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American Journal of Pathology

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https://www.readbyqxmd.com/read/28088007/impairment-of-host-liver-repopulation-by-transplanted-hepatocytes-in-aged-rats-and-the-release-by-short-term-growth-hormone-treatment
#1
Peggy Stock, Maximilian Bielohuby, Martin S Staege, Mei-Ju Hsu, Martin Bidlingmaier, Bruno Christ
Hepatocyte transplantation is an alternative to whole liver transplantation. Yet, efficient liver repopulation by transplanted hepatocytes is low in livers of old animals. This restraint might be because of the poor proliferative capacity of aged donor hepatocytes or the regenerative impairment of the recipient livers. The age-dependent liver repopulation by transplanted wild-type hepatocytes was investigated in juvenile and senescent rats deficient in dipeptidyl-peptidase IV. Repopulation was quantified by flow cytometry and histochemical estimation of dipeptidyl-peptidase IV enzyme activity of donor cells in the negative host liver...
January 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28088287/insulin-like-growth-factor-binding-protein-3-deficiency-leads-to-behavior-impairment-with-monoaminergic-and-synaptic-dysfunction
#2
Hongmei Dai, Yu-Ichi Goto, Masayuki Itoh
Insulin-like growth factor binding protein (IGFBP)-3 regulates IGF bioactivity, induces apoptosis, and inhibits cell growth independent of IGFs, but the functional role of IGFBP3 in the brain is not clear. In the present study, we revealed the effect of IGFBP3 on the brain by characterizing the phenotype of Igfbp3-null mice. Compared with wild-type mice, Igfbp3-null mice had significantly decreased IGF-1 content in the brain but no change in weights of brain and body. In Igfbp3-null mice, the number of dendritic spines was significantly reduced, and the dendritic diameter was thickening...
January 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28087162/mir-24-inhibition-increases-menin-expression-and-decreases-cholangiocarcinoma-proliferation
#3
Laurent Ehrlich, Chad Hall, Julie Venter, David Dostal, Francesca Bernuzzi, Pietro Invernizzi, Fanyin Meng, Jerome P Trzeciakowski, Tianhao Zhou, Holly Standeford, Gianfranco Alpini, Terry C Lairmore, Shannon Glaser
Menin (MEN1) is a tumor-suppressor protein in neuroendocrine tissue. Because cholangiocytes can take on a neuroendocrine phenotype, we tested the novel hypothesis that menin regulates cholangiocarcinoma proliferation. Menin and miR-24 expression levels were measured in the following intrahepatic and extrahepatic cholangiocarcinoma (CCA) cell lines, Mz-ChA-1, TFK-1, SG231, CCLP, HuCCT-1, and HuH-28, as well as the nonmalignant human intrahepatic biliary line, H69. miR-24 miRNA and menin protein levels were manipulated in vitro in Mz-ChA-1 cell lines...
January 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28082121/changes-in-the-luminal-environment-of-the-colonic-epithelial-cells-and-physiopathological-consequences
#4
REVIEW
François Blachier, Martin Beaumont, Mireille Andriamihaja, Anne-Marie Davila, Annaig Lan, Marta Grauso, Lucie Armand, Robert Benamouzig, Daniel Tomé
Evidence, mostly from experimental models, has accumulated, indicating that modifications of bacterial metabolite concentrations in the large intestine luminal content, notably after changes in the dietary composition, may have important beneficial or deleterious consequences for the colonic epithelial cell metabolism and physiology in terms of mitochondrial energy metabolism, reactive oxygen species production, gene expression, DNA integrity, proliferation, and viability. Recent data suggest that for some bacterial metabolites, like hydrogen sulfide and butyrate, the extent of their oxidation in colonocytes affects their capacity to modulate gene expression in these cells...
January 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28082120/modulation-of-antiviral-immunity-by-heme-oxygenase-1
#5
REVIEW
Janyra A Espinoza, Pablo A González, Alexis M Kalergis
Heme oxygenase-1 (HO-1) is a stress-inducible, anti-inflammatory, and cytoprotective enzyme expressed in most cell types in the organism. Under several stress stimuli, HO-1 expression and activity is up-regulated to catalyze the rate-limiting enzymatic step of heme degradation into carbon monoxide, free iron, and biliverdin. Besides its effects on cell metabolism, HO-1 is also capable of modulating host innate and adaptive immune responses in response to sepsis, transplantation, and autoimmunity, and preventing oxidative damage associated with inflammation...
January 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28082119/periostin-promotes-scar-formation-through-the-interaction-between-pericytes-and-infiltrating-monocytes-macrophages-after-spinal-cord-injury
#6
Kazuya Yokota, Kazu Kobayakawa, Takeyuki Saito, Masamitsu Hara, Ken Kijima, Yasuyuki Ohkawa, Akihito Harada, Ken Okazaki, Kohei Ishihara, Shigeo Yoshida, Akira Kudo, Yukihide Iwamoto, Seiji Okada
Scar formation is a prominent pathological feature of traumatic central nervous system (CNS) injury, which has long been implicated as a major impediment to the CNS regeneration. However, the factors affecting such scar formation remain to be elucidated. We herein demonstrate that the extracellular matrix protein periostin (POSTN) is a key player in scar formation after traumatic spinal cord injury (SCI). Using high-throughput RNA sequencing data sets, we found that the genes involved in the extracellular region, such as POSTN, were significantly expressed in the injured spinal cord...
January 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28082118/elevated-expression-of-moesin-in-muscular-dystrophies
#7
Mark Pines, Oshrat Levi, Olga Genin, Adi Lavy, Corrado Angelini, Valérie Allamand, Orna Halevy
Fibrosis is the main complication of muscular dystrophies. We identified moesin, a member of the ezrin-radixin-moesin family, in dystrophic muscles of mice representing Duchenne and congenital muscular dystrophies (DMD and CMD, respectively) and dysferlinopathy, but not in the wild type. High levels of moesin were also observed in muscle biopsy specimens from DMD, Ullrich CMD, and merosin-deficient CMD patients, all of which present high levels of fibrosis. The myofibroblasts, responsible for extracellular matrix protein synthesis, and the macrophages infiltrating the dystrophic muscles were the source of moesin...
January 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28068512/modulation-of-intersectin-1s-lung-expression-induces-obliterative-remodeling-and-severe-plexiform-arteriopathy-in-the-murine-pulmonary-vascular-bed
#8
Monal Patel, Dan Predescu, Cristina Bardita, Jiwang Chen, Niranjan Jeganathan, Melanie Pritchard, Salvatore DiBartolo, Roberto Machado, Sanda Predescu
Murine models of pulmonary arterial hypertension (PAH) that recapitulate the plexiform and obliterative arteriopathy seen in PAH patients and help in defining the molecular mechanisms involved are missing. Herein, we investigated whether intersectin-1s (ITSN) deficiency and prolonged lung expression of an ITSN fragment with endothelial cell (EC) proliferative potential (EHITSN), present in the lungs of PAH animal models and human patients, induce formation of plexiform/obliterative lesions and defined the molecular mechanisms involved...
January 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28068511/inhibition-of-glycogen-synthase-kinase-3-accelerated-liver-regeneration-after-acetaminophen-induced-hepatotoxicity-in-mice
#9
Bharat Bhushan, Samikshya Poudel, Michael W Manley, Nairita Roy, Udayan Apte
Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of β-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice...
January 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28063737/discovery-of-centrosomal-protein-70-as-an-important-player-in-the-development-and-progression-of-breast-cancer
#10
Xingjuan Shi, Dengwen Li, Yujue Wang, Shiyu Liu, Juan Qin, Jun Wang, Jie Ran, Yu Zhang, Qinghai Huang, Xiangdong Liu, Jun Zhou, Min Liu
Centrosome abnormalities have been implicated in the development and progression of breast cancer. However, the molecular players involved in the above processes remain largely uncharacterized. Herein, we identify centrosomal protein 70 (Cep70) as an important factor that mediates breast cancer growth and metastasis. Cep70 is up-regulated in breast cancer tissues and cell lines, and its expression is closely correlated with several clinicopathologic variables associated with breast cancer progression. Mechanistic studies reveal that the up-regulation of Cep70 in breast cancer occurs at the mRNA level and is independent of gene amplification...
January 5, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28088288/a-novel-mouse-model-of-staphylococcus-aureus-vascular-graft-infection-noninvasive-imaging-of-biofilm-development-in%C3%A2-vivo
#11
Hélène Van de Vyver, Philipp R Bovenkamp, Verena Hoerr, Katrin Schwegmann, Lorena Tuchscherr, Silke Niemann, Laura Kursawe, Christina Grosse, Annette Moter, Uwe Hansen, Ute Neugebauer, Michael T Kuhlmann, Georg Peters, Sven Hermann, Bettina Löffler
Staphylococcus aureus causes very serious infections of vascular grafts. Knowledge of the molecular mechanisms of this disease is largely lacking because of the absence of representable models. Therefore, the aim of this study was to set up a mouse model of vascular graft infections that closely mimics the human situation. A catheter was inserted into the right carotid artery of mice, which acted as a vascular graft. Mice were infected i.v. using 8 different S. aureus strains, and development of the infection was followed up...
January 4, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28061324/oral-corticosterone-administration-reduces-insulitis-but-promotes-insulin-resistance-and-hyperglycemia-in-male-nonobese-diabetic-mice
#12
Susan J Burke, Heidi M Batdorf, Adrianna E Eder, Michael D Karlstad, David H Burk, Robert C Noland, Z Elizabeth Floyd, J Jason Collier
Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic...
January 4, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28062081/neonatal-hypoxia-results-in-peripheral-nerve-abnormalities
#13
Benjamin L L Clayton, Aaron Huang, Danuta Dukala, Betty Soliven, Brian Popko
Although the adverse effects of neonatal hypoxia associated with premature birth on the central nervous system are well known, the contribution of hypoxic damage to the peripheral nervous system (PNS) has not been addressed. We demonstrate that neonatal hypoxia results in hypomyelination and delayed axonal sorting in mice leading to electrophysiological and motor deficits that persist into adulthood. These findings support a potential role for PNS hypoxic damage in the motor impairment that results from premature birth and suggest that therapies designed to protect the PNS may provide clinical benefit...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28056339/asbestos-induced-mesothelial-to-fibroblastic-transition-is-modulated-by-the-inflammasome
#14
Joyce K Thompson, Maximilian B MacPherson, Stacie L Beuschel, Arti Shukla
Despite the causal relationship established between malignant mesothelioma (MM) and asbestos exposure, the exact mechanism by which asbestos induces this neoplasm and other asbestos-related diseases is still not well understood. MM is characterized by chronic inflammation, which is believed to play an intrinsic role in the origin of this disease. We recently found that asbestos activates the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in a protracted manner, leading to an up-regulation of IL-1β and IL-18 production in human mesothelial cells...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28056338/hanac-col4a1-mutation-in-mice-leads-to-skeletal-muscle-alterations-due-to-a-primary-vascular-defect
#15
Simon Guiraud, Tiffany Migeon, Arnaud Ferry, Zhiyong Chen, Souhila Ouchelouche, Marie-Christine Verpont, Yoshikazu Sado, Valérie Allamand, Pierre Ronco, Emmanuelle Plaisier
Collagen IV is a major component of basement membranes (BMs). The α1(IV) chain, encoded by the COL4A1 gene, is expressed ubiquitously and associates with the α2(IV) chain to form the α1α1α2(IV) heterotrimer. Several COL4A1 mutations affecting a conformational domain containing integrin-binding sites are responsible for the systemic syndrome of hereditary angiopathy, nephropathy, aneurysms, and cramps (HANAC). To analyze the pathophysiology of HANAC, Col4a1 mutant mice bearing the p.Gly498Val mutation were generated...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28056337/marked-enteropathy-in-an-accelerated-macaque-model-of-aids
#16
Joshua D Croteau, Elizabeth L Engle, Suzanne E Queen, Erin N Shirk, M Christine Zink
Enteropathy in HIV infection is not eliminated with combination antiretroviral therapy and is possibly linked to microbial translocation. We used a rapidly progressing SIV/pigtailed macaque model of HIV to examine enteropathy and microbial translocation. Histologic evidence of intestinal disease was observed in only half of infected macaques during late-stage infection (LSI). Combination antiretroviral therapy initiated during acute infection prevented intestinal disease. In the ileum and colon, enteropathy was associated with increased caspase-3 staining, decreased CD3(+) T cells, and increased SIV-infected cells...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28041995/osteoprotegerin-and-%C3%AE-2-agonists-mitigate-muscular-dystrophy-in-slow-and-fast-twitch-skeletal-muscles
#17
Sébastien S Dufresne, Antoine Boulanger-Piette, Jérôme Frenette
Our recent work showed that daily injections of osteoprotegerin (OPG)-immunoglobulin fragment complex (OPG-Fc) completely restore the function of fast-twitch extensor digitorum longus muscles in dystrophic mdx mice, a murine model of Duchenne muscular dystrophy. However, despite marked improvements, OPG-Fc was not as effective in preventing the loss of function of slow-twitch soleus and diaphragm muscles. Because β2-agonists enhance the function of slow- and fast-twitch dystrophic muscles and because their use is limited by their adverse effects on bone and cardiac tissues, we hypothesized that OPG-Fc, a bone and skeletal muscle protector, acts synergistically with β2-agonists and potentiates their positive effects on skeletal muscles...
December 30, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/28041994/a-dominant-mutation-in-rpe65-d477g-delays-dark-adaptation-and-disturbs-the-visual-cycle-in-the-mutant-knock-in-mice
#18
Younghwa Shin, Gennadiy Moiseyev, Dibyendu Chakraborty, Jian-Xing Ma
RPE65 is an indispensable component of the retinoid visual cycle in vertebrates, through which the visual chromophore 11-cis-retinal (11-cis-RAL) is generated to maintain normal vision. Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65. Herein, we investigated D477G missense mutation, an unprecedented dominant-acting mutation of RPE65 identified in patients with autosomal dominant RP...
December 30, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/28034602/contribution-of-secreted-nadase-and-streptolysin-o-to-the-pathogenesis-of-epidemic-serotype-m1-streptococcus-pyogenes-infections
#19
Luchang Zhu, Randall J Olsen, Jessica D Lee, Adeline R Porter, Frank R DeLeo, James M Musser
Streptococcus pyogenes secretes many toxins that facilitate human colonization, invasion, and dissemination. NADase (SPN) and streptolysin O (SLO) are two toxins that play important roles in pathogenesis. We previously showed that increased production of SPN and SLO in epidemic serotype M1 and M89 S. pyogenes strains is associated with rapid intercontinental spread and enhanced virulence. The biological functions of SPN and SLO have been extensively studied using eukaryotic cell lines, but the relative contribution of each of these two toxins to pathogenesis of epidemic M1 or M89 strains remains unexplored...
December 27, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27998729/in%C3%A2-vivo-imaging-of-inflamed-glomeruli-reveals-dynamics-of-neutrophil-extracellular-trap-formation-in-glomerular-capillaries
#20
Clare L V Westhorpe, James E Bayard, Kim M O'Sullivan, Pam Hall, Qiang Cheng, A Richard Kitching, Michael J Hickey
Neutrophil extracellular traps (NETs) have been documented in glomeruli of patients with glomerulonephritis. However, the dynamics of NET formation in the glomerulus and their functional contribution to acute glomerular injury are poorly understood. Herein, we used in vivo multiphoton microscopy to investigate NET formation in the acutely inflamed glomerulus. Glomerular inflammation was induced using an antibody against the glomerular basement membrane. After induction of glomerular inflammation, multiphoton microscopy revealed that approximately 20% of glomeruli contained structures composed of extracellular DNA within the capillaries...
December 17, 2016: American Journal of Pathology
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