19,021 results match your criteria Am. J. Pathol.[Journal]


ASSOCIATION OF INITIAL VIRAL LOAD IN SARS-CoV-2 PATIENTS WITH OUTCOME AND SYMPTOMS.

Am J Pathol 2020 Jul 3. Epub 2020 Jul 3.

Department of Pathology, NYU Langone Health, New York City, NY; Department of Dermatology, NYU Langone Health, New York City, NY. Electronic address:

The dynamics of viral load (VL) of the 2019 novel coronavirus (SARS-CoV-2) and its association with different clinical parameters remain poorly characterized in the United States patient population. Herein we investigate associations between VL and parameters such as severity of symptoms, disposition (admission vs direct discharge), length of hospitalization, and admission to the intensive care unit, length of need for oxygen support and overall survival in a cohort of 205 patients from a tertiary care center in New York City. VL was determined using q-PCR and Log10 transformed for normalization. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.07.001DOI Listing

HEPATIC STELLATE CELL-SPECIFIC PLATELET-DERIVED GROWTH FACTOR RECEPTOR α LOSS REDUCES FIBROSIS AND PROMOTES REPAIR FOLLOWING HEPATOCELLULAR INJURY.

Am J Pathol 2020 Jun 29. Epub 2020 Jun 29.

Department of Pathology, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address:

Platelet-derived growth factor receptor α (PDGFRα) plays roles in cell survival, proliferation, and differentiation, however its function in chronic liver injury sequelae like fibrosis is unknown. Hepatic stellate cells (HSCs), the primary mediators of fibrosis, undergo activation, which entails differentiation to myofibroblasts, proliferation, migration and collagen deposition, partially in response to PDGFs. To examine the role of PDGFRα in HSCs, we bred lecithin retinol acyltransferase (Lrat)-Cre recombinase and Pdgfra-floxed mice to generate Lrat-Cre Pdgfra-/- (KO) animals which were subjected to chronic liver injury through carbon tetrachloride (CCl) treatment, bile duct ligation (BDL), and 0. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.06.006DOI Listing

Structural Integrity of the Alveolar-Capillary Barrier in Cynomolgus Monkeys Challenged with Fully Virulent and Toxin-Deficient Strains of Bacillus Anthracis.

Am J Pathol 2020 Jun 26. Epub 2020 Jun 26.

Laboratory of Biochemistry and Vascular Biology, Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration (FDA), Silver Spring, Maryland, USA, 20993.

Inhalational anthrax, a disease caused by inhaling Bacillus anthracis spores, leads to respiratory distress, vascular leakage, high-level bacteremia, and often death within days. Anthrax lethal toxin (LT) and edema toxin (ET), which are composed of protective antigen (PA) plus either lethal factor (LF) or edema factor (EF), respectively, play an important yet incompletely defined role in the pulmonary pathophysiology. To better understand their contribution, we examined the structural integrity of the alveolar capillary barrier in archival formalin-fixed lungs of cynomolgus monkeys challenged with the fully virulent B. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.06.007DOI Listing

The Renin-Angiotensin-Aldosterone System (RAAS) is One of the Effectors by Which Vascular Endothelial Growth Factor (VEGF)/anti-VEGF Controls the Endothelial Cell Barrier.

Am J Pathol 2020 Jun 23. Epub 2020 Jun 23.

University of Illinois at Chicago Department of Ophthalmology & Visual Sciences; Department of Physiology and Biophysics 1905 West Taylor St Chicago, IL 60612. Electronic address:

Leakage of retinal blood vessels, which is an essential element of diabetic retinopathy (DR), is driven by chronic elevation of vascular endothelial growth factor (VEGF). VEGF quickly relaxes the endothelial cell barrier by triggering signaling events that post-translationally modify preexisting components of intercellular junctions. VEGF also changes expression of genes, which are known to regulate barrier function. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.06.004DOI Listing

Characterization of tumor blood vasculature expression of human invasive bladder cancer by laser capture microdissection and transcriptional profiling.

Am J Pathol 2020 Jun 22. Epub 2020 Jun 22.

Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. Electronic address:

Tumor-associated blood vessels differ from normal vessels and play key roles in tumor progression. We aimed at identifying biomolecules that are differentially expressed in human bladder cancer-associated blood vessels in order to find novel biomarkers and mechanisms involved in tumor-associated angiogenesis. We compared the transcriptome of tumor blood vasculature from human invasive bladder carcinoma (I-BLCA) and normal bladder tissue vasculature and performed differential expression and unsupervised hierarchical clustering analyses. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.020DOI Listing

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Am J Pathol 2020 Jun 20. Epub 2020 Jun 20.

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.2020.06.003DOI Listing

Retraction notice to Plexin-B1 and Semaphorin 4D Cooperate to Promote Perineural Invasion in a RhoA/ROK-Dependent Manner Am J Pathol 180 (2012) 1232-1242.

Am J Pathol 2020 Jul;190(7):1581

Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, Maryland; Marlene and Stuart Greenebaum Cancer Center, Baltimore, Maryland.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.004DOI Listing

This Month in AJP.

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Am J Pathol 2020 Jan 22;190(1). Epub 2019 Nov 22.

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.2019.11.001DOI Listing
January 2020

Acoustic trauma causes cochlear pericyte-to-myofibroblast-like cell transformation and vascular degeneration, and transplantation of new pericytes prevents vascular atrophy.

Am J Pathol 2020 Jun 17. Epub 2020 Jun 17.

Oregon Hearing Research Center, Department of Otolaryngology/Head & Neck Surgery, Oregon Health & Science University, Portland, OR, USA. Electronic address:

Acoustic trauma disrupts cochlear blood flow and damages sensory hair cells. Damage and regression of capillaries after acoustic trauma have long been observed, but the underlying mechanism of pathology has not been understood. We show here that loud sound causes change of phenotype from NG2+/α-SMA- to NG2+/α-SMA+ in some pericytes (PCs) on strial capillaries that is strongly associated with up-regulation of TGF-β1. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.019DOI Listing

Resolvin E1 Reduces Leukotriene B-Induced Intracellular Calcium Increase and Mucin Secretion in Rat Conjunctival Goblet Cells.

Am J Pathol 2020 Jun 16. Epub 2020 Jun 16.

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

Leukotriene B (LTB) is a major proinflammatory mediator important in host defense whereas resolvins (Rvs) are produced during the resolution phase of inflammation. We determined the actions of both RvE1 and RvD1 on LTB-induced responses of goblet cells cultured from rat conjunctiva. The responses measured were an increase in the intracellular [Ca] ([Ca]) and high molecular weight glycoprotein secretion. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.06.001DOI Listing

Up-regulation of Matrix Metalloproteinase-2 by Scleral Monocyte-derived Macrophages Contributes to Myopia Development.

Am J Pathol 2020 Jun 15. Epub 2020 Jun 15.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China. Electronic address:

Myopia is a leading cause of visual impairment worldwide. This sight compromising condition is associated with scleral thinning, extracellular matrix (ECM) remodeling and inappropriate optical axial length elongation. Even though macrophages are present in the sclera, their involvement in this condition is unknown. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.06.002DOI Listing

Perivascular fibro-adipogenic progenitor tracing during post-traumatic osteoarthritis.

Am J Pathol 2020 Jun 10. Epub 2020 Jun 10.

Department of Pathology, Johns Hopkins University, Ross Research Building, Room 524A, 720 Rutland Avenue, Baltimore, MD, 21205, United States; UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA, 90095. Electronic address:

Perivascular mural cells surround capillaries and microvessels, and have diverse regenerative or fibrotic functions after tissue injury. Subsynovial fibrosis is a well known pathologic feature of osteoarthritis, yet transgenic animals to visualize perivascular cell contribution to fibrosis during arthritic changes have not been developed. Here, inducible Pdgfra-CreER reporter mice were subjected to joint destabilization surgery in order to induce arthritic changes, and cell lineage traced over an 8 week period with a focus on the joint-associated fat pad. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.017DOI Listing

The membrane protein sortilin can be targeted to inhibit pancreatic cancer cell invasion.

Am J Pathol 2020 Jun 8. Epub 2020 Jun 8.

School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia. Electronic address:

Pancreatic cancer has a dismal prognosis and there is no targeted therapy against this malignancy. The neuronal membrane protein sortilin is emerging as a regulator of cancer cell development, but its expression and impact in pancreatic cancer is unknown. In this study, we found that sortilin expression was higher in pancreatic cell lines vs normal pancreatic ductal epithelial cells, as demonstrated by Western blot and mass spectrometry. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.018DOI Listing

Lung and eye disease develop concurrently in supplemental oxygen-exposed neonatal mice.

Am J Pathol 2020 Jun 8. Epub 2020 Jun 8.

Leukocyte Signalling Laboratory, Department of Immunology and Pathology, Central Clinical School, Monash University, 89 Commercial Road, Melbourne, Victoria 3004, Australia. Electronic address:

Bronchopulmonary dysplasia and retinopathy of prematurity are two debilitating disorders that develop in preterm infants exposed to supplemental oxygen to prevent respiratory failure. Both can lead to lifelong disabilities such as chronic obstructive pulmonary disease and vision loss. Due to the lack of a standard experimental model of coincident disease, the underlying associations between BPD and ROP are not well characterized. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.016DOI Listing

This Month in AJP.

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Am J Pathol 2020 06 21;190(6):1137. Epub 2020 Apr 21.

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.2020.04.002DOI Listing

Clinicopathological significance of nerves in esophageal cancer.

Am J Pathol 2020 May 29. Epub 2020 May 29.

School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW 2305, Australia. Electronic address:

Nerves are emerging promoters of cancer progression, but the innervation of esophageal cancer and its clinicopathological significance remain unclear. In this study, nerves were investigated by immunohistochemistry in a cohort of 260 esophageal cancers, including 40 matched lymph node metastases and 137 normal adjacent esophageal tissues. Nerves were detected in 38% of esophageal cancers and were more associated with squamous cell carcinomas (p=0. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.012DOI Listing

Filoviruses Infect Rhesus Macaque Synoviocytes in Vivo and Primary Human Synoviocytes in Vitro.

Am J Pathol 2020 May 29. Epub 2020 May 29.

Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland.

The most commonly reported symptom of post-Ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent Ebola virus infection has not been well characterized in human patients or animal models. Through the use of immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by Ebola virus/Kikwit, Ebola virus/Makona-C05, and Marburg virus/Angola in the rhesus macaque model. Furthermore, we found through histologic analysis, immunohistochemistry, RNAscope in situ hybridization, and transmission electron microscopy that synoviocytes of the stifle, shoulder, and hip are a target for mouse-adapted Ebola virus/Yambuku-Mayinga infection during acute disease in rhesus macaques. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.013DOI Listing
May 2020
4.591 Impact Factor

M2 macrophages and phenotypic modulation of intestinal smooth muscle cells characterize Inflammatory stricture formation in the rat.

Am J Pathol 2020 May 29. Epub 2020 May 29.

Gastrointestinal diseases Research Unit and Queen's University, Kingston, ON K7L 2V7, Canada. Electronic address:

The progression of Crohn's disease to intestinal stricture formation is poorly controlled and the pathogenesis is unclear, although increased smooth muscle mass is present. Earlier, stricture formation was described in in the rat model of TNBS-induced colitis, now re-examined for early cellular features of stricture development. While inflammation of the mid-descending colon typically resolved, a subset showed characteristic stricturing by Day 16, with an inflammatory infiltrate in the neuromuscular layers that included eosinophils, CD3-positive T cells and CD68-positive macrophages. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.015DOI Listing

Long Noncoding RNA MEG3 Inhibits Apoptosis of Retinal Pigment Epithelium Cells Induced by High Glucose via the miR-93/Nrf2 Axis.

Am J Pathol 2020 May 28. Epub 2020 May 28.

Department of Ophthalmology, Provincial People's Hospital Affiliated to Nanchang University, Nanchang, P.R. China. Electronic address:

Diabetic retinopathy (DR) is the leading cause of visual impairment in developed nations. Though plasma miR-93 is associated with the risk of DR, the function and regulatory mechanism of miR-93 during DR remains unclear. Blood samples were collected from 12 DR patients and 12 healthy controls. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.008DOI Listing
May 2020
4.591 Impact Factor

Restoration of Regulatory T-cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor.

Am J Pathol 2020 May 29. Epub 2020 May 29.

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

Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.011DOI Listing

Genetic Deletion of Galectin-3 Altered the Temporal Evolution of Macrophage Infiltration and Healing Affecting the Cardiac Remodeling and Function after Myocardial Infarction in Mice.

Am J Pathol 2020 May 28. Epub 2020 May 28.

Facultad de Medicina-CONICET, Departamento de Patología, Instituto de Fisiopatología Cardiovascular, Buenos Aires, Argentina; Laboratorio de Patología Cardiovascular Experimental e Hipertensión Arterial, Instituto de Investigaciones Biomédicas, Universidad Católica Argentina-CONICET, Buenos Aires, Argentina. Electronic address:

We studied the role of galectin-3 (Gal-3) in the expression of alternative activation markers (M2) on macrophage, cytokine expression, and fibrosis through the temporal evolution of healing, ventricular remodeling, and function after myocardial infarction (MI) in mice. Male C57BL/6J and Gal-3 knockout mice were subjected to permanent coronary artery ligation or sham for 1 and 4 weeks. We studied i) mortality, ii) macrophage infiltration and expression of markers of alternative activation at the infarct zone, iii) cytokine expression, iv) matrix metalloproteinase 2 activity, v) fibrosis, and vi) cardiac function and remodeling. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.010DOI Listing

Platelet c-type lectin-like receptor reduces cholestatic liver injury in mice.

Am J Pathol 2020 May 28. Epub 2020 May 28.

First Department of Surgery, Faculty of Medicine University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, Japan 409-3898.

Cholestatic liver injury leads to liver dysfunction. The available evidence suggests that platelets can either promote or reduce liver injury and fibrosis. We focused on the functions of the c-type lectin-like receptor (CLEC-2), a new special platelet receptor that binds with podoplanin activating platelets. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.009DOI Listing

Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma.

Am J Pathol 2020 May 27. Epub 2020 May 27.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York; Center for Molecular and Translational Human Infectious Diseases, Houston Methodist Research Institute, Houston, Texas. Electronic address:

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for >100 years. Patients (n = 25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28, 2020, to April 14, 2020. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251400PMC

Rare Pulmonary Connective Tissue Type Mast Cells Regulate Lung Endothelial Cell Angiogenesis.

Am J Pathol 2020 May 22. Epub 2020 May 22.

Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, University of Rochester, Rochester, New York; Department of Biomedical Genetics, Aab Cardiovascular Research Institute, University of Rochester, Rochester, New York. Electronic address:

Within the human lung, mast cells typically reside adjacent to the conducting airway and assume a mucosal phenotype (MC). In rare pathologic conditions, connective tissue phenotype mast cells (MCs) can be found in the lung parenchyma. MCs accumulate in the lungs of infants with severe bronchopulmonary dysplasia, a chronic lung disease associated with preterm birth, which is characterized by pulmonary vascular dysmorphia. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.017DOI Listing

Beyond Stiffness: Collagen Signaling in Pancreatic Cancer and Pancreas Regeneration.

Am J Pathol 2020 May 22. Epub 2020 May 22.

Division of Surgical Oncology, Department of Surgery, and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

This commentary highlights the article by Ruggeri et al that reports the importance of discoidin domain receptor 1 in tissue homeostasis in pancreatic injury and pancreatic ductal adenocarcinoma pathogenesis. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.05.005DOI Listing
May 2020
4.591 Impact Factor

This Month in AJP.

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Am J Pathol 2020 Jul 19;190(7):1355. Epub 2020 May 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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http://dx.doi.org/10.1016/j.ajpath.2020.05.003DOI Listing

Corrections.

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Am J Pathol 2020 Jul 17;190(7):1580. Epub 2020 May 17.

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http://dx.doi.org/10.1016/j.ajpath.2020.05.001DOI Listing

Correction.

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Am J Pathol 2020 Jul 17;190(7):1580. Epub 2020 May 17.

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http://dx.doi.org/10.1016/j.ajpath.2020.05.002DOI Listing

TRAF3 Modulates Cartilage Degradation Through Its Suppression of Interleukin 17 Signaling.

Am J Pathol 2020 May 19. Epub 2020 May 19.

Department of Orthopedic Surgery, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; The Key Laboratory of Stem Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address:

Interleukin 17A (IL-17A) plays a critical role in the pathogenesis of autoimmune diseases through driving inflammatory cascades. However, the role of IL-17 in osteoarthritis (OA) is not well understood. Tumor necrosis factor-receptor-associated factor 3 (TRAF3) is a receptor proximal negative regulator of IL-17 signaling. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.016DOI Listing

High Levels of Chromosomal Copy Number Alterations and TP53 Mutations Correlate with Poor Outcome in Younger Breast Cancer Patients.

Am J Pathol 2020 May 13. Epub 2020 May 13.

Genetics Branch, National Cancer Institute, NIH, Bethesda, Maryland. Electronic address:

Prognosis in young patients with breast cancer is generally poor, yet considerable differences in clinical outcomes between individual patients exist. To understand the genetic basis of the disparate clinical courses, we collected tumors from 34 younger women, 17 with good and 17 with poor outcomes, as determined by disease-specific survival during a follow-up period of 17 years. The clinicopathologic parameters of the tumors were complemented with DNA image cytometry profiles, enumeration of copy numbers of eight breast cancer genes by multicolor fluorescence in situ hybridization, and targeted sequence analysis of 563 cancer genes. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.015DOI Listing

A Single Amino Acid Replacement in Penicillin-Binding Protein 2X in Streptococcus pyogenes Significantly Increases Fitness on Subtherapeutic Benzylpenicillin Treatment in a Mouse Model of Necrotizing Myositis.

Am J Pathol 2020 May 11. Epub 2020 May 11.

Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas; Clinical Microbiology Laboratory, Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York. Electronic address:

Invasive strains of Streptococcus pyogenes with significantly reduced susceptibility to β-lactam antibiotics have been recently described. These reports have caused considerable concern in the international infectious disease, medical microbiology, and public health communities because S. pyogenes has remained universally susceptible to β-lactam antibiotics for 70 years. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.014DOI Listing
May 2020
4.591 Impact Factor

The Unraveling: Cardiac and Musculoskeletal Defects and Their Role in Common Alzheimer Disease Morbidity and Mortality.

Am J Pathol 2020 May 11. Epub 2020 May 11.

Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana; Section of Cardiology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address:

Alzheimer disease (AD) is characterized by deterioration of cognitive capabilities, and an estimated 44 million people worldwide are living with the disease. Beyond memory deficits, the most common AD co-morbidities include swallowing defects (muscle), fractures (bone, muscle), and heart failure. The underlying causes of these co-morbidities and their role in AD pathophysiology are currently unknown. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.013DOI Listing
May 2020
4.591 Impact Factor

CD4 T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

Am J Pathol 2020 May 8. Epub 2020 May 8.

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

Retinal ischemic events as a result of occlusion of the ocular vasculature share similar causes of central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell-mediated responses, is thought to be intricately involved, but the exact roles remain elusive. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.011DOI Listing

This Month in AJP.

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Am J Pathol 2020 05 31;190(5):917. Epub 2020 Mar 31.

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.2020.03.002DOI Listing

Galectin-9 Is a Novel Regulator of Epithelial Restitution.

Am J Pathol 2020 May 4. Epub 2020 May 4.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia; Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Increasingly, the ß-galactoside binding lectins, termed galectins, are being recognized as critical regulators of cell function and organismal homeostasis. Within the context of the mucosal surface, galectins are established regulators of innate and adaptive immune responses, microbial populations, and several critical epithelial functions, including cell migration, proliferation, and response to injury. However, given their complex tissue distribution and expression patterns, the role within specific processes remains poorly understood. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.010DOI Listing

Neurodegeneration and Motor Deficits in the Absence of Astrogliosis upon Transgenic Mutant TDP-43 Expression in Mature Mice.

Am J Pathol 2020 May 1. Epub 2020 May 1.

Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing and fatal disease characterized by muscular atrophy due to loss of upper and lower motor neurons. Pathogenic mutations in the TARDBP gene that encodes TDP-43 have been identified in familial ALS. We have previously reported transgenic mice with neuronal expression of human TDP-43 carrying the pathogenic A315T mutation (iTDP-43 mice) using a tetracycline-controlled inducible promotor system. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.009DOI Listing

L1CAM-ILK-YAP Mechanotransduction Drives Proliferative Activity of Epithelial Cells in Middle Ear Cholesteatoma.

Am J Pathol 2020 Apr 29. Epub 2020 Apr 29.

Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.

Middle-ear cholesteatoma (cholesteatoma) is a chronic otitis media with an enhanced proliferation of epithelial cells. Negative pressure in the middle ear is thought to be important for the etiology of cholesteatoma. However, the mechanism of cholesteatoma formation remains unclear. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.007DOI Listing

Computer-Aided Pathologic Diagnosis of Nasopharyngeal Carcinoma Based on Deep Learning.

Am J Pathol 2020 Apr 29. Epub 2020 Apr 29.

Department of Pathology, Cancer Research Institute, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Diseases, Shenzhen, China. Electronic address:

The pathologic diagnosis of nasopharyngeal carcinoma (NPC) by various different pathologists is often inefficient and inconsistent. We have therefore introduced a deep learning algorithm into this process and compared the performance of the model with that of three pathologists with different levels of experience to demonstrate its clinical value. In this retrospective study, a total of 1970 whole slide images of 731 cases were collected and divided into training, validation, and testing sets. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.008DOI Listing
April 2020
4.591 Impact Factor

The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes.

Am J Pathol 2020 05 27;190(5):1080-1094. Epub 2020 Apr 27.

Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.01.011DOI Listing

Mouse Models of Heart Failure with Preserved or Reduced Ejection Fraction.

Am J Pathol 2020 Apr 25. Epub 2020 Apr 25.

Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee. Electronic address:

Heart failure (HF) is a chronic, complex condition with increasing incidence worldwide, necessitating the development of novel therapeutic strategies. This has led to the current clinical strategies, which only treat symptoms of HF without addressing the underlying causes. Multiple animal models have been developed in an attempt to recreate the chronic HF phenotype that arises following a variety of myocardial injuries. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.006DOI Listing

Transcriptomic Characterization of Human Choroidal Neovascular Membranes Identifies Calprotectin as a Novel Biomarker for Patients with Age-Related Macular Degeneration.

Am J Pathol 2020 Apr 24. Epub 2020 Apr 24.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg. Electronic address:

Recent studies deciphering the transcriptional profile of choroidal neovascularization (CNV) in body donor eyes with neovascular age-related macular degeneration are limited by the time span from death to preservation and the associated 5'-RNA degradation. This study therefore used CNV and control specimens that were formalin-fixed and paraffin-embedded immediately after surgical extraction and analyzed them by a 3'-RNA sequencing approach. Transcriptome profiles were analyzed to estimate content of immune and stromal cells and to define disease-associated gene signatures by using statistical and bioinformatics methods. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.004DOI Listing

Trp53 Mutation in Keratin 5 (Krt5)-Expressing Basal Cells Facilitates the Development of Basal Squamous-Like Invasive Bladder Cancer in the Chemical Carcinogenesis of Mouse Bladder.

Am J Pathol 2020 Apr 24. Epub 2020 Apr 24.

Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

The biological processes of urothelial carcinogenesis are not fully understood, particularly regarding the relationship between specific genetic events, cell of origin, and molecular subtypes of subsequent tumors. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced mouse bladder cancer is widely accepted as a useful model that recapitulates the pathway of human bladder tumorigenesis from dysplasia to invasive cancer via carcinoma in situ. However, the long and variable time of tumorigenesis often hinders efficient preclinical or translational research. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.005DOI Listing

Discoidin Domain Receptor 1 (DDR1) Is Necessary for Tissue Homeostasis in Pancreatic Injury and Pathogenesis of Pancreatic Ductal Adenocarcinoma.

Am J Pathol 2020 Apr 24. Epub 2020 Apr 24.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Surgery, University of Michigan, Ann Arbor, Michigan. Electronic address:

Pancreatic ductal adenocarcinoma (PDA) and chronic pancreatitis are characterized by a dense collagen-rich desmoplastic reaction. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagens that can regulate cell proliferation, migration, adhesion, and remodeling of the extracellular matrix. To address the role of DDR1 in PDA, Ddr1-null (Ddr) mice were crossed with the Kras; Trp53; Ptf1a (KPC) model of metastatic PDA. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.03.020DOI Listing

Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases.

Am J Pathol 2020 Apr 24. Epub 2020 Apr 24.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

Maintaining oxygen homeostasis is a most basic cellular process for adapting physiological oxygen variations, and its abnormality typically leads to various disorders in the human body. The key molecules of the oxygen-sensing system include the transcriptional regulator hypoxia-inducible factor (HIF), which controls a wide range of oxygen responsive target genes (eg, EPO and VEGF), the certain members of the oxygen/2-oxoglutarate-dependent dioxygenases, including the HIF proline hydroxylase (PHD, alias EglN), and an E3 ubiquitin ligase component for HIF destruction called von Hippel-Lindau. In this review, we summarize the physiological role and highlight the pathologic function for each protein of the oxygen-sensing system. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.003DOI Listing

Podocytes: The Role of Lysosomes in the Development of Nephrotic Syndrome.

Am J Pathol 2020 06 16;190(6):1172-1174. Epub 2020 Apr 16.

Nephrology Unit, Department of Emergency and Transplant Organs, University Aldo Moro of Bari, Bari, Italy. Electronic address:

This commentary highlights the article by Li et al that links ceramide accumulation in podocytes to cellular damage and nephrotic syndrome. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.04.001DOI Listing

Down-Regulation of Mitochondrial Metabolism after Tendon Release Primes Lipid Accumulation in Rotator Cuff Muscle.

Am J Pathol 2020 Jul 16;190(7):1513-1529. Epub 2020 Apr 16.

Department of Orthopedics, Balgrist University Hospital, Zurich, Switzerland.

Atrophy and fat accumulation are debilitating aspects of muscle diseases and are rarely prevented. Using a vertical approach combining anatomic techniques with omics methodology in a tenotomy-induced sheep model of rotator cuff disease, we tested whether mitochondrial dysfunction is implicated in muscle wasting and perturbed lipid metabolism, speculating that both can be prevented by the stimulation of β-oxidation with l-carnitine. The infraspinatus muscle lost 22% of its volume over the first 6 weeks after tenotomy before the area-percentage of lipid increased from 8% to 18% at week 16. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.03.019DOI Listing

An in Situ Atlas of Mitochondrial DNA in Mammalian Tissues Reveals High Content in Stem and Proliferative Compartments.

Am J Pathol 2020 Jul 15;190(7):1565-1579. Epub 2020 Apr 15.

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

Mitochondria regulate ATP production, metabolism, and cell death. Alterations in mitochondrial DNA (mtDNA) sequence and copy number are implicated in aging and organ dysfunction in diverse inherited and sporadic diseases. Because most measurements of mtDNA use homogenates of complex tissues, little is known about cell-type-specific mtDNA copy number heterogeneity in normal physiology, aging, and disease. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.03.018DOI Listing

Mesenchymal Stem Cell/Multipotent Stromal Cell Augmentation of Wound Healing: Lessons from the Physiology of Matrix and Hypoxia Support.

Am J Pathol 2020 Jul 12;190(7):1370-1381. Epub 2020 Apr 12.

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania; R&D Service, VA Pittsburgh Health System, Pittsburgh, Pennsylvania; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Cutaneous wounds requiring tissue replacement are often challenging to treat and result in substantial economic burden. Many of the challenges inherent to therapy-mediated healing are due to comorbidities of disease and aging that render many wounds as chronic or nonhealing. Repeated failure to resolve chronic wounds compromises the reserve or functioning of localized reparative cells. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.03.017DOI Listing

Aged Mice Exhibit Severe Exacerbations of Dry Eye Disease with an Amplified Memory Th17 Cell Response.

Am J Pathol 2020 Jul 11;190(7):1474-1482. Epub 2020 Apr 11.

Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts. Electronic address:

The prevalence as well as the severity of dry eye disease increase with age. Memory T helper 17 (Th17) cells (CD4IL-17ACD44) drive the chronic and relapsing course of dry eye disease. Here, we investigated the contribution of memory Th17 cells to age-related dry eye disease, and evaluated memory Th17 cell depletion with anti-IL-15 antibody as a strategy to abrogate the severe exacerbations of dry eye disease observed in aged mice. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.03.016DOI Listing

Phosphorylated Ezrin (Thr567) Regulates Hippo Pathway and Yes-Associated Protein (Yap) in Liver.

Am J Pathol 2020 Jul 11;190(7):1427-1437. Epub 2020 Apr 11.

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

The activation of CD81 [the portal of entry of hepatitis C virus (HCV)] by agonistic antibody results in phosphorylation of Ezrin via Syk kinase and is associated with inactivation of the Hippo pathway and increase in yes-associated protein (Yap1). The opposite occurs when glypican-3 or E2 protein of HCV binds to CD81. Hepatocyte-specific glypican-3 transgenic mice have decreased levels of phosphorylated (p)-Ezrin (Thr567) and Yap, increased Hippo activity, and suppressed liver regeneration. Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.03.014DOI Listing