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1.  Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells 
Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-α, IFN-γ, and IL-1β). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-κB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.
PMCID: PMC3741488  PMID: 23946691
β cells; ERK1/2; iNOS; NO
2.  Pseudomyxoma Peritonei: A Rare Cause of Oliguric Acute Kidney Injury 
Chonnam Medical Journal  2013;49(2):87-90.
Pseudomyxoma peritonei is a rare clinical condition that causes the accumulation of mucinous ascites, which gradually results in the compression of intra-abdominal organs. Most published reports of pseudomyxoma peritonei concern the mass effect of the resulting ascites, which presents as abdominal pain or intestinal ileus in severe cases. However, few reports of renal complications of the disease have been published. Here, we present a case of oliguric acute kidney injury caused by external compression by pseudomyxoma peritonei. After decompression with external drainage, the patient's renal function rapidly improved.
PMCID: PMC3759688  PMID: 24010072
Acute kidney injury; Oliguria; Pseudomyxoma peritonei
3.  Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells 
Biomolecules & Therapeutics  2013;21(4):258-263.
We demonstrate herein that silibinin, a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-α, and IL1β. We also showed that silibinin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibitor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling.
PMCID: PMC3819897  PMID: 24244809
Silibinin; Macrophages; p38 MAPK; Nitric oxide
4.  Effects of contiguous scars in dermoscopic evaluation of clinically atypical melanocytic nevi 
PMCID: PMC3329219  PMID: 22507589
Dermoscopy; atypical nevi; atypical melanocytic nevi; biopsy; scar
5.  The Frequency of Reexpansion Pulmonary Edema after Trocar and Hemostat Assisted Thoracostomy in Patients with Spontaneous Pneumothorax 
Yonsei Medical Journal  2012;54(1):166-171.
Several risk factors for development of reexpansion pulmonary edema (REPE) after drainage of pneumothoraces have been reported, but the association between the method of thoracostomy and the development of REPE is unknown. The aim of this study was to compare the frequency of REPE after treatment of spontaneous pneumothorax with trocar or hemostat assisted closed thoracostomy.
Materials and Methods
We performed a prospective, observational study including 173 patients with spontaneous pneumothorax who visited the emergency department from January 2007 to December 2008. In 2007, patients were treated with hemostat-assisted drainage, whereas patients in 2008 were treated with trocar-assisted drainage. The main outcome was the development of REPE, determined by computed tomography of the chest 8 hours after closed thoracostomy. Outcomes in both groups were compared using univariate and multivariate analyses.
Ninety-two patients were included, 48 (42 males) of which underwent hemostat-assisted drainage and 44 (41 males) underwent trocar-assisted drainage. The groups were similar in mean age (24±10 vs. 26±14 respectively). The frequencies of REPE after hemostat- and trocar-assisted drainage were 63% (30 patients) and 86% (38 patients) respectively (p=0.009). In multivariate analysis, trocar-assisted drainage was the major contributing factor for developing REPE (odds ratio=5.7, 95% confidence interval, 1.5-21). Age, gender, size of pneumothorax, symptom duration and laboratory results were similar between the groups.
Closed thoracostomy using a trocar is associated with an increased risk of REPE compared with hemostat-assisted drainage in patients with spontaneous pneumothorax.
PMCID: PMC3521265  PMID: 23225814
Pneumothorax; thoracostomy; pulmonary edema
6.  Three-dimensional finite element analysis of the deformation of the human mandible: a preliminary study from the perspective of orthodontic mini-implant stability 
Korean Journal of Orthodontics  2012;42(4):159-168.
The aims of this study were to investigate mandibular deformation under clenching and to estimate its effect on the stability of orthodontic mini-implants (OMI).
Three finite element models were constructed using computed tomography (CT) images of 3 adults with different mandibular plane angles (A, low; B, average; and C, high). An OMI was placed between #45 and #46 in each model. Mandibular deformation under premolar and molar clenching was simulated. Comparisons were made between peri-orthodontic mini-implant compressive strain (POMI-CSTN) under clenching and orthodontic traction forces (150 g and 200 g).
Three models with different mandibular plane angles demonstrated different functional deformation characteristics. The compressive strains around the OMI were distributed mesiodistally rather than occlusogingivally. In model A, the maximum POMI-CSTN under clenching was observed at the mesial aspect of #46 (1,401.75 microstrain [µE]), and similar maximum POMI-CSTN was observed under a traction force of 150 g (1,415 µE).
The maximum POMI-CSTN developed by clenching failed to exceed the normally allowed compressive cortical bone strains; however, additional orthodontic traction force to the OMI may increase POMI-CSTN to compromise OMI stability.
PMCID: PMC3481986  PMID: 23112947
Orthodontic mini-implant; Stability; Neuromuscular force; Anatomy; Finite element method
7.  Dependence Potential of Propofol: Behavioral Pharmacology in Rodents 
Biomolecules & Therapeutics  2012;20(2):234-238.
Propofol is an anesthetic commonly used to provide sedation or to induce and maintain an anesthetic stated. However, there are reports which indicate propofol may cause psychological dependence or be abused. In the present study, we used various behavioral tests including climbing test, jumping test, conditioned place preference, and self-administration test to assess the dependence potential and abuse liability of propofol compared to a positive control (methamphetamine) or a negative control (saline or intralipid). Among the tests, the conditioned place preference test was conducted with a biased method, and the selfadministration test was performed under a fixed ratio (FR) 1 schedule, 1 h per session. No difference was found in the climbing test and jumping test, but propofol (30 mg/kg, i.p.) increased the rewarding effect in the conditioned place preference test, and it showed a positive reinforcing effect compared to the vehicle. These results indicate that propofol tends to show psychological dependence rather than physical dependence, and it seems not to be related with dopaminergic system.
PMCID: PMC3792224  PMID: 24116301
Propofol; Psychological dependence; Physical dependence; Animal behavioral test
8.  Zap70 functions to maintain stemness of mouse embryonic stem cells by negatively regulating Jak1/Stat3/c-Myc signaling 
Stem cells (Dayton, Ohio)  2010;28(9):1476-1486.
Zeta-chain associated protein kinase-70 (Zap70), a Syk family tyrosine kinase, has been reported to be present exclusively in normal T cells, Natural Killer (NK) cells, and B cells, serving as a pivotal regulator of antigen-mediated receptor signaling and development. In this study, we report that Zap70 is expressed in undifferentiated mouse embryonic stem cells (mESCs) and may critically regulate self-renewal and pluripotency in mESCs. We found that Zap70 knocked-down mESCs (Zap70KD) show sustained self-renewal and defective differentiation. In addition, we present evidence that the sustained self-renewal in Zap70KD is associated with enhanced Jak/Stat3 signaling and c-Myc induction. These altered signaling appears to result from up-regulated LIFR and down-regulated SHP-1 phosphatase activity. Based on these results, we propose that, in undifferentiated mESCs, Zap70 plays important roles in modulating the balance between self-renewal capacity and pluripotent differentiation ability as a key regulator of the Jak/Stat3/c-Myc signaling pathway.
PMCID: PMC3164580  PMID: 20641039
Zap70; mouse embryonic stem cells; Jak/Stat3; c-Myc; SHP-1; LIFR; self-renewal; pluripotency; stemness
9.  Seroprevalence of Toxoplasma gondii Infection and Characteristics of Seropositive Patients in General Hospitals in Daejeon, Korea 
To figure out the epidemiological status and relevance with other diseases in toxoplasmosis, we checked serum IgG antibody titers of 1,265 patients and medical records of seropositive patients. Seropositive rates were 6.6% by latex agglutination test (LAT) and 6.7% by ELISA. No significant differences were detected between sexes and age groups. The peak seroprevalence was detected in the 40-49-year-old age group. According to clinical department, Toxoplasma-positive rates were high in patients in psychiatry, ophthalmology, health management, emergency medicine, and thoracic surgery. Major coincidental diseases in seropositive cases were malignant neoplasms, diabetes mellitus, arthritis, chronic hepatitis B, chronic renal diseases, schizophrenia, and acute lymphadenitis, in the order of frequency. In particular, some patients with chronic hepatitis B and malignant neoplasms had high antibody titers. These results revealed that the seroprevalence of toxoplasmosis in a general hospital-based study was similar to that in a community-based study, and T. gondii seropositivity may be associated with neoplasms, diabetes, and other chronic infections.
PMCID: PMC2688793  PMID: 19488418
Toxoplasma gondii; comorbidity; general hospital; seroprevalence; Daejeon
10.  Molecular and Cytogenetic Characterization of Two Azoospermic Patients with X-Autosome Translocation 
Purpose: To report two azoospermic patients with reciprocal X–autosome translocations.
Methods: Cytogenetic analysis utilizing GTG-banding and Yq microdeletions shown by polymerase chain reaction (PCR) with 12 sequence-tagged site (STS) markers for Y chromosome microdeletions.
Results: Cytogenetic analysis showed one man with 46,Y,t(X;19)(q22;q13.3) and the other with 46,Y,t(X;8)(p22;q11). Neither had any Yq microdeletions shown. The patient with 46,Y, t(X;8)(p22;q11) showed a slightly lower than normal testosterone level. By NCBI-Blast search, we found four testis-specific genes, t-complex-associated-testis-expressed 1-like (TCTE1L), Ferritin, heavy polypeptide-like 17 (FTHL17), Testis expressed sequence 13A (TEX13A), and Testis expressed sequence 13B (TEX13B) located near breakpoints on X chromosome. FTHL17, TEX13A, and TEX13B are spermatogonially-expressed, germ-cell-specific genes.
Conclusion: This is the first clinical report of azoospermia with reciprocal X–autosome translocations on Xp22 and q22. These translocations on Xp22 and q22 may be direct genetic risk factors for azoospermia.
PMCID: PMC3455837  PMID: 14531651
Azoospermia; infertility; spermatogonia; translocation
11.  Development of puffed ginseng-rice snack from ginseng powder and map rice flour using steam and compression process 
A new manufacturing method for producing a puffed ginseng-rice snack (PGRS) was developed using ginseng powder and map rice flour through a steam and compression process (SCP). The physical and sensory properties of the PGRS were characterized. The pellets for puffing were prepared from ginseng powder and map rice flour. The pellets were subjected to 16, 18, and 20% moisture contents and were puffed at 225, 235, and 245° C. The specific volumes of the PGRSs increased with heating temperature and moisture content. However, the breaking strength of the PGRSs decreased. In addition, the SCP imposed special features in the PGRSs that made them more acceptable. The Hunter L-value increased with heating temperature and moisture content. These results indicate that a PGRS with functional additives could be effectively developed into a functional food with the use of a puffing machine, and that the PGRS shows potential as a new snack product.
PMCID: PMC3550922  PMID: 24425934
Puffed ginseng-rice snack; Steam; Compression; Map rice
12.  Induction of Re-Differentiation of Passaged Rat Chondrocytes Using a Naturally Obtained Extracellular Matrix Microenvironment 
Tissue Engineering. Part A  2013;19(7-8):978-988.
Dedifferentiated human chondrocytes severely limit successful hyaline cartilage repair in clinical practice. The primary interest of this study is to evaluate the naturally obtained cell-derived matrix (CDM) as a physical microenvironment for chondrocyte re-differentiation. Once different cell types were cultured for 6 days and decellularized using detergents and enzymes, the fibroblast-derived matrix (FDM), preosteoblast-derived matrix (PDM), and chondrocyte-derived matrix (CHDM) were obtained. From scanning electron microscope observation, each CDM was found to resemble a fibrous mesh with self-assembled fibrils. Both the FDM and PDM showed a more compact matrix structure compared to the CHDM. For compositional analysis, sodium dodecyl sulfate–polyacrylamide gel electrophoresis displayed numerous matrix proteins, which were quite different from each CDM in quantity and type. Specific matrix components, such as fibronectin, type I collagen (Col I), and laminin, were detected using immunofluorescent staining. In addition, the water contact angle suggests that the FDM is more hydrophilic than the PDM or CHDM. The proliferation of rat primary chondrocytes growing on CDMs was better than those growing on a plastic coverslip (control) or gelatin. Meanwhile, synthesis of glycosaminoglycan (GAG) was more effective for passaged chondrocytes (P4) cultivated on CDMs, and the difference was significant compared to cells grown on the control or on gelatin. As for the gene expression of cartilage-specific markers, CDMs exhibited good chondrocyte re-differentiation with time: the dedifferentiating marker, Col I was restrained, whereas the ratio between Col II and Col I, and between aggrecan and Col I, as an indicator of re-differentiation, was greatly improved. In addition, immunofluorescence of Col II showed a very positive signal in chondrocytes cultivated for 2 weeks on the CDMs. In an additional study, when three-dimensional cell pellets made from either plate-grown or matrix-grown dedifferentiated chondrocytes (P5) were cultured for 4 weeks, the results of Safranin-O staining, immunohistochemistry of Col II, and total GAG assay suggested that matrix-grown cells were significantly better in the induction of chondrocyte re-differentiation, than those grown on the plate. This work suggests that the naturally occurring matrix, CDM, can provide a favorable surface texture for cell attachment, proliferation, and more importantly, a chondroinductive microenvironment for the re-differentiation of dedifferentiated chondrocytes.
PMCID: PMC3589875  PMID: 23157423
13.  Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology 
Cell Death and Differentiation  2012;20(4):630-638.
The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Aβ), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Aβ aggregation in vitro. DBP also prevented Aβ-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Aβ-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Aβ into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Aβ by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.
PMCID: PMC3595489  PMID: 23257976
Alzheimer's disease; amyloid beta; vitamin D-binding protein; cytotoxicity; neurodegeneration
14.  Using susceptibility-weighted imaging to determine response to combined anti-angiogenic, cytotoxic, and radiation therapy in patients with glioblastoma multiforme† 
Neuro-Oncology  2013;15(4):480-489.
The goal of this study was to investigate whether the amount of hypointense signal on susceptibility-weighted imaging within the contrast-enhancing lesion (%SWI-h) on the pretreatment scan could determine response in patients with newly diagnosed glioblastoma multiforme who received external beam radiation therapy with concomitant anti-angiogenic therapy (enzastaurin) and cytotoxic chemotherapy (temozolomide).
Twenty-five patients were imaged before therapy (postsurgical resection) and scanned serially every 2 months until progression. Standard clinical MR imaging and SWI were performed on a 3T scanner. %SWI-h was quantified for each patient's pretreatment scan. Time to progression and death were used to characterize patients into non-, immediate-, and sustained-response groups for both events. Cox proportional hazards models were used to assess the association between %SWI-h and both progression-free survival (PFS) and overall survival (OS). Classification and regression tree analysis were used to determine optimal cutoffs on which to split %SWI-h.
For both death- and progression-based response categories, %SWI-h was significantly higher in sustained responders than in nonresponders. Cox model coefficients showed an association between %SWI-h and PFS and OS, both in univariate analysis (PFS: hazard ratio [HR] = 0.966, 95% confidence interval [CI] = 0.942–0.988; and OS: HR = 0.945, 95% CI = 0.915–0.976) and when adjusting for baseline KPS, age, sex, and resection extent (PFS: HR = 0.968, 95% CI = 0.940 –0.994; and OS: HR = 0.943, 95% CI = 0.908 –0.976). A cutoff value of 38.1% significantly differentiated patients into 2 groups based on censored OS and into non- and intermediate-response categories based on time to progression.
These early differences suggest that SWI may be able to predict which patients would benefit most from similar combination therapies and may assist clinicians in making important decisions about patient care.
PMCID: PMC3607266  PMID: 23393208
glioma; response to anti-angiogenic therapy; susceptibility-weighted imaging
15.  Current State of and Needs for Hepatitis B Screening: Results of a Large Screening Study in a Low-Prevalent, Metropolitan Region 
PLoS ONE  2014;9(3):e92266.
In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing.
During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals.
85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8–100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0–93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3–47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6–32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU.
Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.
PMCID: PMC3963888  PMID: 24663387
16.  China's Growing Contribution to Global Intracranial Aneurysm Research (1991–2012): A Bibliometric Study 
PLoS ONE  2014;9(3):e91594.
We sought to analyze the growing worldwide trends of intracranial aneurysm research, investigate China's recent contribution, and compare the contributions of mainland China, Taiwan, and Hong Kong.
Global and China intracranial aneurysm-related publications were retrieved from the Web of Science database from 1991 to 2012. Excel 2007, Matlab, and Thomson Data Analyzer (TDA) software were used to analyze the search results for number of publications, cited frequency, h-index, and organization contributions.
16468 global papers were identified that were cited 273500 times until 2013-08-15. The United States accounted for 31.497% of the articles, 58.64% of the citations, and the highest h-index (127). Japan and Germany followed in frequency. China's articles ranked eighth (third in 2012) in total number, with most of the contributions occurring since 2002 (91.33%). China was at the early stage of the logic growth curve (exponential growth), with the citation frequency and h-index per year increasing. The quality of the publications was low. The main research centers were located in Beijing, Shanghai, Taiwan, and Hong Kong. The main Asian funding body was the National Natural Science Foundation of China. The number of publications and frequency of citations of papers from mainland China was greater than that of Taiwan or Hong Kong.
Global intracranial aneurysm research has been developing swiftly since 1991, with the United States making the largest contribution. Research in China started later, in 2002. Since then, China has increased its rate of publication, and became the third largest contributor by 2012.
PMCID: PMC3951469  PMID: 24622581
17.  Role of additional PCBM layer between ZnO and photoactive layers in inverted bulk-heterojunction solar cells 
Scientific Reports  2014;4:4306.
In order to induce greater light absorption, nano-patterning is often applied to the metal-oxide buffer layer in inverted bulk-heterojunction(BHJ) solar cells. However, current homogeneity was significantly disturbed at the interface, leading to an efficiency that was not fully optimized. In this work, an additional PC61BM layer was inserted between the ZnO ripple and the photoactive layer to enhance the electron extraction. The insertion of additional PC61BM layer provided substantial advantages in the operation of inverted BHJ solar cells; specifically, it enhanced current homogeneity and lowered accumulation and trapping of photogenerated charges at the ZnO interface. Inclusion of the additional PC61BM layer led to effective quenching of electron–hole recombination by a reduction in the number of accumulated charges at the surface of ZnO ripples. This resulted in a 16% increase in the efficiency of inverted BHJ solar cells to 7.7%, compared to solar cells without the additional PC61BM layer.
PMCID: PMC3945486  PMID: 24603531
18.  Catechin-capped gold nanoparticles: green synthesis, characterization, and catalytic activity toward 4-nitrophenol reduction 
Nanoscale Research Letters  2014;9(1):103.
An eco-friendly approach is described for the green synthesis of gold nanoparticles using catechin as a reducing and capping agent. The reaction occurred at room temperature within 1 h without the use of any external energy and an excellent yield (99%) was obtained, as determined by inductively coupled plasma mass spectrometry. Various shapes of gold nanoparticles with an estimated diameter of 16.6 nm were green-synthesized. Notably, the capping of freshly synthesized gold nanoparticles by catechin was clearly visualized with the aid of microscopic techniques, including high-resolution transmission electron microscopy, atomic force microscopy, and field emission scanning electron microscopy. Strong peaks in the X-ray diffraction pattern of the as-prepared gold nanoparticles confirmed their crystalline nature. The catalytic activity of the as-prepared gold nanoparticles was observed in the reduction of 4-nitrophenol to 4-aminophenol in the presence of NaBH4. The results suggest that the newly prepared gold nanoparticles have potential uses in catalysis.
PMCID: PMC3944744  PMID: 24589224
Green synthesis; Catechin; Gold nanoparticles; Catalysis; 4-Nitrophenol reduction
19.  A One-Step, Solvothermal Reduction Method for Producing Reduced Graphene Oxide Dispersions in Organic Solvents 
ACS nano  2010;4(7):3845-3852.
Refluxing graphene oxide (GO) in N-methyl-2-pyrrolidinone (NMP) results in deoxygenation and reduction to yield a stable colloidal dispersion. The solvothermal reduction is accompanied by a color change from light brown to black. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) images of the product confirm the presence of single sheets of the solvothermally reduced graphene oxide (SRGO). X-ray photoelectron spectroscopy (XPS) of SRGO indicates a significant increase in intensity of the C=C bond character, while the oxygen content decreases markedly after the reduction is complete. X-ray diffraction analysis of SRGO shows a single broad peak at 26.24° 2θ (3.4 Å), confirming the presence of graphitic stacking of reduced sheets. SRGO sheets are redispersible in a variety of organic solvents, which may hold promise as an acceptor material for bulk heterojunction photovoltaic cells, or electromagnetic interference shielding applications.
PMCID: PMC3939021  PMID: 20586422
graphene; graphite oxide; solvothermal; reduced graphene oxide; composite; solar cell; reduction
20.  Cardiac Disease Increases Risk of Non-amnestic Mild Cognitive Impairment: Stronger impact in women 
JAMA neurology  2013;70(3):374-382.
Non-amnestic mild cognitive impairment (naMCI), a putative precursor of vascular and other non-Alzheimer’s disease dementias, is hypothesized to have a vascular etiology. We investigated the association of cardiac disease with amnestic (aMCI) and non-amnestic (naMCI) MCI.
A prospective, population-based, cohort study with a median 4.0 years of follow-up.
Olmsted County, Minnesota.
Participants were evaluated at baseline and every 15 months using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing. A diagnosis of normal cognition, MCI, or dementia was made by consensus. Cardiac disease at baseline was assessed from the participant’s medical records.
Main outcome measures
Incident MCI, aMCI, naMCI.
Among 1,450 subjects free of MCI or dementia at baseline, 366 developed MCI. Cardiac disease was associated with an increased risk of naMCI (hazard ratio [HR] 95% confidence interval; 1.77 [1.16–2.72]). However, the association varied by sex (P for interaction = .02). Cardiac disease was associated with an increased risk of naMCI (HR, 3.07 [1.58–5.99]) in women, but not in men (HR, 1.16 [0.68–1.99]. Cardiac disease was not associated with any MCI or aMCI.
Cardiac disease is an independent risk factor for naMCI, within sex comparisons showed a stronger association in women. Prevention and management of cardiac disease and vascular risk factors may reduce the risk of naMCI.
PMCID: PMC3734560  PMID: 23358884
21.  Quantitative detection of zeta-chain-associated protein 70 expression in chronic lymphocytic leukemia 
Leukemia & lymphoma  2012;54(3):10.3109/10428194.2012.715349.
Overexpression of zeta-chain-associated protein 70 (ZAP-70) was recently recognized as an independent prognostic marker for the aggressive form of chronic lymphocytic leukemia (CLL). The objective of this study was to demonstrate the feasibility and implementation of quantitative detection of ZAP-70 protein in B cells to clearly distinguish patients with CLL with the aggressive form of the disease. B cells were isolated from patient blood and lysed. Released ZAP-70 protein was detected using an immunomagnetic fluorescence assay. The assay protocol was developed using Jurkat cells and recombinant ZAP-70 (rZAP-70). The limit of detection was determined to be lower than 125 Jurkat cells and 39 pg of rZAP-70 protein. The signal response was linear over a wide dynamic range, from 125 to 40 000 Jurkat cells per test (R2 = 0.9987) and from 0 to 40 000 pg rZAP-70 protein per test (R2 = 0.9928). The results from 20 patients with CLL correlated strongly with flow cytometry analysis. Concordance between the two methods for positive and negative results was 100% (7/7) and 92% (12/13), respectively, while the overall concordance between the two methods was 95%. The assay reported here is a simple, reliable and reproducible method for quantitative detection of ZAP-70 in patient leukemic cells, without the need for cell fixation or permeabilization. The ZAP-70 signal was linear over a wide dynamic range, which we believe enables quantitative assessment of small changes in ZAP-70 expression over the course of the disease and in response to therapeutic intervention.
PMCID: PMC3862258  PMID: 22839722
Chronic lymphocytic leukemia (CLL); ZAP-70; flow cytometry; immunomagnetic fluorescence assay; Signalyte-II spectrofluorometer
22.  Decreased Pattern-Recognition Receptor-Mediated Cytokine mRNA Expression in Obese Children With Otitis Media With Effusion 
To assess innate and humoral immune responses in middle ear effusion of obese pediatric patients with otitis media with effusion (OME).
We evaluated 219 children with OME, of whom 21 were obese and 198 were non-obese. We compared the expression in middle ear effusion of mRNAs encoding toll-like receptors (TLR) 2, 4, 5, and 9; nucleotide-binding oligomerization domains (NOD) 1 and 2; retinoic acid-inducible gene (RIG)-I; interleukins (IL)-6, -10, and -12; interferon (IFN)-γ; and tumor necrosis factor (TNF)-α mRNAs. We also compared the expression of immunoglobulins IgG, IgA, and IgM and the bacterial detection rate in the two groups.
TLR2-mediated expression of IL-6 mRNA, TLR4-mediated expression of IL-6 and IL-10 mRNA, TLR5-mediated expression of IL-6, IL-10, and TNF-α mRNA, TLR9-mediated expression of IL-6 mRNA, and NOD2-mediated expression of IL-6, IL-12, and TNF-α mRNA were significantly lower in obese than in non-obese children (P<0.05). However, concentrations of IgG, IgA, and IgM in middle ear effusion were lower in obese than in non-obese children, but none of these differences was significant (P>0.05).
Mean body mass index was higher and pattern-recognition receptor-mediated cytokine mRNA expression was lower in obese than in non-obese children with OME.
PMCID: PMC3932355  PMID: 24587874
Otitis media; Obesity; Pattern-recognition receptors; Immunoglobulin; Immunity; Bacteria
23.  Diagnostic Algorithm to Reflect Regressive Changes of Human Papilloma Virus in Tissue Biopsies 
Yonsei Medical Journal  2014;55(2):331-338.
Landmark indicators have not yet to be developed to detect the regression of cervical intraepithelial neoplasia (CIN). We propose that quantitative viral load and indicative histological criteria can be used to differentiate between atypical squamous cells of undetermined significance (ASCUS) and a CIN of grade 1.
Materials and Methods
We collected 115 tissue biopsies from women who tested positive for the human papilloma virus (HPV). Nine morphological parameters including nuclear size, perinuclear halo, hyperchromasia, typical koilocyte (TK), abortive koilocyte (AK), bi-/multi-nucleation, keratohyaline granules, inflammation, and dyskeratosis were examined for each case. Correlation analyses, cumulative logistic regression, and binary logistic regression were used to determine optimal cut-off values of HPV copy numbers. The parameters TK, perinuclear halo, multi-nucleation, and nuclear size were significantly correlated quantitatively to HPV copy number.
An HPV loading number of 58.9 and AK number of 20 were optimal to discriminate between negative and subtle findings in biopsies. An HPV loading number of 271.49 and AK of 20 were optimal for discriminating between equivocal changes and obvious koilocytosis.
We propose that a squamous epithelial lesion with AK of >20 and quantitative HPV copy number between 58.9-271.49 represents a new spectrum of subtle pathological findings, characterized by AK in ASCUS. This can be described as a distinct entity and called "regressing koilocytosis".
PMCID: PMC3936611  PMID: 24532500
HPV; loading concentration; ASCUS; CIN; regressing koilocytosis
24.  Computed Tomography and Magnetic Resonance Images of Adrenocortical Oncocytoma Cases 
Journal of Korean Medical Science  2014;29(3):445-451.
We present two cases of adrenocortical oncocytomas that were well-delineated on multi-detector computed tomography and magnetic resonance imaging. The images showed a well-enhanced large mass with multiple stippled calcifications in a 10-yr-old girl who was consulted due to precocious puberty. A well-enhanced solid mass with necrotic components was incidentally noticed in a 54-yr-old man. These lesions were resected and diagnosed as adrenocortical oncocytomas through immunohistochemical studies and electron microscopy. Adrenocortical oncocytomas are rare disease entities, therefore, we report these interesting, rare adrenocortical oncocytomas here with radiologic findings, and discuss differential diagnosis.
Graphical Abstract
PMCID: PMC3945144  PMID: 24616598
Adrenal Glands; Neoplasms-Oncocytoma; Computed Tomography; Magnetic Resonance Imaging
25.  Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma 
Dermatomyositis is an idiopathic inflammatory myopathy with typical cutaneous manifestations. It has been proposed that dermatomyositis may be caused by autoimmune responses to viral infections. Previous studies have shown an association between dermatomyositis and malignant tumors such as ovarian cancer, lung cancer, and colorectal cancer. However, a chronic hepatitis B virus (HBV) infection associated with dermatomyositis and hepatocellular carcinoma (HCC) has been very rarely reported. Here, we report a rare case of dermatomyositis coinciding with HBV-associated HCC. A 55-year-old male was confirmed to have HCC and dermatomyositis based on proximal muscle weakness, typical skin manifestations, elevated muscle enzyme levels, and muscle biopsy findings. This case suggests that HCC and/or a chronic HBV infection may be factors in the pathogenesis of dermatomyositis through a paraneoplastic mechanism.
PMCID: PMC3956994  PMID: 24648807
Dermatomyositis; Hepatitis B virus; Hepatocellular carcinoma

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