The effecet of UNCL inactivation on the expression of mechanical stress related genes in cultured human PDL fibroblasts

A mutation of UNCL, an inner nuclear membrane RNAbinding protein, has been found to eliminate mechanotransduction in Drosophila. UNCL is expressed in human periodontal tissue including in periodontal ligament (PDL) fibroblasts. However, it is unclear how a mechanical stimulus is translated into cellular responses in PDL fibroblasts. The aim of this study was to evaluate the effect of UNCl on mechanical stress related genes in PDL fibroblasts in response to mechanical stress. The mRNA of TGF-β, COX-2, and MMP-2 was up-regulated after UNCL inactivation in PDL fibroblasts under the compression force. Under the tensile force, inactivation of UNCL decreased the expression of Biglycan, RANKL, MMP-2, and TIMP-2 mRNAs while it increased the expression of TIMP-1. p38-MAPK was expressed in PDL fibroblasts under compression forces whereas phospho-ERK1/2, p65- NFkB, and c-fos were expressed under tension forces. The expression and phosphorylation of the mechanical stress related genes, kinases, and transcription factors were changed according to the types of stress. Furthermore, most of them were regulated by the inactivation of UNCL. This suggests that UNCL is involved in the regulation of mechanical stress related genes through the signaling pathway in PDL fibroblasts

A Case of Cogan's Syndrome With Angina

Cogan's syndrome is a rare systemic inflammatory disease and can be diagnosed on the basis of typical inner ear and ocular involvement with the presence of large vessel vasculitis. We report a case of Cogan's syndrome with stable angina resulting from coronary ostial stenosis caused by aortitis

Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ

SummaryFrequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs

Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin

Evaluation of the TEST 1 erythrocyte sedimentation rate system and intra- and inter-laboratory quality control using new latex control materials

Background: The erythrocyte sedimentation rate (ESR) test has been considered to be a simple procedure, not requiring quality control (QC). However, QC is essential for accuracy and precision. We evaluated the TEST 1 ESR system and performed QC procedures using newly developed latex control materials in three hospitals. Methods: Using tripotassium ethylenediaminetetraacetic acid blood samples (n=184), we compared TEST 1 ESR values with Westergren ESR data and evaluated intra-assay precision. Three levels of latex control materials were used to assess inter-assay precision. Reference range assessment was done using samples from 220 healthy individuals. Inter-laboratory QC with latex control materials in three hospitals was performed. Results: Correlation between TEST 1 ESR and Westergren ESR results was good (p<0.001). Intra-assay precision [coefficients of variation (CV) 6.6%-21.7%] with patient samples and inter-assay precision (CV 0.0%-6.8%) with latex control materials were satisfactory. The reference ranges of 2-10 mm/h for males and 2-19 mm/h for females were established. Inter-laboratory QC data with latex control materials in three hospitals demonstrated good accuracy and satisfactory precision (CV 0.0%-14.4%). Conclusions: Our results demonstrate that the TEST 1 QC is reliable and the latex control materials are valuable for inter-laboratory proficiency testing. Clin Chem Lab Med 2010; 48: 1043-8.Cha CH, 2009, AM J CLIN PATHOL, V131, P189, DOI 10.1309/AJCPOU1ASTLRANIJ*CLIN LAB STAND I, 2008, C28A3 CLSIPiva E, 2007, CLIN BIOCHEM, V40, P491, DOI 10.1016/j.clinbiochem.2006.12.002Padro-Miquel A, 2007, CLIN CHEM LAB MED, V45, P930, DOI 10.1515/CCLM.2007.150Romero A, 2003, CLIN CHEM LAB MED, V41, P232Plebani M, 2002, AM J CLIN PATHOL, V117, P621LEE BH, 2002, J CLIN PATHOL QUALIT, V24, P167GIAVARINA D, 2002, CLIN LAB, V48, P459Piva E, 2001, CLIN CHEM LAB MED, V39, P451*CLIN LAB STAND I, 2000, H2A4 CLSIPlebani M, 1998, AM J CLIN PATHOL, V110, P334BULL BS, 1993, J CLIN PATHOL, V46, P198BULL BS, 1991, PRACTICAL LAB HEMATOFABRY TL, 1987, BLOOD, V70, P1572WESTERGREN A, 1926, AM REV TUBERC, V14, P94