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American Journal of Pathology

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https://www.readbyqxmd.com/read/27914218/disruptive-influences-on-research-in-academic-pathology-departments-proposed-changes-to-the-common-rule-governing-informed-consent-for-research-use-of-biospecimens-and-to-rules-governing-return-of-research-results
#1
REVIEW
Mark E Sobel, Jennifer C Dreyfus
Academic pathology departments will be dramatically affected by proposed United States federal government regulatory initiatives. Pathology research will be substantially altered if proposed changes to the Common Rule (Code of Federal Regulations: Protection of Human Subjects title 45 CFR 46) and regulations governing the return of individual research results are approved and finalized, even more so now that the Precision Medicine initiative has been launched. Together, these changes are disruptive influences on academic pathology research as we know it, straining limited resources and compromising advances in diagnostic and academic pathology...
November 30, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27912078/mouse-double-minute-2-homolog-actively-suppresses-p53-activity-in-oocytes-during-mouse-folliculogenesis
#2
Chen-Xi Zhang, Qin Zhang, Yin-Yin Xie, Xue-Yan He, Cong Xiang, Xiao-Shuang Hou, Ying Zhou, Lai Chen, Guo-Xin Zhang, Geng Liu
The p53 signaling network is indispensible in cellular stress responses and tumor suppression. Negative regulations of p53 by mouse double minute 2 and 4 homologs (MDM2) and (MDM4) are an integrated component of the network and have been implicated in regulating the stress responses and the maintenance of normal development and homeostasis of multiple somatic cell lineages. However, the regulatory role of MDM2 on p53 and stress responses in female germ cells remains undetermined. Here, we used the Cre-loxP system to delete Mdm2 in oocytes at different stages of folliculogenesis in mice...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27912077/nlrp3-activation-induces-il-18-synthesis-and-affects-the-epithelial-barrier-function-in-reactive-cholangiocytes
#3
Luca Maroni, Laura Agostinelli, Stefania Saccomanno, Claudio Pinto, Debora Giordano, Chiara Rychlicki, Samuele De Minicis, Luciano Trozzi, Jesus M Banales, Espen Melum, Tom H Karlsen, Antonio Benedetti, Gianluca Svegliati Baroni, Marco Marzioni
Microbial products are thought to influence the progression of cholangiopathies, in particular primary sclerosing cholangitis (PSC). Inflammasomes are molecular platforms that respond to microbial products through the synthesis of proinflammatory cytokines. We investigated the role of inflammasome activation in cholangiocyte response to injury. Nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing protein 3 (Nlrp3) expression was tested in cholangiocytes of normal and cholestatic livers...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27912076/activating-transcription-factor-3-is-essential-for-cigarette-smoke-induced-mucin-expression-via-interaction-with-activator-protein-1
#4
Yan-Ping Wu, Yin-Fang Wu, Chao Zhang, Hong-Bin Zhou, Chao Cao, Miao Li, Chen Zhu, Song-Min Ying, Zhi-Hua Chen, Hua-Hao Shen, Wen Li
Mucus hypersecretion is an important pathologic feature of chronic obstructive pulmonary disease. Activating transcription factor 3 (ATF3) is an adaptive-response gene that participates in various cellular processes. However, little is known about its role in cigarette smoke (CS)-induced mucus hyperproduction. This study aimed to investigate the role and molecular mechanisms of ATF3 in CS-induced Mucin 5AC (MUC5AC) expression. ATF3 was elevated in lung tissues of mice exposed to CS for 12 weeks. Treatment with CS extract significantly induced ATF3 expression and MUC5AC production in human bronchial epithelial cells, NCI-H292, and mouse tracheal epithelial cells...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27908613/sparc-interacts-with-actin-in-skeletal-muscle-in%C3%A2-vitro-and-in%C3%A2-vivo
#5
Louise H Jørgensen, Pia Lørup Jepsen, Anders Boysen, Line B Dalgaard, Lars G Hvid, Niels Ørtenblad, Dea Ravn, Jeeva Sellathurai, Jakob Møller-Jensen, Hanns Lochmüller, Henrik D Schrøder
The cytoskeleton is an integral part of skeletal muscle structure, and reorganization of the cytoskeleton occurs during various modes of remodeling. We previously found that the extracellular matrix protein secreted protein acidic and rich in cysteine (SPARC) is up-regulated and expressed intracellularly in developing muscle, during regeneration and in myopathies, which together suggests that SPARC might serve a specific role within muscle cells. Using co-immunoprecipitation combined with mass spectrometry and verified by staining for direct protein-protein interaction, we find that SPARC binds to actin...
November 28, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27870928/mir-182-5p-inhibition-ameliorates-ischemic-acute-kidney-injury
#6
Julia Wilflingseder, Kíra Jelencsics, Helga Bergmeister, Judith Sunzenauer, Heinz Regele, Farsad Eskandary, Roman Reindl-Schwaighofer, Alexander Kainz, Rainer Oberbauer
Acute kidney injury (AKI) remains a major clinical event with high mortality rates. We previously identified renal miR-182 as the main driver of post-transplantation AKI. Therefore, we tested the causal inference of miR-182 by inhibiting its renal expression in vivo. In 45 rats AKI was induced by right nephrectomy and contralateral clamping of the renal pedicle for 40 minutes. Systemically administered antisense oligonucleotide (ASO) inhibited miR-182 in the kidneys up to 96 hours. The maximum creatinine elevation was on day 2 after injury (ASO 2...
November 18, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27870927/cd30-induces-heat-shock-protein-90-and-signal-integration-in-classic-hodgkin-lymphoma-cells
#7
Mariko Watanabe, Kazumi Nakano, Marshall E Kadin, Masaaki Higashihara, Toshiki Watanabe, Ryouichi Horie
Previous studies report deregulation of multiple signaling pathways in classic Hodgkin lymphoma (cHL) cells. However, the mechanisms of how these pathways are integrated are not fully understood. Herein, we show involvement of cHL hallmark antigen CD30 in this process. CD30 facilitates phosphorylation of heat shock factor 1, activates heat shock promoter element, and induces heat shock protein (HSP) 90. CD30 repression and subsequent inhibition of HSP90 suppresses NF-κB, extracellular signal-regulated kinase, AKT, and STAT pathways in cHL cell lines...
November 18, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27865760/this-month-in-ajp
#8
(no author information available yet)
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
November 17, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27865759/mirna-coordinated-networks-as-promising-therapeutic-targets-for-acute-kidney-injury
#9
Anton J van Zonneveld, Ton J Rabelink, Roel Bijkerk
This commentary highlights the article by Wilflingseder et al that investigates the relationship between in vivo inhibition of miR-182 by antisense oligonucleotides and improved post-injury kidney function.
November 17, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27865758/bone-morphogenetic-protein-2-and-transforming-growth-factor-%C3%AE-1-inhibit-the-expression-of-the-proinflammatory-cytokine-il-34-in-rheumatoid-arthritis-synovial-fibroblasts
#10
Marguerite Chemel, Regis Brion, Aude-Isabelle Segaliny, Audrey Lamora, Celine Charrier, Benedicte Brulin, Yves Maugars, Benoit Le Goff, Dominique Heymann, Franck Verrecchia
IL-34 is a proinflammatory cytokine implicated in rheumatoid arthritis (RA). The current study aimed to assess the IL-34 expression in response to two members of the transforming growth factor (TGF)-β family, TGF-β1 and bone morphogenetic protein (BMP)-2, in synovial fibroblasts from RA patients. IL-34, TGF-β1, and BMP-2 productions were measured in patient synovial fluids by enzyme-linked immunosorbent assay. IL-34 mRNA levels were quantified by real-time quantitative PCR in human synovial fibroblasts and murine mesenchymal stem cells...
November 17, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27863214/type-ii-natural-killer-t-cells-that-recognize-sterol-carrier-protein-2-are-implicated-in-vascular-inflammation-in-the-rat-model-of-systemic-connective-tissue-diseases
#11
Yusuke Nishioka, Madoka Yamaguchi, Ai Kawakami, Maya Munehiro, Sakiko Masuda, Utano Tomaru, Akihiro Ishizu
We previously generated a rat model that developed systemic connective tissue diseases, including synovitis, myositis, and small-vessel vasculitis (SVV), and established a vascular endothelial cell-reactive T-cell clone, VASC-1, from the model. VASC-1 was determined to be a type II natural killer T-cell clone. In this study, we attempted to identify the antigen recognized by VASC-1. The monkey-derived cell line COS-7 was used because VASC-1 does not bind naturally to COS-7, although the amino acid sequences are well conserved between monkey CD1d and rat CD1d...
November 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27863213/tubular-cytoplasmic-expression-of-snai1-in-renal-transplant-biopsies-a-sign-of-diseased-epithelial-phenotype
#12
Marco Prunotto, Lyubov Chaykovska, Massimo Bongiovanni, Milo Frattini, Thomas Cagarelli, Franziska Weibel, Maurizio Bruschi, Antonio Garcia de Herreros, Solange Moll
The aim of the present study was to analyze in vivo the role of SNAI1 on renal fibrosis. Unilateral ureteral obstruction injury was induced in Snai1 knockout mice. Snai1 gene deletion was, however, only partial and could therefore not be correlated to reduced fibrosis. Expression of SNAI1 protein and epithelial-mesenchymal transformation markers was then assessed in human chronic allograft nephropathy biopsy specimens. Significant up-regulation of SNAI1 protein was detected within cytoplasm of proximal tubules localized, for some of them, near foci of fibrosis and tubular atrophy...
November 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27863212/antiangiogenic-therapeutic-potential-of-peptides-derived-from-the-molecular-motor-kif13b-that-transports-vegfr2-to-plasmalemma-in-endothelial-cells
#13
Kaori H Yamada, Hojin Kang, Asrar B Malik
Vascular endothelial growth factor receptor 2 (VEGFR2) localized on the surface of endothelial cells (ECs) is a key determinant of the magnitude and duration of angiogenesis induced by vascular endothelial growth factor (VEGF). The kinesin family plus-end motor KIF13B transports VEGFR2 to the EC surface, and as such, specific inhibition of polarized VEGFR2 trafficking prevents angiogenesis. We designed a series of bioactive peptides based on deep analysis of VEGFR2-binding domain of KIF13B that compete specifically with VEGFR2 binding of KIF13B and thereby potently inhibit angiogenesis...
November 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27855279/chronic-phenotype-characterization-of-a-large-animal-model-of-hereditary-tyrosinemia-type-1
#14
Faysal Elgilani, Shennen A Mao, Jaime M Glorioso, Meng Yin, Ianko D Iankov, Anisha Singh, Bruce Amiot, Piero Rinaldo, Ronald J Marler, Richard L Ehman, Markus Grompe, Joseph B Lillegard, Raymond D Hickey, Scott L Nyberg
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disease caused by deficiency in fumarylacetoacetate hydrolase, the last enzyme in the tyrosine catabolic pathway. In this study, we investigated whether fumarylacetoacetate hydrolase deficient (FAH(-/-)) pigs, a novel large-animal model of HT1, develop fibrosis and cirrhosis characteristic of the human disease. FAH(-/-) pigs were treated with the protective drug 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3 cyclohexandione (NTBC) at a dose of 1 mg/kg per day initially after birth...
November 14, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27855278/cadherin-11-is-a-cell-surface-marker-up-regulated-in-activated-pancreatic-stellate-cells-and-is-involved-in-pancreatic-cancer-cell-migration
#15
Chiara Birtolo, Hung Pham, Susan Morvaridi, Chintan Chheda, Vay Liang W Go, Andrzej Ptasznik, Mouad Edderkaoui, Michael Weisman, Erika Noss, Michael Brenner, Brent Larson, Maha Guindi, Qiang Wang, Stephen J Pandol
Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined...
November 14, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27855277/respiratory-chain-complex-disorganization-impairs-mitochondrial-and-cellular-integrity-phenotypic-variation-in-cytochrome-c-oxidase-deficiency
#16
Hideyuki Hatakeyama, Yu-Ichi Goto
The relationships between the molecular abnormalities in mitochondrial respiratory chain complexes and their negative contributions to mitochondrial and cellular functions have been proved to be essential for better understandings in mitochondrial medicine. Herein, we established the method to identify disease phenotypic differences among patients with muscle histopathological cytochrome c oxidase (COX) deficiency, as one of the representative clinical features in mitochondrial diseases, by using patients' myoblasts that are derived from biopsied skeletal muscle tissues...
November 14, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27846381/mechanistic-insights-into-pathological-changes-in-the-diabetic-retina-implications-for-targeting-diabetic-retinopathy
#17
REVIEW
Sayon Roy, Timothy S Kern, Brian Song, Caren Stuebe
Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina...
November 12, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27846380/pulmonary-vasculopathy-associated-with-figf-gene-mutation
#18
Evan Bailey, Ye Cui, Alicia Casey, Joan M Stoler, Xingbin Ai, Dongdong Ma, Robert Handin, Piotr Sliz, Sara O Vargas, Souheil Y El-Chemaly
Vascular endothelial growth factor (VEGF)-D is capable of inducing angiogenesis and lymphangiogenesis through signaling via VEGF receptor (VEGFR)-2 and VEGFR-3, respectively. Mutations in the FIGF (c-fos-induced growth factor) gene encoding VEGF-D have not been reported previously. We describe a young male with a hemizygous mutation in the X-chromosome gene FIGF (c.352 G>A) associated with early childhood respiratory deficiency. Histologically, lungs showed ectatic pulmonary arteries and pulmonary veins...
November 12, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27842214/sortilin-deficiency-reduces-ductular-reaction-hepatocyte-apoptosis-and-liver-fibrosis-in-cholestatic-induced-liver-injury
#19
Einav Hubel, Ashish Saroha, Woo-Jae Park, Yael Pewzner-Jung, Elise G Lavoie, Anthony H Futerman, Rafael Bruck, Sigal Fishman, Jonathan A Dranoff, Oren Shibolet, Isabel Zvibel
Sortilin, a member of the vacuolar protein sorting 10 domain receptor family, traffics newly synthesized proteins from the trans-Golgi network to secretory pathways, endosomes, and cell surface. Sortilin-trafficked molecules, including IL-6 and acid sphingomyelinase (aSMase), mediate cholangiocyte proliferation and liver inflammation, hepatic stellate cell activation, hepatocyte apoptosis, and fibrosis. Based on these sortilin-regulated functions, we investigated its role in biliary damage leading to hepatocellular injury and fibrosis...
November 11, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27842213/toll-like-receptor-2-toll-like-receptor-4-myeloid-differentiation-response-gene-88-and-trif-selectively-regulate-susceptibility-of-p0106-125-induced-murine-experimental-autoimmune-neuritis
#20
Anna Brunn, Mirna Mihelcic, Mariana Carstov, Lisa Feind, Eva C Wieser, Julia Schmidt, Olaf Utermöhlen, Martina Deckert
The functional relevance of the innate immune system has not yet been dissected in P0106-125-induced murine experimental autoimmune neuritis. Therefore, the role of Toll-like receptor (TLR) 2, TLR4, myeloid differentiation response gene 88, and TRIF, factors critically involved in the TLR signaling pathway, was studied in experimental autoimmune neuritis. In the absence of TLR2, TLR4, myeloid differentiation response gene 88, or TRIF, the clinical course was significantly attenuated compared to wild-type mice...
November 11, 2016: American Journal of Pathology
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