18,707 results match your criteria The American journal of pathology[Journal]


Augmenter of liver regeneration protects against ethanol-induced acute liver injury by promoting autophagy.

Am J Pathol 2018 Dec 13. Epub 2018 Dec 13.

Department of Cell Biology, Capital Medical University and the Municipal Key Laboratory for Liver Protection and Regulation of Regeneration, Beijing, China. Electronic address:

Alcoholic liver disease is associated with high morbidity and mortality, and treatment options are limited to date. Augmenter of liver regeneration (ALR) may protect against hepatic injury caused by chemical poisons, including ethanol. Autophagy appears to positively influence survival in cases of liver dysfunction, though the mechanisms are poorly understood. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.006DOI Listing
December 2018

Ganglioside synthase knock-out reduces prion disease incubation time in mouse models.

Am J Pathol 2018 Dec 13. Epub 2018 Dec 13.

Department of Laboratory Animal Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.

Localization of the abnormal and normal isoforms of prion proteins to detergent-resistant membrane microdomains, lipid rafts, is important for the conformational conversion. Lipid rafts are enriched in sialic acid-containing glycosphingolipids, namely gangliosides. Alteration in the ganglioside composition of lipid rafts can affect the localization of lipid raft-associated proteins. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.009DOI Listing
December 2018
1 Read

Heparan Sulfate Proteoglycan Synthesis is Dysregulated in Human Osteoarthritic Cartilage.

Am J Pathol 2018 Dec 13. Epub 2018 Dec 13.

Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK. Electronic address:

Osteoarthritis (OA) is a common degenerative joint disease, characterized by cartilage loss and subchondral bone remodelling in response to abnormal mechanical load. Heparan sulfate (HS) proteoglycans bind to many proteins that regulate cartilage homeostasis, including growth factors, morphogens, proteases, and their inhibitors, and modulate their localization, retention, and biological activity. Changes in HS expression and structure may thus have important consequences for joint health. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.011DOI Listing
December 2018

Dynamin-1-like protein inhibition drives megamitochondria formation as an adaptive response in alcohol-induced hepatotoxicity.

Am J Pathol 2018 Dec 13. Epub 2018 Dec 13.

Institute of Hepatology London, Foundation for Liver Research, London, United Kingdom; King's College London, Faculty of Life Sciences and Medicine, London, United Kingdom. Electronic address:

Despite the growing global burden of alcoholic liver diseases, therapeutic options are limited and novel targets are urgently needed. Accumulating evidence suggests that mitochondria adapt in response to ethanol and formation of megamitochondria in the livers of patients is recognized as a hallmark of alcoholic liver diseases. The processes involved in ethanol-induced hepatic mitochondrial changes, the impact on mitochondria-shaping proteins, and the significance of megamitochondria formation remain unknown. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.008DOI Listing
December 2018

LINE-1 retrotransposons become deregulated during the development of ovarian cancer precursor lesions.

Am J Pathol 2018 Dec 13. Epub 2018 Dec 13.

Department of Oncology; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathology; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; Gynecology and Obstetrics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

There is growing evidence that the majority of high-grade serous ovarian carcinomas likely arise from local dissemination of precursor lesions of the fallopian tube. Evolution of these lesions from early "p53 signatures" to latter-stage, serous tubal intraepithelial carcinomas (STICs) is characterized by cytologic atypia, accumulation of somatic mutations, and genomic instability, the etiologies of which remain unclear. Long interspersed element 1 (LINE-1) retrotransposon is expressed in many carcinomas, including high-grade serous ovarian carcinoma, where it contributes to genomic instability; however, the timing of LINE-1 activation during this evolution has yet to be elucidated. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.005DOI Listing
December 2018

Expression of Bone Morphogenetic Proteins In Multiple Sclerosis Lesions.

Am J Pathol 2018 Dec 13. Epub 2018 Dec 13.

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain. Electronic address:

Bone morphogenetic proteins (BMPs) are secreted proteins that belong to the transforming growth factor-beta superfamily. In the adult brain, they modulate neurogenesis, favor astrogliogenesis, and inhibit oligodendrogenesis. As BMPs may be involved in the failure of remyelination in multiple sclerosis (MS), we characterized the expression of BMP-2, -4, -5, and -7; BMP type II receptor (BMPRII); and phosphorylated (p)SMAD 1/5/8 in lesions of MS and other demyelinating diseases. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.007DOI Listing
December 2018

Novel mTORC1 Mechanism Suggests Therapeutic Targets for COMPopathies.

Am J Pathol 2018 Dec 7. Epub 2018 Dec 7.

Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center, Houston, Texas; School of Dentistry, University of Texas Health Science Center, Houston, Texas.

Cartilage oligomeric matrix protein (COMP) is a large, multifunctional extracellular protein that, when mutated, is retained in the rough endoplasmic reticulum (ER). This retention elicits ER stress, inflammation, and oxidative stress, resulting in dysfunction and death of growth plate chondrocytes. While identifying the cellular pathologic mechanisms underlying the murine mutant (MT)-COMP model of pseudoachondroplasia, increased midline-1 (MID1) expression and mammalian target of rapamycin complex 1 (mTORC1) signaling was found. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.008DOI Listing
December 2018

This Month in AJP.

Authors:
Chhavi Chauhan

Am J Pathol 2018 Dec 10. Epub 2018 Dec 10.

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http://dx.doi.org/10.1016/j.ajpath.2018.12.001DOI Listing
December 2018

Podocytes: Way to Go.

Am J Pathol 2018 Dec 11. Epub 2018 Dec 11.

Department of Medicine, Rush University Medical Center, Chicago, Illinois.

This commentary highlights the article by Hara et al that discusses the clinical implications of mitotic catastrophe in podocyte health during diabetic kidney disease. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.003DOI Listing
December 2018

Mild Traumatic Brain Injury in Mice Beneficially Alters Lung NK1R and Structural Protein Expression to Enhance Survival after Pseudomonas aeruginosa Infection.

Am J Pathol 2018 Nov 23. Epub 2018 Nov 23.

Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts. Electronic address:

Mild traumatic brain injury (mTBI) in a murine model increases survival to a bacterial pulmonary challenge compared with blunt tail trauma (TT). We hypothesize substance P and its receptor, the neurokinin 1 receptor (NK1R; official name TACR1), play a role in the increased survival of mTBI mice. Mice were subjected to mTBI or TT, and 48 hours after trauma, the levels of NK1R mRNA and protein were significantly up-regulated in mTBI lungs. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.019DOI Listing
November 2018

Mitotic Catastrophe Causes Podocyte Loss in the Urine of Human Diabetics.

Am J Pathol 2018 Nov 23. Epub 2018 Nov 23.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; Arkana Laboratories, Little Rock, Arkansas. Electronic address:

Mitotic catastrophe (MC) is a major cause of podocyte loss in vitro and in vivo. We evaluated urine samples (a total of 184 from diabetic patients; n = 41) from diabetic patients and determined the presence of podocytes in the urine and studied their characteristics, specifically asking whether apoptosis versus MC is present. We also evaluated diabetic glomeruli in renal biopsy specimens by electron microscopy (n = 54). Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.016DOI Listing
November 2018
5 Reads

Acid Ceramidase Deficiency in Mice Leads to Severe Ocular Pathology and Visual Impairment.

Am J Pathol 2018 Nov 22. Epub 2018 Nov 22.

Institute of Medical Science, University of Toronto, Toronto Canada; Department of Pediatrics, Medical College of Wisconsin, Milwaukee USA; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Department of Biochemistry, Medical College of Wisconsin, Milwaukee USA; University Health Network, Toronto, Canada. Electronic address:

Farber Disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.018DOI Listing
November 2018
1 Read

Antibiotic-Induced Dysbiosis of Gut Microbiota Impairs Corneal Nerve Regeneration by Affecting CCR2-Negative Macrophage Distribution.

Am J Pathol 2018 Dec;188(12):2786-2799

International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University Medical School, Guangzhou, People's Republic of China; Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, People's Republic of China; Department of Ophthalmology, Henan Provincial People's Hospital, Zhengzhou, People's Republic of China; Section of Leukocyte Biology, Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas. Electronic address:

Although antibiotics are useful, they can also bring negative effects. We found that antibiotic-treated mice exhibit an alteration in the gene expression profile of corneal tissues and a decrease in corneal nerve density. During corneal wound healing, antibiotic treatment was found to impair corneal nerve regeneration, an effect that could be largely reversed by reconstitution of the gut microbiota via fecal transplant. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284554PMC
December 2018
4.591 Impact Factor

The danger signal extracellular ATP is involved in the immuno-mediated damage of alpha-sarcoglycan deficient muscular dystrophy.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Center of Translational and Experimental Myology, Istituto Giannina Gaslini, Genova, Italy. Electronic address:

In muscular dystrophies the muscle membrane fragility results in a tissue-specific increase of danger-associated molecules (DAMPs) and infiltration of inflammatory cells. The DAMP extracellular adenosine triphosphate (eATP) released by dying myofibers steadily activates muscle and immune purinergic receptors exerting dual negative effects: a direct damage linked to altered intracellular calcium homeostasis in muscle cells and an indirect toxicity through the "triggering" of the immune response and inhibition of regulatory T cells. Accordingly, pharmacological and genetic inhibition of eATP signaling improves the phenotype in models of chronic inflammatory diseases. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.008DOI Listing
November 2018
4 Reads

Loss of integrin αvβ8 in murine hepatocytes accelerates liver regeneration.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK; Lung Biology Center, Department of Medicine, University of California, San Francisco, California, USA. Electronic address:

Recent fate-mapping studies in mice have provided substantial evidence that mature adult hepatocytes are a major source of new hepatocytes following liver injury. In other systems, integrin αvβ8 has a major role in activating transforming growth factor beta (TGFβ), a potent inhibitor of hepatocyte proliferation. We hypothesized that depletion of hepatocyte integrin αvβ8 would increase hepatocyte proliferation and accelerate liver regeneration following injury. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.007DOI Listing
November 2018
6 Reads

The atypical chemokine receptor 2 limits progressive fibrosis after acute ischemic kidney injury.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address:

Following renal ischemia-reperfusion injury (IRI) resolution of inflammation allows tubular regeneration, whereas ongoing inflammatory injury mediated by infiltrating leukocytes leads to nephron loss and renal fibrosis, typical hallmarks of chronic kidney disease. The atypical chemokine receptor 2 (ACKR2) is a chemokine decoy receptor, that binds and scavenges inflammatory CC-chemokines and reduces local leukocyte accumulation. We hypothesized that ACKR2 limits leukocyte infiltration, inflammation, and fibrotic tissue remodeling after renal IRI, thus preventing progression to chronic kidney disease. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.016DOI Listing
November 2018
6 Reads

Elevated membrane cholesterol disrupts lysosomal degradation to induce Aβ accumulation: the potential mechanism underlying augmentation of Aβ pathology by type 2 diabetes mellitus.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Section of Cell Biology and Pathology, Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Morioka 7-430, Obu, Aichi 474-8511, Japan. Electronic address:

Endocytic membrane trafficking system is altered in the brains of early-stage Alzheimer disease (AD) patients, and endocytic disturbance affects the metabolism of β-amyloid protein (Aβ), a key molecule in AD pathogenesis. It is widely accepted that type 2 diabetes mellitus (T2DM) is one of the strongest risk factors for development of AD. Supporting this link, experimentally induced T2DM enhances AD pathology in various animal models. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183051
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http://dx.doi.org/10.1016/j.ajpath.2018.10.011DOI Listing
November 2018
6 Reads

Role of endoplasmic reticulum stress in pro-inflammatory cytokine-mediated inhibition of trophoblast invasion in placenta-related complications of pregnancy.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3EG. Electronic address:

Shallow extravillous trophoblast (EVT) invasion is central to the pathophysiology of many pregnancy complications. Invasion is mediated partially by matrix metalloproteinases (MMPs). MMP-2 is highly expressed in early pregnancy. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.015DOI Listing
November 2018
4 Reads

Hepatocyte Peroxisome Proliferator-Activated Receptor α Enhances Liver Regeneration after Partial Hepatectomy in Mice.

Am J Pathol 2018 Nov 16. Epub 2018 Nov 16.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Capital Medical University, Beijing, China. Electronic address:

Peroxisome proliferator-activated receptor α (PPARα) is a key nuclear receptor involved in the control of lipid homeostasis. In rodents, PPARα is also a potent hepatic mitogen. Hepatocyte-specific disruption of PPARα inhibits agonist-induced hepatocyte proliferation; however, little is known about the exact role of PPARα in partial hepatectomy (PHx)-induced liver regeneration. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183019
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http://dx.doi.org/10.1016/j.ajpath.2018.10.009DOI Listing
November 2018
6 Reads
4.591 Impact Factor

Fibrosis rescue improves cardiac function in dystrophin-deficient mice and Duchenne patient-specific cardiomyocytes by immunoproteasome modulation.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Universitá degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milan, Italy. Electronic address:

Patients affected by Duchenne muscular dystrophy (DMD) develop a progressive dilated cardiomyopathy characterized by inflammatory cell infiltration, necrosis, and cardiac fibrosis. Standard treatments consider the use of β-blockers and angiotensin-converting enzyme inhibitors that are symptomatic and unspecific towards DMD disease. Medications that target DMD cardiac fibrosis are in early stages of development. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.010DOI Listing
November 2018
3 Reads

Retinal Vascular Abnormalities and Microglia Activation in Mice with Deficiency in CYP46A1-Mediated Cholesterol Removal.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH. Electronic address:

CYP46A1 is the cytochrome P450 enzyme that converts cholesterol to 24-hydroxycholesterol, a cholesterol elimination product and a potent liver X receptor (LXR) ligand. We conducted retinal characterizations of Cyp46a1 mice that had normal fasting blood glucose levels but up to 1.8-fold increase in retinal cholesterol. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.013DOI Listing
November 2018
3 Reads

Tyrosinase is a novel endogenous regulator of developmental and inflammatory lymphangiogenesis.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Department of Ophthalmology, University of Cologne, Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany. Electronic address:

Lymphangiogenesis is critically involved in tissue fluid balance, graft rejection, and tumor metastasis. Endogenous regulation of lymphangiogenesis is poorly understood. Here we use the lymphatic vessel architecture at the limbal border of the normally avascular cornea, a quantitative trait under strong genetic influence, as a model system to identify new candidate genes regulating lymphangiogenesis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440173089
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http://dx.doi.org/10.1016/j.ajpath.2018.10.014DOI Listing
November 2018
3 Reads

Inflammatory Stress Causes N-Glycan Processing Deficiency in Ocular Autoimmune Disease.

Am J Pathol 2018 Nov 15. Epub 2018 Nov 15.

Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address:

High levels of proinflammatory cytokines have been associated with a loss of tissue function in ocular autoimmune diseases, but the basis for this relationship remains poorly understood. Here we investigate a new role for tumor necrosis factor α in promoting N-glycan-processing deficiency at the surface of the eye through inhibition of N-acetylglucosaminyltransferase expression in the Golgi. Using mass spectrometry, complex-type biantennary oligosaccharides were identified as major N-glycan structures in differentiated human corneal epithelial cells. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.012DOI Listing
November 2018
9 Reads

This Month in AJP.

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Am J Pathol 2019 Jan 15;189(1). Epub 2018 Nov 15.

The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.001DOI Listing
January 2019

A Novel Transgenic Rat Model of Robust Cerebral Microvascular Amyloid with Prominent Vasculopathy.

Am J Pathol 2018 Dec 13;188(12):2877-2889. Epub 2018 Nov 13.

George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, Rhode Island; Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island. Electronic address:

Accumulation of fibrillar amyloid β protein in blood vessels of the brain, a condition known as cerebral amyloid angiopathy (CAA), is a common pathology of elderly individuals, a prominent comorbidity of Alzheimer disease, and a driver of vascular cognitive impairment and dementia. Although several transgenic mouse strains have been generated that develop varying levels of CAA, consistent models of associated cerebral microhemorrhage and vasculopathy observed clinically have been lacking. Reliable preclinical animal models of CAA and microhemorrhage are needed to investigate the molecular pathogenesis of this condition. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183049
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http://dx.doi.org/10.1016/j.ajpath.2018.07.030DOI Listing
December 2018
4 Reads
4.591 Impact Factor

Nuclear Receptor 77: Key Functions and Therapeutic Prospects in Inflammation-Related Lung Diseases.

Am J Pathol 2018 Nov 7. Epub 2018 Nov 7.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. Electronic address:

The transcription factor nuclear receptor 77 (Nur77) belongs to the NR4A subfamily of nuclear hormone receptors. It features an atypical ligand-binding site that precludes canonical ligand binding, leading to the designation orphan nuclear receptor. However, recent studies show that small molecules can interact with the receptor and modulate its activity by inducing a conformational change in the Nur77 ligand-binding site. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.002DOI Listing
November 2018
3 Reads

Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders: Pathomechanisms and Treatment Development.

Am J Pathol 2018 Nov 7. Epub 2018 Nov 7.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Philadelphia, Pennsylvania; PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, Pennsylvania; Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.

Ectopic mineralization is a global problem and leading cause of morbidity and mortality. The pathomechanisms of ectopic mineralization are poorly understood. Recent studies on heritable ectopic mineralization disorders with defined gene defects have been helpful in elucidation of the mechanisms of ectopic mineralization in general. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.014DOI Listing
November 2018
5 Reads

The Accumulation of Heparan Sulfate S-Domains in Kidney Transthyretin Deposits Accelerates Fibril Formation and Promotes Cytotoxicity.

Am J Pathol 2018 Nov 7. Epub 2018 Nov 7.

Department of Biochemistry, Wakayama Medical University, Wakayama, Japan; Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. Electronic address:

The highly sulfated domains of heparan sulfate (HS), alias HS S-domains, are made up of repeated trisulfated disaccharide units [iduronic acid (2S)-glucosamine (NS, 6S)] and are selectively remodeled by extracellular endoglucosamine 6-sulfatases (Sulfs). Although HS S-domains are critical for signal transduction of several growth factors, their roles in amyloidoses are not yet fully understood. Herein, we found HS S-domains in the kidney of a patient with transthyretin amyloidosis. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.015DOI Listing
November 2018
4 Reads

Morphologic and Molecular Features of Breast Ductal Carcinoma In Situ.

Authors:
Souzan Sanati

Am J Pathol 2018 Oct 29. Epub 2018 Oct 29.

Department of Pathology and Immunology, Washington University in St Louis, St Louis, Missouri 63110. Electronic address:

Ductal carcinoma in situ (DCIS) encompasses a highly heterogeneous group of lesions that differ with regard to their clinical presentations, histologic features, biomarker profiles, genetic abnormalities, and potential for progression. DCIS is a non-obligatory precursor for invasive carcinoma. With the advent of screening mammography the incidence of DCIS has significantly increased. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.07.031DOI Listing
October 2018
1 Read

Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era: Current and Future Molecular-Based Testing.

Am J Pathol 2018 Oct 29. Epub 2018 Oct 29.

Historically, ductal carcinoma in situ (DCIS) of the breast has been managed aggressively with surgery and radiation due to a risk of progression to invasive ductal carcinoma. However, this treatment paradigm has been challenged by overtreatment concerns and evidence suggesting that DCIS can be stratified according to risk of recurrence, or risk of progression to invasive disease. Traditional methods of risk stratification include histologic grade and hormone receptor status. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.020DOI Listing
October 2018
3 Reads

Adult Hepatocytes Are Hedgehog-Responsive Cells in the Setting of Liver Injury: Evidence for Smoothened-Mediated Activation of NF-κB/Epidermal Growth Factor Receptor/Akt in Hepatocytes that Counteract Fas-Induced Apoptosis.

Am J Pathol 2018 Nov;188(11):2605-2616

Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address:

Although hedgehog (Hh) signaling pathway is inactive in adult healthy liver, it becomes activated during acute and chronic liver injury and, thus, modulates the reparative process and disease progression. We developed a novel mouse model with liver-specific knockout of Smoothened (Smo LKO), and animals were subjected to Fas-induced liver injury in vivo. Results showed that Smo deletion in hepatocytes enhances Fas-induced liver injury. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207910PMC
November 2018
7 Reads

This Month in AJP.

Authors:

Am J Pathol 2018 Dec 19;188(12):2703. Epub 2018 Oct 19.

The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. Read More

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December 2018

CAPS Mutations Are Potentially Associated with Unexplained Recurrent Pregnancy Loss.

Am J Pathol 2019 Jan 17;189(1):124-131. Epub 2018 Oct 17.

Graduate School of Peking Union Medical College, Beijing, China; Center for Genetics, National Research Institute for Family Planning, Beijing, China.

Recurrent pregnancy loss (RPL) is a major concern for women's reproductive health. Several studies have proved that genetics is a major factor leading to unexplained RPL, but the maternal pathogenic genes involved in RPL remain largely unknown. A consanguineous family, including the parents who were cousins and their three daughters who had been diagnosed as having nonsyndromic unexplained RPL, was recruited in this study. Read More

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January 2019
9 Reads

Reduced Terminal Complement Complex Formation in Mice Manifests in Low Bone Mass and Impaired Fracture Healing.

Am J Pathol 2019 Jan 17;189(1):147-161. Epub 2018 Oct 17.

Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany. Electronic address:

The terminal complement complex (TCC) is formed on activation of the complement system, a crucial arm of innate immunity. TCC formation on cell membranes results in a transmembrane pore leading to cell lysis. In addition, sublytic TCC concentrations can modulate various cellular functions. Read More

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January 2019

Prolyl Hydroxylase Domain-2 Protein Regulates Lipopolysaccharide-Induced Vascular Inflammation.

Am J Pathol 2019 Jan 17;189(1):200-213. Epub 2018 Oct 17.

Cardiovascular Research Institute, Section of Athero and Lipo, Department of Medicine, Baylor College of Medicine, Houston, Texas. Electronic address:

Acute lung injury and its more severe form, acute respiratory distress syndrome, are life-threatening respiratory disorders. Overwhelming pulmonary inflammation and endothelium disruption are commonly observed. Endothelial cells (ECs) are well recognized as key regulators in leukocyte adhesion and migration in response to bacterial infection. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.012DOI Listing
January 2019
6 Reads

Vector Tick Transmission Model of Spotted Fever Rickettsiosis.

Am J Pathol 2019 Jan 11;189(1):115-123. Epub 2018 Oct 11.

Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas.

Many aspects of rickettsial infections have been characterized, including pathogenic and immune pathways and mechanisms of rickettsial survival within the vertebrate host and tick vector. However, very few studies are focused on the complex pathogen-vector-host interactions during tick feeding. Therefore, our objective was to develop a tick transmission model of the spotted fever group of rickettsial infections to study the initial events in disease development. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.005DOI Listing
January 2019

AP39, a Modulator of Mitochondrial Bioenergetics, Reduces Antiangiogenic Response and Oxidative Stress in Hypoxia-Exposed Trophoblasts: Relevance for Preeclampsia Pathogenesis.

Am J Pathol 2019 Jan 11;189(1):104-114. Epub 2018 Oct 11.

Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address:

Although the cause of preeclampsia, a pregnancy complication with significant maternal and neonatal morbidity, has not been fully characterized, placental ischemia attributable to impaired spiral artery remodeling and abnormal secretion of antiangiogenic factors are thought to be important in the pathogenesis of the disease. Placental ischemia could impair trophoblast mitochondrial function and energy production, leading to the release of reactive oxygen species (ROS). ROS have been shown to stabilize hypoxia-inducible factor (HIF)-1α, which, in turn, may induce transcription of antiangiogenic factors, soluble fms-like tyrosine kinase 1 (sFLT1), and soluble endoglin in trophoblasts. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183027
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http://dx.doi.org/10.1016/j.ajpath.2018.09.007DOI Listing
January 2019
6 Reads

ALPK1 Expression Is Associated with Lymph Node Metastasis and Tumor Growth in Oral Squamous Cell Carcinoma Patients.

Am J Pathol 2019 Jan 11;189(1):190-199. Epub 2018 Oct 11.

Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan. Electronic address:

Oral squamous cell carcinoma (OSCC) is the most common malignant cancer, with high mortality rates in advanced stages. Recent studies have shown that the expression of ALPK1 mRNA and its inhibitory differentiation function are associated with cancer progression. However, the expression and clinicopathologic features of ALPK1 in OSCC remain unexplored. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.003DOI Listing
January 2019
2 Reads

Prenatal Intra-Amniotic Endotoxin Induces Fetal Gut and Lung Immune Responses and Postnatal Systemic Inflammation in Preterm Pigs.

Am J Pathol 2018 Nov 9;188(11):2629-2643. Epub 2018 Oct 9.

Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark; Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark; Department of Pediatrics, Odense University Hospital, Odense, Denmark. Electronic address:

Prenatal inflammation is a major risk for preterm birth and neonatal morbidity, but its effects on postnatal immunity and organ functions remain unclear. Using preterm pigs as a model for preterm infants, we investigated whether prenatal intra-amniotic (IA) inflammation modulates postnatal systemic immune status and organ functions. Preterm pigs exposed to IA lipopolysaccharide (LPS) for 3 days were compared with controls at birth and postnatal day 5 after formula feeding. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183029
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http://dx.doi.org/10.1016/j.ajpath.2018.07.020DOI Listing
November 2018
6 Reads
4.590 Impact Factor

Astroprincin (FAM171A1, C10orf38): A Regulator of Human Cell Shape and Invasive Growth.

Am J Pathol 2019 Jan 10;189(1):177-189. Epub 2018 Oct 10.

Department of Pathology, University of Helsinki, Helsinki, Finland. Electronic address:

Our group originally found and cloned cDNA for a 98-kDa type 1 transmembrane glycoprotein of unknown function. Because of its abundant expression in astrocytes, it was called the protein astroprincin (APCN). Two thirds of the evolutionarily conserved protein is intracytoplasmic, whereas the extracellular domain carries two N-glycosidic side chains. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183033
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http://dx.doi.org/10.1016/j.ajpath.2018.09.006DOI Listing
January 2019
5 Reads

Protein Degradation and the Pathologic Basis of Disease.

Am J Pathol 2019 Jan 10;189(1):94-103. Epub 2018 Oct 10.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

The abundance of any protein is determined by the balance of protein synthesis and protein degradation. Regulated protein degradation has emerged as a powerful means of precisely controlling individual protein abundance within cells and is largely mediated by the ubiquitin-proteasome system (UPS). By controlling the levels of key regulatory proteins, the UPS contributes to nearly every aspect of cellular function. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183060
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http://dx.doi.org/10.1016/j.ajpath.2018.09.004DOI Listing
January 2019
1 Read

miR-135a-5p Functions as a Glioma Proliferation Suppressor by Targeting Tumor Necrosis Factor Receptor-Associated Factor 5 and Predicts Patients' Prognosis.

Am J Pathol 2019 Jan 10;189(1):162-176. Epub 2018 Oct 10.

Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin, People's Republic of China; Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, People's Republic of China. Electronic address:

miR-135a-5p has been reported as a tumor suppressor in several extracranial tumors. However, its exact roles in gliomagenesis and relevance to the patients' prognoses are largely unknown. Herein, we detected the miR-135a-5p and tumor necrosis factor receptor-associated factor 5 (TRAF5) levels in 120 human glioma specimens and 20 nontumoral brain tissues; we found the miR-135a-5p level decreased, whereas the TRAF5 level increased, with the elevation of glioma grade. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.019DOI Listing
January 2019
4 Reads
4.590 Impact Factor

Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts.

Am J Pathol 2018 Dec 28;188(12):2890-2901. Epub 2018 Sep 28.

Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland; Turku Center for Disease Modeling, University of Turku, Turku, Finland; Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address:

The role of adrenal androgens as drivers for castration-resistant prostate cancer (CRPC) growth in humans is generally accepted; however, the value of preclinical mouse models of CRPC is debatable, because mouse adrenals do not produce steroids activating the androgen receptor. In this study, we confirmed the expression of enzymes essential for de novo synthesis of androgens in mouse adrenals, with high intratissue concentration of progesterone (P) and moderate levels of androgens, such as androstenedione, testosterone, and dihydrotestosterone, in the adrenal glands of both intact and orchectomized (ORX) mice. ORX alone had no effect on serum P concentration, whereas orchectomized and adrenalectomized (ORX + ADX) resulted in a significant decrease in serum P and in a further reduction in the low levels of serum androgens (androstenedione, testosterone, and dihydrotestosterone), measured by mass spectrometry. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.07.029DOI Listing
December 2018
1 Read

Functional Role of microRNAs in the Progression of Breast Ductal Carcinoma in situ.

Am J Pathol 2018 Sep 28. Epub 2018 Sep 28.

Department of Pathology at the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States. Electronic address:

microRNAs (miRNAs) are small RNAs that influence gene expression by targeting messenger RNAs (mRNAs). Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.06.025DOI Listing
September 2018
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Human Placenta Expresses α-Adrenergic Receptors and May Be Implicated in Pathogenesis of Preeclampsia and Fetal Growth Restriction.

Am J Pathol 2018 Dec 29;188(12):2774-2785. Epub 2018 Sep 29.

Center for Perinatal Research, Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio. Electronic address:

α-Adrenergic receptors (αARs) are G-protein-coupled receptors involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. We examined placental expression and function of αAR subtypes in women with severe preeclampsia (sPE) with and without intrauterine growth restriction (IUGR). Placental biopsies were analyzed from 52 women with i) sPE (n = 8); ii) sPE + IUGR (n = 9); iii) idiopathic IUGR (n = 8); iv) idiopathic preterm birth (n = 16); and v) healthy term controls (n = 11). Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284550PMC
December 2018

Reversing CXCL10 Deficiency Ameliorates Kidney Disease in Diabetic Mice.

Am J Pathol 2018 Dec 29;188(12):2763-2773. Epub 2018 Sep 29.

Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada. Electronic address:

The excessive accumulation of extracellular matrix material in the kidney is a histopathologic hallmark of diabetic kidney disease that correlates closely with declining function. Although considerable research has focused on the role of profibrotic factors, comparatively little attention has been paid to the possibility that a diminution in endogenous antifibrotic factors may also contribute. Among the latter, the ELR CXC chemokines, CXCL9, CXCL10, and CXCL11, have been shown to provide a stop signal to prevent excessive fibrosis. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.017DOI Listing
December 2018

High-Temperature Requirement A 1 Causes Photoreceptor Cell Death in Zebrafish Disease Models.

Am J Pathol 2018 Dec 29;188(12):2729-2744. Epub 2018 Sep 29.

Department of Ophthalmology, Osaka University Medical School, Suita, Japan.

Age-related macular degeneration (AMD) is an important cause of blindness. It is characterized by a retinal pigment epithelium (RPE) disorder that leads to death of photoreceptor cells (PRCs). AMD has a strong genetic association with high-temperature requirement A 1 (HTRA1). Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.012DOI Listing
December 2018
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Intrauterine Programming of Glucocorticoid-Insulin-Like Growth Factor-1 Axis-Mediated Developmental Origin of Osteoporosis Susceptibility in Female Offspring Rats with Prenatal Caffeine Exposure.

Am J Pathol 2018 Dec 28;188(12):2863-2876. Epub 2018 Sep 28.

Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, People's Republic of China; Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, People's Republic of China. Electronic address:

Epidemiologic investigations suggest that excessive intake of caffeine during pregnancy is one of the risk factors for osteoporosis in adult offspring. However, the phenomena and mechanisms have remained obscure. This study found that prenatal caffeine exposure (PCE) leads to persistent bone dysplasia in gestational day 20 and postnatal week 12 offspring rats and increases the susceptibility to osteoporosis in postnatal week 28 offspring rats. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.008DOI Listing
December 2018

Colonoscopic-Guided Pinch Biopsies in Mice as a Useful Model for Evaluating the Roles of Host and Luminal Factors in Colonic Inflammation.

Am J Pathol 2018 Dec 28;188(12):2811-2825. Epub 2018 Sep 28.

Department of Medicine, Weill Cornell Medicine, New York, New York. Electronic address:

Colonic inflammation, a hallmark of inflammatory bowel disease, can be influenced by host intrinsic and extrinsic factors. There continues to be a need for models of colonic inflammation that can both provide insights into disease pathogenesis and be used to investigate potential therapies. Herein, we tested the utility of colonoscopic-guided pinch biopsies in mice for studying colonic inflammation and its treatment. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.016DOI Listing
December 2018
9 Reads

Enteroviral Infection Leads to Transactive Response DNA-Binding Protein 43 Pathology in Vivo.

Am J Pathol 2018 Dec 28;188(12):2853-2862. Epub 2018 Sep 28.

Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons in the cerebral cortex, brainstem, and spinal cord, leading to progressive paralysis and eventual death. Approximately 95% of all ALS cases are sporadic without known causes. Enteroviruses have been suspected to play a role in ALS because of their ability to target motor neurons and to cause muscle weakness and paralysis. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.08.013DOI Listing
December 2018
35 Reads