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American Journal of Pathology

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https://www.readbyqxmd.com/read/29777664/this-month-in-ajp
#1
(no author information available yet)
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
May 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29758183/increasing-cardiomyocyte-atrogin-1-reduces-aging-associated-fibrosis-and-regulates-remodeling-in-vivo
#2
Roberto Mota, Traci L Parry, Cecelia Yates, Zhaoyan Qiang, Samuel C Eaton, Jean Marie Mwiza, Deepthi Tulasi, Jonathan C Schisler, Cam Patterson, Tania Zaglia, Marco Sandri, Monte S Willis
The muscle-specific ubiquitin ligase atrogin-1 (MAFbx) has been identified as a critical regulator of pathologic and physiologic cardiac hypertrophy; it regulates these processes by ubiquitinating transcription factors (NFAT and FOXO1/3). However, the role of Atrogin-1 in regulating transcription factors in aging has not previously been described. Atrogin-1 cardiomyocyte-specific transgenic (Tg+) adult mice (αMHC promoter driven) have normal cardiac function and size. Here we demonstrate that 18-month-old Atrogin-1 Tg+ hearts exhibit significantly increased anterior wall thickness without functional impairment vs wild-type mice...
May 11, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29753790/il-17-promotes-scar-formation-by-inducing-macrophage-infiltration
#3
Julei Zhang, Qiao Qiao, Mengdong Liu, Ting He, Jihong Shi, Xiaozhi Bai, Yijie Zhang, Yan Li, Weixia Cai, Shichao Han, Hao Guan, Dahai Hu
Trauma or burn injuries that affect the deep dermis often produce a hypertrophic scar, which limits patients' joint movement and generates an aesthetic problem. Inflammation is believed to be one of the main pathogenic mechanisms. We found that IL-17 was increased in scar tissues from patients with hypertrophic scar compared with normal skin. Recombinant mouse IL-17 was subcutaneously injected into mice that underwent full-thickness excision surgery to investigate the role of IL-17 in scar formation. Mice stimulated with IL-17 showed aggravated fibrogenesis, delayed wound healing, and increased inflammation...
May 11, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29753791/obstructive-lymphangitis-precedes-colitis-in-murine-norovirus-infected-stat1-deficient-mice
#4
Audrey Seamons, Piper M Treuting, Stacey Meeker, Charlie Hsu, Jisun Paik, Thea Brabb, Sabine S Escobar, Jonathan S Alexander, Aaron Ericsson, Jason G Smith, Lillian Maggio-Price
Murine norovirus (MNV) is an RNA virus that can prove lethal in mice with impaired innate immunity. We found that MNV-4 infection of Stat1-/- mice was not lethal, but produced a 100% penetrant, previously undescribed lymphatic phenotype characterized by chronic-active lymphangitis with hepatitis, splenitis, and chronic cecal and colonic inflammation. Lesion pathogenesis progressed from early ileal enteritis and regional dilated lymphatics to lymphangitis, granulomatous changes in the liver and spleen, and ultimately, typhlocolitis...
May 10, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29753789/diverse-cavity-types-and-evidence-that-mechanical-action-on-the-necrotic-granuloma-drives-tuberculous-cavitation
#5
Elizabeth A Ihms, Michael E Urbanowski, William R Bishai
Effacement of normal lung parenchyma by cavities is an important sequela of pulmonary tuberculosis. Despite its clinical significance, the pathogenesis of tuberculous cavitation is poorly understood, with controversy as to whether the fundamental mechanism involves matrix depletion, lipid pneumonia, or mechanical factors. In this study, a repetitive aerosol infection model using Mycobacterium tuberculosis was used to generate cavities in 20 New Zealand White rabbits. Serial computed tomography was performed to monitor cavity progression over 14 weeks...
May 10, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29751934/cytoskeleton-associated-protein-4-is-a-novel-serodiagnostic-marker-for-lung-cancer
#6
Kengo Yanagita, Ryo Nagashio, Shi-Xu Jiang, Yuki Kuchitsu, Kazuo Hachimura, Masaaki Ichinoe, Satoshi Igawa, Eriko Fukuda, Naoki Goshima, Yukitoshi Satoh, Yoshiki Murakumo, Makoto Saegusa, Yuichi Sato
Our aim was to develop a serodiagnostic marker for lung cancer. Monoclonal antibodies were generated, and one antibody designated as KU-Lu-1, recognizing cytoskeleton-associated protein 4 (CKAP4), was studied further. To evaluate the utility of KU-Lu-1 antibody as a serodiagnostic marker for lung cancer, reverse-phase protein array analysis was performed with sera of 271 lung cancer patients and 100 healthy controls. CKAP4 was detected in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed...
May 2, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29698634/function-related-protein-expression-in-fuchs-endothelial-corneal-dystrophy-cells-and-tissue-models
#7
Mathieu Thériault, Sébastien P Gendron, Isabelle Brunette, Patrick J Rochette, Stéphanie Proulx
Fuchs endothelial corneal dystrophy (FECD) is a corneal pathology that affects the endothelial cell ability to maintain deturgescence, resulting in a progressive loss of corneal transparency. In this study, we investigated the expression of function-related proteins in corneal endothelial cells using FECD or healthy corneal endothelial cells, either in a cell culture 2D model or in an engineered corneal endothelium 3D tissue model. No statistically significant difference in gene regulation was observed for the function-related families ATP1, SLC4, SLC16, AQP, TJP, and CDH between the FECD and the healthy cell models...
April 23, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684366/human-streptococcal-necrotizing-fasciitis-histopathology-mirrored-in-a-murine-model
#8
Nadia Keller, Federica Andreoni, Claudine Reiber, Helga Luethi-Schaller, Reto Andreas Schuepbach, Holger Moch, Ewerton Marques Maggio, Annelies Sophie Zinkernagel
Streptococcal necrotizing fasciitis (NF) causes high morbidity and mortality despite state-of-the-art therapy. Low incidence and rapid disease progression, necessitating immediate initiation of therapy, have proven challenging aspects for setting up prospective randomized trials. This has resulted in little therapeutic progress over the last decade. The validation of reliable murine NF models to study both pathogenesis and optimized therapeutic regimens of streptococcal NF are thus essential. In this study, we characterized a murine NF model and compared the pathology to an in-depth tissue analysis of streptococcal NF in patients...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684365/leucocyte-dynamics-during-the-evolution-of-human-coronary-atherosclerosis-conclusions-from-a-7-fold-chromogen-based-immunohistochemical-evaluation
#9
Melissa Zuiderwijk, Marlieke Geerts, Connie Janssen van Rhijn, Antoon van den Bogaerdt, Jaap F Hamming, Rogier A van Dijk, Jan H Lindeman
Atherosclerosis is a complex process with strong inflammatory component. We developed a straightforward 7-fold staining protocol for simultaneous assessment of dominant leucocyte classes, vascularization, and expression of the putative foam cell maker CD36. The method was applied on human coronaries covering the full spectrum of atherosclerotic disease. Results confirm the progressive association of macrophages and T-cells with the process, and a global presence of mast cells. B-cells exclusively present in adventitial follicles that accompany the process plaque destabilization (thin cap and ruptured lesions) and are otherwise absent...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684364/inhibition-of-mitochondrial-fission-preserves-photoreceptors-after-retinal-detachment
#10
Xiangjun She, Xinmin Lu, Tong Li, Junran Sun, Jian Liang, Yuanqi Zhai, Shiqi Yang, Qing Gu, Fang Wei, Hong Zhu, Fenghua Wang, Xueting Luo, Xiaodong Sun
Photoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgeries have been well developed to restore retinal structures, post-op patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684363/immunolabeling-of-cleared-human-pancreata-provides-insights-into-three-dimensional-pancreatic-anatomy-and-pathology
#11
Michaël Noë, Neda Rezaee, Kaushal Asrani, Michael Skaro, Vincent P Groot, Pei-Hsun Wu, Matthew T Olson, Seung-Mo Hong, Sung Joo Kim, Matthew J Weiss, Christopher L Wolfgang, Martin A Makary, Jin He, John L Cameron, Denis Wirtz, Nicholas J Roberts, G Johan A Offerhaus, Lodewijk A A Brosens, Laura D Wood, Ralph H Hruban
Visualizing pathologies in three dimensions (3D) can provide unique insights into the biology of human diseases. A rapid and easy-to-implement dibenzyl ether-based technique was used to clear thick sections of surgically resected human pancreatic parenchyma. Protocols were applicable to both fresh and formalin-fixed paraffin-embedded tissue. The penetration of antibodies into dense pancreatic parenchyma was optimized using both gradually increasing antibody concentrations and centrifugal flow. Immunolabeling with antibodies against CK19 was visualized using both light sheet and confocal laser scanning microscopy...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684362/characterization-of-the-small-intestinal-lesion-in-celiac-disease-by-label-free-quantitative-mass-spectrometry
#12
Astrid E V Tutturen, Siri Dørum, Trevor Clancy, Henrik M Reims, Asbjørn Christophersen, Knut E A Lundin, Ludvig M Sollid, Gustavo A de Souza, Jorunn Stamnaes
Global characterization of tissue proteomes from small amounts of biopsy material has become feasible due to advances in mass spectrometry and bioinformatics tools. In celiac disease (CD), dietary gluten induces an immune response which is accompanied by pronounced remodeling of the small intestine. Removal of gluten from the diet abrogates the immune response and the tissue architecture normalizes. In this study differences in global protein expression of small intestinal biopsies from CD patients were quantified by analyzing formalin-fixed, paraffin-embedded material using liquid-chromatography mass spectrometry and label-free protein quantitation...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684361/high-frequency-of-ovarian-cyst-development-in-vhl-2b-snf5-mice
#13
Yasumichi Kuwahara, Leslie M Kennedy, Anthony N Karnezis, E Lorena Mora-Blanco, Arlin B Rogers, Christopher D Fletcher, David G Huntsman, Charles W M Roberts, W Kimryn Rathmell, Bernard E Weissman
The new paradigm of mutations in chromatin modifying genes as driver events in the development of cancers has proved challenging to resolve the complex influences over disease phenotypes. In particular, impaired activities of members of the SWI/SNF chromatin remodeling complex have appeared in an increasing variety of tumors. Mutations in SNF5, a member of this ubiquitously expressed complex, arise in almost all cases of malignant rhabdoid tumor in the absence of additional genetic alterations. Therefore, we studied how activation of additional oncogenic pathways might shift the phenotype of disease driven by SNF5 loss...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684360/interleukin-6-drives-neutrophil-mediated-pulmonary-inflammation-associated-with-bacteraemia-in-murine-models-of-colitis
#14
Sean W Mateer, Andrea Mathe, Jessica Bruce, Gang Liu, Steven Maltby, Michael Fricker, Bridie J Goggins, Hock L Tay, Ellen Marks, Grace Burns, Richard Y Kim, Kyra Minahan, Marjorie M Walker, Robert C Callister, Paul S Foster, Jay C Horvat, Philip M Hansbro, Simon Keely
Inflammatory bowel disease (IBD) is associated with a number of immune-mediated extra-intestinal manifestations. Over half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid- and dextran sulfate sodium-induced models of colitis...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684359/the-g-protein-coupled-receptor-alx-fpr2-regulates-adaptive-immune-responses-in-mouse-submandibular-glands
#15
Ching-Shuen Wang, Olga J Baker
ALX/FPR2 is a G-protein-coupled receptor that has multiple binding partners, including the endogenous lipid mediators resolvin D1 (RvD1), lipoxin A4 (LXA4 ), and the Ca2+ -dependent phospholipid-binding protein Annexin A1. Previous studies demonstrated that RvD1 activates ALX/FPR2 to resolve salivary gland inflammation in the NOD/ShiLtJ mouse model for Sjögren's syndrome. Moreover, mice lacking the ALX/FPR2 display an exacerbated salivary gland inflammation in response to lipopolysaccharide. Additionally, activation of ALX/FPR2 has been shown to be important for regulating antibody production in B cells...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684358/novel-protective-role-of-nicotinamide-phosphoribosyltransferase-in-acetaminophen-induced-acute-liver-injury-in-mice
#16
Li Qin Zhang, Marianne Nsumu, Peixin Huang, Daniel P Heruth, Sean M Riordan, Katherine Shortt, Nini Zhang, Dmitry N Grigoryev, Ding-You Li, Craig A Friesen, Leon Van Haandel, J Steven Leeder, Jody Olson, Shui Qing Ye
Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the US. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore the role and mechanisms of nicotinamide phosphoribosyltransferase (NAMPT) in acetaminophen-induced ALI. C57BL/6 Nampt gene wild-type (Nampt+/+ )-, heterozygous knockout (Nampt+/- )-, and overexpression (NamptOE )-mice were treated with overdose of acetaminophen, followed by histological, biochemical, and transcriptomic evaluation of liver injury...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684357/genome-wide-somatic-copy-number-alterations-and-mutations-in-high-grade-pancreatic-intraepithelial-neoplasia
#17
Tatsuo Hata, Masaya Suenaga, Luigi Marchionni, Anne Macgregor-Das, Jun Yu, Koji Shindo, Koji Tamura, Ralph H Hruban, Michael Goggins
To obtain a better understanding of the genetic alterations of high-grade pancreatic intraepithelial neoplasia (HG-PanIN), we performed whole-genome copy number analysis using single nucleotide polymorphism microarrays and targeted next-generation sequencing of 11 microdissected HG-PanIN and two low-grade PanIN (LG-PanIN) lesions associated with HG-PanIN. HG-PanIN mutation profiles were compared to those of their associated invasive pancreatic ductal adenocarcinoma. All PanIN lesions harbored somatic KRAS mutations...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29673755/understanding-liver-regeneration-from-mechanisms-to-regenerative-medicine
#18
REVIEW
Hélène Gilgenkrantz, Alexandra Collin de l'Hortet
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities...
April 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29673754/this-month-in-ajp
#19
(no author information available yet)
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
April 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29654721/pleiotropic-role-of-p53-in-injury-and-liver-regeneration-after-acetaminophen-overdose
#20
Prachi Borude, Bharat Bhushan, Sumedha Gunewardena, Jephte Akakpo, Hartmut Jaeschke, Udayan Apte
p53 is the major cellular gatekeeper involved in proliferation, cell death, migration, and homeostasis. The role of p53 in pathogenesis of drug-induced liver injury is unknown. We investigated the role of p53 in liver injury and regeneration after acetaminophen (APAP) overdose, the most common cause of acute liver failure in the Western world. Eight-week-old male WT and p53KO mice were treated with 300mg/kg APAP (APAP300) and the dynamics of liver injury and regeneration were studied over time course of 0 to 96 hours...
April 11, 2018: American Journal of Pathology
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