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American Journal of Pathology

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https://www.readbyqxmd.com/read/28315676/the-major-histocompatibility-complex-class-iii-haplotype-ltab-ncr3-regulates-adjuvant-induced-but-not-antigen-induced-autoimmunity
#1
Anthony C Y Yau, Jonatan Tuncel, Rikard Holmdahl
Rheumatoid arthritis is a complex disease associated with >100 risk loci, with the strongest association from the major histocompatibility complex (MHC) region. Here, we analyzed a new genetic association in the MHC class-III region (MHC-III) using adjuvant- and antigen-induced arthritis models. In addition, we used models for multiple sclerosis for comparison and dissected the MHC-III-mediated mechanisms of importance for antibody and T-cell responses to antigens. With the use of a panel of MHC-III recombinant inbred strains, we found that the 33-kb Ltab-Ncr3 haplotype in MHC-III was linked to the induction of arthritis with incomplete Freund's adjuvant, with similar effects in arthritis induced by several oil adjuvants (hexadecane, heptadecane, squalene, arlacel)...
March 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28315675/low-intensity-training-and-the-c5a-complement-antagonist-nox-d21-rescue-the-mdx-phenotype-through-modulation-of-inflammation
#2
Janek Hyzewicz, Jun Tanihata, Mutsuki Kuraoka, Yuko Nitahara-Kasahara, Teiva Beylier, Urs T Ruegg, Axel Vater, Shin'ichi Takeda
Inflammatory events occurring in dystrophic muscles contribute to the progression of Duchenne muscular dystrophy (DMD). Low-intensity training (LIT) attenuates the phenotype of mdx mice, an animal model for DMD. Therefore, we postulated that LIT could have anti-inflammatory properties. We assessed levels of inflammatory cytokines and infiltrated immune cells in gastrocnemius muscle of mdx mice after LIT. We detected high levels of complement component C5a, chemokine ligand (CCL) 2, CD68(+) monocytes/macrophages, and proinflammatory M1 macrophages in muscles of mdx mice...
March 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28315674/dichotomy-between-receptor-interacting-protein-1-and-receptor-interacting-protein-3-mediated-necroptosis-in-experimental-pancreatitis
#3
Jianghong Wu, Tunike Mulatibieke, Jianbo Ni, Xiao Han, Bin Li, Yue Zeng, Rong Wan, Xingpeng Wang, Guoyong Hu
Pancreatic acinar cell necrosis and inflammatory responses are two key pathologic processes in acute pancreatitis (AP), which determines the severity and outcome of the disease. Recent studies suggest that necroptosis, a programed form of necrosis, is involved in the pathogenesis of AP, but the underlying mechanisms remain unknown. We investigated the expression of necrosome components, including receptor-interacting protein (RIP) 1, RIP3, and mixed lineage kinase domain-like (MLKL), and the molecular mechanisms in pancreatitis-associated necroptosis...
March 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28315314/nicotine-promotes-cholangiocarcinoma-growth-in-xenograft-mice
#4
Allyson K Martínez, Kendal Jensen, Chad Hall, April O'Brien, Laurent Ehrlich, Tori White, Fanyin Meng, Tianhao Zhou, John Greene, Francesca Bernuzzi, Pietro Invernizzi, David E Dostal, Terry Lairmore, Gianfranco Alpini, Shannon Glaser
Nicotine, the main addictive substance in tobacco, is known to play a role in the development and/or progression of a number of malignant tumors. However, nicotine's involvement in the pathogenesis of cholangiocarcinoma is controversial. Therefore, we studied the effects of nicotine on the growth of cholangiocarcinoma cells in vitro and the progression of cholangiocarcinoma in a mouse xenograft model. The predominant subunit responsible for nicotine-mediated proliferation in normal and cancer cells, the α7 nicotinic acetylcholine receptor (α7-nAChR), was more highly expressed in human cholangiocarcinoma cell lines compared with normal human cholangiocytes...
March 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28315313/transforming-growth-factors-%C3%AE-and-%C3%AE-are-essential-for-modeling-cholangiocarcinoma-desmoplasia-and-progression-in-a-three-dimensional-organotypic-culture-model
#5
Miguel A Manzanares, Akihiro Usui, Deanna J Campbell, Catherine I Dumur, Gabrielle T Maldonado, Michel Fausther, Jonathan A Dranoff, Alphonse E Sirica
To gain insight into the cellular and molecular interactions mediating the desmoplastic reaction and aggressive malignancy of mass-forming intrahepatic cholangiocarcinoma (ICC), we modeled ICC desmoplasia and progression in vitro. A unique three-dimensional (3D) organotypic culture model was established; within a dilute collagen-type I hydrogel, a novel clonal strain of rat cancer-associated myofibroblasts (TDFSM) was co-cultured with a pure rat cholangiocarcinoma cell strain (TDECC) derived from the same ICC type as TDFSM...
March 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28302495/neural-egfl-like-1-is-a-downstream-regulator-of-runt-related-transcription-factor-2-in-chondrogenic-differentiation-and-maturation
#6
Chenshuang Li, Jie Jiang, Zhong Zheng, Kevin S Lee, Yanheng Zhou, Eric Chen, Cymbeline T Culiat, Yiqiang Qiao, Xuepeng Chen, Kang Ting, Xinli Zhang, Chia Soo
Recent studies indicate that neural EGFL-like 1 (Nell-1), a secretive extracellular matrix molecule, is involved in chondrogenic differentiation. Herein, we demonstrated that Nell-1 serves as a key downstream target of runt-related transcription factor 2 (Runx2), a central regulator of chondrogenesis. Unlike in osteoblast lineage cells where Nell-1 and Runx2 demonstrate mutual regulation, further studies in chondrocytes revealed that Runx2 tightly regulates the expression of Nell-1; however, Nell-1 does not alter the expression of Runx2...
March 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284719/hypoxia-mediated-mechanisms-associated-with-antiangiogenic-treatment-resistance-in-glioblastomas
#7
REVIEW
Sean Mahase, Rachel N Rattenni, Pieter Wesseling, William Leenders, Clarissa Baldotto, Rajan Jain, David Zagzag
Glioblastomas (GBMs) are malignant tumors characterized by their vascularity and invasive capabilities. Antiangiogenic therapy (AAT) is a treatment option that targets GBM-associated vasculature to mitigate the growth of GBMs. However, AAT demonstrates transient effects, because many patients eventually develop resistance to this treatment. Several recent studies attempt to explain the molecular and biochemical basis of resistance to AAT in GBM patients. Experimental investigations suggest that the induction of extensive intratumoral hypoxia plays a key role in GBM escape from AAT...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284718/novel-jak3-activating-mutations-in-extranodal-nk-t-cell-lymphoma-nasal-type
#8
Sung H Sim, Soyeon Kim, Tae M Kim, Yoon K Jeon, Soo J Nam, Yong-Oon Ahn, Bhumsuk Keam, Hyun H Park, Dong-Wan Kim, Chul W Kim, Dae S Heo
Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3(A573V), two JAK3(H583Y), and one JAK3(G589D) mutation...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284717/evidence-mechanism-and-clinical-relevance-of-the-transdifferentiation-from-lung-adenocarcinoma-to-squamous-cell-carcinoma
#9
REVIEW
Shenda Hou, Shiyu Zhou, Zhen Qin, Liu Yang, Xiangkun Han, Shun Yao, Hongbin Ji
Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct subtypes of non-small-cell lung carcinoma. Interestingly, approximately 4% to 9% of human non-small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. More important, these two different pathological components frequently share identical oncogenic mutations, indicative of a potential transition. Indeed, recent data have provided convincing evidence in supporting the ADC to SCC transdifferentiation in lungs...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284716/th17-il-17-cause-acceleration-of-inflammation-and-fat-loss-by-inducing-%C3%AE-2-glycoprotein-1-azgp1-in-rheumatoid-arthritis-with-high-fat-diet
#10
Hyun Sik Na, Jeong-Eun Kwon, Seung Hoon Lee, JooYeon Jhun, Sung-Min Kim, Se-Young Kim, Eun-Kyung Kim, KyungAh Jung, Sung-Hwan Park, Mi-La Cho
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints. High-fat diet (HFD) is a risk factor for RA and is related to inflammation but responds minimally to medication. Given the association between HFD and inflammation, it is important to understand the function of inflammation-related T cells in RA with HFD. Collagen-induced arthritis (CIA), a model of RA, was induced in HFD mice by injection of collagen II, and metabolic markers and T cells were analyzed. The metabolic index and IgG assay results were higher in HFD-CIA mice than in nonfat diet-CIA mice...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284715/hyaluronan-binding-protein-involved-in-hyaluronan-depolymerization-controls-endochondral-ossification-through-hyaluronan-metabolism
#11
Masayuki Shimoda, Hiroyuki Yoshida, Sakiko Mizuno, Toru Hirozane, Keisuke Horiuchi, Yuta Yoshino, Hideaki Hara, Yae Kanai, Shintaro Inoue, Muneaki Ishijima, Yasunori Okada
Hyaluronan (HA) plays an important role in the development and maintenance of tissues, and its degradation is implicated in many pathologic conditions. We recently reported that HA-binding protein involved in HA depolymerization (HYBID/KIAA1199; encoded by CEMIP) is a key molecule in HA depolymerization, but its developmental and pathologic functions remain elusive. We generated Hybid-deficient mice using the Cre/locus of crossover in P1 (loxP) system and analyzed their phenotypes. Hybid-deficient mice were viable and fertile, but their adult long bones were shorter than those of wild-type animals...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28283178/activation-of-constitutive-androstane-receptor-prevents-cholesterol-gallstone-formation
#12
Shihai Cheng, Min Zou, Qinhui Liu, Jiangying Kuang, Jing Shen, Shiyun Pu, Lei Chen, Hong Li, Tong Wu, Rui Li, Yanping Li, Wei Jiang, Zhiyong Zhang, Jinhan He
Cholesterol gallstone disease (CGD) is one of the most common gastrointestinal diseases. Lithogenic hepatic bile secretion precedes the formation of cholesterol gallstones. Constitutive androstane receptor (CAR), a member of nuclear family, plays an important role in cholesterol and bile acid metabolism. To examine whether activation of CAR can prevent cholesterol gallstone formation, we treated C57BL6/J mice maintained on a lithogenic diet with CAR agonist 1,4-bis-[2-(3, 5-dichlorpyridyloxy)] benzene and performed bile duct cannulation to study the dynamics of biliary lipids...
March 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28279656/hepatic-induction-of-fatty-acid-binding-protein-4-plays-a-pathogenic-role-in-sepsis-in-mice
#13
Bingfang Hu, Yujin Li, Li Gao, Yan Guo, Yiwen Zhang, Xiaojuan Chai, Meishu Xu, Jiong Yan, Peipei Lu, Songrong Ren, Su Zeng, Yulan Liu, Wen Xie, Min Huang
Sepsis is defined as the host's deleterious systemic inflammatory response to microbial infections. Herein, we report an essential role of the fatty acid binding protein 4 (FABP4; alias adipocyte protein 2 or aP2), a lipid-binding chaperone, in sepsis response. Bioinformatic analysis of the Gene Expression Omnibus data sets showed the level of FABP4 was higher in the nonsurvival sepsis patients' whole blood compared to the survival cohorts. The expression of Fabp4 was induced in a liver-specific manner in cecal ligation and puncture (CLP) and lipopolysaccharide treatment models of sepsis...
March 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28279655/nontypeable-haemophilus-influenzae-promoted-proliferation-of-kras-induced-early-adenomatous-lesions-is-completely-dependent-on-toll-like-receptor-signaling
#14
Christopher Jungnickel, Philipp A Schnabel, Rainer Bohle, Rainer Wiewrodt, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic obstructive pulmonary disease is a risk factor for lung cancer. COPD is characterized by chronic airway inflammation and lung infections. The airways of patients with COPD are frequently colonized with bacteria [eg, nontypeable Haemophilus influenzae (NTHi)] that cause pulmonary inflammation and exacerbations. Pulmonary adenocarcinomas are frequently associated with an activating mutation in the KRAS gene. We determined the function of Toll-like receptor (TLR) signaling on the progression of KRas-induced early adenomatous lesions in the lung...
March 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28273432/p53-and-mir-34a-feedback-promotes-lung-epithelial-injury-and-pulmonary-fibrosis
#15
Shwetha K Shetty, Nivedita Tiwari, Amarnath S Marudamuthu, Bijesh Puthusseri, Yashodhar P Bhandary, Jian Fu, Jeffrey Levin, Steven Idell, Sreerama Shetty
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. The pathogenesis of interstitial lung diseases, including its most common form, IPF, remains poorly understood. Alveolar epithelial cell (AEC) apoptosis, proliferation, and accumulation of myofibroblasts and extracellular matrix deposition results in progressive loss of lung function in IPF. We found induction of tumor suppressor protein, p53, and apoptosis with suppression of urokinase-type plasminogen activator (uPA) and the uPA receptor in AECs from the lungs of IPF patients, and in mice with bleomycin, cigarette smoke, silica, or sepsis-induced lung injury...
March 5, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28222276/influenza-casts-a-lung-shadow
#16
Xavier De Luna, Kevan L Hartshorn
This commentary highlights the article by Pociask et al that provides new insights into the lingering effects of influenza infection.
February 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28219647/this-month-in-ajp
#17
(no author information available yet)
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
February 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28212814/human-striatal-dopaminergic-and-regional-serotonergic-synaptic-degeneration-with-lewy-body-disease-and-inheritance-of-apoe-%C3%AE%C2%B54
#18
Nadia Postupna, Caitlin S Latimer, Eric B Larson, Emily Sherfield, Julie Paladin, Carol A Shively, Matthew J Jorgensen, Rachel N Andrews, Jay R Kaplan, Paul K Crane, Kathleen S Montine, Suzanne Craft, C Dirk Keene, Thomas J Montine
Cognitive impairment in older individuals is a complex trait that in population-based studies most commonly derives from an individually varying mixture of Alzheimer disease, Lewy body disease, and vascular brain injury. We investigated the molecular composition of synaptic particles from three sources: consecutive rapid autopsy brains from the adult changes in thought study, a population-based cohort; four aged nonhuman primate brains optimally processed for molecular investigation; and targeted replacement transgenic mice homozygous for APOE ε4...
February 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28208054/high-glucose-induced-hypomethylation-promotes-binding-of-sp-1-to-myo-inositol-oxygenase-implication-in-the-pathobiology-of-diabetic-tubulopathy
#19
Isha Sharma, Rajesh K Dutta, Neel K Singh, Yashpal S Kanwar
The catabolic enzyme myo-inositol oxygenase (MIOX) is expressed in proximal tubules and up-regulated in the diabetic state. Previously, we reported its transcriptional and translation regulation by high glucose (HG), osmolytes, and fatty acids. However, its epigenetic regulation is unknown. Bisulfite sequencing revealed that both human and mouse MIOX promoters, enriched with CpG sites, are hypomethylated and unmethylated under HG ambience and hyperglycemic states associated with increased MIOX expression. Eletrophoretic mobility shift assays revealed increased binding of unmethylated oligos with nucleoproteins of cells maintained under HG...
February 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28196718/the-neuropeptide-galanin-is-up-regulated-during-cholestasis-and-contributes-to-cholangiocyte-proliferation
#20
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Sharon DeMorrow
During the course of cholestatic liver diseases, mitotically dormant cholangiocytes proliferate and subsequently acquire a neuroendocrine phenotype. Galanin is a neuroendocrine factor responsible for regulation of physiological responses, such as feeding behavior and mood, and has been implicated in the development of fatty liver disease, although its role in biliary hyperplasia is unknown. Biliary hyperplasia was induced in rats via bile duct ligation (BDL) surgery, and galanin was increased in serum and liver homogenates from BDL rats...
February 11, 2017: American Journal of Pathology
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