthy controls (13 males,12 females, age±SD=64±8 years), using leave-one-out cross-validation. For AD vs controls, we obtain a correct classification rate of 94%, a sensitivity of 96%, and a specificity of 92%. For MCI vs controls, we obtain a classification rate of 83%, a sensitivity of 83%, and a specificity of 84%. This accuracy is superior to that of hippocampal volumetry and is comparable to recently published SVM-based whole-brain classification methods, which relied on a different strategy. This new method may become a useful tool to assist in the diagnosis of Alzheimer's disease.
doi:10.1016/j.neuroimage.2009.05.036
PMCID: PMC3001345  PMID: 19463957
Alzheimer's disease; MCI; Hippocampus; Magnetic resonance imaging; Support vector machines
4.  Clostridium difficile toxin A binds colonocyte Src causing dephosphorylation of focal adhesion kinase and paxillin 
Experimental cell research  2009;315(19):3336-3344.
C. difficile toxin A impairs tight junction function of colonocytes by glucosylation of Rho family proteins causing actin filament disaggregation and cell rounding. We investigated the effect of toxin A on focal contact formation by assessing its action on focal adhesion kinase (FAK) and the adapter protein paxillin. Exposure of NCM460 human colonocytes to toxin A for 1 hour resulted in complete dephosphorylation of FAK and paxillin, while protein tyrosine phosphatase activity was reduced. Blockage of toxin A-associated glucosyltransferase activity by co-incubation with UDP 2′3′dialdehyde did not reduce toxin A-induced FAK and paxillin dephosphorylation. GST-pull down and in vitro kinase activity experiments demonstrated toxin A binding directly to the catalytic domain of Src with suppression of its kinase activity. Direct binding of toxin A to Src, independent of any effect on protein tyrosine phosphatase or Rho glucosylation, inhibits Src kinase activity followed by FAK/paxillin inactivation. These mechanisms may contribute to toxin A-inhibition of colonocyte focal adhesion that occurs in human colonic epithelium exposed to toxin A.
doi:10.1016/j.yexcr.2009.05.020
PMCID: PMC2783309  PMID: 19481075
5.  Anti-nuclear antibody reactivity in lupus may be partly hardwired into the primary B cell repertoire 
Molecular immunology  2009;46(16):3420-3426.
When monoclonal ANAs and non-ANAs generated from a genetically simplified mouse model of lupus, B6.Sle1, were recently compared, the ANAs exhibited 3 sequence motifs in their immunoglobulin heavy chains, including increased cationicity in CDR3 (“motif A”), reduced anionicity in CDR2 (“motif B”) and increased aspartate at H50 (“motif C”). The present study was designed to elucidate the extent to which these ANA-associated sequence motifs might be hard-wired into the primary B-cell repertoire in lupus. The immunoglobulin heavy chain sequence of total splenic B cells, follicular B-cells and marginal zone B-cells from B6.Sle1 congenic mice and C57BL/6 controls were amplified by single cell PCR and compared. Analysis of the primary immunoglobulin heavy chain repertoire indicated that the first 2 sequence motifs “A” and “B” were already encoded in the naïve repertoire of B6.Sle1z mice, whereas the third motif “C” was introduced in part by somatic mutation. Site-directed mutagenesis confirmed that non-anionic CDR2 and cationic CDR3 residues in the immunoglobulin heavy chain facilitated nuclear antigen binding in concert, whereas aspartate at H50 strongly vetoed DNA-binding, while preserving nucleosome reactivity. Hence, antinuclear antibodies appear to arise as a consequence of 2 distinct processes–genetically programmed selection of specific CDR charge motifs into the primary immunoglobulin repertoire, with secondary contribution from somatic mutation. Polymorphisms in the lupus susceptibility gene Ly108 that impair central B-cell tolerance may be mechanistically responsible for these early repertoire differences in lupus.
doi:10.1016/j.molimm.2009.07.014
PMCID: PMC2757519  PMID: 19699528
Autoimmunity; B-cells; autoantibodies; genetics; immunoglobulin repertoire
6.  Exposures to Particulate Matter and Polycyclic Aromatic Hydrocarbons and Oxidative Stress in Schoolchildren 
Environmental Health Perspectives  2009;118(4):579-583.
Background
Air pollution is known to contribute to respiratory and cardiovascular mortality and morbidity. Oxidative stress has been suggested as one of the main mechanisms for these effects on health.
Objective
The aim of this study was to analyze the effects of exposure to particulate matter (PM) with aerodynamic diameters ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) on urinary malondialdehyde (MDA) levels in schoolchildren.
Methods
The study population consisted of 120 schoolchildren. The survey and measurements were conducted in four cities—two in China (Ala Shan and Beijing) and two in Korea (Jeju and Seoul)—between 4 and 9 June 2007. We measured daily ambient levels of PM and their metal components at the selected schools during the study period. We also measured urinary 1-hydroxypyrene (1-OHP) and 2-naphthol, to assess PAH exposure, and MDA, to assess oxidative stress. Measurements were conducted once a day for 5 consecutive days. We constructed a linear mixed model after adjusting for individual variables to estimate the effects of PM and PAH on oxidative stress.
Results
We found statistically significant increases in urinary MDA levels with ambient PM concentrations from the current day to the 2 previous days (p < 0.0001). Urinary 1-OHP level also showed a positive association with urinary MDA level, which was statistically significant with or without PM in the model (p < 0.05). Outdoor PM and urinary 1-OHP were synergistically associated with urinary MDA levels. Some metals bound to PM10 (aluminum, iron, strontium, magnesium, silicon, arsenic, barium, zinc, copper, and cadmium) and PM2.5 (magnesium, iron, strontium, arsenic, cadmium, zinc, aluminum, mercury, barium, and copper) also had significant associations with urinary MDA level.
Conclusion
Exposure to PM air pollution and PAHs was associated with oxidative stress in schoolchildren.
doi:10.1289/ehp.0901077
PMCID: PMC2854738  PMID: 20368125
children; metal; oxidative stress; PAH; panel study; particulate matter
7.  Expression of TLR2, TLR4, and TLR9 in dermatomyositis and polymyositis 
Clinical Rheumatology  2009;29(3):273-279.
The aim of this study was to investigate the expressions of Toll-like receptor (TLR) 2, TLR4, TLR9, and their correlations with the expression of cytokines that are associated with activation of CD4+ T cells and inflammation including interferon γ (IFNγ), interleukin 4 (IL4), interleukin 17 (IL17), and tumor necrosis factor α (TNFα) in muscle tissues of patients with dermatomyositis (DM) and polymyositis (PM). The expressions of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were measured by real-time reverse transcription–polymerase chain reaction in muscle tissues from 14 patients with DM and PM (nine patients with DM, five patients with PM) and three controls. The expressions of TLR2, TLR4, and TLR9 were also localized with immunohistochemistry. The expression levels of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were significantly high in patients with DM and PM compared with those in the controls, and the expression levels of TLR4 and TLR9 had significant positive correlations with the expressions of IFNγ, IL4, IL17, and TNFα. Immunohistochemistry showed that TLR2, TLR4, and TLR9 were expressed by infiltrating cells of perimysium in DM, whereas they were expressed by infiltrating cells of endomysium in PM. These results suggest that the involvement of TLR4 and TLR9 in immunopathogenesis of DM and PM might be connected with activation of CD4+ T cells.
doi:10.1007/s10067-009-1316-7
PMCID: PMC2812423  PMID: 19953283
Dermatomyositis; Polymyositis; Toll-like receptors
8.  Icodextrin Improves the Serum Potassium Profile with the Enhancement of Nutritional Status in Continuous Ambulatory Peritoneal Dialysis Patients 
The impact of glucose-free icodextrin (ID) for overnight dwell as compared to conventional glucose-containing dialysate (GD) on potassium (K+) metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients has not yet been investigated. Serum K+ in a total of 255 stable patients (116 on GD and 139 on ID) on CAPD for more than 6 months and in 139 patients on ID before and after ID use (Pre-ID and Post-ID) were observed along with nutritional markers in a 2-year study period (Jan. 2006 to Dec. 2007). The prevalence of hypokalemia was similar between patients on GD and ID (16.7% vs 17.3%), but was lower on Post-ID than Pre-ID (17.3% vs 20.5%) without statistic significance. The mean serum K+ level was higher on ID than on GD (P<0.05) as well as Post-ID than Pre-ID (P<0.001). In the multivariate analysis, serum K+ levels were positively correlated with serum albumin, and creatinine in all patients (P<0.05), and ID-use in younger patients (age≤56, P<0.001). Serum albumin, creatinine, total CO2, and body mass index were significantly higher on Post-ID than Pre-ID. Icodextrin dialysate for chronic overnight dwell could increase serum K+ levels and lower the prevalence of hypokalemia compared to conventional glucose-containing dialysate. The improved chronic K+ balance in CAPD patients on icodextrin could be related to enhanced nutritional status rather than its impact on acute intracellular K+ redistribution.
doi:10.5049/EBP.2009.7.2.79
PMCID: PMC3041488  PMID: 21468190
serum albumin; hypokalemia; icodextrin; nutritional status; peritoneal dialysis
9.  Knockdown of RCAN1.4 Increases Susceptibility to FAS-mediated and DNA-damage-induced Apoptosis by Upregulation of p53 Expression 
Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1) gene in the modulation of cell survival under stress, little is known about its role in death-inducing signal pathways. In this study, we addressed the effects of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in enhanced Fas- and etoposide-induced apoptosis, which was associated with increased expression and translocation of Bax to mitochondria. Our results suggest that enhanced expression and activation of p53 was responsible for the upregulation of Bax and the increased sensitivity to apoptosis, which could be reversed by p53 knockdown. To explain the observed upregulation of p53, we propose a downregulation of the ubiquitin ligase HDM2, probably translationally. These findings show the importance of appropriate RCAN1.4 expression in the modulation of cell survival and reveal a link between RCAN1.4 and p53.
doi:10.4196/kjpp.2009.13.6.483
PMCID: PMC2802310  PMID: 20054496
RCAN1; Apoptosis; p53; Bax; HDM2
10.  Brain Magnetic Resolution Imaging to Diagnose Bing-Neel Syndrome 
Radiologic findings of Bing-Neel syndrome, which is an extremely uncommon complication resulting from malignant lymphocyte infiltration into the central nervous system (CNS) in patients with Waldenström's macroglobulinemia (WM), have been infrequently reported due to extreme rarity of the case. A 75-year-old man with WM presented at a neurology clinic with progressive gait and memory disturbances, and dysarthria of 2 months duration. Cerebrospinal fluid and serum protein electrophoresis and immunofixation electrophoresis showed IgM kappa-type monoclonal gammopathy. Brain magnetic resonance imaging revealed multifocal, hyperintense lesions on T2 weighted-images. Brain diffusion-weighted imaging (DWI) demonstrated hyperintensities in cerebral and cerebellar lesions that appeared isointense on apparent diffusion coefficient maps, which were compatible with vasogenic edema. Although histologic analysis is a confirmative study to prove direct cell infiltration into the brain, brain MRI with DWI may be a good supportive study to diagnose Bing-Neel syndrome.
doi:10.3340/jkns.2009.46.6.588
PMCID: PMC2803279  PMID: 20062579
Bing-Neel syndrome; Waldenström's macroglobulinemia; MRI
11.  Comparison of Percutaneous Endoscopic Lumbar Discectomy and Open Lumbar Microdiscectomy for Recurrent Disc Herniation 
Objective
The purpose of this study was to compare clinical and radiological outcomes of percutaneous endoscopic lumbar discectomy (PELD) and open lumbar microdiscectomy (OLM) for recurrent disc herniation.
Methods
Fifty-four patients, who underwent surgery, either PELD (25 patients) or repeated OLM (29 patients), due to recurrent disc herniation at L4-5 level, were divided into two groups according to the surgical methods. Excluded were patients with sequestrated disc, calcified disc, severe neurological deficit, or instability. Clinical outcomes were assessed using Visual Analogue Scale (VAS) score and Oswestry Disability Index (ODI). Radiological variables were assessed using plain radiography and/or magnetic resonance imaging.
Results
Mean operating time and hospital stay were significantly shorter in PELD group (45.8 minutes and 0.9 day, respectively) than OLM group (73.8 minutes and 3.8 days, respectively) (p < 0.001). Complications occurred in 4% in PELD group and 10.3% in OLM group in the perioperative period. At a mean follow-up duration of 34.2 months, the mean improvements of back pain, leg pain, and functional improvement were 4.0, 5.5, and 40.9% for PELD group and 2.3, 5.1, and 45.0% for OLM group, respectively. Second recurrence occurred in 4% after PELD and 10.3% after OLM. Disc height did not change after PELD, but significantly decreased after OLM (p = 0.0001). Neither sagittal rotation angle nor volume of multifidus muscle changed significantly in both groups.
Conclusion
Both PELD and repeated OLM showed favorable outcomes for recurrent disc herniation, but PELD had advantages in terms of shorter operating time, hospital stay, and disc height preservation.
doi:10.3340/jkns.2009.46.6.515
PMCID: PMC2803265  PMID: 20062565
Reherniation; Discectomy; Lumbar spine
12.  Toll-Like Receptor 4 Decoy, TOY, Attenuates Gram-Negative Bacterial Sepsis 
PLoS ONE  2009;4(10):e7403.
Lipopolysaccharide (LPS), the Gram-negative bacterial outer membrane glycolipid, induces sepsis through its interaction with myeloid differentiation protein-2 (MD-2) and Toll-like receptor 4 (TLR4). To block interaction between LPS/MD-2 complex and TLR4, we designed and generated soluble fusion proteins capable of binding MD-2, dubbed TLR4 decoy receptor (TOY) using ‘the Hybrid leucine-rich repeats (LRR) technique’. TOY contains the MD-2 binding ectodomain of TLR4, the LRR motif of hagfish variable lymphocyte receptor (VLR), and the Fc domain of IgG1 to make it soluble, productive, and functional. TOY exhibited strong binding to MD-2, but not to the extracellular matrix (ECM), resulting in a favorable pharmacokinetic profile in vivo. TOY significantly extended the lifespan, when administered in either preventive or therapeutic manners, in both the LPS- and cecal ligation/puncture-induced sepsis models in mice. TOY markedly attenuated LPS-triggered NF-κB activation, secretion of proinflammatory cytokines, and thrombus formation in multiple organs. Taken together, the targeting strategy for sequestration of LPS/MD-2 complex using the decoy receptor TOY is effective in treating LPS- and bacteria-induced sepsis; furthermore, the strategy used in TOY development can be applied to the generation of other novel decoy receptor proteins.
doi:10.1371/journal.pone.0007403
PMCID: PMC2754608  PMID: 19816595
13.  Bone Marrow T Cells are Superior to Splenic T Cells to Induce Chimeric Conversion After Non-Myeloablative Bone Marrow Transplantation 
Background/Aims
The bone marrow functions not only as the primary B-lymphocyte-producing organ but also as a secondary lymphoid organ for CD4 and CD8 cell responses and a site of preferential homing and persistence for memory T cells. Bone marrow T (BM-T) cells are distinguished from peripheral blood T cells by surface phenotype, cytokine secretion profile, and immune functions. In this study, we evaluated the alloreactive potential of donor lymphocyte infusion (DLI) using BM-T cells in mixed chimerism compared to that using spleen T (SP-T) cells.
Methods
Cells were prepared using established procedures. BM-T cells were obtained as a by-product of T-cell depletion in BM grafting and then cryopreserved for subsequent DLI. We performed DLI using BM-T cells in allogeneic mixed chimera mice on post-BMT day 21.
Results
When the same dose of T cells, 5-10×105 (Thy1.2+), fractionated from BM and spleen were administered into mixed chimeras, the BM-T group showed complete chimeric conversion, with self-limited graft-versus-host disease (GVHD) and no pathological changes. However, the SP-T group showed persistent mixed chimerism, with pathological signs of GVHD in the liver and intestine.
Conclusions
Our results suggest that DLI using BM-T cells, even in small numbers, is more potent at inducing chimeric conversion in mixed chimerism than DLI using SP-T cells. Further study is needed to determine whether cryopreserved BM-T cells are an effective cell source for DLI to consolidate donor-dominant chimerism in clinical practice without concerns about GVHD.
doi:10.3904/kjim.2009.24.3.252
PMCID: PMC2732786  PMID: 19721863
Chimerism, mixed; Infusion, donor lymphocyte; T-cells, bone marrow
14.  Secondary Amyloidosis Associated with Multiple Sclerosis 
Background
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Secondary amyloidosis can occur as a complication of chronic systemic inflammatory and infectious diseases. Until now there has been no report of secondary amyloidosis associated with MS. We report herein a case of renal biopsy-proven secondary amyloidosis in a patient with MS.
Case Report
A 41-year-old woman with MS was hospitalized due to aggravated quadriparesis and edema in both lower extremities. Laboratory findings showed nephrotic-range proteinuria and hypoalbuminemia. A percutaneous renal biopsy procedure was performed, the results of which revealed secondary amyloid-A-type amyloidosis associated with MS.
Conclusions
This is the first report of secondary amyloidosis associated with MS.
doi:10.3988/jcn.2009.5.3.146
PMCID: PMC2760720  PMID: 19826566
multiple sclerosis; secondary amyloidosis; nephrotic syndrome
15.  Petrous Apex Cholesterol Granuloma Presenting as Endolymphatic Hydrops: A Case Report 
A petrous apex cholesterol granuloma (PACG) is the most common lesion of the petrous apex mass. Affected patients present with various symptoms such as hearing loss, vertigo, headache, tinnitus, facial spasms, and diplopia. We report the case of a 32-yr-old man with a PACG, who was first misdiagnosed with Ménière's disease. He was placed on a low-salt diet, and prescribed medication from another hospital, for several months, but the symptoms persisted and worsened. The patient presented to the emergency room complaining of left facial twitching and numbness. To rule out a central neurological lesion, temporal bone magnetic resonance imaging was carried out and a 2.5 cm mass with high signal intensity on T1- and T2-weighted imaging, without gadolinium enhancement, was found. Because of the hearing and facial problems, we drained cholesterol-bearing material via an infralabyrinthine approach using a computer aided image-guided surgical device, the BrainLAB®. After the operation, the vertigo and hearing loss were no longer present. It is likely that the patent's Ménière's disease-like symptoms were due to the compression of the endolymphatic sac by a PACG.
doi:10.3342/ceo.2009.2.3.151
PMCID: PMC2751881  PMID: 19784409
Cholesterol granuloma; Petrous apex; Endolymphatic hydrops
16.  Comparison of Surgical Outcomes in Thoracolumbar Fractures Operated with Posterior Constructs Having Varying Fixation Length with Selective Anterior Fusion 
Yonsei Medical Journal  2009;50(4):546-554.
Purpose
Surgical treatment in the case of thoracolumbar burst fractures is very controversial. Posterior instrumentation is most frequently used, however, but the number of levels to be instrumented still remains a matter of debate.
Materials and Methods
A total of 94 patients who had a single burst fracture between T11 and L2 were selected and were managed using posterior instrumentation with anterior fusion when necessary. They were divided into three groups as follows; Group I (n = 28) included patients who were operated by intermediate segment fixation, Group II (n = 32) included patients operated by long segment fixation, and Group III (n = 34) included those operated by intermediate segment fixation with a pair of additional screws in the fractured vertebra. The mean follow-up period was twenty one months. The outcomes were analyzed in terms of kyphosis angle (KA), regional kyphosis angle (RA), sagittal index (SI), anterior height compression rate, Frankel classification, and Oswestry Disability Index questionnaire.
Results
In Groups II and III, the correction values of KA, RA, and SI were much better than in Group I. At the final follow up, the correction values of KA (6.3 and 12.1, respectively) and SI (6.2 and 12.0, respectively) were in Groups II and III found to be better in the latter.
Conclusion
The intermediate segment fixation with an additional pair of screws at the fracture level vertebra gives results that are comparable or even better than long segment fixation and gives an advantage of preserving an extra mobile segment.
doi:10.3349/ymj.2009.50.4.546
PMCID: PMC2730618  PMID: 19718404
Thoracolumbar burst fracture; posterior instrumentation; intermediate segment fixation; fixation length; selective anterior fusion
17.  Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells 
Experimental & Molecular Medicine  2009;41(6):440-452.
When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2α phosphorylation. Transcription of two downstream targets of eIF2α, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuronal differentiation of mouse embryonic stem (mES) cells. Finally, chemical endoplasmic reticulum (ER) stress inducers, thapsigargin, tunicamycin, and brefeldin A, dose-dependently increased both mRNA and protein expressions of NF-L, and, its expression was specific to BIP-positive rBMSCs. Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation.
doi:10.3858/emm.2009.41.6.049
PMCID: PMC2705864  PMID: 19322020
bone marrow; cell differentiation; embryonic stem cells; endoplasmic reticulum; neuron; stem cells; stress, physiological; stromal cells
18.  The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-κB in Macrophages: Implication for Atherosclerosis 
Background
CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation.
Methods
In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface.
Results
Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-κB. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of IκB, and nuclear translocation of NF-κB p65 and p50 subunits.
Conclusion
These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.
doi:10.4110/in.2009.9.3.90
PMCID: PMC2803300  PMID: 20107538
macrophage; atherosclerosis; inflammation; CD147; cyclophilin A
19.  Multiple Levels of Lumbar Spondylolysis - A Case Report - 
Asian Spine Journal  2009;3(1):35-38.
We report here on an unusual case of multiple levels of asymmetric lumbar spondylolysis in a 19-year-old woman. The patient had severe low back pain of increasing intensity with lumbar instability, which was evident on the dynamic radiographs. MRI demonstrated the presence of abnormalities and the three dimensional CT scan revealed asymmetric complete spondylolysis at the left L2, L3 and L4 levels and the right L1, L2 and L3 levels. This case was treated surgically by posterior and posterolateral fusion at L2-3-4 with intersegmental fixation using pedicle screws and an auto iliac bone graft. The patient was relieved of her low back pain after the surgery.
doi:10.4184/asj.2009.3.1.35
PMCID: PMC2852035  PMID: 20404945
Lower back pain; Multiple spondylolysis; Fusion
20.  20-Year-Follow up of Treatment Using Spine Osteotomy and Halo-pelvic Traction for Tuberculous Kyphosis - A Case Report - 
Asian Spine Journal  2009;3(1):27-31.
A 23-year-old male whose medical history included tuberculous spondylitis presented with a kyphotic deformity and incomplete paraplegia of twenty days duration. Preoperative radiographs demonstrated a T12-L4 kyphotic Cobb's angle of 100° with a complete block showing on the lumbar myelogram at L4-5. The patient underwent anterior osteotomy and release. After the operation, a halo-pelvic apparatus was fit onto the patient, and distraction was begun. After distraction for 2 months, posterior osteotomy and release was performed for final correction, and distraction was maintained for another three weeks. Finally, the kyphotic deformity was corrected to a Cobb's angle of 62° from T12 to L4. Supplementary anterior fusion was done, and the apparatus was removed after consolidation of the fusion mass.
Even twenty years after correction of a tuberculous kyphosis, he had no neurological deterioration, and could work as a farmer using agricultural machines. Correction angle and sagittal balance were well maintained.
doi:10.4184/asj.2009.3.1.27
PMCID: PMC2852040  PMID: 20404943
Tuberculous kyphosis; Halo-pelvic traction; Spine osteotomy
21.  Comparison of Icodextrin and 2.5% Glucose in Potassium Metabolism by Acute K+ load via Dialysate in Continuous Ambulatory Peritoneal Dialysis Patients 
This study aimed to compare the increment in plasma potassium concentration ([K+]) as well as the role of internal K+ balance for its changes following acute K+ supplementation between conventional 2.5% glucose (GD) and non-glucose containing dialysate (icodextrin, ID) in continuous ambulatory peritoneal dialysis (CAPD) patients. A total of 9 stable CAPD patients (5 men and 4 women; age, 56±13 years; 7 type-2 diabetics and 2 non-diabetics) on daily 4 exchanges of 2 L of glucose dialysate underwent the 6-hr dwell on fasting in the morning with 2 L of 2.5% glucose mixed with 20 mEq/L of KCl, and then the same regimen was repeated with icodextrin after 1-wk interval. The degree of intraperitoneal absorption was comparable, 65±2% in GD and 68±2% in ID, respectively (p=NS). However, despite the similar plasma K+ levels at the baseline of both regimens, its increment was significantly less in GD than ID, which was accompanied by more marked increase in the calculated intracellular K+ redistribution (68±3% vs. 52±3%, p<0.05). The basal levels of insulin were similar between the GD and ID groups. However, the change, checked up after 2 hours' dwell, from the basal insulin levels was much lower on ID. ID with a lesser degree of transcelluar K+ shift by the decreased secretion of insulin is more effective than the conventional glucose solution for acute K+ repletion via dialysate during CAPD. Furthermore, these results suggested that the role of insulin for the internal K+ balance was intact even in type-2 diabetic patients on CAPD.
doi:10.5049/EBP.2009.7.1.25
PMCID: PMC3041482  PMID: 21468182
hypokalemia; peritoneal dialysis, continuous ambulatory; potassium supplementation; icodextrin
22.  Peripapillary Retinal Nerve Fiber Layer Thickness Change After Panretinal Photocoagulation in Patients With Diabetic Retinopathy 
Purpose
To examine the effect of panretinal photocoagulation (PRP) on the retinal nerve fiber layer (RNFL) thickness in patients with diabetic retinopathy.
Methods
Subjects included 118 eyes for a treatment group and 164 eyes for a control group. The peripapillary RNFL thickness was measured before and 6 months after PRP in treatment group. In control group, the peripapillary RNFL thickness was measured at baseline and 6 months later. The relationships between changes in RNFL thickness and the number of laser burns, duration of diabetes, HbA1c level, and vision change were analyzed.
Results
After 6 months, the RNFL thickness decreased an average of 2.12 µm and 0.93 µm in the treatment and control groups. However, the changes between the two groups were not statistically significant. The relationship between the number of laser burns and changes in RNFL thickness was not significant. No differences were found between changes in the RNFL thickness and the duration of diabetes in either group. However, in the treatment group a higher HbA1c level was correlated with a greater decrease in post-PRP RNFL thickness. This relationship was not observed in the control group. The difference in the change of the RNFL thickness between the two groups was statistically significant. Vision increased an average of 0.02 and 0.01 after 6 months in the treatment and control groups, respectively. However, this difference was not statistically significant.
Conclusions
Although a decrease in peripapillary RNFL thickness was observed in the treatment group after 6 months, it was not statistically significant compared to control group. However, the decrease was greater when the blood HbA1c level was higher.
doi:10.3341/kjo.2009.23.1.23
PMCID: PMC2655739  PMID: 19337475
Diabetic retinopathy; Glycosylated hemoglobin; Panretinal photocoagulation; Optical coherence tomography; Peripapillary retinal nerve fiber layer
23.  Umbilical Artery Doppler Study as a Predictive Marker of Perinatal Outcome in Preterm Small for Gestational Age Infants 
Yonsei Medical Journal  2009;50(1):39-44.
Purpose
To evaluate the merit of umbilical artery Doppler study as a predictive marker of perinatal outcome in preterm small for gestational age (SGA) infants.
Materials and Methods
A total of 218 patients at 27 - 36 weeks of gestational age (GA) who received antenatal umbilical artery Doppler velocimetry and delivered singleton infants with SGA. The ratio of peak-systolic to end-diastolic blood flow velocities (S/D) in the umbilical artery was measured in each patient. The patients were divided into 3 groups: the normal group with S/D ratios of less than 95th percentile (n = 134), elevated S/D ratio group of 95th or more percentile (n = 41), and those with absent/reversed end diastolic flow (n = 43). Maternal characteristics and neonatal outcomes of these groups were comparatively analyzed.
Results
The gestational age (GA) at the time of diagnosis of SGA, the mean GA at delivery, and the mean birth weight showed statistically significant difference among three groups (p < 0.001). Also, poor perinatal outcome was significantly increased in infants with abnormal S/D ratio (13.4% vs. 31.7% vs. 67.4%, p < 0.001). Multivariate logistic regression analysis revealed umbilical artery Doppler study as a significant independent factor for prediction of poor perinatal outcome (odds ratio: 3.7, 95% confidence interval 1.4 - 9.5, p = 0.007).
Conclusion
Antenatal umbilical artery Doppler velocimetry is shown as a significantly efficient marker in predicting perinatal outcome in preterm SGA infants.
doi:10.3349/ymj.2009.50.1.39
PMCID: PMC2649859  PMID: 19259346
Preterm small for gestational age infant; umbilical artery Doppler velocimetry; perinatal outcome
24.  Prevalence of clonorchiasis in patients with gastrointestinal disease: A Korean nationwide multicenter survey 
AIM: To investigate prevalence of Clonorchis sinensis in patients with gastrointestinal symptoms, and the relation of the infection to hepatobiliary diseases in 26 hospitals in Korea.
METHODS: Consecutive patients who had been admitted to the Division of Gastroenterology with gastrointestinal symptoms were enrolled from March to April 2005. Of those who had been diagnosed with clonorchiasis, epidemiology and correlation between infection and hepatobiliary diseases were surveyed by questionnaire.
RESULTS: Of 3080 patients with gastrointestinal diseases, 396 (12.9%) had clonorchiasis and 1140 patients (37.2%) had a history of eating raw freshwater fish. Of those with a history of raw freshwater fish ingestion, 238 (20.9%) patients had clonorchiasis. Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than non-infected patients [34/396 (8.6%) vs 145/2684 (5.4%), P = 0.015]. Cholangiocarcinoma and clonorchiasis showed statistically significant positive cross-relation (P = 0.008). Choledocholithiasis, cholecystolithiasis, cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate with clonorchiasis.
CONCLUSION: Infection rate of clonorchiasis was still high in patients with gastrointestinal diseases in Korea, and has not decreased very much during the last two decades. Cholangiocarcinoma was related to clonorchiasis, which suggested an etiological role for the parasite.
doi:10.3748/wjg.15.86
PMCID: PMC2653299  PMID: 19115472
Clonorchis sinensis; Epidemiology; Cholangiocarcinoma; Korea; Multicenter study; Clonorchiasis

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