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American Journal of Pathology

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https://www.readbyqxmd.com/read/28222276/influenza-casts-a-lung-shadow
#1
Xavier De Luna, Kevan L Hartshorn
This commentary highlights the article by Pociask et al that provides new insights into the lingering effects of influenza infection.
February 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28219647/this-month-in-ajp
#2
(no author information available yet)
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
February 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28212814/human-striatal-dopaminergic-and-regional-serotonergic-synaptic-degeneration-with-lewy-body-disease-and-inheritance-of-apoe-%C3%AE%C2%B54
#3
Nadia Postupna, Caitlin S Latimer, Eric B Larson, Emily Sherfield, Julie Paladin, Carol A Shively, Matthew J Jorgensen, Rachel N Andrews, Jay R Kaplan, Paul K Crane, Kathleen S Montine, Suzanne Craft, C Dirk Keene, Thomas J Montine
Cognitive impairment in older individuals is a complex trait that in population-based studies most commonly derives from an individually varying mixture of Alzheimer disease, Lewy body disease, and vascular brain injury. We investigated the molecular composition of synaptic particles from three sources: consecutive rapid autopsy brains from the adult changes in thought study, a population-based cohort; four aged nonhuman primate brains optimally processed for molecular investigation; and targeted replacement transgenic mice homozygous for APOE ε4...
February 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28208054/high-glucose-induced-hypomethylation-promotes-binding-of-sp-1-to-myo-inositol-oxygenase-implication-in-the-pathobiology-of-diabetic-tubulopathy
#4
Isha Sharma, Rajesh K Dutta, Neel K Singh, Yashpal S Kanwar
The catabolic enzyme myo-inositol oxygenase (MIOX) is expressed in proximal tubules and up-regulated in the diabetic state. Previously, we reported its transcriptional and translation regulation by high glucose (HG), osmolytes, and fatty acids. However, its epigenetic regulation is unknown. Bisulfite sequencing revealed that both human and mouse MIOX promoters, enriched with CpG sites, are hypomethylated and unmethylated under HG ambience and hyperglycemic states associated with increased MIOX expression. Eletrophoretic mobility shift assays revealed increased binding of unmethylated oligos with nucleoproteins of cells maintained under HG...
February 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28196718/the-neuropeptide-galanin-is-up-regulated-during-cholestasis-and-contributes-to-cholangiocyte-proliferation
#5
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Sharon DeMorrow
During the course of cholestatic liver diseases, mitotically dormant cholangiocytes proliferate and subsequently acquire a neuroendocrine phenotype. Galanin is a neuroendocrine factor responsible for regulation of physiological responses, such as feeding behavior and mood, and has been implicated in the development of fatty liver disease, although its role in biliary hyperplasia is unknown. Biliary hyperplasia was induced in rats via bile duct ligation (BDL) surgery, and galanin was increased in serum and liver homogenates from BDL rats...
February 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28193481/epigenetic-and-transcriptomic-regulation-of-lung-repair-during-recovery-from-influenza-infection
#6
Derek A Pociask, Keven M Robinson, Kong Chen, Kevin J McHugh, Michelle E Clay, Grace T Huang, Panayiotis V Benos, Yvonne M W Janssen-Heininger, Jay K Kolls, Vikas Anathy, John F Alcorn
Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild-to-moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models; however, little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection...
February 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28189565/blockade-of-p38-mitogen-activated-protein-kinase-inhibits-murine-sclerodermatous-chronic-graft-versus-host-disease
#7
Takashi Matsushita, Mutsumi Date, Miyu Kano, Kie Mizumaki, Momoko Tennichi, Tadahiro Kobayashi, Yasuhito Hamaguchi, Minoru Hasegawa, Manabu Fujimoto, Kazuhiko Takehara
Bone marrow transplantation (BMT) of B10.D2 mice into sublethally irradiated BALB/c mice across minor histocompatibility loci is a well-established animal model for human sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) and systemic sclerosis (SSc). The p38 mitogen-activated protein kinase (MAPK) pathway is a key regulator of inflammation and cytokine production. Furthermore, the activation of p38 MAPK plays an important role in collagen production in SSc. We investigated the effects of p38 MAPK inhibitor, VX-702, on Scl-cGVHD mice...
February 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28189564/h7n9-influenza-a-virus-exhibits-importin-%C3%AE-7-mediated-replication-in-the-mammalian-respiratory-tract
#8
Stephanie Bertram, Swantje Thiele, Carola Dreier, Patricia Resa-Infante, Annette Preuß, Debby van Riel, Chris K P Mok, Folker Schwalm, Joseph S M Peiris, Hans-Dieter Klenk, Gülsah Gabriel
The acute respiratory distress syndrome (ARDS) is the leading cause of death in influenza A virus (IAV)-infected patients. Hereby, the cellular importin-α7 gene plays a major role. It promotes viral replication in the lung, thereby increasing the risk for the development of pneumonia complicated by ARDS. Herein, we analyzed whether the recently emerged H7N9 avian IAV has already adapted to human importin-α7 use, which is associated with high-level virus replication in the mammalian lung. Using a cell-based viral polymerase activity assay, we could detect a decreased H7N9 IAV polymerase activity when importin-α7 was silenced by siRNA...
February 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28188112/thrombin-induces-inositol-trisphosphate-mediated-spatially-extensive-responses-in-lung-microvessels
#9
Rachel Escue, Kathirvel Kandasamy, Kaushik Parthasarathi
Activation of plasma membrane receptors initiates compartmentalized second messenger signaling. Whether this compartmentalization facilitates the preferential intercellular diffusion of specific second messengers is unclear. Toward this, the receptor-mediated agonist, thrombin, was instilled into microvessels in a restricted region of isolated blood-perfused mouse lungs. Subsequently, the thrombin-induced increase in endothelial F-actin was determined using confocal fluorescence microscopy. Increased F-actin was evident in microvessels directly treated with thrombin and in those located in adjoining thrombin-free regions...
February 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28183533/chronic-embolic-pulmonary-hypertension-caused-by-pulmonary-embolism-and-vascular-endothelial-growth-factor-inhibition
#10
Evandro M Neto-Neves, Mary B Brown, Maria V Zaretskaia, Samin Rezania, Adam G Goodwill, Brian P McCarthy, Scott A Persohn, Paul R Territo, Jeffrey A Kline
Our understanding of the pathophysiological basis of chronic thromboembolic pulmonary hypertension (CTEPH) will be accelerated by an animal model that replicates the phenotype of human CTEPH. Sprague-Dawley rats were administered a combination of a single dose each of plastic microspheres and vascular endothelial growth factor receptor antagonist in polystyrene microspheres (PE) + tyrosine kinase inhibitor SU5416 (SU) group. Shams received volume-matched saline; PE and SU groups received only microspheres or SU5416, respectively...
February 7, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28183532/growth-factor-midkine-promotes-nuclear-factor-of-activated-t-cells-regulated-t-cell-activation-and-th1-cell-differentiation-in-lupus-nephritis
#11
Tomohiro Masuda, Kayaho Maeda, Waichi Sato, Tomoki Kosugi, Yuka Sato, Hiroshi Kojima, Noritoshi Kato, Takuji Ishimoto, Naotake Tsuboi, Kenji Uchimura, Yukio Yuzawa, Shoichi Maruyama, Kenji Kadomatsu
Activated T cells play crucial roles in the pathogenesis of autoimmune diseases, including lupus nephritis (LN). The activation of calcineurin/nuclear factor of activated T cells (NFAT) and STAT4 signaling is essential for T cells to perform various effector functions. Here, we identified the growth factor midkine (MK; gene name, Mdk) as a novel regulator in the pathogenesis of 2,6,10,14-tetramethylpentadecane-induced LN via activation of NFAT and IL-12/STAT4 signaling. Wild-type (Mdk(+/+)) mice showed more severe glomerular injury than MK-deficient (Mdk(-/-)) mice, as demonstrated by mesangial hypercellularity and matrix expansion, and glomerular capillary loops with immune-complex deposition...
February 7, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28183531/cardiomyocyte-hypertrophy-in-arrhythmogenic-cardiomyopathy
#12
Mustafa Gerçek, Muhammed Gerçek, Sebastian Kant, Sakine Simsekyilmaz, Astrid Kassner, Hendrik Milting, Elisa A Liehn, Rudolf E Leube, Claudia A Krusche
Arrhythmogenic cardiomyopathy (AC) is a hereditary disease leading to sudden cardiac death or heart failure. AC pathology is characterized by cardiomyocyte loss and replacement fibrosis. Our goal was to determine whether cardiomyocytes respond to AC progression by pathological hypertrophy. To this end, we examined tissue samples from AC patients with end-stage heart failure and tissue samples that were collected at different disease stages from desmoglein 2-mutant mice, a well characterized AC model. We find that cardiomyocyte diameters are significantly increased in right ventricles of AC patients...
February 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28183530/tnf%C3%AE-are-mice-display-abnormal-lymphatics-and-develop-tertiary-lymphoid-organs-in-the-mesentery
#13
Sonia Rehal, Pierre-Yves von der Weid
Chronic inflammatory diseases are associated with a persistent and enhanced response to environmental antigens. As an adaptive response to this exaggerated immune state, affected tissue typically develops tertiary lymphoid organs. Studies of Crohn disease (CD), a chronic inflammatory disease of the intestinal tract, report tertiary lymphoid organs present within the mucosal wall, along with other lymphatic diseases, such as lymphangiogenesis and obstructed lymphatic vessels. These observations suggest that downstream mesenteric lymphatic vessels and lymph drainage into mesenteric lymph nodes may be compromised...
February 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28167045/dexamethasone-induced-ocular-hypertension-in-mice-effects-of-myocilin-and-route-of-administration
#14
Gaurang C Patel, Tien N Phan, Prabhavathi Maddineni, Ramesh B Kasetti, J Cameron Millar, Abbot F Clark, Gulab S Zode
Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious adverse effect of prolonged GC therapy that can lead to iatrogenic glaucoma and permanent vision loss. An appropriate mouse model can help us understand precise molecular mechanisms and etiology of GC-induced OHT. We therefore developed a novel, simple, and reproducible mouse model of GC-induced OHT. GC-induced myocilin expression in the trabecular meshwork (TM) has been suggested to play an important role in GC-induced OHT. We further determined whether myocilin contributes to GC-OHT...
February 3, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28167044/hypoxia-directs-human-extravillous-trophoblast-differentiation-in-a-hypoxia-inducible-factor-dependent-manner
#15
Anna K Wakeland, Francesca Soncin, Matteo Moretto-Zita, Ching-Wen Chang, Mariko Horii, Don Pizzo, Katharine K Nelson, Louise C Laurent, Mana M Parast
Villous cytotrophoblasts are epithelial stem cells of the early human placenta, able to differentiate either into syncytiotrophoblasts in floating chorionic villi or extravillous trophoblasts (EVTs) at the anchoring villi. The signaling pathways regulating differentiation into these two lineages are incompletely understood. The bulk of placental growth and development in the first trimester occurs under low oxygen tension. One major mechanism by which oxygen regulates cellular function is through the hypoxia-inducible factor (HIF), a transcription factor complex stabilized under low oxygen tension to mediate cellular responses, including cell fate decisions...
February 3, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28162981/caveolin-1-and-g-protein-coupled-receptor-kinase-2-coregulate-endothelial-nitric-oxide-synthase-activity-in-sinusoidal-endothelial-cells
#16
Songling Liu, Richard T Premont, Shweta Singh, Don C Rockey
Liver injury leads to a vasculopathy in which post-translational modifications of endothelial nitric oxide synthase (eNOS) lead to impaired nitric oxide synthesis. We hypothesized that caveolin 1 (CAV1), a well-known eNOS interactor, regulates eNOS activity in sinusoidal endothelial cells (SECs) via its interaction with G-protein-coupled receptor kinase-2 (GRK2) that also post-translationally modifies eNOS. Liver injury with portal hypertension was established using bile duct ligation in rats. CAV1 function was modified using a CAV1 scaffolding domain construct and cDNAs encoding wild-type CAV1, and CAV1 phosphorylation was increased in injured SECs, resulting in increased GRK2-CAV1 interaction and decreased eNOS activity...
February 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28162229/the-increased-transforming-growth-factor-%C3%AE-signaling-induced-by-diabetes-protects-retinal-vessels
#17
Zeina Dagher, Chiara Gerhardinger, Joseph Vaz, Michael Goodridge, Francesco Tecilazich, Mara Lorenzi
The roles of transforming growth factor (TGF)-β in extracellular matrix production and vascular remodeling, coupled with increased TGF-β expression and signaling in diabetes, suggest TGF-β as an important contributor to the microangiopathy of diabetic retinopathy and nephropathy. To investigate whether increased TGF-β signaling could be a therapeutic target for preventing retinopathy, we used a pharmacologic approach (SM16, a selective inhibitor of the type 1 TGF-β receptor activin receptor-like kinase 5, orally active) to inhibit the increased, but not the basal, Tgf-β signaling in retinal vessels of diabetic rats...
February 1, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28157489/cathepsin-h-mediated-degradation-of-hdac4-for-matrix-metalloproteinase-expression-in-hepatic-stellate-cells-implications-of-epigenetic-suppression-of-matrix-metalloproteinases-in-fibrosis-through-stabilization-of-class-iia-histone-deacetylases
#18
Zemin Yang, Yu Liu, Lan Qin, Pengfei Wu, Zanxian Xia, Mei Luo, Yilan Zeng, Hidekazu Tsukamoto, Zongyun Ju, Danmei Su, Han Kang, Zhixiong Xiao, Sujun Zheng, Zhongping Duan, Richard Hu, Qiang Wang, Stephen J Pandol, Yuan-Ping Han
In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts)...
February 1, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28157488/placental-stem-villus-arterial-remodeling-associated-with-reduced-hydrogen-sulfide-synthesis-contributes-to-human-fetal-growth-restriction
#19
Liangjian Lu, John Kingdom, Graham J Burton, Tereza Cindrova-Davies
Intrauterine fetal growth restriction (IUGR) is often associated with compromised umbilical arterial flow, indicating increased placental vascular resistance. Oxidative stress is causatively implicated. Hydrogen sulfide maintains differentiated smooth muscle in vascular beds, and its synthetic enzyme cystathionine-γ-lyase (CSE) is down-regulated in growth-restricted placentas. We hypothesized that remodeling of resistance arteries in stem villi contributes to IUGR by compromising umbilical blood flow via oxidative stress, reducing hydrogen sulfide signaling...
February 1, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28109768/is-centrosomal-protein-70-a-centrosomal-protein-with-new-roles-in-breast-cancer-dissemination-and-metastasis-a-facilitator-of-epithelial-mesenchymal-transition
#20
Pedro A Lazo
This commentary highlights the article by Shi et al that identified centrosomal protein 70 as a key mediator of breast cancer growth and metastasis.
January 18, 2017: American Journal of Pathology
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