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American Journal of Pathology

Chhavi Chauhan
No abstract text is available yet for this article.
February 13, 2019: American Journal of Pathology
Kathrin E Witzke, Frederik Großerueschkamp, Hendrik Jütte, Melanie Horn, Florian Roghmann, Nicolas von Landenberg, Thilo Bracht, Angela Kallenbach-Thieltges, Heiko Käfferlein, Thomas Brüning, Karin Schork, Martin Eisenacher, Katrin Marcus, Joachim Noldus, Andrea Tannapfel, Barbara Sitek, Klaus Gerwert
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...
February 9, 2019: American Journal of Pathology
Yao-Fei Pei, Xiang-Nan Xu, Zhi-Fei Wang, Fu-Wei Wang, Wei-Ding Wu, Jun-Feng Geng, Xi-Qiang Liu
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. The down-regulation of MBD2 in LUAD was correlated with metastasis and poor survival. Additionally, MBD2 inhibited tumor metastasis by maintaining the expression of the mir-200s, which suppressed the invasive properties of tumors...
February 5, 2019: American Journal of Pathology
Tina Richey, James S Foster, Angela D Williams, Anna Bryn Williams, Alexa Stroh, Sallie Macy, Craig Wooliver, R Eric Heidel, Siva Karthik Varanasi, Elizabeth N Ergen, Dianne J Trent, Stephen A Kania, Stephen J Kennel, Emily B Martin, Jonathan S Wall
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...
February 5, 2019: American Journal of Pathology
Nazanin Tatari, Hesam Movassagh, Lianyu Shan, Latifa Koussih, Abdelilah S Gounni
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...
January 31, 2019: American Journal of Pathology
Meghali Nighot, Manmeet Rawat, Rana-Al Sadi, Eliseo F Castillo, Prashant Nighot, Thomas Ma
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. Our aim was to delineate the intracellular pathways that mediate the LPS-induced increase in intestinal permeability using in vitro and in vivo intestinal epithelial models...
January 31, 2019: American Journal of Pathology
Delu Song, Yoshiyasu Ueda, Rupak Bhuyan, Imran Mohammed, Takashi Miwa, Damodar Gullipali, Hangsoo Kim, Lin Zhou, Ying Song, Hannah Schultz, Albert Bargoud, Joshua L Dunaief, Wen-Chao Song
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 (FHR/R ) share features with human atypical hemolytic uremic syndrome. Here, we report that FHR/R mice exhibited retinal vascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FHR/R mice. Optical coherence tomography imaging of FHR/R mice showed retinal degeneration, edema, and detachment...
January 31, 2019: American Journal of Pathology
Chellappagounder Thangavel, Cristiano Mendes Gomes, Stephen A Zderic, Elham Javed, Sankar Addya, Jagmohan Singh, Sreya Das, Ruth Birbe, Robert B Den, Satish Rattan, Deepak A Deshpande, Raymond B Penn, Samuel Chacko, Ettickan Boopathi
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. We identified and characterized regulatory regions responsible for CAV1, CAV2, and CAV3 gene expression in mice with obstruction-induced BSM hypertrophy, and in men with benign prostatic hyperplasia...
January 29, 2019: American Journal of Pathology
Naoki Ikari, Akiko Serizawa, Shohei Mitani, Masakazu Yamamoto, Toru Furukawa
Liver metastasis is a major cause of death in patients with gastric cancer. We evaluated molecular alterations in clinically resected liver metastases of gastric cancer to identify candidate biomarkers and therapeutic targets. Seventy-four patients, including 37 with liver metastasis that underwent gastrectomy and hepatectomy for gastric cancer and 37 without liver metastasis that underwent gastrectomy for gastric cancer, were studied. Next-generation resequencing was performed for 412 cancer-associated genes in metastatic and/or primary tumors from 30 patients and somatic mutations in TP53, LRP1B, PIK3CA, ADAMTS20, PAX7, FN1, FOXO3, WRN, PTEN, ETV4, and RNF213 were found in metastatic tumors...
January 28, 2019: American Journal of Pathology
Bethany Baumann, Andrés Martin Acosta, Zachary Richards, Ryan Deaton, Anastasiya Sapatynska, Adam Murphy, Andre Kajdacsy-Balla, Peter H Gann, Larisa Nonn
A subset of men with prostate cancer develops aggressive disease. We sought to determine if miR-182, a microRNA with reported oncogenic functions in prostate, associates 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. MiR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0.0001). The ratio of cancer to benign miR-182 expression per patient was inversely associated with recurrence in a multivariate logistic regression model (OR=0...
January 28, 2019: American Journal of Pathology
Lili Xie, Mao Mao, Cong Wang, Lusi Zhang, Zheng Pan, Jingming Shi, Xuanchu Duan, Songbo Jia, Bing Jiang
This study aimed to identify potential biomarkers for primary open-angle glaucoma (POAG) diagnosis. First, lncRNA and message RNA (mRNA) expression profiles in the aqueous humor (AH) from 10 POAG and 10 control patients were accessed by microarray analyses. Moreover, coding-non-coding gene co-expression networks were drawn to predict potential lncRNA functions. LncRNAs-T267384, ENST00000607393, and T342877 expression were further tested by quantitative real-time PCR in AH from 29 POAG and 30 cataract patients, in iris tissues from 16 POAG patients and 10 controls, and in plasma from 49 POAG patients and 55 healthy controls...
January 21, 2019: American Journal of Pathology
Sakiko Masuda, Mayu Nonokawa, Emika Futamata, Yuka Nishibata, Sari Iwasaki, Takahiro Tsuji, Yutaka Hatanaka, Daigo Nakazawa, Satoshi Tanaka, Utano Tomaru, Tamihiro Kawakami, Tatsuya Atsumi, Akihiro Ishizu
Anti-neutrophil 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. The principal degradation factor of NETs in vivo is DNase I; however, NETs resistant to DNase I can persist in tissues and lead to the production of ANCAs...
January 21, 2019: American Journal of Pathology
Shuang-Yu Lv, Binbin Cui, Yanjie Yang, Hua Du, Xiaomei Zhang, Yuchen Zhou, Wenling Ye, Xiaobo Nie, Yang Li, Qun Wang, Wei-Dong Chen, Yan-Dong Wang
Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. This study explored the mechanisms and effects of supraspinal spexin on inflammatory pain. The results from the mouse formalin test show that intracerebroventricular (i.c.v.) administration of spexin decreased licking/biting time during the late and early phases. The non-amidated spexin had no effect on pain response...
January 18, 2019: American Journal of Pathology
Behzad Javaheri, Eleanor Herbert, Mark Hopkinson, Ahmed Al-Jazzar, Andrew A Pitsillides
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 signalling. Sclerostin, encoded by Sost gene, is the main negative regulator of the pro-formative and anti-resorptive role of the Wnt signaling pathway in the skeleton. We hypothesized that the partial inactivation of sclerostin function by genetic manipulation will rescue the osteopenia induced by high endogenous glucocorticoid levels...
January 18, 2019: American Journal of Pathology
Veronica Ulici, Kathryn L Kelley, Lara Longobardi, Margaret A McNulty, Eric W Livingston, Ted A Bateman, Cheryle A Séguin, Craig R Louer, Richard F Loeser
MAP kinases, including 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 (JNK1fl/fl Col2-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. Alcian blue staining of embryos (E17.5) showed abnormal fusion of the posterior spinal elements...
January 18, 2019: American Journal of Pathology
Fuyuki Sato, Tsuyoshi Otsuka, Akira Kohsaka, Hue Thi Le, Ujjal K Bhawal, Yasuteru Muragaki
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. Conversely, Dec2 and Per1 expression was increased compared with that of control mice. In Smad3 knockout mice, immunohistochemical staining revealed that Dec1 expression decreased, whereas Dec2 and Per1 expression increased in the endothelial cells of the kidney and liver...
January 18, 2019: American Journal of Pathology
Chhavi Chauhan
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
January 16, 2019: American Journal of Pathology
Jessica D Hathaway-Schrader, Heidi M Steinkamp, Michael B Chavez, Nicole A Poulides, Joy E Kirkpatrick, Michael E Chew, Emily Huang, Alexander V Alekseyenko, Jose I Aguirre, Chad M Novince
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...
January 14, 2019: American Journal of Pathology
Risheng Ye, Toshiharu Onodera, Pierre-Gilles Blanchard, Christine M Kusminski, Victoria Esser, Rolf A Brekken, Philipp E Scherer
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. However, mice with β1 syntrophin deletion in exocrine acinar cells exhibit increased severity of cerulein-induced acute pancreatitis...
January 14, 2019: American Journal of Pathology
Yumiko Hayashi, Weizhen Jia, Hiroyasu Kidoya, Fumitaka Muramatsu, Yohei Tsukada, Nobuyuki Takakura
Galectin-3 (Gal-3; gene LGALS3) is a member of the beta-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, here we show that highly metastatic mouse melanoma B16/BL6 cells express less Gal-3 than B16 cells with a lower metastatic potential...
January 14, 2019: American Journal of Pathology
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