18,757 results match your criteria The American journal of pathology[Journal]


Genetic strain and sex differences in a hyperoxia-induced mouse model of varying severity of bronchopulmonary dysplasia.

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA; St. Christopher's Hospital for Children, Philadelphia, PA. Electronic address:

Bronchopulmonary dysplasia (BPD) is a disease prevalent in preterm babies with a need for supplemental oxygen resulting in impaired lung development and dysregulated vascularization. Epidemiological studies have shown that males are more prone to BPD and have a delayed recovery compared to females for reasons unknown. Here, we tried to recapitulate mild, moderate, and severe BPD, using two different strains of mice: CD1 (outbred) and C57BL/6 (inbred), in males and females. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.014DOI Listing
February 2019

β-Catenin and yes-associated protein 1 cooperate in hepatoblastoma pathogenesis.

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Department of Gynecology, Shiyan Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, China. Electronic address:

Hepatoblastoma (HB), the most common pediatric primary liver neoplasm, show nuclear localization of β-catenin and yes-associated protein1 (YAP1) in almost 80% of the cases. Co-expression of constitutively active S127A-YAP1 and ΔN90 deletion-mutant-β-catenin (YAP1-ΔN90-β-catenin) causes HB in mice. Since heterogeneity in downstream signaling is being identified owing to mutational differences even in β-catenin gene alone, we investigated if co-expression of point-mutants of β-catenin (S33Y or S45Y) with S127A-YAP1 led to similar tumors as YAP1-ΔN90-β-catenin. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.02.002DOI Listing
February 2019

Intrinsic Bone Defects in Cystinotic Mice.

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, Rome, Italy.

Cystinosis is a rare lysosomal storage disorder caused by loss of function mutations of the CTNS gene, encoding cystinosin, a symporter that mediates cystine efflux from lysosomes. About 95% of patients with cystinosis display renal Fanconi syndrome, short stature, osteopenia, and rickets . In this study, we investigated whether the absence of cystinosin primarily affects bone remodeling activity, apart from the influences of the Fanconi syndrome on bone mineral metabolism. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.015DOI Listing
February 2019

TEA domain transcription factor 4 (TEAD4) is the major mediator of Yap oncogenic activity in mouse and human hepatoblastoma.

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA. Electronic address:

Hepatoblastoma (HB) is the most common type of pediatric liver cancer. Activation of Yes-associated protein (YAP) has been implicated in HB molecular pathogenesis. The transcriptional co-activator Yap regulates downstream gene expression through interaction with the TEA domain (TEAD) proteins. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.016DOI Listing
February 2019

Epidermis Activated Gsdma3 Enhances Thermogenesis of Brown Adipose Tissue through Interleukin-6/Stat3 Signaling.

Am J Pathol 2019 Feb 18. Epub 2019 Feb 18.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Drum Tower Hospital, Model Animal Research Center, Nanjing University, Nanjing, China.

Missense mutations in the Gasdermin-A3 (Gsdma3) gene are associated with skin inflammation and hair loss in mice. However, the physiological function of Gsdma3 remains unclear. Here we reported that mice carrying the Gsdma3 Y344H mutation that encodes a presumptive activated form of Gsdma3, show increased heat production along with lower body fat percentages. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.012DOI Listing
February 2019

Identification of CCDC180 and LRRC4 as Potential Immunohistochemical Markers for Liposarcoma Based on Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded Tissue.

Am J Pathol 2019 Feb 18. Epub 2019 Feb 18.

Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Recent technical improvements in both mass spectrometry and protein extraction have made it possible to use formalin-fixed, paraffin-embedded (FFPE) tissues for proteome analysis. In this study, comparable proteome analysis of FFPE tissues revealed multiple candidate marker molecules for differentiating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from lipoma. One-hundred and eighty-one unique proteins were identified for ALT/WDL. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.013DOI Listing
February 2019

This Month in AJP.

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Am J Pathol 2019 Feb 13. Epub 2019 Feb 13.

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.2019.02.001DOI Listing
February 2019

Integrated Fourier Transform Infrared Imaging and Proteomics for Identification of a Candidate Histochemical Biomarker in Bladder Cancer.

Am J Pathol 2019 Feb 9. Epub 2019 Feb 9.

Department of Biophysics, Ruhr University Bochum, Bochum, Germany. Electronic address:

Histopathological differentiation between severe urocystitis with reactive urothelial atypia and carcinoma in situ (CIS) can be difficult, particularly after a treatment that deliberately induces an inflammatory reaction, such as intravesical instillation of Bacillus Calmette-Guèrin. However, precise grading in bladder cancer is critical for therapeutic decision making and thus requires reliable immunohistochemical biomarkers. Herein, an exemplary potential biomarker in bladder cancer was identified by the novel approach of Fourier transform infrared imaging for label-free tissue annotation of tissue thin sections. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183073
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http://dx.doi.org/10.1016/j.ajpath.2018.11.018DOI Listing
February 2019
2 Reads

MBD2 inhibits the malignant characteristic of lung adenocarcinoma through the epigenetic modulation of TET1 and mir-200s.

Am J Pathol 2019 Feb 5. Epub 2019 Feb 5.

Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, P. R. China; Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province; Key Laboratory of Gastroenterology of Zhejiang Province. Electronic address:

It has been reported that disorders of epigenetic modulation play a critical role in carcinogenesis. MBD2 is known to act as an epigenetic modulator in various types of tumors; however, the role of MBD2 in lung adenocarcinoma (LUAD) remains unclear. Here, we demonstrated the down-regulation of MBD2 in LUAD compared with adjacent nontumor tissues. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183107
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http://dx.doi.org/10.1016/j.ajpath.2019.01.010DOI Listing
February 2019
6 Reads

Macrophage-Mediated Phagocytosis and Dissolution of Amyloid-Like Fibrils in Mice, Monitored by Optical Imaging.

Am J Pathol 2019 Feb 5. Epub 2019 Feb 5.

Department of Medicine, University of Tennessee Medical Center, Knoxville, TN. Electronic address:

Light chain-associated amyloidosis is characterized by the extracellular deposition of amyloid fibrils in abdominothoracic organs, skin, soft tissue, and peripheral nerves. Phagocytic cells of the innate immune system appear to be ineffective at clearing the material; however, human light chain amyloid extract, injected subcutaneously into mice, is rapidly cleared in a process that requires neutrophil activity. To better elucidate the phagocytosis of light chain fibrils, a potential method of cell-mediated dissolution, amyloid-like fibrils were labeled with the pH-sensitive dye pHrodo red and a near infrared fluorophore. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.011DOI Listing
February 2019

Semaphorin 3E inhibits house dust mite-induced angiogenesis in a mouse model of allergic asthma.

Am J Pathol 2019 Jan 31. Epub 2019 Jan 31.

Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. R3E 0T5. Electronic address:

Increased angiogenesis is a characteristic feature of remodeling in asthmatic airways which stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. Previously, we showed an important role of semaphorins 3E (Sema3E) in growth factor-induced airway smooth muscle proliferation and migration in vitro, and in down-regulating airway inflammation, Th2/Th17 cytokine response, mucus cell hyperplasia, and airway hyperresponsiveness in vivo. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.008DOI Listing
January 2019

Lipopolysaccharide-Induced Increase in Intestinal Permeability Is Mediated by TAK-1 Activation of IKK and MLCK/MYLK Gene.

Am J Pathol 2019 Jan 31. Epub 2019 Jan 31.

Department of Medicine, Pennsylvania State University, School of Medicine, Hershey, PA; Department of Internal Medicine, University of New Mexico School of Medicine. Electronic address:

Lipopolysaccharides (LPS) are a major component of Gram-negative bacterial cell wall and play an important role in promoting intestinal inflammatory responses. Our recent studies have shown that physiologically relevant concentrations of LPS (0 to 2,000 pg/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability without causing cell death. However, the intracellular pathways and the mechanisms that mediate LPS-induced increase in intestinal TJ permeability remain unclear. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.016DOI Listing
January 2019

Complement Factor H Mutation W1206R Causes Retinal Thrombosis and Ischemic Retinopathy in Mice.

Am J Pathol 2019 Jan 31. Epub 2019 Jan 31.

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address:

Single nucleotide polymorphisms and rare mutations in Factor H (FH; official name CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FH) share features with human atypical hemolytic uremic syndrome. Here, we report that FH mice exhibited retinal vascular occlusion and ischemia. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.009DOI Listing
January 2019
1 Read

NF-κB and GATA-6 Repress Transcription of Caveolins in Bladder Smooth Muscle Hypertrophy.

Am J Pathol 2019 Jan 29. Epub 2019 Jan 29.

Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania,; Division of Urology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Caveolins (CAV) are structural proteins of caveolae that function as signaling platforms to regulate smooth muscle contraction. Loss of CAV proteins expression is associated with impaired contraction in obstruction-induced bladder smooth muscle (BSM) hypertrophy. In this study, microarray analysis of bladder RNA revealed down-regulation of CAV1, CAV2, and CAV3 gene transcription in BSM from models of obstructive bladder disease in mice and humans. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.013DOI Listing
January 2019

Near-Comprehensive Resequencing of Cancer-Associated Genes in Surgically Resected Metastatic Liver Tumors of Gastric Cancer.

Am J Pathol 2019 Jan 29. Epub 2019 Jan 29.

Institute for Integrated Medical Sciences, Tokyo Women's Medical University School of Medicine, Tokyo, Japan; Department of Surgical Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan; Department of Histopathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address:

Liver metastasis is a major cause of death in patients with gastric cancer. The molecular alterations in clinically resected liver metastases of gastric cancer were evaluated to identify candidate biomarkers and therapeutic targets. Seventy-four patients, including 37 with liver metastasis who underwent gastrectomy and hepatectomy for gastric cancer and 37 without liver metastasis who underwent gastrectomy for gastric cancer, were studied. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.015DOI Listing
January 2019
1 Read

Association of High miR-182 Levels with Low-Risk Prostate Cancer.

Am J Pathol 2019 Jan 29. Epub 2019 Jan 29.

Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago. Electronic address:

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.014DOI Listing
January 2019

Potential Biomarkers for Primary Open-Angle Glaucoma Identified by Long Noncoding RNA Profiling in the Aqueous Humor.

Am J Pathol 2019 Jan 22. Epub 2019 Jan 22.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, People's Republic of China. Electronic address:

This study aimed to identify potential biomarkers for primary open-angle glaucoma (POAG) diagnosis. First, long noncoding RNA (lncRNA) and mRNA expression profiles in the aqueous humor (AH) from 10 POAG and 10 control patients were accessed by microarray analyses. Coding-noncoding gene coexpression networks were drawn to predict potential lncRNA functions. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.011DOI Listing
January 2019
2 Reads
4.591 Impact Factor

Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

Am J Pathol 2019 Jan 21. Epub 2019 Jan 21.

Department of Medical Laboratory Science, Hokkaido University Hospital, Sapporo, Japan. Electronic address:

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the production of ANCAs and systemic necrotizing vasculitis in small vessels. Disordered regulation of neutrophil extracellular traps (NETs) is critically involved in the pathogenesis of AAV. NETs are web-like DNA decorated with antimicrobial proteins; they are extruded from activated neutrophils. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.007DOI Listing
January 2019
2 Reads

Correction.

Authors:

Am J Pathol 2019 Feb;189(2):479

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http://dx.doi.org/10.1016/j.ajpath.2018.12.002DOI Listing
February 2019
1 Read

A Link between the Gut and Bone: Bone Health Impacted by Changes in Gut Microbiota.

Authors:
Larry J Suva

Am J Pathol 2019 Feb;189(2):229-230

Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas. Electronic address:

This commentary highlights the article by Hathaway-Schrader et al that studies the impact of antibiotic-disruption of the gut microbiota on long-term bone development. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.004DOI Listing
February 2019
1 Read

Spexin/NPQ Induces Fos and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model.

Am J Pathol 2019 Jan 19. Epub 2019 Jan 19.

State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address:

Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. 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.2018.12.009DOI Listing
January 2019
8 Reads
4.591 Impact Factor

Sost Haploinsufficiency Provokes Peracute Lethal Cardiac Tamponade without Rescuing the Osteopenia in a Mouse Model of Excess Glucocorticoids.

Am J Pathol 2019 Jan 19. Epub 2019 Jan 19.

Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom.

Glucocorticoid-induced secondary osteoporosis is the most predictable side effect of this anti-inflammatory. One of the main mechanisms by which glucocorticoids achieve such deleterious outcome in bone is by antagonizing Wnt/β-catenin signaling. Sclerostin, encoded by Sost gene, is the main negative regulator of the proformative and antiresorptive role of the Wnt signaling pathway in the skeleton. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.007DOI Listing
January 2019
3 Reads

Impaired Annulus Fibrosis Development and Vertebral Fusion Cause Severe Scoliosis in Mice with Deficiency of c-Jun NH2-Terminal Kinases 1 and 2.

Am J Pathol 2019 Jan 19. Epub 2019 Jan 19.

Division of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address:

Mitogen-activated protein kinases, including c-Jun NH2-terminal kinase (JNK), play an important role in the development and function of a large variety of tissues. We analyzed the skeletal phenotype of JNK1 and JNK2 double-knockout (dKO) mice (JNK1Col2-Cre/JNK2) and control genotypes, including single knockouts, at different embryonic and postnatal stages. The JNK1/2 dKO mice displayed a severe scoliotic phenotype that began during development and was grossly apparent around weaning age. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.010DOI Listing
January 2019
2 Reads

Smad3 Suppresses Epithelial Cell Migration and Proliferation Via the Clock Gene Dec1, Which Negatively Regulates the Expression of Clock Genes Dec2 and Per1.

Am J Pathol 2019 Jan 19. Epub 2019 Jan 19.

Department of Pathology, Wakayama Medical University School of Medicine, Wakayama, Japan.

Smad3 has circadian expression; however, whether Smad3 affects the expression of clock genes is poorly understood. Here, we investigated the regulatory mechanisms between Smad3 and the clock genes Dec1, Dec2, and Per1. In Smad3 knockout mice, the amplitude of locomotor activity was decreased, and Dec1 expression was decreased in the suprachiasmatic nucleus, liver, kidney, and tongue compared with control mice. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.01.006DOI Listing
January 2019
2 Reads

Antibiotic Perturbation of Gut Microbiota Dysregulates Osteoimmune Cross Talk in Postpubertal Skeletal Development.

Am J Pathol 2019 Feb 16;189(2):370-390. Epub 2019 Jan 16.

Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina; Endocrinology Division, Department of Pediatrics, Medical University of South Carolina College of Medicine, Charleston, South Carolina. Electronic address:

Commensal gut microbiota-host immune responses are experimentally delineated via gnotobiotic animal models or alternatively by antibiotic perturbation of gut microbiota. Osteoimmunology investigations in germ-free mice, revealing that gut microbiota immunomodulatory actions critically regulate physiologic skeletal development, highlight that antibiotic perturbation of gut microbiota may dysregulate normal osteoimmunological processes. We investigated the impact of antibiotic disruption of gut microbiota on osteoimmune response effects in postpubertal skeletal development. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360355PMC
February 2019
3 Reads

This Month in AJP.

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Am J Pathol 2019 Jan 17. Epub 2019 Jan 17.

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.2019.01.004DOI Listing
January 2019
1 Read

Development of a Novel Model of Central Retinal Vascular Occlusion and the Therapeutic Potential of the Adrenomedullin-Receptor Activity-Modifying Protein 2 System.

Am J Pathol 2019 Feb 15;189(2):449-466. Epub 2019 Jan 15.

Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan. Electronic address:

Central retinal vein occlusion (CRVO) is an intractable disease that causes visual acuity loss with retinal ischemia, hemorrhage, and edema. In this study, we developed an experimental CRVO model in mice and evaluated the therapeutic potential of the pleiotropic peptide adrenomedullin (ADM) and its receptor activity-modifying protein 2 (RAMP2). The CRVO model, which had phenotypes resembling those seen in the clinic, was produced by combining i. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.021DOI Listing
February 2019
4 Reads

β1 Syntrophin Supports Autophagy Initiation and Protects against Cerulein-Induced Acute Pancreatitis.

Am J Pathol 2019 Jan 14. Epub 2019 Jan 14.

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

Syntrophins are a family of proteins forming membrane-anchored scaffolds and serving as adaptors for various transmembrane and intracellular signaling molecules. To understand the physiological roles of β1 syntrophin, one of the least characterized members, we generated mouse models to eliminate β1 syntrophin specifically in the endocrine or exocrine pancreas. β1 syntrophin is dispensable for the morphology and function of insulin-producing β cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183031
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http://dx.doi.org/10.1016/j.ajpath.2019.01.002DOI Listing
January 2019
5 Reads
4.591 Impact Factor

Galectin-3 Inhibits Cancer Metastasis by Negatively Regulating Integrin β3 Expression.

Am J Pathol 2019 Jan 14. Epub 2019 Jan 14.

Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan; Division of Signal Transduction, Immunology Frontier Research Center, Osaka University, Suita, Japan. Electronic address:

Galectin-3 (Gal-3; gene LGALS3) is a member of the β-galactose-binding lectin family. Previous studies showed that Gal-3 is expressed in several tissues across species and functions as a regulator of cell proliferation, apoptosis, adhesion, and migration, thus affecting many aspects of events, such as angiogenesis and tumorigenesis. Although several reports have suggested that the level of Gal-3 expression correlates positively with tumor progression, herein we show that highly metastatic mouse melanoma B16/BL6 cells express less Gal-3 than B16 cells with a lower metastatic potential. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183065
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http://dx.doi.org/10.1016/j.ajpath.2018.12.005DOI Listing
January 2019
4 Reads

Liver Regeneration after Acetaminophen Hepatotoxicity: Mechanisms and Therapeutic Opportunities.

Am J Pathol 2019 Jan 14. Epub 2019 Jan 14.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas. Electronic address:

Acetaminophen (N-acetyl-para-aminophenol; APAP) overdose is the most common cause of acute liver failure in the Western world, with limited treatment opportunities. For years, research on APAP overdose has been focused on investigating the mechanisms of hepatotoxicity, with limited success in advancing therapeutic strategies. Acute liver injury after any insult, including APAP overdose, is followed by compensatory liver regeneration, which promotes recovery and is a crucial determinant of the final outcome. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183084
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http://dx.doi.org/10.1016/j.ajpath.2018.12.006DOI Listing
January 2019
14 Reads

Induced Pluripotent Stem Cell-Derived Endothelial Cells: Overview, Current Advances, Applications, and Future Directions.

Am J Pathol 2019 Jan 14. Epub 2019 Jan 14.

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Endothelial cells are prevalent in our bodies and serve multiple functions. By lining the vasculature, they provide a barrier to tissues and facilitate the transport of molecules and cells. They also maintain hemostasis and modulate blood flow by reacting to chemokines and releasing signal molecules. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183047
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http://dx.doi.org/10.1016/j.ajpath.2018.12.004DOI Listing
January 2019
6 Reads

Disruption of P2X7 Signaling Increases Susceptibility to Cerebral Toxoplasmosis.

Am J Pathol 2019 Jan 14. Epub 2019 Jan 14.

Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

Toxoplasmosis is a neglected disease that affects millions of individuals worldwide. Toxoplasma gondii infection is an asymptomatic disease, with lethal cases occurring mostly in HIV patients and organ transplant recipients. Nevertheless, atypical strains of T. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183056
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http://dx.doi.org/10.1016/j.ajpath.2019.01.001DOI Listing
January 2019
6 Reads

Loss of Wnt Secretion by Macrophages Promotes Hepatobiliary Injury after Administration of 3,5-Diethoxycarbonyl-1, 4-Dihydrocollidine Diet.

Am J Pathol 2019 Jan 2. Epub 2019 Jan 2.

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

Exposure of mice to a diet containing 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) induces porphyrin accumulation, cholestasis, immune response, and hepatobiliary damage mimicking hepatic porphyria and sclerosing cholangitis. Although β-catenin signaling promotes hepatocyte proliferation, and macrophages are a source of Wnts, the role of macrophage-derived Wnts in modulating hepatobiliary injury/repair remains unresolved. We investigated the effect of macrophage-specific deletion of Wntless, a cargo protein critical for cellular Wnt secretion, by feeding macrophage-Wntless-knockout (Mac-KO) and wild-type littermates a DDC diet for 14 days. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.010DOI Listing
January 2019
2 Reads

Leptin Receptor as a Potential Target to Inhibit Human Testicular Seminoma Growth.

Am J Pathol 2019 Jan 2. Epub 2019 Jan 2.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy. Electronic address:

Although in past decades the adipokine leptin and its own receptor have been considered as significant cancer biomarkers, their potential involvement in human testicular seminoma growth and progression remains unexplored. Here, we showed that the expression of leptin and its receptor was significantly higher in human testicular seminoma compared with normal adult testis. Human seminoma cell line TCam-2 also expressed leptin along with the long and short isoforms of leptin receptor, and in response to leptin treatment showed enhanced activation of its downstream effectors. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.012DOI Listing
January 2019
3 Reads

Molecular Evaluation of Breast Ductal Carcinoma in Situ with Oncotype DX DCIS.

Am J Pathol 2018 Dec 31. Epub 2018 Dec 31.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.

A subset of patients with ductal carcinoma in situ of the breast develop ipsilateral invasive breast cancer following breast conserving surgery with or without adjuvant radiotherapy. Risk assessment and PgRediction of adverse outcomes for individual patients based on traditional clinical and pathological parameters are limited. The Oncotype DCIS Score is a commercially available multigene assay that has been independently validated in PgRospective clinical trial and a population-based cohort. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.12.003DOI Listing
December 2018
1 Read

Peroxisome Proliferator-Activated Receptor-γ Knockdown Impairs Bone Morphogenetic Protein-2-Induced Critical-Size Bone Defect Repair.

Am J Pathol 2018 Dec 26. Epub 2018 Dec 26.

Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, and Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California. Electronic address:

The Food and Drug Administration-approved clinical dose (1.5 mg/mL) of bone morphogenetic protein-2 (BMP2) has been reported to induce significant adverse effects, including cyst-like adipose-infiltrated abnormal bone formation. These undesirable complications occur because of increased adipogenesis, at the expense of osteogenesis, through BMP2-mediated increases in the master regulatory gene for adipogenesis, peroxisome proliferator-activated receptor-γ (PPARγ). Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.019DOI Listing
December 2018
2 Reads

Enteric Murine Ganglionitis Induced by Autoimmune CD8 T Cells Mimics Human Gastrointestinal Dysmotility.

Am J Pathol 2018 Dec 27. Epub 2018 Dec 27.

Department of Neuropathology, University of Cologne, Cologne. Electronic address:

Inflammatory bowel diseases frequently cause gastrointestinal dysmotility, suggesting that they may also affect the enteric nervous system. So far, the precise mechanisms that lead to gastrointestinal dysmotility in inflammatory bowel diseases have not been elucidated. To determine the effect of CD8 T cells on gastrointestinal motility, transgenic mice expressing ovalbumin on enteric neurons were generated. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.016DOI Listing
December 2018
1 Read

Spatiotemporally Skewed Activation of Programmed Cell Death Receptor 1-Positive T Cells after Epstein-Barr Virus Infection and Tumor Development in Long-Term Fully Humanized Mice.

Am J Pathol 2018 Dec 26. Epub 2018 Dec 26.

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Laboratory of Regenerative Immune Therapies Applied, Excellence Cluster REBIRTH and German Centre for Infection Research, Partner Site Hannover, Hannover, Germany. Electronic address:

Humanized mice developing functional human T cells endogenously and capable of recognizing cognate human leukocyte antigen-matched tumors are emerging as relevant models for studying human immuno-oncology in vivo. Herein, mice transplanted with human CD34 stem cells and bearing endogenously developed human T cells for >15 weeks were infected with an oncogenic recombinant Epstein-Barr virus (EBV), encoding enhanced firefly luciferase and green fluorescent protein. EBV-firefly luciferase was detectable 1 week after infection by noninvasive optical imaging in the spleen, from where it spread rapidly and systemically. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.014DOI Listing
December 2018
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Nrf2-Mediated Expansion of Pilosebaceous Cells Accelerates Cutaneous Wound Healing.

Am J Pathol 2018 Dec 26. Epub 2018 Dec 26.

Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland. Electronic address:

The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor is a key regulator of the cellular stress response. Therefore, pharmacologic Nrf2 activation is a promising strategy for skin protection and cancer prevention. This study found that genetic Nrf2 activation in keratinocytes accelerates wound repair. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183065
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http://dx.doi.org/10.1016/j.ajpath.2018.11.017DOI Listing
December 2018
5 Reads

Blocking NF-κB Activation in Ly6c Monocytes Attenuates Necrotizing Enterocolitis.

Am J Pathol 2018 Dec 27. Epub 2018 Dec 27.

Center for Intestinal and Liver Inflammation Research, Stanley Manne Children's Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; Division of Neonatology, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Stanley Manne Children's Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Necrotizing enterocolitis (NEC) is a devastating disease affecting premature infants with intestinal inflammation and necrosis. The neonatal intestinal inflammatory response is rich in macrophages, and blood monocyte count is low in human NEC. We previously found that NF-κB mediates the intestinal injury in experimental NEC. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183031
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http://dx.doi.org/10.1016/j.ajpath.2018.11.015DOI Listing
December 2018
6 Reads

CCNA2 Ablation in Aged Mice Results in Abnormal rRNA Granule Accumulation in Hippocampus.

Am J Pathol 2019 Feb 21;189(2):426-439. Epub 2018 Dec 21.

Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio. Electronic address:

Mounting evidence in the literature suggests that RNA-RNA binding protein aggregations can disturb neuronal homeostasis and lead to symptoms associated with normal aging as well as dementia. The specific ablation of cyclin A2 in adult neurons results in neuronal polyribosome aggregations and learning and memory deficits. Detailed histologic and ultrastructural assays of aged mice revealed that post-mitotic hippocampal pyramidal neurons maintain cyclin A2 expression and that proliferative cells in the dentate subgranular zone express cyclin A2. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.020DOI Listing
February 2019
1 Read

Pancreatic Ductal Adenocarcinoma and Its Precursor Lesions: Histopathology, Cytopathology, and Molecular Pathology.

Am J Pathol 2019 Jan;189(1):9-21

Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Electronic address:

Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms with poor outcomes. At the time of diagnosis, the disease is usually at an advanced stage and only a minority is eligible for surgical resection. To improve the prognosis, it is essential to diagnose and treat the disease in an early stage before its progression into an invasive disease. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.004DOI Listing
January 2019
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Tumefactive Inflammatory Diseases of the Pancreas.

Am J Pathol 2019 Jan;189(1):82-93

The James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Advances in the past two decades have resulted in the recognition of several tumefactive pancreatic lesions that, on histologic evaluation, show a varying combination of inflammation and fibrosis. Autoimmune pancreatitis, the prototypic tumefactive pancreatic fibroinflammatory lesion, is composed of two distinct diseases, type 1 autoimmune pancreatitis and the less common type 2 autoimmune pancreatitis. Although designated as autoimmune pancreatitis, the two diseases show little morphologic or pathogenic overlap. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183020
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http://dx.doi.org/10.1016/j.ajpath.2018.05.022DOI Listing
January 2019
8 Reads

Circulating Tumor Cells and Cell-Free DNA in Pancreatic Ductal Adenocarcinoma.

Am J Pathol 2019 Jan;189(1):71-81

Hepato-Pancreato-Biliary Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital Campus, London, United Kingdom.

Pancreatic cancer is detected late in the disease process and has an extremely poor prognosis. A blood-based biomarker that can enable early detection of disease, monitor response to treatment, and potentially allow for personalized treatment would be of great benefit. This review analyzes the literature regarding two potential biomarkers, circulating tumor cells (CTCs) and cell-free DNA (cfDNA), with regard to pancreatic ductal adenocarcinoma. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.03.020DOI Listing
January 2019
5 Reads

Pancreatic Ductal Adenocarcinoma: Recent Updates.

Am J Pathol 2019 Jan;189(1):6-8

Department of Pathology and Laboratory Medicine, Geisel School of Medicine at Dartmouth and Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Electronic address:

This Guest Editorial introduces this month's special Pancreatic Cancer Theme Issue, a series of reviews intended to highlight the pathologic to molecular profiles and diagnoses of benign and neoplastic pancreatic lesions. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.006DOI Listing
January 2019
1 Read

miRNA and Gene Expression in Pancreatic Ductal Adenocarcinoma.

Am J Pathol 2019 Jan;189(1):58-70

Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan.

Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease that is mostly diagnosed late in the course of the illness. Unlike other cancers in which measurable successes have been achieved with traditional chemotherapy, targeted therapy, and, recently, immunotherapy, PDAC has proved to be poorly responsive to these treatments, with only marginal to modest incremental benefits using conventional cytotoxic therapy. There is, therefore, a great unmet need to develop better therapies based on improved understanding of biology and identification of predictive and prognostic biomarkers that would guide therapy. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.10.005DOI Listing
January 2019
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The Paradoxical Web of Pancreatic Cancer Tumor Microenvironment.

Am J Pathol 2019 Jan;189(1):44-57

Department of Surgery, City of Hope National Medical Center, Duarte, California. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is projected to become the second leading cause of cancer death in the United States. Despite significant advances in understanding the disease, there has been minimal increase in PDAC patient survival. PDAC tumors are unique in the fact that there is significant desmoplasia. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029440183015
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http://dx.doi.org/10.1016/j.ajpath.2018.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315325PMC
January 2019
6 Reads

Artificial Intelligence and Pathobiology Join Forces in The American Journal of Pathology.

Am J Pathol 2019 Jan;189(1):4-5

Department of Pathology, Stony Brook University, Stony Brook, New York. Electronic address:

This Editorial describes the extension in scope of The American Journal of Pathology. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.11.002DOI Listing
January 2019
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Familial Pancreatic Ductal Adenocarcinoma.

Am J Pathol 2019 Jan;189(1):36-43

Samuel Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC), although a rare disease, has a poor prognosis. With 5-year overall survival of 8%, there is a critical need to detect PDAC early or at a premalignant stage. Current screening methods are largely imaging based, but a more focused screening approach based on modifiable and nonmodifiable risk factors may improve the efficacy and likely outcomes of screening. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.06.026DOI Listing
January 2019
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Current Approaches to Pancreatic Cancer Screening.

Am J Pathol 2019 Jan;189(1):22-35

Yale Center for Pancreatic Diseases, Yale School of Medicine, New Haven, Connecticut; Yale Center for Pancreatic Diseases, Department of Digestive Diseases, Yale School of Public Health, New Haven, Connecticut. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. Read More

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http://dx.doi.org/10.1016/j.ajpath.2018.09.013DOI Listing
January 2019
2 Reads