Expression of 15-Hydroxyprostaglandin Dehydrogenase in Human Chorion Is Associated with Peroxisome Proliferator-Activated Receptor Isoform Expression in Term Labor.
In this study, we investigated whether PPARs are involved in control of PGDH expression in chorion. The chorionic tissues were collected from the following groups of the women with singleton pregnancy: term no labor (TNL), term labor (TL) and preterm labor (PTL). Chorionic trophoblasts were isolated and cultured in vitro. Immunocytochemistry analysis showed that PPARα, PPARβ, and PPARγ were localized to trophoblasts in chorion. The protein levels of PGDH, PPARβ, and PPARγ were localized to trophoblasts in chorion. The protein levels of PPARα, PPARβ, and PPARγ were reduced i...
Source: The American Journal of Pathology - June 23, 2015 Category: Pathology Authors: He P, Li Y, Ding X, Sun Q, Huang Y, Gu H, Ni X Tags: Am J Pathol Source Type: research

FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling.
Abstract Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in&nbs...
Source: The American Journal of Pathology - June 23, 2015 Category: Pathology Authors: Mak VC, Wong OG, Siu MK, Wong ES, Ng WY, Wong RW, Chan KK, Ngan HY, Cheung AN Tags: Am J Pathol Source Type: research

Microphthalmia-Associated Transcription Factor: A Central Regulator of Pigment Epithelium-Derived Factor Controlling Human Melanoma Progression.
uis Orgaz J Abstract This Correspondence relates to the article by Dadras et al (A Novel Role for Microphthalmia-Associated Transcription Factor-Regulated Pigment Epithelium-Derived Factor during Melanoma Progression. Am J Pathol 2015, 185:252-265). PMID: 26093986 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - June 23, 2015 Category: Pathology Authors: Jiménez Cuenca B, Fernández-Barral A, Luis Orgaz J Tags: Am J Pathol Source Type: research

Authors' Reply.
J, Fisher DE Abstract This Correspondence is a Reply to Microphthalmia-Associated Transcription Factor: A Central Regulator of Pigment Epithelium-Derived Factor Controlling Human Melanoma Progression by Jimenez Cuenca et al. PMID: 26093987 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - June 23, 2015 Category: Pathology Authors: Authors' Reply. Tags: Am J Pathol Source Type: research

The Macrophage Phagocytic Receptor CD36 Promotes Fibrogenic Pathways on Removal of Apoptotic Cells during Chronic Kidney Injury.
Abstract The removal of apoptotic cells is an innate function of tissue macrophages; however, its role in disease progression is unclear. The present study was designed to investigate the role of macrophage CD36, a recognized receptor of apoptotic cells and oxidized lipids, in two models of kidney injury: unilateral ureteral obstruction (UUO) and ischemia reperfusion. To differentiate the macrophage CD36-specific effects in vivo, we generated CD36 chimeric mice by bone marrow transplantation and evaluated the two models. Fibrosis severity was substantially decreased at day 14 after UUO with a correspondi...
Source: The American Journal of Pathology - June 16, 2015 Category: Pathology Authors: Pennathur S, Pasichnyk K, Bahrami NM, Zeng L, Febbraio M, Yamaguchi I, Okamura DM Tags: Am J Pathol Source Type: research

Podocyte Injury-Driven Lipid Peroxidation Accelerates the Infiltration of Glomerular Foam Cells in Focal Segmental Glomerulosclerosis.
Abstract Intracapillary foam cell infiltration with podocyte alterations is a characteristic pathology of focal segmental glomerulosclerosis. We investigated the possible role of podocyte injury in glomerular macrophage and foam cell infiltration in a podocyte-selective injury model (NEP25 mice) and hypercholesterolemic model [low-density lipoprotein receptor deficiency (LDLR(-/-)) mice] with doxorubicin (Adriamycin)-induced nephropathy. Acute podocyte selective injury alone failed to induce glomerular macrophages in the NEP25 mice. However, in the doxorubicin-treated hypercholesterolemic LDLR(-/-) mice, glomerula...
Source: The American Journal of Pathology - June 10, 2015 Category: Pathology Authors: Hara S, Kobayashi N, Sakamoto K, Ueno T, Manabe S, Takashima Y, Hamada J, Pastan I, Fukamizu A, Matsusaka T, Nagata M Tags: Am J Pathol Source Type: research

Activation of AMP-Activated Protein Kinase Prevents TGF-β1-Induced Epithelial-Mesenchymal Transition and Myofibroblast Activation.
Activation of AMP-Activated Protein Kinase Prevents TGF-β1-Induced Epithelial-Mesenchymal Transition and Myofibroblast Activation. Am J Pathol. 2015 Jun 9; Authors: Thakur S, Viswanadhapalli S, Kopp JB, Shi Q, Block K, Gorin Y, Abboud HE Abstract Transforming growth factor (TGF)-β contributes to tubulointerstitial fibrosis. We investigated the mechanism by which TGF-β exerts its profibrotic effects and specifically the role of AMP-activated protein kinase (AMPK) in kidney tubular epithelial cells and interstitial fibroblasts. In proximal tubular epithelial cells, TGF-β1 treatment c...
Source: The American Journal of Pathology - June 9, 2015 Category: Pathology Authors: Thakur S, Viswanadhapalli S, Kopp JB, Shi Q, Block K, Gorin Y, Abboud HE Tags: Am J Pathol Source Type: research

A Road to Chronic Kidney Disease: Toward Glomerulosclerosis via Dendrin.
Abstract This commentary highlights the article by Weins et al that describes a potential mechanism to delay the onset and progression of end-stage kidney disease. PMID: 26067153 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - June 8, 2015 Category: Pathology Authors: Becherucci F, Lazzeri E, Romagnani P Tags: Am J Pathol Source Type: research

The Homeoprotein DLX4 Stimulates NF-κB Activation and CD44-Mediated Tumor-Mesothelial Cell Interactions in Ovarian Cancer.
In this study, we identified that DLX4 stimulates attachment of ovarian tumor cells to peritoneal mesothelial cells in vitro and increases the numbers of peritoneal implants in xenograft models. DLX4 induced expression of the cell surface molecule CD44 in ovarian tumor cells, and inhibition of CD44 abrogated the ability of DLX4 to stimulate tumor-mesothelial cell interactions. The induction of CD44 by DLX4 was attributed to increased activity of NF-κB that was stimulated by the inflammatory cytokine IL-1β, a transcriptional target of DLX4. The stimulatory effects of DLX4 on CD44 levels and tumor-mesothelial...
Source: The American Journal of Pathology - June 8, 2015 Category: Pathology Authors: Haria D, Trinh BQ, Ko SY, Barengo N, Liu J, Naora H Tags: Am J Pathol Source Type: research

Regeneration through Reprogramming Adult Cell Identity in Vivo.
Regeneration through Reprogramming Adult Cell Identity in Vivo. Am J Pathol. 2015 Jun 6; Authors: Smith DK, Zhang CL Abstract The discovery and in vivo application of cell fate reprogramming concepts have jumpstarted new technologies aimed at the functional regeneration of damaged tissues. Because most adult organ systems retain only a limited potential for self-regeneration after trauma, the production of fate-specific cells by in vivo transdifferentiation offers a targeted method for tissue bioengineering. Proof-of-principle studies have demonstrated the induction of neural precursor ...
Source: The American Journal of Pathology - June 6, 2015 Category: Pathology Authors: Smith DK, Zhang CL Tags: Am J Pathol Source Type: research

Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus.
Abstract The human polyomavirus is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from p...
Source: The American Journal of Pathology - June 6, 2015 Category: Pathology Authors: Haley SA, O'Hara BA, Nelson CD, Brittingham FL, Henriksen KJ, Stopa EG, Atwood WJ Tags: Am J Pathol Source Type: research

miRNA Control of Tissue Repair and Regeneration.
Abstract Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes, including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced ...
Source: The American Journal of Pathology - June 6, 2015 Category: Pathology Authors: Sen CK, Ghatak S Tags: Am J Pathol Source Type: research

The Amniotic Band Syndrome in the Rat Is Associated with the Activation of Transforming Growth Factor β.
This study addressed if the activation of the transforming growth factor-β1 (Tgfb1) pathway is, in part, associated with amniotic band formation and growth restriction induced in rats by amniocentesis, as by a previously published model. For this purpose, quantification of Tgfb1, α-smooth muscle actin, and collagen type I mRNA and protein levels were determined by qPCR and Western blot analysis, respectively, in the fetus, its amniotic membrane, and the uterus of experimental and control rats. We found that Tgfb1 mRNA levels are increased in the fetus and the amniotic membrane at 6 hours, whereas α-smooth ...
Source: The American Journal of Pathology - June 5, 2015 Category: Pathology Authors: Romero-Valdovinos M, Galván-Montaño A, Olivo-Díaz A, Maravilla P, Bobadilla NA, Vadillo-Ortega F, Flisser A Tags: Am J Pathol Source Type: research

Twist Contributes to Proliferation and Epithelial-to-Mesenchymal Transition-Induced Fibrosis by Regulating YB-1 in Human Peritoneal Mesothelial Cells.
Abstract Twist is overexpressed in high glucose (HG) damage of human peritoneal mesothelial cells (HPMCs) in vitro. Herein, we further identified its precise function related to fibrosis of peritoneal membranes (PMs). The overexpression and activation of Twist and YB-1 (official name, YBX1) and a transformed fibroblastic phenotype of HPMCs were found to be positively related to epithelial-mesenchymal transition progress and PM fibrosis ex vivo in 93 patients who underwent continuous ambulatory peritoneal dialysis (PD), and also in HG-induced immortal HPMCs and an animal model of PD. Evidence from chromat...
Source: The American Journal of Pathology - June 5, 2015 Category: Pathology Authors: He L, Che M, Hu J, Li S, Jia Z, Lou W, Li C, Yang J, Sun S, Wang H, Chen X Tags: Am J Pathol Source Type: research

Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of lamp-2-deficient mice.
Abstract Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy, and variable mental retardation. To elucidate the function of LAMP-2 in the central nervous system, we investigated the neuropathological changes in Lamp-2-deficient mice. Immunohistochemical observations revealed that Lamp-1 and cathepsin D-positive lysosomal structures increased in the large neurons of the mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive materials were detected in these neurons. By means of ult...
Source: The American Journal of Pathology - May 24, 2015 Category: Pathology Authors: Furuta A, Kikuchi H, Fujita H, Yamada D, Fujiwara Y, Kabuta T, Nishino I, Wada K, Uchiyama Y Tags: Am J Pathol Source Type: research

Note of concern.
Authors: PMID: 25998251 [PubMed - in process] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - May 24, 2015 Category: Pathology Tags: Am J Pathol Source Type: research

Homozygosity and Heterozygosity for Null Col5a2 Alleles Produce Embryonic Lethality and a Novel Classic Ehlers-Danlos Syndrome-Related Phenotype.
We describe mice with null alleles for the Col5a2. Col5a2(-/-) homozygosity is embryonic lethal at approximately 12 days post conception. Unlike previously described mice null for Col5a1, which die at 10.5 days post conception and virtually lack collagen fibrils, Col5a2(-/-) embryos have readily detectable collagen fibrils, thicker than in wild-type controls. Differences in Col5a2(-/-) and Col5a1(-/-) fibril formation and embryonic survival suggest that α1(V)3 homotrimers, a rare collagen V isoform that occurs in the absence of sufficient levels of α2(V) chains, serve functional roles that partially compensate ...
Source: The American Journal of Pathology - May 16, 2015 Category: Pathology Authors: Park AC, Phillips CL, Pfeiffer FM, Roenneburg DA, Kernien JF, Adams SM, Davidson JM, Birk DE, Greenspan DS Tags: Am J Pathol Source Type: research

NADPH Oxidase-Derived Peroxynitrite Drives Inflammation in Mice and Human Nonalcoholic Steatohepatitis via TLR4-Lipid Raft Recruitment.
Abstract The molecular events that link NADPH oxidase activation and the induction of Toll-like receptor (TLR)-4 recruitment into hepatic lipid rafts in nonalcoholic steatohepatitis (NASH) are unclear. We hypothesized that in liver, NADPH oxidase activation is key in TLR4 recruitment into lipid rafts, which in turn up-regulates NF-κB translocation to the nucleus and subsequent DNA binding, leading to NASH progression. Results from confocal microscopy showed that liver from murine and human NASH had NADPH oxidase activation, which led to the formation of highly reactive peroxynitrite, as shown by 3-nitrotyros...
Source: The American Journal of Pathology - May 16, 2015 Category: Pathology Authors: Das S, Alhasson F, Dattaroy D, Pourhoseini S, Seth RK, Nagarkatti M, Nagarkatti PS, Michelotti GA, Diehl AM, Kalyanaraman B, Chatterjee S Tags: Am J Pathol Source Type: research

Glypican-5 Increases Susceptibility to Nephrotic Damage in Diabetic Kidney.
In this study, diabetic kidney showed that accumulation of fibroblast growth factor (Fgf)2 strikingly induced progressive proteinuria that was avoided in Gpc5 knockdown mice. The efficacy of Gpc5 inhibition was exerted through expression of the Fgf receptors 3 and 4 provoked in the diabetic kidney attributively. Extraglomerular Fgf2 was pathogenic in DN, and Gpc5 effectively inhibited the glomerular accumulation of Fgf2, the subsequent increase of mesangial extracellular matrix, and the podocytes' small GTPase activity. These findings elucidate the pivotal role of GPC5, identified as a susceptible gene in the genome-wide a...
Source: The American Journal of Pathology - May 15, 2015 Category: Pathology Authors: Okamoto K, Honda K, Doi K, Ishizu T, Katagiri D, Wada T, Tomita K, Ohtake T, Kaneko T, Kobayashi S, Nangaku M, Tokunaga K, Noiri E Tags: Am J Pathol Source Type: research

Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice.
Abstract Arterial medial calcification (AMC) is a hallmark of aging, diabetes, and chronic kidney disease. Smooth muscle cell (SMC) transition to an osteogenic phenotype is a common feature of AMC, and is preceded by expression of runt-related transcription factor 2 (Runx2), a master regulator of bone development. Whether SMC-specific Runx2 expression is required for osteogenic phenotype change and AMC remains unknown. We therefore created an improved targeting construct to generate mice with floxed Runx2 alleles (Runx2(f/f)) that do not produce truncated Runx2 proteins after Cre recombination, thereby preventing ...
Source: The American Journal of Pathology - May 15, 2015 Category: Pathology Authors: Lin ME, Chen T, Leaf EM, Speer MY, Giachelli CM Tags: Am J Pathol Source Type: research

Automated Quantification of Tumor Viability in a Rabbit Liver Tumor Model after Chemoembolization: Infrared Imaging.
Abstract The rabbit VX2 tumor is a fast-growing carcinoma model commonly used to study new therapeutic devices, such as catheter-based therapies for patients with inoperable hepatocellular carcinoma. The evaluation of tumor viability after such locoregional therapies is essential to directing hepatocellular carcinoma management. We used infrared microspectroscopy for the automatic characterization and quantification of the VX2 liver tumor viability after drug-eluting beads transarterial chemoembolization (DEB-TACE). The protocol consisted of K-means clustering followed by principal component analysis (PCA) and lin...
Source: The American Journal of Pathology - May 12, 2015 Category: Pathology Authors: D'inca H, Namur J, Ghegediban SH, Wassef M, Pascale F, Laurent A, Manfait M Tags: Am J Pathol Source Type: research

Molecular and Genomic Alterations in Glioblastoma Multiforme.
Abstract In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathw...
Source: The American Journal of Pathology - May 11, 2015 Category: Pathology Authors: Crespo I, Vital AL, Gonzalez-Tablas M, Del Carmen Patino M, Otero A, Lopes MC, de Oliveira C, Domingues P, Orfao A, Tabernero MD Tags: Am J Pathol Source Type: research

Postinfarction Cardiac Remodeling Proceeds Normally in Granulocyte Colony-Stimulating Factor Knockout Mice.
In conclusion, overexpression of VEGF may compensate for the G-CSF deficit through preservation of cellular components, including blood vessels, in the postinfarction heart. PMID: 25976246 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - May 11, 2015 Category: Pathology Authors: Morishita K, Takemura G, Tsujimoto A, Kanamori H, Okada H, Chousa M, Ushimaru S, Mikami A, Kawamura I, Takeyama T, Kawaguchi T, Watanabe T, Goto K, Morishita M, Ushikoshi H, Kawasaki M, Ogura S, Minatoguchi S Tags: Am J Pathol Source Type: research

Intestinal Antigen-Presenting Cells: Key Regulators of Immune Homeostasis and Inflammation.
Abstract The microbiota that populate the mammalian intestine are critical for proper host physiology, yet simultaneously pose a potential danger. Intestinal antigen-presenting cells, namely macrophages and dendritic cells (DCs), are integral components of the mucosal innate immune system that maintain co-existence with the microbiota in face of this constant threat. Intestinal macrophages and DCs integrate signals from the microenvironment to orchestrate innate and adaptive immune responses that ultimately lead to durable tolerance of the microbiota. Tolerance is not a default response, however, because macrophag...
Source: The American Journal of Pathology - May 11, 2015 Category: Pathology Authors: Flannigan KL, Geem D, Harusato A, Denning TL Tags: Am J Pathol Source Type: research

Induction of Canonical Wnt Signaling by Synovial Overexpression of Selected Wnts Leads to Protease Activity and Early Osteoarthritis-Like Cartilage Damage.
In conclusion, our data show that canonical Wnts and WISP1, which we found overexpressed in the synovium during experimental OA, may conduce to OA pathology. PMID: 25976248 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - May 11, 2015 Category: Pathology Authors: van den Bosch MH, Blom AB, Sloetjes AW, Koenders MI, van de Loo FA, van den Berg WB, van Lent PL, van der Kraan PM Tags: Am J Pathol Source Type: research

Restoration of Functional Glycosylation of α-Dystroglycan in FKRP Mutant Mice Is Associated with Muscle Regeneration.
Restoration of Functional Glycosylation of α-Dystroglycan in FKRP Mutant Mice Is Associated with Muscle Regeneration. Am J Pathol. 2015 May 11; Authors: Awano H, Blaeser A, Keramaris E, Xu L, Tucker J, Wu B, Lu P, Lu QL Abstract Mutations in fukutin-related protein (FKRP) gene are characterized with lack of functionally glycosylated α-dystroglycan (F-α-DG). Surprisingly, a few muscle fibers express strong F-α-DG. Herein, we investigated the restoration of F-α-DG in the FKRP mutant muscles and showed that the restoration of glycosylation is associated with muscle regenerat...
Source: The American Journal of Pathology - May 11, 2015 Category: Pathology Authors: Awano H, Blaeser A, Keramaris E, Xu L, Tucker J, Wu B, Lu P, Lu QL Tags: Am J Pathol Source Type: research

Tertiary Lymphoid Structures in Rheumatoid Arthritis: NF-κB-Inducing Kinase-Positive Endothelial Cells as Central Players.
Tertiary Lymphoid Structures in Rheumatoid Arthritis: NF-κB-Inducing Kinase-Positive Endothelial Cells as Central Players. Am J Pathol. 2015 May 8; Authors: Noort AR, van Zoest KP, van Baarsen LG, Maracle CX, Helder B, Papazian N, Romera-Hernandez M, Tak PP, Cupedo T, Tas SW Abstract Tertiary lymphoid structures (TLSs) in chronic inflammation, including rheumatoid arthritis (RA) synovial tissue (ST), often contain high endothelial venules and follicular dendritic cells (FDCs). Endothelial cell (EC)-specific lymphotoxin β (LTβ) receptor signaling is critical for the formation of lymph n...
Source: The American Journal of Pathology - May 8, 2015 Category: Pathology Authors: Noort AR, van Zoest KP, van Baarsen LG, Maracle CX, Helder B, Papazian N, Romera-Hernandez M, Tak PP, Cupedo T, Tas SW Tags: Am J Pathol Source Type: research

Discovery and Classification of Fusion Transcripts in Prostate Cancer and Normal Prostate Tissue.
Abstract Fusion transcript formation is one of the fundamental mechanisms that drives the development of prostate cancer. Because of the advance of high-throughput parallel sequencing, many fusion transcripts have been discovered. However, the discovery rate of fusion transcripts specific for prostate cancer is lagging behind the discoveries made on chromosome abnormalities of prostate cancer. Recent analyses suggest that many fusion transcripts are present in both benign and cancerous tissues. Some of these fusion transcripts likely represent important components of normal gene expression in cells. It is necessar...
Source: The American Journal of Pathology - May 8, 2015 Category: Pathology Authors: Luo JH, Liu S, Zuo ZH, Chen R, Tseng GC, Yu YP Tags: Am J Pathol Source Type: research

Impact of Bacterial and Viral Challenge on Multidrug Resistance in First- and Third-Trimester Human Placenta.
Abstract The ABC transporters P-glycoprotein (P-gp, official gene symbol ABCB1) and breast cancer resistance protein (BCRP, official gene symbol ABCG2) protect the conceptus from exposure to toxins and xenobiotics present in the maternal circulation. Viral or bacterial challenges alter expression of placental multidrug transporters in rodents. We hypothesized that exposure to lipopolysaccharide (LPS, bacterial antigen) and polyinosinic-polycytidylic acid (poly(I:C), viral antigen) would decrease P-gp and BCRP in the human placenta. Placental explants from first and third trimesters were challenged with 0.1 to 10 &...
Source: The American Journal of Pathology - May 7, 2015 Category: Pathology Authors: Lye P, Bloise E, Javam M, Gibb W, Lye SJ, Matthews SG Tags: Am J Pathol Source Type: research

Insights into End-Organ Injury in HIV Infection: Dynamics of Monocyte Trafficking to the Brain in SIV Encephalitis.
Abstract This commentary highlights the article by Nowlin et al, which explores the dynamic roles of macrophages in early and late central nervous system lentiviral disease. PMID: 25963553 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - May 5, 2015 Category: Pathology Authors: Persidsky Y Tags: Am J Pathol Source Type: research

SIV Encephalitis Lesions Are Composed of CD163(+) Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS.
Abstract Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163(+)) and inflammatory (MAC387(+)) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2'-deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387(+) macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163(+) macrophages accumulated...
Source: The American Journal of Pathology - May 5, 2015 Category: Pathology Authors: Nowlin BT, Burdo TH, Midkiff CC, Salemi M, Alvarez X, Williams KC Tags: Am J Pathol Source Type: research

Multiple Mechanisms of Unfolded Protein Response-Induced Cell Death.
Abstract Eukaryotic cells fold and assemble membrane and secreted proteins in the endoplasmic reticulum (ER), before delivery to other cellular compartments or the extracellular environment. Correctly folded proteins are released from the ER, and poorly folded proteins are retained until they achieve stable conformations; irreparably misfolded proteins are targeted for degradation. Diverse pathological insults, such as amino acid mutations, hypoxia, or infection, can overwhelm ER protein quality control, leading to misfolded protein buildup, causing ER stress. To cope with ER stress, eukaryotic cells activate the ...
Source: The American Journal of Pathology - May 5, 2015 Category: Pathology Authors: Hiramatsu N, Chiang WC, Kurt TD, Sigurdson CJ, Lin JH Tags: Am J Pathol Source Type: research

The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regulator of the Oncogenic Nucleophosmin-MYC Axis.
Abstract The transcriptional factor MYC and the nucleophosphoprotein nucleophosmin (NPM) act in concert to regulate the proliferation of both normal and cancer cells. MYC directly interacts with NPM to form an NPM-MYC binary complex, which is recruited to the promoter of MYC target genes to induce the transcription of proteins required for transformation, thus forming an oncogenic NPM-MYC axis. However, the regulatory molecules and mechanisms that control the transcription of MYC target genes by NPM remain to be determined. Herein, we describe a novel function of the nucleolar protein glioblastoma tumor-suppressiv...
Source: The American Journal of Pathology - May 5, 2015 Category: Pathology Authors: Kim JY, Cho YE, Park JH Tags: Am J Pathol Source Type: research

Monocyte Traffic, Dorsal Root Ganglion Histopathology, and Loss of Intraepidermal Nerve Fiber Density in SIV Peripheral Neuropathy.
Abstract HIV-associated sensory neuropathy remains the most common neurological complication of HIV infection and is characterized by dorsal root ganglion (DRG) inflammation and intraepidermal nerve fiber density (IENFD) loss. Chronic peripheral immune cell activation and accumulation may cause damage to the DRG, but has not been fully investigated yet. By using an SIV-infected, CD8-lymphocyte-depleted rhesus macaque model, we defined immune cells surrounding DRG neurons and their role in DRG pathology to measure cell traffic from the bone marrow to the DRGs using 5-bromo-2-deoxyuridine (BrdU) pulse, and to serial...
Source: The American Journal of Pathology - May 5, 2015 Category: Pathology Authors: Lakritz JR, Bodair A, Shah N, O'Donnell R, Polydefkis MJ, Miller AD, Burdo TH Tags: Am J Pathol Source Type: research

Endothelial to Mesenchymal Transition Contributes to Endothelial Dysfunction in Pulmonary Artery Hypertension.
Abstract Pulmonary arterial hypertension is a progressive disease characterized by lung endothelial cell dysfunction and vascular remodeling. Normally, the endothelium forms an integral cellular barrier to regulate vascular homeostasis. During embryogenesis endothelial cells exhibit substantial plasticity that contribute to cardiac development by undergoing endothelial-to-mesenchymal transition (EndoMT). Here, we determined the presence of EndoMT in the pulmonary vasculature in vivo and the functional effects of pulmonary artery endothelial cells (PAECs) that undergo EndoMT in vitro. Histologic assessmen...
Source: The American Journal of Pathology - May 5, 2015 Category: Pathology Authors: Good RB, Gilbane AJ, Trinder SL, Denton CP, Coghlan G, Abraham DJ, Holmes AM Tags: Am J Pathol Source Type: research

Oncogenic Activity of miRNA 650 in Prostate Cancer Is Mediated by Suppression of CSR1 Expression.
Abstract Cellular stress response 1 (CSR1) is a tumor suppressor gene whose expression was frequently down-regulated in prostate cancer. The mechanism of its down-regulation, however, is not clear. Here, we show that the 3' untranslated region of CSR1 contains a target site of miR-650. High level of miR-650 was found in prostate cancer samples and cell lines. Degradation of miR-650 by specific inhibitor dramatically increased the expression levels of CSR1. Interaction between miR-650 and its target site in the 3' untranslated region was validated through luciferase reporter system. Mutation at the target site comp...
Source: The American Journal of Pathology - May 5, 2015 Category: Pathology Authors: Zuo ZH, Yu YP, Ding Y, Liu S, Martin A, Tseng G, Luo JH Tags: Am J Pathol Source Type: research

Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer.
Abstract We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations in a subset of bladder cancers. However, the prognostic significance of FOXA1 inactivation and the effect of FOXA1 loss on urothelial differentiation remain unknown. Application of a univariate analysis (log-rank) and a multivariate Cox proportional hazards regression model revealed that loss of FOXA1 expression is an i...
Source: The American Journal of Pathology - April 25, 2015 Category: Pathology Authors: Reddy OL, Cates JM, Gellert LL, Crist HS, Yang Z, Yamashita H, Taylor JA, Smith JA, Chang SS, Cookson MS, You C, Barocas DA, Grabowska MM, Ye F, Wu XR, Yi Y, Matusik RJ, Kaestner KH, Clark PE, DeGraff DJ Tags: Am J Pathol Source Type: research

The PTEN-AKT-mTOR/RICTOR Pathway in Nasal Natural Killer Cell Lymphoma Is Activated by miR-494-3p via PTEN But Inhibited by miR-142-3p via RICTOR.
Abstract Nasal natural killer (NK) cell lymphoma (NNL) is an Epstein-Barr virus-associated lymphoma of cytotoxic NK cell origin. The Epstein-Barr virus-encoded miR-BART20-5p inhibits T-bet (TBX21), the master transcription factor of cytotoxic NK cells. To further explore the roles of miRNAs in NNLs, we measured the miRNA expression profiles of 36 NNLs. miR-21, miR-142-3p, miR-126, miR-451, and miR-494-3p were the top five miRNAs with the highest expression levels. By using pathway analysis, we identified associations between all of the five miRNAs with the PTEN-AKT-mTOR pathway, in which PTEN suppresses the oncoge...
Source: The American Journal of Pathology - April 25, 2015 Category: Pathology Authors: Chen HH, Huang WT, Yang LW, Lin CW Tags: Am J Pathol Source Type: research

Infectious Disease Theme Issue: Molecular Pathogenesis Lessons from the World of Infectious Diseases Research.
Abstract This Guest Editorial introduces this month's special Infectious Disease Theme Issue, a series of reviews focusing on the molecular pathogenic processes of four representative pathogens, including two bacteria (brucellae and Staphylococcus aureus), a virus (influenza), and a parasite (Trypanosoma cruzi). PMID: 25906759 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - April 20, 2015 Category: Pathology Authors: Musser JM, DeLeo FR Tags: Am J Pathol Source Type: research

Pathogenesis and Immunobiology of Brucellosis: Review of Brucella-Host Interactions.
Abstract This review of Brucella-host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifesty...
Source: The American Journal of Pathology - April 16, 2015 Category: Pathology Authors: de Figueiredo P, Ficht TA, Rice-Ficht A, Rossetti CA, Adams LG Tags: Am J Pathol Source Type: research

Profiles of Cancer Stem Cell Subpopulations in Cholangiocarcinomas.
In conclusion, CSCs were rich in human CCAs, implicating CCAs as stem cell-based diseases. CSC subpopulations generate different types of cancers depending on the microenvironment. Remarkably, CSCs reproduce the original human CCAs when injected into cirrhotic livers. PMID: 25892683 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - April 16, 2015 Category: Pathology Authors: Cardinale V, Renzi A, Carpino G, Torrice A, Bragazzi MC, Giuliante F, DeRose AM, Fraveto A, Onori P, Napoletano C, Franchitto A, Cantafora A, Grazi G, Caporaso N, D'Argenio G, Alpini G, Reid LM, Gaudio E, Alvaro D Tags: Am J Pathol Source Type: research

Inflammation in the Pathogenesis of Lyme Neuroborreliosis.
Abstract Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL1...
Source: The American Journal of Pathology - April 13, 2015 Category: Pathology Authors: Ramesh G, Didier PJ, England JD, Santana-Gould L, Doyle-Meyers LA, Martin DS, Jacobs MB, Philipp MT Tags: Am J Pathol Source Type: research

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype.
In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. PMID: 25871534 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - April 11, 2015 Category: Pathology Authors: Leal EC, Carvalho E, Tellechea A, Kafanas A, Tecilazich F, Kearney C, Kuchibhotla S, Auster ME, Kokkotou E, Mooney DJ, LoGerfo FW, Pradhan-Nabzdyk L, Veves A Tags: Am J Pathol Source Type: research

Tumor Vessel Up-Regulation of INSR Revealed by Single Cell Expression Analysis of the Tyrosine Kinome and Phosphatome in Human Cancers.
This study demonstrates the feasibility of large-scale analyses to chart the transcriptome in situ in human cancers and their ability to identify novel cancer biomarkers. PMID: 25864925 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - April 9, 2015 Category: Pathology Authors: Kiflemariam S, Ljungström V, Pontén F, Sjöblom T Tags: Am J Pathol Source Type: research

Interleukin-1α, an Epithelial Danger Signal, Is a Potent Activator of Fibroblasts and Reactivator of Intestinal Inflammation.
Interleukin-1α, an Epithelial Danger Signal, Is a Potent Activator of Fibroblasts and Reactivator of Intestinal Inflammation. Am J Pathol. 2015 Apr 9; Authors: Scarpa M, Kessler S, Sadler T, West G, Homer C, McDonald C, de la Motte C, Fiocchi C, Stylianou E Abstract Intestinal epithelial cell (IEC) death is typical of inflammatory bowel disease (IBD). We investigated: i) whether IEC-released necrotic cell products (proinflammatory mediators) amplify mucosal inflammation, ii) the capacity of necrotic cell lysates from HT29 cells or human IECs to induce human intestinal fibroblasts' (HIF) producti...
Source: The American Journal of Pathology - April 9, 2015 Category: Pathology Authors: Scarpa M, Kessler S, Sadler T, West G, Homer C, McDonald C, de la Motte C, Fiocchi C, Stylianou E Tags: Am J Pathol Source Type: research

Heparanase Stimulates Chondrogenesis and Is Up-Regulated in Human Ectopic Cartilage: A Mechanism Possibly Involved in Hereditary Multiple Exostoses.
Abstract Hereditary multiple exostoses is a pediatric skeletal disorder characterized by benign cartilaginous tumors called exostoses that form next to growing skeletal elements. Hereditary multiple exostoses patients carry heterozygous mutations in the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2, but studies suggest that EXT haploinsufficiency and ensuing partial HS deficiency are insufficient for exostosis formation. Searching for additional players, we analyzed presence and distribution of heparanase in human exostoses. Heparanase was readily detectable in most chondrocytes, particularly in cell clus...
Source: The American Journal of Pathology - April 8, 2015 Category: Pathology Authors: Huegel J, Enomoto-Iwamoto M, Sgariglia F, Koyama E, Pacifici M Tags: Am J Pathol Source Type: research

Deletion of Ocular Transforming Growth Factor β Signaling Mimics Essential Characteristics of Diabetic Retinopathy.
Deletion of Ocular Transforming Growth Factor β Signaling Mimics Essential Characteristics of Diabetic Retinopathy. Am J Pathol. 2015 Apr 6; Authors: Braunger BM, Leimbeck SV, Schlecht A, Volz C, Jägle H, Tamm ER Abstract Diabetic retinopathy, a major cause of blindness, is characterized by a distinct phenotype. The molecular causes of the phenotype are not sufficiently clear. Here, we report that deletion of transforming growth factor β signaling in the retinal microenvironment of newborn mice induces changes that largely mimic the phenotype of nonproliferative and proliferative diabet...
Source: The American Journal of Pathology - April 6, 2015 Category: Pathology Authors: Braunger BM, Leimbeck SV, Schlecht A, Volz C, Jägle H, Tamm ER Tags: Am J Pathol Source Type: research

Pathophysiological Function of Endogenous Calcitonin Gene-Related Peptide in Ocular Vascular Diseases.
Abstract Calcitonin gene-related peptide (CGRP; official name CALCA) has a variety of functions and exhibits both angiogenic and anti-inflammatory properties. We previously reported the angiogenic effects of the CGRP family peptide adrenomedullin in oxygen-induced retinopathy; however, the effects of CGRP on ocular angiogenesis remain unknown. Herein, we used CGRP knockout (CGRP(-/-)) mice to investigate the roles of CGRP in ocular vascular disease. Observation of pathological retinal angiogenesis in the oxygen-induced retinopathy model revealed no difference between CGRP(-/-) and wild-type mice. However, much hig...
Source: The American Journal of Pathology - April 6, 2015 Category: Pathology Authors: Toriyama Y, Iesato Y, Imai A, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Yamauchi A, Igarashi K, Tanaka M, Liu T, Xian X, Zhai L, Owa S, Murata T, Shindo T Tags: Am J Pathol Source Type: research

Autoimmune Pathogenesis of Chagas Heart Disease: Looking Back, Looking Ahead.
Abstract Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of the individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas>100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contri...
Source: The American Journal of Pathology - April 6, 2015 Category: Pathology Authors: Bonney KM, Engman DM Tags: Am J Pathol Source Type: research

Local Origin of Mesenchymal Cells in a Murine Orthotopic Lung Transplantation Model of Bronchiolitis Obliterans.
Abstract Bronchiolitis obliterans is the leading cause of chronic graft failure and long-term mortality in lung transplant recipients. Here, we used a novel murine model to characterize allograft fibrogenesis within a whole-lung microenvironment. Unilateral left lung transplantation was performed in mice across varying degrees of major histocompatibility complex mismatch combinations. B6D2F1/J (a cross between C57BL/6J and DBA/2J) (H2-b/d) lungs transplanted into DBA/2J (H2-d) recipients were identified to show histopathology for bronchiolitis obliterans in all allogeneic grafts. Time course analysis showed an evo...
Source: The American Journal of Pathology - April 4, 2015 Category: Pathology Authors: Mimura T, Walker N, Aoki Y, Manning CM, Murdock BJ, Myers JL, Lagstein A, Osterholzer JJ, Lama VN Tags: Am J Pathol Source Type: research