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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/28920945/neutrophils-a-cornerstone-of-liver-ischemia-and-reperfusion-injury
#1
Thiago Henrique Caldeira de Oliveira, Pedro Elias Marques, Paul Proost, Mauro Martins M Teixeira
Ischemia-reperfusion injury (IRI) is the main cause of morbidity and mortality due to graft rejection after liver transplantation. During IRI, an intense inflammatory process occurs in the liver. This hepatic inflammation is initiated by the ischemic period but occurs mainly during the reperfusion phase, and is characterized by a large neutrophil recruitment to the liver. Production of cytokines, chemokines, and danger signals results in activation of resident hepatocytes, leukocytes, and Kupffer cells. The role of neutrophils as the main amplifiers of liver injury in IRI has been recognized in many publications...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28920944/the-dosage-dependent-effect-exerted-by-the-nm23-h1-h2-homolog-ndk-1-on-distal-tip-cell-migration-in-c-elegans
#2
Zsolt Farkas, Luca Fancsalszky, Éva Saskői, Alexandra Gráf, Krisztián Tárnok, Anil Mehta, Krisztina Takács-Vellai
Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is involved in these processes. NM23-H1 inhibits the migratory and invasive potential of some cancer cells. Correspondingly, numerous invasive cancer cell lines (eg, breast, colon, oral, hepatocellular carcinoma, and melanoma) display low endogenous NM23 levels. In this review, we summarize mechanisms, which are linked to the anti-metastatic activity of NM23...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28920943/expression-function-and-regulation-of-the-embryonic-transcription-factor-tbx1-in-parathyroid-tumors
#3
Chiara Verdelli, Laura Avagliano, Vito Guarnieri, Filomena Cetani, Stefano Ferrero, Leonardo Vicentini, Edoardo Beretta, Alfredo Scillitani, Pasquale Creo, Gaetano Pietro Bulfamante, Valentina Vaira, Sabrina Corbetta
Transcription factors active in embryonic parathyroid cells can be maintained in adult parathyroids and be involved in tumorigenesis. TBX1, the candidate gene of 22q11.2-DiGeorge syndrome, which includes congenital hypoparathyroidism, is involved in parathyroid embryogenesis. The study aimed to investigate expression, function, and regulation of the parathyroid embryonic transcription factor TBX1 in human parathyroid adult normal and tumor tissues. TBX1 transcripts were detected in normal parathyroids and were deregulated in parathyroid tumors...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28892098/correlation-between-e-cadherin-interactions-survivin-expression-and-apoptosis-in-mdck-and-ts-src-mdck-cell-culture-models
#4
Janne Capra, Sinikka Eskelinen
Survivin, a member of inhibitor of apoptosis (IAP) protein family, is a multifunctional protein expressed in most cancers. In addition to inhibition of apoptosis, it regulates proliferation and promotes migration. Its presence and function in cells is strongly regulated via transcription factors, intracellular localization, and degradation. We analyzed the presence of survivin at protein level in various culture environments and under activation of Src tyrosine kinase in epithelial canine kidney MDCK cells in order to elucidate factors controlling survivin 'lifespan'...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28892097/ligand-mediated-cytoplasmic-retention-of-the-ah-receptor-inhibits-macrophage-mediated-acute-inflammatory-responses
#5
Gulsum E Muku, Tejas S Lahoti, Iain A Murray, Michael A Podolsky, Kayla J Smith, Troy D Hubbard, Guray Kuzu, Krishne Gowda, Shantu G Amin, Gary H Perdew
The Ah receptor (AHR) has been shown to exhibit both inflammatory and anti-inflammatory activity in a context-specific manner. In vivo macrophage-driven acute inflammation models were utilized here to test whether the selective Ah receptor modulator 1-allyl-7-trifluoromethyl-1H-indazol-3-yl]-4-methoxyphenol (SGA360) would reduce inflammation. Exposure to SGA360 was capable of significantly inhibiting lipopolysaccharide (LPS)-mediated endotoxic shock in a mouse model, both in terms of lethality and attenuating inflammatory signaling in tissues...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28892096/development-and-characterization-of-cholangioids-from-normal-and-diseased-human-cholangiocytes-as-an-in-vitro-model-to-study-primary-sclerosing-cholangitis
#6
Lorena Loarca, Thiago M De Assuncao, Nidhi Jalan-Sakrikar, Steve Bronk, Anuradha Krishnan, Bing Huang, Leslie Morton, Christy Trussoni, Lorena Marcano Bonilla, Eugene Krueger, Steve O'Hara, Patrick Splinter, Guang Shi, María José Lorenzo Pisarello, Gregory J Gores, Robert C Huebert, Nicholas F LaRusso
Primary sclerosing cholangitis (PSC) is an incurable, fibroinflammatory biliary disease for which there is no effective pharmacotherapy. We recently reported cholangiocyte senescence as an important phenotype in PSC while others showed that portal macrophages accumulate in PSC. Unfortunately, our ability to explore cholangiocyte senescence and macrophage accumulation has been hampered by limited in vitro models. Thus, our aim was to develop and characterize a three-dimensional (3D) model of normal and diseased bile ducts (cholangioids) starting with normal human cholangiocytes (NHC), senescent NHC (NHC-sen), and cholangiocytes from PSC patients...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28892095/cholecystectomy-as-a-risk-factor-of-metabolic-syndrome-from-epidemiologic-clues-to-biochemical-mechanisms
#7
Yongsheng Chen, Shuodong Wu, Yu Tian
Cholecystectomy has long been regarded as a safe procedure with no deleterious influence on the body. However, recent studies provide clues that link cholecystectomy to a high risk for metabolic syndrome (MetS). In the present review, we describe the epidemiologic evidence that links cholecystectomy to MetS. Various components of MetS are investigated, including visceral obesity, dyslipidemia, elevated blood pressure, impaired fasting glucose, and insulin resistance. The possible mechanisms that associate cholecystectomy with MetS are discussed on the basis of experimental studies...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28892094/deletion-of-pkd1-in-renal-stromal-cells-causes-defects-in-the-renal-stromal-compartment-and-progressive-cystogenesis-in-the-kidney
#8
Xuguang Nie, Lois J Arend
Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1 and PKD2 gene mutations, is one of the most common genetic diseases, affecting up to 1 in 500 people. Mutations of PKD1 account for over 85% of ADPKD cases. However, mechanisms of disease progression and explanations for the wide range in disease phenotype remain to be elucidated. Moreover, functional roles of PKD1 in the renal stromal compartment are poorly understood. In this work, we tested if Pkd1 is essential for development and maintenance of the renal stromal compartment and if this role contributes to pathogenesis of polycystic kidney disease using a novel tissue-specific knockout mouse model...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28892093/rapid-generation-of-col7a1-mouse-model-of-recessive-dystrophic-epidermolysis-bullosa-and-partial-rescue-via-immunosuppressive-dermal-mesenchymal-stem-cells
#9
Beau R Webber, Kyle T O'Connor, Ron T McElmurry, Elise N Durgin, Cindy R Eide, Christopher J Lees, Megan J Riddle, Wendy E Mathews, Natasha Y Frank, Mark A Kluth, Christoph Ganss, Branden S Moriarity, Markus H Frank, Mark J Osborn, Jakub Tolar
Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating and ultimately lethal blistering disease caused by mutations to the Col7a1 gene. Development of novel cell therapies for the treatment of RDEB would be fostered by having immunodeficient mouse models able to accept human cell grafts; however, immunodeficient models of many genodermatoses such as RDEB are lacking. To overcome this limitation, we combined the clustered regularly interspaced short palindromic repeats and associated nuclease (CRISPR/Cas9) system with microinjection into NOD/SCID IL2rγc(null) (NSG) embryos to rapidly develop an immunodeficient Col7a1(-/-) mouse model of RDEB...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28892092/high-concordance-of-a-closed-system-rt-qpcr-breast-cancer-assay-for-her2-mrna-compared-to-clinically-determined-immunohistochemistry-fluorescence-in-situ-hybridization-and-quantitative-immunofluorescence
#10
Brad E Wasserman, Daniel E Carvajal-Hausdorf, Kenneth Ho, Wendy Wong, Natalie Wu, Victor C Chu, Edwin W Lai, Jodi M Weidler, Michael Bates, Veronique Neumeister, David L Rimm
Historically, mRNA measurements have been tested on several commercially available platforms, but none have gained broad acceptance for assessment of HER2. An mRNA measurement, as a continuous value, has the potential for use in adjudication of the equivocal category. Here we use a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in a closed, single-use cartridge, automated system. Multiple cores (1 mm in diameter) were retrospectively collected from 80 formalin-fixed paraffin-embedded (FFPE) tissue blocks with invasive breast cancer seen by Yale Pathology Labs between 1998 and 2011...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28869589/stem-cell-therapies-for-myocardial-infarction-in-clinical-trials-bioengineering-and-biomaterial-aspects
#11
Akon Higuchi, Nien-Ju Ku, Yeh-Chia Tseng, Chih-Hsien Pan, Hsing-Fen Li, S Suresh Kumar, Qing-Dong Ling, Yung Chang, Abdullah A Alarfaj, Murugan A Munusamy, Giovanni Benelli, Kadarkarai Murugan
Cardiovascular disease remains the leading cause of death and disability in advanced countries. Stem cell transplantation has emerged as a promising therapeutic strategy for acute and chronic ischemic cardiomyopathy. The current status of stem cell therapies for patients with myocardial infarction is discussed from a bioengineering and biomaterial perspective in this review. We describe (a) the current status of clinical trials of human pluripotent stem cells (hPSCs) compared with clinical trials of human adult or fetal stem cells, (b) the gap between fundamental research and application of human stem cells, (c) the use of biomaterials in clinical and pre-clinical studies of stem cells, and finally (d) trends in bioengineering to promote stem cell therapies for patients with myocardial infarction...
September 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28869588/activation-of-pluripotent-genes-in-hepatic-progenitor-cells-in-the-transition-of-nonalcoholic-steatohepatitis-to-pre-malignant-lesions
#12
Gang Xu, Juan Ye, Xue-Jing Liu, Ning-Ping Zhang, Yi-Ming Zhao, Jia Fan, Xiu-Ping Liu, Jian Wu
Nonalcoholic steatohepatitis is considered as a precancerous condition. However, hepatic carcinogenesis from NASH is poorly understood. This study aims to investigate the activation of pluripotent genes (c-Myc, Oct-4, KLF-4, and Nanog) and morphogenic gene (Gli-1) in hepatic progenitor cells from patient specimens and in an animal model to determine the possibility of normal stem/progenitor cells becoming the origin of NASH-HCC. In this study, expression of pluripotent and morphogenic genes in human NASH-HCC tissues was significantly upregulated compared to adjacent non-tumor liver tissues...
September 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28869587/epigenetic-foundations-of-pluripotent-stem-cells-that-recapitulate-in-vivo-pluripotency
#13
Masaki Yagi, Shinya Yamanaka, Yasuhiro Yamada
In mammalian development, dynamic epigenetic reprogramming occurs in pre-implantation embryos and primordial germ cells and plays a critical role in conferring pluripotency on embryonic cells. Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, have been derived and maintained in vitro under culture conditions that include stimulators and inhibitors of extrinsic signaling. Recent advances in stem cell cultivation have opened the possibility of capturing naive pluripotency, which is reminiscent of the pluripotency of inner cell mass cells, in vitro...
September 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28846077/metabolic-cooperation-between-co-cultured-lung-cancer-cells-and-lung-fibroblasts
#14
Michael I Koukourakis, Dimitra Kalamida, Achilleas G Mitrakas, Maria Liousia, Stamatia Pouliliou, Efthimios Sivridis, Alexandra Giatromanolaki
Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of the metabolic protein expression profile and of their growth and migration abilities. Using western blotting, confocal microscopy and RT-PCR, we observed that in co-cultures MRC5 respond by upregulating pyruvate dehydrogenase (PDH) and the monocarboxylate transporter MCT1...
August 28, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28825696/a-simple-method-based-on-sanger-sequencing-and-ms-word-wildcard-searching-to-identify-cas9-induced-frameshift-mutations
#15
Hui Jie, Zhuoling Li, Ping Wang, Linjie Zhao, Qian Zhang, Xiaomin Yao, Xiangrong Song, Yinglan Zhao, Shaohua Yao
Recent advances in targeted genome editing have enabled sequence-specific modifications in eukaryotic genomes. As it can be easily reprogrammed, the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 nuclease system has been studied extensively and is now a widely used genome editing tool. Generally, Cas9 nucleases are designed to target the coding regions in exons of protein-coding genes, which are expected to cause frameshift indel mutations and interrupt protein expression. In such cases, it is often necessary to separate single clones that harbor double frameshift mutant alleles from clones that harbor the wild-type allele or an in-frame mutant allele...
August 21, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28825695/augmenter-of-liver-regeneration-potentiates-doxorubicin-anticancer-efficacy-by-reducing-the-expression-of-abcb1-and-abcg2-in-hepatocellular-carcinoma
#16
Yuan-Yuan Guo, Yuan Wu, Xiao-Wei Jia, Wei An
Hepatocellular carcinoma (HCC) is highly chemoresistant and therefore challenges both physicians and patients. Augmenter of liver regeneration (ALR), previously also known as 'hepatic stimulator substance', is reported to inhibit the epithelial-mesenchymal transition (EMT) in HCC, one of the frequent events that occur in cancer metastasis, suggesting that ALR is involved in HCC. In this study, we report for the first time that the transfection of ALR enhances the antitumor effect of chemotherapy with doxorubicin, a typical anticancer drug, on HCC in vitro and in vivo...
August 21, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28805807/notch-signaling-pathway-and-gene-expression-profiles-during-early-in-vitro-differentiation-of-liver-derived-mesenchymal-stromal-cells-to-osteoblasts
#17
Ksymena Urbanek, Marta Lesiak, Daniel Krakowian, Halina Koryciak-Komarska, Wirginia Likus, Piotr Czekaj, Damian Kusz, Aleksander L Sieroń
Notch signaling is a key signaling pathway for cell proliferation and differentiation. Therefore, we formulated a working hypothesis that Notch signaling can be used to detect early osteoblastic differentiation of mesenchymal stromal cells. Changes in expression and distribution of Notch 1, 2, 3, and Delta1 in the cytoplasm and nuclei of rat liver-derived mesenchymal stromal cells differentiating into osteoblasts were investigated, together with the displacement of intracellular domains (ICDs) of the receptors...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28805806/lung-tumor-exome-files-with-t-cell-receptor-recombinations-a-mouse-model-of-t-cell-infiltrates-reflecting-mutation-burdens
#18
Yaping N Tu, Wei Lue Tong, Timothy J Fawcett, George Blanck
Tumor exomes and RNASeq data were originally intended for obtaining tumor mutations and gene expression profiles, respectively. However, recent work has determined that tumor exome and RNAseq read files contain reads representing T-cell and B-cell receptor (TcR and BcR) recombinations, presumably due to infiltrating lymphocytes. Furthermore, the recovery of immune receptor recombination reads has demonstrated correlations with specific, previously appreciated aspects of tumor immunology. To further understand the usefulness of recovering TcR and BcR recombinations from tumor exome files, we developed a scripted algorithm for recovery of reads representing these recombinations from a previously described mouse model of lung tumorigenesis...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28805805/whole-tumor-section-quantitative-image-analysis-maximizes-between-pathologists-reproducibility-for-clinical-immunohistochemistry-based-biomarkers
#19
Michael Barnes, Chukka Srinivas, Isaac Bai, Judith Frederick, Wendy Liu, Anindya Sarkar, Xiuzhong Wang, Yao Nie, Bryce Portier, Monesh Kapadia, Olcay Sertel, Elizabeth Little, Bikash Sabata, Jim Ranger-Moore
Pathologists have had increasing responsibility for quantitating immunohistochemistry (IHC) biomarkers with the expectation of high between-reader reproducibility due to clinical decision-making especially for patient therapy. Digital imaging-based quantitation of IHC clinical slides offers a potential aid for improvement; however, its clinical adoption is limited potentially due to a conventional field-of-view annotation approach. In this study, we implemented a novel solely morphology-based whole tumor section annotation strategy to maximize image analysis quantitation results between readers...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28783138/flow-cytometric-sorting-coupled-with-exon-capture-sequencing-identifies-somatic-mutations-in-archival-lymphoma-tissues
#20
Nenggang Jiang, Christopher Chen, Qiang Gong, Kristen Shields, Yuping Li, YuanYuan Chen, Joo Song, Timothy W McKeithan, Wing C Chan
The enormous number of archived formalin-fixed paraffin-embedded (FFPE) tissues available are a valuable resource of material for research. However, the use of such tissues poses many challenges, among which is the difficulty of isolating different cell populations within the tissue. In this study, we used tissue from two types of non-Hodgkin lymphoma as a model to demonstrate a method we have established and optimized to separate FFPE samples into distinct tumor and nonmalignant populations. Using FFPE reactive tonsil sections, various approaches for antigen retrieval and labeling, and the effectiveness of flow cytometric sorting were tested...
August 7, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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