Impact Ionization Induced by Accelerated Photoelectrons for Wide-Range and Highly Sensitive Detection of Volatile Organic Compounds at Room Temperature.

Ionization-based volatile organic compound (VOC) sensors that use photons or electrons operating at room temperature have attracted considerable attention as a promising alternative to conventional metal oxide-based sensors that require high temperature for sensing function. However, the photoionization sensors cannot ionize many gas species for their limited photon energy, and field emission-based ionization sensors that rely on the breakdown voltage of specific gas species in a pure state may not tell different concentration. This work demonstrates the detection of VOCs using impact ionization induced by accelerated photoelectrons. Although the photoelectrons emitted by relatively low photon energy typically have insufficient kinetic energy to cause impact ionization, in this approach, they are accelerated between microgap electrodes to enhance their kinetic energy such that the impact ionization of VOCs can be achieved. The demonstrated gas sensor sensitively detects toluene concentration in a wide range from 1000 ppm to 100 ppb with fast response and recovery time at room temperature. Additionally, diverse VOC species including benzene, p-xylene, and even acetylene with high ionization energy can be detected. The proposed method could be a viable solution for VOC sensors with low cost, scalable producibility, and high performance.

Reversible and continuous latching using a carbon internanotube interface.

Mechanical multistability is greatly beneficial in microelectromechanical systems because it offers multiple stable positioning of movable microstructures without a continuous energy supply. Although mechanical latching components based on multistability have been widely used in microsystems, their latching positions are inherently discrete and the number of stable positions is quite limited because of the lithographical minimum feature size limit of microstructures. We report a novel use of aligned carbon nanotube (CNT) arrays as latching elements in a movable micromechanical device. This CNT-array-based latching mechanism allows stable latching at multiple latching positions, together with reversible and bidirectional latching capabilities. The latching element with integrated CNTs on the sidewalls of microstructures can be adopted for diverse microelectromechanical systems that need precise positioning of movable structures without the necessity of continuous power consumption.

Biodistribution and in vivo efficacy of genetically modified human mesenchymal stem cells systemically transplanted into a mouse bone fracture model.

Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in clinical application due to their ability to undergo multi-lineage differentiation. Recently, ex vivo genetic modification of hMSCs was attempted to increase their differentiation potential. The present study was conducted to evaluate the biodistribution and in vivo efficacy of genetically modified hMSCs. To accomplish this, Runx2, which is a key transcription factor associated with osteoblast differentiation, was transduced into hMSCs using lentiviral vectors expressing green fluorescent protein (GFP) or luciferase. Here, we developed an experimental fracture in mice femur to investigate the effects of Runx2-transduced hMSCs on bone healing and migration into injury site. We conducted bio-luminescence imaging (BLI) using luciferase-tagged vector and quantitative real-time PCR using GFP probe to investigate the biodistribution of Runx2-transduced hMSCs in the fracture model. The biodistribution of hMSC cells in the fractured femur was observed at 14 days post-transplantation upon both BLI imaging and real-time PCR. Moreover, the fractured mice transplanted with Runx2-transduced hMSCs showed superior bone healing when compared to mock-transduced hMSC and MRC5 fibroblasts which were used as control. These data suggested that transplanted genetically modified hMSCs systemically migrate to the fractured femur, where they contribute to bone formation in vivo.

Transferability of a modified embryonic stem cell test using a new endpoint for developmental neurotoxicity.

We developed and analyzed a new surrogate endpoint of the mouse embryonic stem cell test (EST) for developmental neurotoxicity. To determine the sensitivity, specificity, and transferability of the new endpoint, a pre-validation team from three independent laboratories optimized and standardized the protocol for neuronal differentiation of mouse embryonic stem cells (mESCs) by measuring the neuronal differentiation rates of mESCs under different culture conditions, such as the presence or absence of basic fibroblast growth factor (bFGF) in the growth media and varying lengths of culture. In addition, a component ratio of neuronal cells was measured by using flow cytometry analysis of ß-III tubulin (Tuj1)-positive cells and real-time polymerase chain reaction analysis of microtubule-associated protein 2 (MAP2) mRNA. Our results showed that the best growth was achieved by culturing mESCs for 12 d in N2B27 medium without bFGF or ascorbic acid. Lead (II) acetate and aroclor 1254 were used to test the usefulness of the new endpoint. When we used the known ID(50) values for lead (II) acetate in the EST model, it was classified as non-embryotoxic; however, when we used the new ID(50) values that we determined in this study, it was classified as weakly embryotoxic. Aroclor 1254 and penicillin G were also classified as weakly embryotoxic and non-embryotoxic compounds, respectively, when cardiac and neuronal differentiation ID(50) values were used. Therefore, our new surrogate endpoint for developmental neurotoxicity is not only sensitive and specific but also transferable among laboratories.

Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test.

The embryonic stem cell test (EST) is a validated in vitro embryotoxicity test; however, as the inhibition of cardiac differentiation alone is used as a differentiation endpoint in the EST, it may not be a useful test to screen embryotoxic chemicals that affect the differentiation of noncardiac tissues. Previously, methylmercury (MeHg), cadmium and arsenic compounds, which are heavy metals that induce developmental neurotoxicity in vivo, were misclassified as nonembryotoxic with the EST. The aim of this study was to improve the EST to correctly screen such developmental neurotoxicants. We developed a neuronal endpoint (Tuj-1 ID50) using flow cytometry analysis of Tuj-1-positive cells to screen developmental neurotoxicants (MeHg, valproic acid, sodium arsenate and sodium arsenite) correctly using an adherent monoculture differentiation method. Using Tuj-1 ID50 in the EST instead of cardiac ID50, all of the tested chemicals were classified as embryotoxic, while the negative controls were correctly classified as nonembryotoxic. To support the validity of Tuj-1 ID50) , we compared the results from two experimenters who independently tested MeHg using our modified EST. An additional neuronal endpoint (MAP2 ID50), obtained by analyzing the relative quantity of MAP2 mRNA, was used to classify the same chemicals. There were no significant differences in the three endpoint values of the two experimenters or in the classification results, except for isoniazid. In conclusion, our results indicate that Tuj-1 ID50 can be used as a surrogate endpoint of the traditional EST to screen developmental neurotoxicants correctly and it can also be applied to other chemicals.

Central venous stenosis caused by traction of the innominate vein due to a tuberculosis-destroyed lung.

We report a case of central venous stenosis due to a structural deformity caused by a tuberculosis-destroyed lung in a 65-year-old woman. The patient presented with left facial edema. She had a history of pulmonary tuberculosis, and the chest X-ray revealed a collapsed left lung. Angiography showed leftward deviation of the innominate vein leading to kinking and stenosis of the internal jugular vein. Stent insertion improved her facial edema.

Embryotoxicity of lead (II) acetate and aroclor 1254 using a new end point of the embryonic stem cell test.

We developed a new end point of the mouse stem cell test (EST) for developmental neurotoxicity. We tested 2 developmental neurotoxicants, namely, lead (II) acetate and Aroclor 1254, using this EST. Our results showed that lead (II) acetate is nonembryotoxic, and Aroclor 1254 is weakly embryotoxic. To identify a new end point for developmental neurotoxicity, we used the default method of neuronal differentiation for D3 mouse embryonic stem cells with basic fibroblast growth factor (bFGF) and ascorbic acid. Flow cytometry and real-time polymerase chain reaction were used to quantify the inhibition of neuronal differentiation. Our results showed that both lead (II) acetate and Aroclor 1254 reduced the percentage of microtubule-associated protein 2 (MAP-2)-positive cells and the messenger RNA (mRNA) expression level of MAP-2 in a dose-dependent manner. These results suggested that these methods can be used to develop an additional end point of the EST for developmental neurotoxicity using default differentiation of mouse embryonic stem cells.

Clinical Characteristics of Microscopic Colitis in Korea: Prospective Multicenter Study by KASID.

BACKGROUND/AIMS: Microscopic colitis (MC) encompasses collagenous and lymphocytic colitis and is characterized by chronic diarrhea. In cases of MC, colonic mucosae are macroscopically normal, and diagnostic histopathological features are observed only upon microscopic examination. We designed a prospective multicenter study to determine the clinical features, pathological distribution in the colon and prevalence of MC in Korea. METHODS: We prospectively enrolled patients having watery diarrhea no more than 3 times a day between March 2008 and February 2009. We obtained patient histories and performed colonoscopies with random biopsies at each colon segment. RESULTS: A total of 100 patients with chronic diarrhea were enrolled for a normal colonoscopy and stool exam. MC was observed in 22 patients (22%) (M:F 1.2:1; mean age, 47.5 years). Of those 22 patients, 18 had lymphocytic colitis and 4 had collagenous colitis. The entire colon was affected in only 3 cases (13.6%), the ascending colon in 6 cases (27.2%), the transverse colon in 3 cases (13.6%), and the left colon in 3 cases (13.6%). More than 2 segments were affected in 7 cases (31.8%). Nonsteroidal anti-inflammatory drug-associated MCs were observed in 4 cases (18.2%), 3 of which showed improved diarrhea symptoms following discontinuation of the medication. Frequently associated symptoms were abdominal pain and weight loss. Autoimmune diseases were observed in 4 cases (18.2%). Half of the 22 patients with MC improved with conservative care by loperamide or probiotics. CONCLUSIONS: In a prospective multicenter study of Korean patients with chronic diarrhea, the frequency of MC was found to be approximately 20%, similar to the percentage observed in Western countries. Therefore, the identification of MC is important for the adequate management of Korean patients with chronic diarrhea.

[The prevalence of Yersinia infection in adult patients with acute right lower quadrant pain].

BACKGROUND/AIMS: Clinical manifestations of intestinal yersiniosis include enterocolitis, mesenteric adenitis, and terminal ileitis presenting with fever, right lower quadrant pain, and leukocytosis. According to a previous Korean study in 1997, Yersinia was revealed in two among 15 adult patients with mesenteric adenitis (13%). However, recent reports on the prevalence of Yersinia infection in adult patients are few. The aim of this study was to investigate the prevalence of Yersinia infection in adult patients with acute right lower quadrant pain. METHODS: Adult patients (>18 years) who visited Eulji medical center, due to acute right lower quadrant pain were enrolled prospectively from December 2007 to July 2009. Abdominal CT, stool culture, serologic test for Yersinia, and Widal test were performed. RESULTS: Among 115 patients, 5 patients were excluded due to positive Widal test or salmonella culture. In 110 patients, abdominal CT showed right colitis in 20 (18.2%), terminal ileitis in 16 (14.5%), mesenteric adenitis in 13 (11.8%), acute appendicitis in 10 (9.1%), acute diverticulitis in 7 (6.4%), non specific mucosal edema in 36 (32.7%) and no specific lesion in 8 (7.3%). Two (1.8%) of the 110 patients had antibodies to Yersinia. One patient showed acute enteritis and the other patient was diagnosed with acute appendicitis and underwent appendectomy. No Yersinia species were grown on stool or tissue culture. CONCLUSIONS: Nowadays, among adult Korean patients presenting with acute right lower quadrant pain, there have been few incidences of Yersinia infection.

Telomerase reverse transcriptase related with telomerase activity regulates tumorigenic potential of mouse embryonic stem cells.

Embryonic stem cell (ESC) research gave rise to the possibility that stem cell therapy could be used in the treatment of incurable diseases such as neurodegenerative disorders. However, problems related to the tumorigenicity of undifferentiated ESCs must be resolved before such cells can be used in the application of cell replacement therapies. In the present study, we attempted to determine biomarkers that predicted tumor formation of undifferentiated ESCs in vivo. We differentiated mouse ESCs (R1 cell line) into neural lineage using a 5-step method, and evaluated the expression of oncogenes (p53, Bax, c-myc, Bcl2, K-ras), telomerase-related genes (TERT, TRF), and telomerase activity and telomere length during differentiation of ESCs. The expression of oncogenes did not show a significant change during differentiation steps, but the expression of telomerase reverse transcriptase (TERT) and telomerase activity correlated with mouse ESCs differentiation. To investigate the possibility of mouse TERT (mTERT) as a biomarker of tumorigenicity of undifferentiated ESCs, we established mTERT knockdown ESCs using the shRNA lentivirus vector and evaluated its tumorigenicity in vivo using nude mice. Tumor volumes significantly decreased, and appearances of tumor formation in mice were delayed in the TERT-knockdown ESC treated group compared with the undifferentiated ESC treated group. Altogether, these results suggested that mTERT might be potentially beneficial as a biomarker, rather than oncogenes of somatic cells, for the assessment of ESCs tumorigenicity.

Asymptomatic lymphangioma involving the spleen and retroperitoneum in adults.

Lymphangioma, a benign neoplasm of the lymphatic system, is common in children but rare in adults. Its clinical manifestations include abdominal pain, nausea, vomiting and a palpable mass. However, abdominal sonography or abdominal computed tomography (CT) scan can also incidentally reveal lymphangioma. A larger or symptomatic lymphangioma is treated with total resection to prevent recurrence, infection, torsion and enlargement. Although lymphangioma rarely becomes malignant, its prognosis is generally good. We report a cystic lymphangioma of the spleen and retroperitoneum, which was incidentally found in a 56-year-old man who was hospitalized due to a colon mass. Physical examination showed no specific findings. Abdominal CT revealed a 5.7 cm, non-enhanced multilobulated cystic mass with multiple septa in the spleen and a 10 cm lobulated cystic mass in the paraaortic area. Splenectomy and retroperitoneal resection of the cystic mass were conducted. The endothelium of splenic and retroperitoneal cyst was immunohistochemically stained with D2-40 antibody. The patient was finally diagnosed with splenic cystic and retroperitoneal cavernous lymphangioma.

Biological characterization of long-term cultured human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in clinical applications. The reason is that they may have the plasticity needed to differentiate into multiple lineages and the ability to expand ex vivo. For the therapeutic applications of hMSCs to be of practical use, it is crucial to assess the efficacy and safety of hMSCs in long-term ex vivo expansion. In this study, we cultured hMSCs by population doubling (PD) 60, and investigated their growth, osteogenic and adipogenic differential abilities, change of surface markers, telomerase activity, telomere length, and gene expression related to tumorigenesis. An in vivo tumorigenesis assay was also carried out. In long-term expanded hMSCs, the cells became aged above PD 30 and their adipogenic and osteogenic differentiation potential decreased. Telomerase activity unchanged whereas telomere length decreased and karyotypes were not changed. Gene expressions related to tumorigenesis decreased in proportion as the PD of hMSCs increased. In vivo transplantation of long-term cultured hMSCs to nude mice did not result in tumor formation. These findings suggest that diverse tests for cellular therapy should be considered during the ex vivo culture of hMSCs, particularly when a prolonged and extended propagation period is required.

The effects of cyclin-dependent kinase inhibitors on adipogenic differentiation of human mesenchymal stem cells.

The molecular mechanisms that couple growth arrest and cell differentiation were examined during adipogenesis. Here, to understand the cyclin-dependent kinase inhibitor (CKI) genes involved in the progression of adipogenic differentiation, we examined changes in the protein and mRNA expression levels of CKI genes in vitro. During the onset of growth arrest associated with adipogenic differentiation, two independent families of CKI genes, p27Kip1 and p18INK4c, were significantly increased. The expressions of p27Kip1 and p18INK4c, regulated at the level of protein and mRNA accumulation, were directly coupled to adipogenic differentiation. This finding was supported by the inhibition of adipogenic differentiation caused by short interfering RNA (siRNA). In this study, we investigated the regulatory effects of transforming growth factor beta-1 (TGFbeta-1) on CKI genes involved in adipogenic differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs). Only the up-regulation of p18INK4c during adipogenic differentiation, and not that of the p27Kip1 gene was prevented by treatment with TGFbeta-1, one of the factors that inhibit adipogenesis in vitro. This finding indicates a close correlation between adipogenic differentiation and p18INK4c induction in hMSCs. Thus, these data demonstrate a role for the differentiation-dependent cascade expression of cyclin-dependent kinase inhibitors in regulating adipogenic differentiation, thereby providing a molecular mechanism that couples growth arrest and differentiation.