MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'The American Journal of Pathology' source. Thu, 09 Feb 2012 00:42:21 +0100 http://www.medworm.com/index.php?rid=5666106&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22306734%26dopt%3DAbstract In this study, we examined the effects of a novel NO-releasing nanoparticle technology on wound healing in mice. The results show that the NO nanoparticles (NO-np) significantly accelerated wound healing. NO-np modified leukocyte migration and increased tumor growth factor-β production in the wound area, which subsequently promoted angiogenesis to enhance the healing process. By using human dermal fibroblasts, we demonstrate that NO-np increased fibroblast migration and collagen deposition in wounded tissue. Together, these data show that NO-releasing nanoparticles have the ability to modulate and accelerate wound healing in a pleiotropic manner. PMID: 22306734 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5666106 Thu, 02 Feb 2012 05:00:00 +0100 5666106 http://www.medworm.com/index.php?rid=5666107&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22305861%26dopt%3DAbstract Authors: Venkataramani V, Thiele K, Behnes CL, Wulf GG, Thelen P, Opitz L, Salinas-Riester G, Wirths O, Bayer TA, Schweyer S Abstract Increasing evidence suggests an important function of the β-amyloid precursor protein (APP) in malignant disease in human beings, however, the biological basis for this evidence is not well understood at present. To understand the role of APP in transformed pluripotent stem cells, we studied its expression levels in human testicular germ cell tumors using patient tissues, model cell lines, and an established xenograft mouse model. In the present study, we demonstrate the cooperative expression of APP with prominent pluripotency-related genes such as Sox2, NANOG, and Oct-3/4. The closest homologue family member, APLP2, showed no correlation to these ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5666107 Wed, 01 Feb 2012 05:00:00 +0100 5666107 http://www.medworm.com/index.php?rid=5646368&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265049%26dopt%3DAbstract In conclusion, autophagy guards kidney proximal tubules against AKI, possibly by alleviating DNA damage and reactive oxygen species production and by eliminating toxic protein aggregates. Enhancing autophagy may provide a novel therapeutic option to minimize AKI. PMID: 22265049 [PubMed - in process] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5646368 Wed, 01 Feb 2012 05:00:00 +0100 5646368 http://www.medworm.com/index.php?rid=5646367&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265050%26dopt%3DAbstract In this study, we report decreased expression levels of c-Jun mRNA and protein in the lung tissues of patients with advanced chronic obstructive pulmonary disease, and the genetic deletion of c-Jun specifically in alveolar epithelial cells causes progressive emphysema with lung inflammation and alveolar air space enlargement, which are cardinal features of emphysema. Although mice lacking c-Jun specifically in lung alveolar epithelial cells appear normal at the age of 6 weeks, when exposed to long-term cigarette smoke, c-Jun-mutant mice display more lung inflammation with perivascular and peribronchiolar infiltrates compared with controls. These results demonstrate that the c-Jun/activator protein 1 pathway is critical for maintaining lung alveolar cell homeostasis and that loss of its exp... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5646367 Wed, 01 Feb 2012 05:00:00 +0100 5646367 http://www.medworm.com/index.php?rid=5646364&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285670%26dopt%3DAbstract In conclusion, our data show that chemotherapy can activate endothelial cells by inducing multiple pro-angiogenic signaling pathways and exert pro-angiogenic effects in vitro and in vivo. Moreover, we report a previously unrecognized clinical phenomenon that might, in part, be explained by our experimental observations: chemotherapy-associated enhanced vessel formation in tumors from patients with neuroblastoma. PMID: 22285670 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5646364 Thu, 26 Jan 2012 05:00:00 +0100 5646364 http://www.medworm.com/index.php?rid=5646365&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22269109%26dopt%3DAbstract Authors: Abstract The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. PMID: 22269109 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5646365 Fri, 20 Jan 2012 05:00:00 +0100 5646365 http://www.medworm.com/index.php?rid=5646366&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266251%26dopt%3DAbstract Authors: Shishido-Hara Y, Ichinose S, Uchihara T Abstract Progressive multifocal leukoencephalopathy is a fatal demyelinating disorder caused by JC virus infection. JC virus was recently found to target promyelocytic leukemia protein nuclear bodies (PML-NBs), punctuate domains in the nuclei. Thus, the virus progenies cluster in dots as intranuclear inclusions (ie, as dot-shaped inclusions). In the present study, both the viral major and minor capsid proteins were expressed from polycistronic expression vectors with a powerful promoter, and formation into virus-like particles (VLPs) was examined by electron microscopy. When the upstream regulatory sequence including the agnogene (nt 275 to 490) was present, capsid protein expression was suppressed, but numerous VLPs were efficiently... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5646366 Thu, 19 Jan 2012 05:00:00 +0100 5646366 http://www.medworm.com/index.php?rid=5646369&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22260922%26dopt%3DAbstract Authors: Gillrie MR, Lee K, Gowda DC, Davis SP, Monestier M, Cui L, Hien TT, Day NP, Ho M Abstract Plasmodium falciparum is a protozoan parasite of human erythrocytes that causes the most severe form of malaria. Severe P. falciparum infection is associated with endothelial activation and permeability, which are important determinants of the outcome of the infection. How endothelial cells become activated is not fully understood, particularly with regard to the effects of parasite subcomponents. We demonstrated that P. falciparum histones extracted from merozoites (HeH) directly stimulated the production of IL-8 and other inflammatory mediators by primary human dermal microvascular endothelial cells through a signaling pathway that involves Src family kinases and p38 MAPK. The stimu... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5646369 Tue, 17 Jan 2012 05:00:00 +0100 5646369 http://www.medworm.com/index.php?rid=5610963&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22252234%26dopt%3DAbstract In this study, we show that plexin-B1 is overexpressed in tissues and cell lines from neurotropic malignancies and is attracted to nerves that express its ligand, semaphorin 4D, in a Rho/Rho kinase-dependent manner. We also demonstrate that nerves are attracted to tumors through this same system of proteins, suggesting that both plexin-B1 and semaphorin 4D are important in the promotion of PNI. PMID: 22252234 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610963 Sat, 14 Jan 2012 05:00:00 +0100 5610963 http://www.medworm.com/index.php?rid=5610965&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248582%26dopt%3DAbstract Authors: Jana N, Sabita R Abstract Morphine increases the susceptibility to opportunistic infection by attenuating bacterial clearance through inhibition of Fcγ receptor (FcgR)-mediated phagocytosis. Mechanisms by which morphine inhibits this process remain to be investigated. Actin polymerization is essential for FcgR-mediated internalization; therefore, disruption of the signaling mechanisms involved in this process is detrimental to the phagocytic ability of macrophages. To our knowledge, this study is the first to propose the modulation of actin polymerization and upstream signaling effectors [cAMP, Rac1-GTP, and p38 mitogen-activated protein kinase (MAPK)] as key mechanisms by which morphine leads to inhibition of pathogen clearance. Our results indicate that long-term morphi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610965 Fri, 13 Jan 2012 05:00:00 +0100 5610965 http://www.medworm.com/index.php?rid=5610964&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248583%26dopt%3DAbstract In this study, we produced a tamoxifen-inducible mouse model in which β1 integrin could be reduced specifically in the adult cardiomyocyte, so that the function of this integrin could be assessed in the postnatal and mechanically stressed heart. The expression of β1 integrin was reduced to 35% of control levels, but function remained normal at baseline. With aortic constriction, the knockout mice survived but had a blunted hypertrophic response. Integrin knockout myocytes, in contrast to controls, showed reduced integrin-linked kinase expression both at baseline and after hemodynamic stress; focal adhesion kinase expression was reduced after stress. Alterations in multiple signaling pathways were detected in the integrin knockout group after acute and chronic hemodynamic stress. Most rem... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610964 Fri, 13 Jan 2012 05:00:00 +0100 5610964 http://www.medworm.com/index.php?rid=5610967&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245726%26dopt%3DAbstract In this study, mouse TECs and normal ECs were isolated to investigate the drug resistance of TECs and the mechanism by which it is acquired. TECs were more resistant to paclitaxel with the up-regulation of multidrug resistance (MDR) 1 mRNA, which encodes the P-glycoprotein, compared with normal ECs. Normal human microvascular ECs were cultured in tumor-conditioned medium (CM) and became more resistant to paclitaxel through MDR1 mRNA up-regulation and nuclear translocation of Y-box-binding protein 1, which is an MDR1 transcription factor. Vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and Akt were activated in human microvascular ECs by tumor CM. We observed that tumor CM contained a significantly high level of VEGF. A VEGFR kinase inhibitor, Ki8751, and a phosphatidylinosito... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610967 Thu, 12 Jan 2012 05:00:00 +0100 5610967 http://www.medworm.com/index.php?rid=5610966&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245727%26dopt%3DAbstract In conclusion, the expression screening of PTPs in lung cancer reported here has identified PTPN13 as a novel candidate tumor suppressor in NSCLC whose loss increases signaling from epidermal growth factor receptor and HER2 tyrosine kinase receptors. PMID: 22245727 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610966 Thu, 12 Jan 2012 05:00:00 +0100 5610966 http://www.medworm.com/index.php?rid=5610971&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245214%26dopt%3DAbstract In this study, we sought to analyze the pathogenesis of inflammatory FAAs in interleukin-1 receptor antagonist-deficient (IL-1Ra(-/-)) B6 mice. Systolic arterial pressures and plasma lipid levels of IL-1Ra(-/-) mice and wild-type (WT) mice did not differ significantly. However, IL-1Ra(-/-) mice spontaneously developed fusiform FAAs. Real-time PCR of 9-month-old IL-1Ra(-/-) mice revealed significantly increased mRNA levels of IL-1β (6.6-fold), tumor necrosis factor-α (TNF-α) (12.4-fold), and matrix metalloproteinase-9 (6.0-fold) compared with WT mice. Histological analysis revealed numerous inflammatory cells around the FAAs in IL-1Ra(-/-) mice, and elastin staining showed destruction of both the internal and external elastic lamina in IL-1Ra(-/-) mice. Afterward, macrophage function was... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610971 Wed, 11 Jan 2012 05:00:00 +0100 5610971 http://www.medworm.com/index.php?rid=5610970&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245215%26dopt%3DAbstract Authors: Greenblatt MB, Sargent JL, Farina G, Tsang K, Lafyatis R, Glimcher LH, Whitfield ML, Aliprantis AO Abstract Development of personalized treatment regimens is hampered by lack of insight into how individual animal models reflect subsets of human disease, and autoimmune and inflammatory conditions have proven resistant to such efforts. Scleroderma is a lethal autoimmune disease characterized by fibrosis, with no effective therapy. Comparative gene expression profiling showed that murine sclerodermatous graft-versus-host disease (sclGVHD) approximates an inflammatory subset of scleroderma estimated at 17% to 36% of patients analyzed with diffuse, 28% with limited, and 100% with localized scleroderma. Both sclGVHD and the inflammatory subset demonstrated IL-13 cytokine pathway... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610970 Wed, 11 Jan 2012 05:00:00 +0100 5610970 http://www.medworm.com/index.php?rid=5610969&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245216%26dopt%3DAbstract Authors: Sircar K, Huang H, Hu L, Cogdell D, Dhillon J, Tzelepi V, Efstathiou E, Koumakpayi IH, Saad F, Luo D, Bismar TA, Aparicio A, Troncoso P, Navone N, Zhang W Abstract The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genomewide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610969 Wed, 11 Jan 2012 05:00:00 +0100 5610969 http://www.medworm.com/index.php?rid=5610968&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245217%26dopt%3DAbstract Authors: Ohga N, Ishikawa S, Maishi N, Akiyama K, Hida Y, Kawamoto T, Sadamoto Y, Osawa T, Yamamoto K, Kondoh M, Ohmura H, Shinohara N, Nonomura K, Shindoh M, Hida K Abstract An important concept in tumor angiogenesis is that tumor endothelial cells (TECs) are genetically normal and homogeneous. However, we previously reported that TECs differ from normal ECs. Whether the characteristics of TECs derived from different tumors differ remains unknown. To elucidate this, in this study, we isolated two types of TECs from high-metastatic (HM) and low-metastatic (LM) tumors and compared their characteristics. HM tumor-derived TECs (HM-TECs) showed higher proliferative activity and invasive activity than LM tumor-derived TECs (LM-TECs). Moreover, the mRNA expression levels of pro-angiogeni... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5610968 Wed, 11 Jan 2012 05:00:00 +0100 5610968 http://www.medworm.com/index.php?rid=5585627&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22234171%26dopt%3DAbstract In this study, we generated knockout mice deficient in Eif4 hours. These mice displayed growth retardation with a significant reduction of body weight that began from the first week of postnatal development. Neuroanatomical profiling results generated by magnetic resonance imaging analysis revealed a smaller brain volume in null mice compared with controls as well as altered brain morphology with both anterior and posterior brain regions differentially affected. The inactivation of Eif4 hours also led to a reduction in both the number and complexity of neurons. Behavioral studies revealed severe impairments of both fear-related associative learning and memory formation. These alterations suggest that Eif4 hours might contribute to certain deficits associated with Williams-Beuren syndrome. ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585627 Sat, 07 Jan 2012 05:00:00 +0100 5585627 http://www.medworm.com/index.php?rid=5585626&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22234172%26dopt%3DAbstract Authors: Zhong W, Zhao Y, Tang Y, Wei X, Shi X, Sun W, Sun X, Yin X, Sun X, Kim S, McClain CJ, Zhang X, Zhou Z Abstract Alcohol consumption induces liver steatosis; therefore, this study investigated the possible role of adipose tissue dysfunction in the pathogenesis of alcoholic steatosis. Mice were pair-fed an alcohol or control liquid diet for 8 weeks to evaluate the alcohol effects on lipid metabolism at the adipose tissue-liver axis. Chronic alcohol exposure reduced adipose tissue mass and adipocyte size. Fatty acid release from adipose tissue explants was significantly increased in alcohol-fed mice in association with the activation of adipose triglyceride lipase and hormone-sensitive lipase. Alcohol exposure induced insulin intolerance and inactivated adipose protein phospha... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585626 Sat, 07 Jan 2012 05:00:00 +0100 5585626 http://www.medworm.com/index.php?rid=5585625&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22234173%26dopt%3DAbstract In conclusion, our data advance the concept of "stem cell aging" by establishing the critical role of lysosomal dysfunction in the development of SIPS through the cathepsin-induced proteolytic cleavage of SIRT1, a mechanism linking cell stress to apoptosis and SIPS. Ebselen potently protects lysosomal membrane integrity, preventing cathepsin-induced cleavage of SIRT 1 in EPCs and blunting SIPS and apoptotic cell death induced by relevant cardiovascular stressors. The proposed mechanism of SIRT1 depletion in stress has all of the attributes of being a paradigm of SIPS of EPCs. PMID: 22234173 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585625 Sat, 07 Jan 2012 05:00:00 +0100 5585625 http://www.medworm.com/index.php?rid=5585624&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22234174%26dopt%3DAbstract Authors: Harris T, Jimenez L, Kawachi N, Fan JB, Chen J, Belbin T, Ramnauth A, Loudig O, Keller CE, Smith R, Prystowsky MB, Schlecht NF, Segall JE, Childs G Abstract Small, noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. We used comparisons of global miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in our patient population. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient among 736 miRNAs that were evaluated. This result has been previously observed by other groups; however, we ex... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585624 Sat, 07 Jan 2012 05:00:00 +0100 5585624 http://www.medworm.com/index.php?rid=5585629&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230248%26dopt%3DAbstract In this study, we report that ablation of PDGF-C in C57BL/6 mice results in a milder phenotype than in 129/Sv mice, and we present a phenotypic characterization of PDGF-C deficiency in the adult murine CNS. Multiple congenital defects were observed in the CNS of PDGF-C-null C57BL/6 mice, including cerebral vascular abnormalities with abnormal vascular smooth muscle cell coverage. In vivo imaging of mice deficient in PDGF-C also revealed cerebral ventricular abnormalities, such as asymmetry of the lateral ventricles and hypoplasia of the septum, reminiscent of cavum septum pellucidum in humans. We further noted that PDGF-C-deficient mice displayed a distorted ependymal lining of the lateral ventricles, and we found evidence of misplaced neurons in the ventricular lining. We conclude that PD... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585629 Fri, 06 Jan 2012 05:00:00 +0100 5585629 http://www.medworm.com/index.php?rid=5585628&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230249%26dopt%3DAbstract Authors: Wang H, Byfield G, Jiang Y, Smith GW, McCloskey M, Hartnett ME Abstract Avascular, hypoxic retina has been postulated to be a source of angiogenic factors that cause aberrant angiogenesis and intravitreal neovascularization (IVNV) in retinopathy of prematurity (ROP). Vascular endothelial growth factor (VEGF) is an important factor involved. However, VEGF is also required for normal retinal vascular development, which raises concerns about inhibiting its activity to treat IVNV in ROP. Therefore, understanding the effects VEGF has on other factors in the development of avascular retina may be important to prevent aberrant angiogenesis and IVNV. Here, we show that STAT3 was activated by increased retinal VEGF in the rat 50/10 oxygen-induced retinopathy model. Phospho-STAT3 co... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585628 Fri, 06 Jan 2012 05:00:00 +0100 5585628 http://www.medworm.com/index.php?rid=5585633&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226738%26dopt%3DAbstract In this study, we investigated the clinical outcome of MCP-1 expression in patients with prostate cancer (CaP) and the regulation of MCP-1 through angiotensin II (AngII) type 1 receptor (AT1R) in CaP. Specimens were obtained from 138 CaP patients and analyzed by immunostaining for both MCP-1 and macrophages. We investigated the regulation of MCP-1 expression through AT1R both in vivo and in vitro using three human prostate cancer cell lines: LNCaP, C4-2, and C4-2AT6. Specimens with a high Gleason score (≥7) and a high pathological classification (≤pT3), and those with castration-resistant prostate cancer showed significantly higher MCP-1 expression and higher macrophage infiltration than low malignant potential CaP. High MCP-1 expression in CaP correlated significantly with high prosta... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585633 Thu, 05 Jan 2012 05:00:00 +0100 5585633 http://www.medworm.com/index.php?rid=5585632&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226739%26dopt%3DAbstract Authors: Parsonage G, Machado LR, Hui JW, McLarnon A, Schmaler T, Balasothy M, To KF, Chris Vlantis A, Andrew van Hasselt C, Lo KW, Wong WL, Pun Hui E, Chan A, Lee SP Abstract The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Either preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T-cell recruitment to this tumor are poorly understood. Comparing memory T-cell subsets that have naturally infiltrat... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585632 Thu, 05 Jan 2012 05:00:00 +0100 5585632 http://www.medworm.com/index.php?rid=5585631&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226740%26dopt%3DAbstract Authors: Wang H, Jones J, Turner T, He QP, Hardy S, Grizzle WE, Welch DR, Yates C Abstract For men in the United States, prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality. The metastatic spread of PCa is responsible for most deaths related to PCa. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa development and progression remain undetermined. The goals of this study were to correlate the expression levels of KISS1 in PCas with clinicopathologic characteristics and to assess the biological relevance of KISS1 to the viability and motility of PCa cells. Strong KISS1 staining was detected in benign prostate tissues, but the staining was weaker in primary and metastati... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585631 Thu, 05 Jan 2012 05:00:00 +0100 5585631 http://www.medworm.com/index.php?rid=5585630&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227015%26dopt%3DAbstract In this study, we used two nontransformed cyst108 and RK3E epithelial cell lines as models in which to compare the phenotypes of cells expressing BRAF(wt) and BRAF(V600E). We found that transfection of the BRAF(V600E), but not the BRAF(wt), expression vector both suppressed cellular proliferation and induced apoptosis in both cell types. BRAF(V600E) generated reactive oxygen species, induced DNA double-strand breaks, and caused subsequent DNA damage response as evidenced by an increased number of pCHK2 and γH2AX nuclear foci as well as the up-regulation of pCHK2, p53, and p21. Because BRAF and KRAS (alias Ki-ras) mutations have been correlated with GLUT1 up-regulation, which encodes glucose transporter-1, we demonstrated here that expression of BRAF(V600E), but not BRAF(wt), was sufficien... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585630 Wed, 04 Jan 2012 05:00:00 +0100 5585630 http://www.medworm.com/index.php?rid=5585636&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222225%26dopt%3DAbstract Authors: McDonald KG, Leach MR, Brooke KW, Wang C, Wheeler LW, Hanly EK, Rowley CW, Levin MS, Wagner M, Li E, Newberry RD Abstract Dendritic cells (DCs) use all-trans retinoic acid (ATRA) to promote characteristic intestinal responses, including Foxp3(+) Treg conversion, lymphocyte gut homing molecule expression, and IgA production. How this ability to generate ATRA is conferred to DCs in vivo remains largely unstudied. Here, we observed that among DCs, retinaldehyde dehydrogenase (ALDH1), which catalyzes the conversion of retinal to ATRA, was preferentially expressed by small intestine CD103(+) lamina propria (LP) DCs. Retinoids induced LP CD103(+) DCs to generate ATRA via ALDH1 activity. Either biliary or dietary retinoids were required to confer ALDH activity to LP DCs in vivo. ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585636 Mon, 02 Jan 2012 05:00:00 +0100 5585636 http://www.medworm.com/index.php?rid=5585635&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222226%26dopt%3DAbstract Authors: Wang YC, Yo YT, Lee HY, Liao YP, Chao TK, Su PH, Lai HC Abstract The role of aldehyde dehydrogenase 1 (ALDH1) as an ovarian cancer stem cell marker and its clinical significance have rarely been explored. We used an Aldefluor assay to isolate ALDH1-bright (ALDH1(br)) cells from epithelial ovarian cancer cell lines and characterized the properties of the stem cells. ALDH1(br) cells were enriched in ES-2 (1.3%), TOV-21G (1.0%), and CP70 (1.2%) cells. Both ALDH1(br) and ALDH1(low) cells repopulated stem cell heterogeneity, formed spheroids, and grew into tumors in immunocompromised mice, although these processes were more efficient in ALDH1(br) cells. In the ES-2 and CP70 cells, ALDH1(br) cells conferred more chemoresistance, and were more enriched in CD44 (by 1.74-fold and 5... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585635 Mon, 02 Jan 2012 05:00:00 +0100 5585635 http://www.medworm.com/index.php?rid=5585634&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222227%26dopt%3DAbstract Authors: Yi L, Liu Q, Orandle MS, Sadiq-Ali S, Koontz SM, Choi U, Torres-Velez FJ, Jackson SH Abstract Macrophage differentiation and function are pivotal for cell survival from infection and involve the processing of microenvironmental signals that determine macrophage cell fate decisions to establish appropriate inflammatory balance. NADPH oxidase 2 (Nox2)-deficient chronic granulomatous disease (CGD) mice that lack the gp91(phox) (gp91(phox-/-)) catalytic subunit show high mortality rates compared with wild-type mice when challenged by infection with Listeria monocytogenes (Lm), whereas p47(phox)-deficient (p47(phox-/-)) CGD mice show survival rates that are similar to those of wild-type mice. We demonstrate that such survival results from a skewed macrophage differentiation pro... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5585634 Mon, 02 Jan 2012 05:00:00 +0100 5585634 http://www.medworm.com/index.php?rid=5521005&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152994%26dopt%3DAbstract Authors: Thöne J, Ellrichmann G, Seubert S, Peruga I, Lee DH, Conrad R, Hayardeny L, Comi G, Wiese S, Linker RA, Gold R Abstract Laquinimod is a promising, orally available compound that has been successfully evaluated in placebo-controlled phase II/III studies of relapsing-remitting multiple sclerosis (MS). Studies are ongoing to further define laquinimod's modulatory mechanisms. Analyses in the animal model of experimental autoimmune encephalomyelitis (EAE) demonstrate that laquinimod reduces infiltration of leukocytes into the central nervous system, induces a Th1 to Th2/3 shift, and suppresses Th17 responses. To evaluate the potential neuroprotective capacity of laquinimod via modulation of brain-derived neurotrophic factor (BDNF), we analyzed the expression of BDNF in blood s... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5521005 Tue, 20 Dec 2011 15:07:16 +0100 5521005 http://www.medworm.com/index.php?rid=5521004&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154935%26dopt%3DAbstract Authors: Posey KL, Coustry F, Veerisetty AC, Liu P, Alcorn JL, Hecht JT Abstract Cartilage oligomeric matrix protein (COMP), a secreted glycoprotein synthesized by chondrocytes, regulates proliferation and type II collagen assembly. Mutations in the COMP gene cause pseudoachondroplasia and multiple epiphyseal dysplasia. Previously, we have shown that expression of D469del-COMP in transgenic mice causes intracellular retention of D469del-COMP, thereby recapitulating pseudoachondroplasia chondrocyte pathology. This inducible transgenic D469del-COMP mouse is the only in vivo model to replicate the critical cellular and clinical features of pseudoachondroplasia. Here, we report developmental studies of D469del-COMP-induced chondrocyte pathology from the prenatal period to adolescence. ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5521004 Tue, 06 Dec 2011 05:00:00 +0100 5521004 http://www.medworm.com/index.php?rid=5521003&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154936%26dopt%3DAbstract Authors: Coustry F, Posey KL, Liu P, Alcorn JL, Hecht JT Abstract Mutations in the cartilage oligomeric matrix protein gene (COMP; previously PSACH) cause pseudoachondroplasia. This dysplasia results from the intracellular retention of mutant COMP protein and premature death of growth-plate chondrocytes. Toward better understanding of these underlying mechanisms, we examined D469del-COMP activation of the unfolded protein response and cell death pathways in rat chondrosarcoma cells. Using an inducible expression system, we examined the effects of D469del-COMP retention after 4 days of mRNA expression and then 5 days without inducing agent. Retention of D469del-COMP stimulated Chop (Ddit3) and Gadd34 (Ppp1r15a) and triggered reactivation of protein translation that exacerbated intra... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5521003 Tue, 06 Dec 2011 05:00:00 +0100 5521003 http://www.medworm.com/index.php?rid=5521002&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155108%26dopt%3DAbstract Authors: Ohishi M, Ono W, Ono N, Khatri R, Marzia M, Baker EK, Root SH, Wilson TL, Iwamoto Y, Kronenberg HM, Aguila HL, Purton LE, Schipani E Abstract Bone marrow (BM) fibrosis is a feature of severe hyperparathyroidism. Consistent with this observation, mice expressing constitutively active parathyroid hormone (PTH)/PTH-related peptide receptors in osteoblasts (PPR(⁎)Tg) display BM fibrosis. To obtain insight into the nature of BM fibrosis in such a model, a double-mutant mouse expressing constitutively active PPR and green fluorescent protein (GFP) under the control of the type I collagen promoter (PPR(⁎)Tg/GFP) was generated. Confocal microscopy and flow cytometry revealed the presence of a cell population expressing GFP (GFP(+)) that was also positive for the hematopoietic ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5521002 Mon, 05 Dec 2011 05:00:00 +0100 5521002 http://www.medworm.com/index.php?rid=5521001&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155109%26dopt%3DAbstract Authors: Patel RM, Myers LS, Kurundkar AR, Maheshwari A, Nusrat A, Lin PW Abstract An immature intestinal epithelial barrier may predispose infants and children to many intestinal inflammatory diseases, such as infectious enteritis, inflammatory bowel disease, and necrotizing enterocolitis. Understanding the factors that regulate gut barrier maturation may yield insight into strategies to prevent these intestinal diseases. The Claudin family of tight junction proteins plays an important role in regulating epithelial paracellular permeability. Previous reports demonstrate that rodent intestinal barrier function matures during the first 3 weeks of life. We show that murine paracellular permeability markedly decreases during postnatal maturation, with the most significant change occur... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5521001 Mon, 05 Dec 2011 05:00:00 +0100 5521001 http://www.medworm.com/index.php?rid=5521000&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155110%26dopt%3DAbstract Authors: Huang J, Glauber M, Qiu Z, Gazit V, Dietzen DJ, Rudnick DA Abstract The relationship between liver and body mass is exemplified by the precision with which the liver:body mass ratio is restored after partial hepatic resection. Nevertheless, the compartments, against which liver mass is so exquisitely regulated, currently remain undefined. In the studies reported here, we investigated the role of skeletal muscle mass in the regulation of liver:body mass ratio and liver regeneration via the analysis of myostatin-null mice, in which skeletal muscle is hypertrophied. The results showed that liver mass is comparable and liver:body mass significantly diminished in the null animals compared to age-, gender-, and strain-matched controls. In association with these findings, basal h... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5521000 Mon, 05 Dec 2011 05:00:00 +0100 5521000 http://www.medworm.com/index.php?rid=5520999&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155111%26dopt%3DAbstract Authors: Zhou Y, Jiang X, Gu P, Chen W, Zeng X, Gao X Abstract Primary cicatricial alopecias (PCAs) are a group of permanent hair loss disorders, of which the pathogenesis is still poorly understood. The alopecia and excoriation (AE) mouse strain is a dominant mutant generated from ethyl nitrosourea mutagenesis. AE mice exhibit a progressive alopecia phenotype similar to that seen in PCAs, resulting from a point mutation in the gasdermin A3 (Gsdma3) gene. Mutant mice begin to show alopecia on the head from postnatal day 22 and experience complete hair loss by the age of 6 months, along with hyperkeratosis and catagen delay. The results of a histological examination showed that bulge stem cells in AE skin are gradually depleted, as indicated by decreased keratin 15 and CD34 expressi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5520999 Mon, 05 Dec 2011 05:00:00 +0100 5520999 http://www.medworm.com/index.php?rid=5520998&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155112%26dopt%3DAbstract Authors: Horváth B, Mukhopadhyay P, Haskó G, Pacher P Abstract Oxidative stress and inflammation play critical roles in the development of diabetes and its complications. Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions. The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, and neurodegenerative and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications. This review focuses on the role of the endocannabinoid sys... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5520998 Mon, 05 Dec 2011 05:00:00 +0100 5520998 http://www.medworm.com/index.php?rid=5484546&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142808%26dopt%3DAbstract Authors: Kajihara I, Jinnin M, Yamane K, Makino T, Honda N, Igata T, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H Abstract The aim of the present study was to determine the expression and role of thrombospondin-2 (TSP-2) in systemic sclerosis (SSc). Both TSP-2 mRNA levels and protein synthesis in cell lysates were significantly lower in cultured SSc fibroblasts than in normal fibroblasts; however, the TSP-2 protein that accumulated in the conditioned medium of SSc fibroblasts was up-regulated, compared with that of normal fibroblasts, because of an increase in the half-life of the protein. In vivo serum TSP-2 levels were higher in SSc patients than in healthy control subjects, and SSc patients with elevated serum TSP-2 levels tended to have pitting scars and/o... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5484546 Fri, 02 Dec 2011 05:00:00 +0100 5484546 http://www.medworm.com/index.php?rid=5484545&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142809%26dopt%3DAbstract Authors: Perez SE, Getova DP, He B, Counts SE, Geula C, Desire L, Coutadeur S, Peillon H, Ginsberg SD, Mufson EJ Abstract Cholinergic basal forebrain (CBF) nucleus basalis (NB) neurons display neurofibrillary tangles (NFTs) during Alzheimer's disease (AD) progression, yet the mechanisms underlying this selective vulnerability are currently unclear. Rac1, a member of the Rho family of GTPases, may interact with the proapoptotic pan-neurotrophin receptor p75(NTR) to induce neuronal cytoskeletal abnormalities in AD NB neurons. Herein, we examined the expression of Rac1b, a constitutively active splice variant of Rac1, in NB cholinergic neurons during AD progression. CBF tissues harvested from people who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive im... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5484545 Fri, 02 Dec 2011 05:00:00 +0100 5484545 http://www.medworm.com/index.php?rid=5484544&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142810%26dopt%3DAbstract Authors: Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Hotta H, Desaki J, Kishi M, Konishi T, Nishino Y, Miyazawa A, Maruyama N, Shigemoto K Abstract Antibodies against acetylcholine receptors (AChRs) cause pathogenicity in myasthenia gravis (MG) patients through complement pathway-mediated destruction of postsynaptic membranes at neuromuscular junctions (NMJs). However, antibodies against muscle-specific kinase (MuSK), which constitute a major subclass of antibodies found in MG patients, do not activate the complement pathway. To investigate the pathophysiology of MuSK-MG and establish an experimental autoimmune MG (EAMG) model, we injected MuSK protein into mice deficient in complement component five (C5). MuSK-injected mice simultaneously developed severe muscle weakness, ac... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5484544 Fri, 02 Dec 2011 05:00:00 +0100 5484544 http://www.medworm.com/index.php?rid=5484543&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142811%26dopt%3DAbstract Authors: Ceder R, Haig Y, Merne M, Hansson A, Zheng X, Roberg K, Nees M, Iljin K, Bloor BK, Morgan PR, Fadeel B, Grafström RC Abstract Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal or immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of whi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5484543 Fri, 02 Dec 2011 05:00:00 +0100 5484543 http://www.medworm.com/index.php?rid=5484548&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138298%26dopt%3DAbstract Authors: Velagapudi C, Nilsson RP, Lee MJ, Burns HS, Ricono JM, Arar M, Barnes VL, Abboud HE, Barnes JL Abstract Kidney development is regulated by a coordinated reciprocal induction of metanephric mesenchymal (MM) and ureteric bud (UB) cells. Here, established MM and UB progenitor cell lines were recombined in three-dimensional Matrigel implants in SCID mice. Differentiation potential was examined for changes in phenotype, organization, and the presence of specialized proteins using immunofluorescence and bright-field and electron microscopy. Both cell types, when grown alone, were monodispersed throughout the matrix, with UB cells forming infrequent small spheroids, mostly without lumens. When combined, the cells organized into simple organoid structures of polarized epithelia wi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5484548 Thu, 01 Dec 2011 05:00:00 +0100 5484548 http://www.medworm.com/index.php?rid=5484547&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138299%26dopt%3DAbstract Authors: Barrett R, Zhang X, Koon HW, Vu M, Chang JY, Yeager N, Nguyen MA, Michelsen KS, Berel D, Pothoulakis C, Targan SR, Shih DQ Abstract Intestinal fibrostenosis is a hallmark of severe Crohn's disease and can lead to multiple surgeries. Patients with certain TNFSF15 variants overexpress TL1A. The aim of this study was to determine the effect of TL1A overexpression on intestinal inflammation and the development of fibrostenosis. We assessed the in vivo consequences of constitutive TL1A expression on gut mucosal inflammation and fibrostenosis using two murine models of chronic colitis. In the dextran sodium sulfate (DSS) and adoptive T-cell transfer models, there was proximal migration of colonic inflammation, worsened patchy intestinal inflammation, and long gross intestinal st... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5484547 Thu, 01 Dec 2011 05:00:00 +0100 5484547 http://www.medworm.com/index.php?rid=5430372&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22093263%26dopt%3DAbstract Authors: Wang Y, Kirpich I, Liu Y, Ma Z, Barve S, McClain CJ, Feng W Abstract Gut-derived endotoxin is a critical factor in the development and progression of alcoholic liver disease (ALD). Probiotics can treat alcohol-induced liver injury associated with gut leakiness and endotoxemia in animal models, as well as in human ALD; however, the mechanism or mechanisms of their beneficial action are not well defined. We hypothesized that alcohol impairs the adaptive response-induced hypoxia-inducible factor (HIF) and that probiotic supplementation could attenuate this impairment, restoring barrier function in a mouse model of ALD by increasing HIF-responsive proteins (eg, intestinal trefoil factor) and reversing established ALD. C57BJ/6N mice were fed the Lieber DeCarli diet containing 5... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430372 Mon, 21 Nov 2011 13:24:26 +0100 5430372 http://www.medworm.com/index.php?rid=5430373&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22085974%26dopt%3DAbstract Authors: Chinnery HR, McLenachan S, Binz N, Sun Y, Forrester JV, Degli-Esposti MA, Pearlman E, McMenamin PG Abstract During bacterial and viral infections, unmethylated CpG-DNA released by proliferating and dying microbes is recognized by toll-like receptor (TLR) 9 in host cells, initiating innate immune responses. Many corneal infections occur secondary to epithelial breaches and represent a major cause of vision impairment and blindness globally. To mimic this clinical situation, we investigated mechanisms of TLR9 ligand-induced corneal inflammation in mice after epithelial debridement. Application of CpG oligodeoxynucleotides (ODNs) resulted in neutrophil and macrophage infiltration to the cornea and loss of transparency. By 6 hours after CpG-ODN administration, TLR9 mRNA was in... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430373 Fri, 11 Nov 2011 05:00:00 +0100 5430373 http://www.medworm.com/index.php?rid=5430375&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079928%26dopt%3DAbstract Authors: Fernandez DC, Pasquini LA, Dorfman D, Aldana Marcos HJ, Rosenstein RE Abstract Diabetic retinopathy is a leading cause of acquired blindness. Visual function disorders have been observed in diabetic patients with very early retinopathy or even before the onset of retinopathy. The aim of the present work was to analyze the visual pathway in an early stage of experimental diabetes. Diabetes was induced in Wistar rats by an i.p. injection of streptozotocin. A deficit in anterograde transport from the retina to the superior colliculus was observed 6 weeks after streptozotocin injection. At this time point, morphologic studies did not reveal retinal ganglion cell loss or substantial alterations in the superior colliculus. The optic nerve was morphometrically evaluated at intrao... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430375 Wed, 09 Nov 2011 05:00:00 +0100 5430375 http://www.medworm.com/index.php?rid=5430374&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079929%26dopt%3DAbstract Authors: Ying WZ, Wang PX, Sanders PW Abstract Renal failure, a major complication associated with multiple myeloma, is usually related to deposition of monoclonal immunoglobulin free light chains (FLC) and directly contributes to morbidity and mortality in this disease. The present study focused on the cytotoxic effects of monoclonal FLC. Human proximal tubular epithelial cells (HK-2) were examined after incubation with two human monoclonal FLC (termed κ2 and λ3). Incubation of HK-2 cells for 24 and 48 hours with either FLC at 1 mg/mL promoted activation of caspase-9 and caspase-3 and increased the rate of apoptosis. Because prior studies demonstrated that FLC generated intracellular oxidative stress, our studies focused on the redox-sensitive mitogen-activated protein kinase ki... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430374 Wed, 09 Nov 2011 05:00:00 +0100 5430374 http://www.medworm.com/index.php?rid=5430380&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079428%26dopt%3DAbstract Authors: Pavlov VI, Bonte LR, Baldwin WM, Markiewski M, Lambris J, Stahl GL Abstract Diabetes, stress, pharmaceuticals, surgery, and physical trauma can lead to hyperglycemic conditions. A consistent relationship has been found between chronic inflammation and the cardiovascular complications of hyperglycemia. We hypothesized that cardiomyopathy and vasculopathy resulting from acute hyperglycemia are dependent on mannose-binding lectin (MBL) and lectin complement pathway activation. Hyperglycemia was induced in wild-type (WT) C57BL/6 and MBL-null mice after streptozotocin administration. Echocardiographic data and tissue samples were collected after 4, 7, or 14 days of acute hyperglycemia. Hyperglycemic WT mice demonstrated dilated cardiomyopathy with significantly increased short ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430380 Tue, 08 Nov 2011 05:00:00 +0100 5430380 http://www.medworm.com/index.php?rid=5430379&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079429%26dopt%3DAbstract Authors: Ganesan S, Faris AN, Comstock AT, Sonstein J, Curtis JL, Sajjan US Abstract Nontypeable Haemophilus influenzae (NTHi) is an important bacterial pathogen associated with lower respiratory tract colonization and with acute exacerbations and disease progression in chronic obstructive pulmonary disease (COPD). Why the immune system fails to eliminate NTHi and the exact contribution of the organism to COPD progression are not well understood, in part because we lack an animal model that mimics all aspects of COPD. For this study, we used an established murine model that exhibits typical features of COPD. Elastase/LPS-exposed mice infected with NTHi showed persistence of bacteria up to 5 days after infection, whereas mice exposed to elastase, LPS, or PBS cleared all bacteria by ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430379 Tue, 08 Nov 2011 05:00:00 +0100 5430379 http://www.medworm.com/index.php?rid=5430378&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079430%26dopt%3DAbstract Authors: Lacerda-Queiroz N, Rodrigues DH, Vilela MC, Rachid MA, Soriani FM, Sousa LP, Campos RD, Quesniaux VF, Teixeira MM, Teixeira AL Abstract Cerebral malaria is a severe form of the disease that may result, in part, from an overt inflammatory response during infection by Plasmodium falciparum. The understanding of the pathogenesis of cerebral malaria may aid in the development of better therapeutic strategies for patients. The immune response in cerebral malaria involves elevation of circulating levels of cytokines and chemokines associated with leukocyte accumulation and breakdown of the blood-brain barrier in the central nervous system. Platelet-activating factor (PAF) is a mediator of inflammation shown to orchestrate inflammatory processes, including recruitment of leukocyt... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430378 Tue, 08 Nov 2011 05:00:00 +0100 5430378 http://www.medworm.com/index.php?rid=5430377&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079431%26dopt%3DAbstract Authors: Holland OJ, Linscheid C, Hodes HC, Nauser TL, Gilliam M, Stone P, Chamley L, Petroff MG Abstract The fetal semi-allograft can induce expansion and tolerance of antigen-specific maternal T and B cells through paternally inherited major histocompatibility complex and minor histocompatibility antigens (mHAgs). The effects of these antigens have important consequences on the maternal immune system both during and long after pregnancy. Herein, we investigate the possibility that the placental syncytiotrophoblast and deported trophoblastic debris serve as sources of fetal mHAgs. We mapped the expression of four mHAgs (human mHAg 1, KIAA0020, B-cell lymphoma 2-related protein A1, and ribosomal protein S4, Y linked) in the placenta. Each of these proteins was expressed in several ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430377 Tue, 08 Nov 2011 05:00:00 +0100 5430377 http://www.medworm.com/index.php?rid=5430376&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079432%26dopt%3DAbstract Authors: Snelgrove SL, Kausman JY, Lo C, Lo C, Ooi JD, Coates PT, Hickey MJ, Holdsworth SR, Kurts C, Engel DR, Kitching AR Abstract Unilateral ureteral obstruction (UUO) is a well-characterized murine model of renal inflammation leading to fibrosis. Renal dendritic cells (DCs) constitute a significant portion of kidney leukocytes and may participate in local inflammation and have critical roles in antigen presentation. The heterogeneity in renal DC populations and surface marker overlap with monocytes/macrophages has made studying renal DCs difficult. These studies used CD11c-promoter driven reporter/depletion mice to study DCs in vivo. Studying early local inflammatory events (day 3 of UUO), in vivo multiphoton imaging of the intact kidney of CD11c reporter mice revealed more dend... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430376 Tue, 08 Nov 2011 05:00:00 +0100 5430376 http://www.medworm.com/index.php?rid=5430385&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074736%26dopt%3DAbstract This study was undertaken to evaluate the contribution of purinergic signaling to disturbed vasodilation and vascular remodeling during atherosclerosis progression. We used apolipoprotein E-deficient (Apoe(-/-)) mice as an appropriate experimental model for atherosclerosis. Noninvasive transthoracic Doppler echocardiography imaging with adenosine, ATP, and other nucleotides and nonhydrolyzable P2 receptor agonists and antagonists suggests that ATP regulates coronary blood flow in mice through activation of P2Y (most likely, endothelial ATP/UTP-selective P2Y(2)) receptors, rather than via its dephosphorylation to adenosine. Strikingly, compared to age-matched wild-type controls, young (10- to 15-week-old) Apoe(-/-) mice displayed diminished coronary reactivity in response to ATP but not ade... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430385 Mon, 07 Nov 2011 05:00:00 +0100 5430385 http://www.medworm.com/index.php?rid=5430384&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074737%26dopt%3DAbstract Authors: Otani A, Kojima H, Guo C, Oishi A, Yoshimura N Abstract The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (LD) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a conditio... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430384 Mon, 07 Nov 2011 05:00:00 +0100 5430384 http://www.medworm.com/index.php?rid=5430383&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074738%26dopt%3DAbstract Authors: Holler CJ, Webb RL, Laux AL, Beckett TL, Niedowicz DM, Ahmed RR, Liu Y, Simmons CR, Dowling AL, Spinelli A, Khurgel M, Estus S, Head E, Hersh LB, Murphy MP Abstract β-Secretase, the rate-limiting enzymatic activity in the production of the amyloid-β (Aβ) peptide, is a major target of Alzheimer's disease (AD) therapeutics. There are two forms of the enzyme: β-site Aβ precursor protein cleaving enzyme (BACE) 1 and BACE2. Although BACE1 increases in late-stage AD, little is known about BACE2. We conducted a detailed examination of BACE2 in patients with preclinical to late-stage AD, including amnestic mild cognitive impairment, and age-matched controls, cases of frontotemporal dementia, and Down's syndrome. BACE2 protein and enzymatic activity increased as early as precl... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430383 Mon, 07 Nov 2011 05:00:00 +0100 5430383 http://www.medworm.com/index.php?rid=5430382&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074739%26dopt%3DAbstract Authors: Kinoshita Y, Kalir T, Rahaman J, Dottino P, Stave Kohtz D Abstract Diverse cell phenotypes arise in tumors just as they do in developing organisms, and tumor recurrence frequently arises from the selective survival of divergent-resistant cells. Although the expanding tumor cell population may be successfully targeted, drug-resistant cells may persist and sustain the tumor or enter dormancy before igniting a future relapse. Herein, we show that partial knockdown of nucleoporin p62 (NUP62) by small-interfering RNA confers cisplatin resistance to cultured high-grade ovarian carcinoma cells. Treatment with NUP62 small-interfering RNA and cisplatin leaves resistant cells in a state of dormancy; some dormant cells can be induced to proliferate by transient induction of NUP62 exp... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430382 Mon, 07 Nov 2011 05:00:00 +0100 5430382 http://www.medworm.com/index.php?rid=5430381&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074740%26dopt%3DAbstract In this study, we used gene therapy in the form of antisense oligonucleotides (ASOs) specifically to silence Kirsten-ras [Kras(alias Ki-ras)] expression in a rat model of renal fibrosis caused by unilateral ureteric obstruction. We demonstrate that renal Kras expression increases by 70% in this model compared with in sham-operated animals and that treatment with ASOs can reduce total renal Kras by >90% to levels well below basal. This silencing is associated with a dramatic inhibition of interstitial fibrosis, a fivefold reduction in α-smooth muscle actin expression, and a 2.4-fold reduction in collagen I deposition. This inhibition was observed despite histologic evidence of marked interstitial inflammation. These findings demonstrate that silencing Kras expression can markedly inhibi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430381 Mon, 07 Nov 2011 05:00:00 +0100 5430381 http://www.medworm.com/index.php?rid=5430395&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067905%26dopt%3DAbstract In this study, our data show that co-culture of leukocytes isolated from breast tumor tissue leads to uptake of fibronectin (FN) on or in the tumor exosomes (Exo(fib+)). The induction of FN and exosomal uptake is tumor tissue derived and leukocyte specific, because leukocytes isolated from the peripheral blood of naïve mice failed to induce FN uptake by tumor exosomes. Furthermore, depletion of both CD25(+) cells and Gr-1(+) cells from tumor-associated leukocytes causes a reduction of Exo(fib+), suggesting that tumor-associated CD25(+) cells and Gr-1(+) cells participate in FN production and uptake by tumor exosomes, resulting in Exo(fib+). As a result of tumor cells absorbing Exo(fib+), two major events are induced: focal adhesion kinase/Src-dependent signaling pathways are activated, an... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430395 Sat, 05 Nov 2011 04:00:00 +0100 5430395 http://www.medworm.com/index.php?rid=5430394&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067906%26dopt%3DAbstract Authors: Chen M, Copland DA, Zhao J, Liu J, Forrester JV, Dick AD, Xu H Abstract Neovascular retinal disease is a leading cause of blindness orchestrated by inflammatory responses. Although noninfectious uveoretinitis is mediated by CD4(+) T cells, in the persistent phase of disease, angiogenic responses are observed, along with degeneration of the retina. Full clinical manifestation relies on myeloid-derived cells, which are phenotypically distinct from, but potentially sharing common effector responses to, age-related macular degeneration. To interrogate inflammation-mediated angiogenesis, we investigated experimental autoimmune uveoretinitis, an animal model for human uveitis. After the initial acute phase of severe inflammation, the retina sustains a persistent low-grade inflam... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430394 Sat, 05 Nov 2011 04:00:00 +0100 5430394 http://www.medworm.com/index.php?rid=5430393&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067907%26dopt%3DAbstract Authors: Gobbetti T, Cenac N, Motta JP, Rolland C, Martin L, Andrade-Gordon P, Steinhoff M, Barocelli E, Vergnolle N Abstract Proteases and proteinase-activated receptor (PAR) activation are involved in several intestinal inflammatory conditions. We hypothesized that serine proteases and PAR activation could also modulate the intestinal injury induced by ischemia-reperfusion (I-R). C57Bl/6 mice were subjected to 90 minutes of intestinal ischemia followed or not by reperfusion. Sham-operated animals served as controls. After ischemia, plasma and tissue serine protease activity levels were increased compared to the activity measured in plasma and tissues from sham-operated mice. This increase was maintained or further enhanced after 2 and 5 hours of reperfusion, respectively. Trypsin... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430393 Sat, 05 Nov 2011 04:00:00 +0100 5430393 http://www.medworm.com/index.php?rid=5430392&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067908%26dopt%3DAbstract Authors: Choi SK, Galan M, Partyka M, Trebak M, Belmadani S, Matrougui K Abstract Type 2 diabetes is a key risk factor for ischemia-dependent pathology; therefore, a significant medical need exists to develop novel therapies that increase the formation of new vessels. We explored the therapeutic potential of epidermal growth factor receptor tyrosine kinase (EGFRtk) and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibition in impaired ischemia-induced neovascularization in type 2 diabetes. Unilateral femoral artery ligation was performed in diabetic (db(--)/db(--)) and their control (db(--)/db(+)) mice for 4 weeks, followed by treatments with EGFRtk and ERK1/2 inhibitors (AG1478, 10 mg/kg/day and U0126, 400 μg/kg/day, respectively) for 3 weeks. Neovascularization, blood flo... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430392 Sat, 05 Nov 2011 04:00:00 +0100 5430392 http://www.medworm.com/index.php?rid=5430391&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067909%26dopt%3DAbstract Authors: Juskewitch JE, Knudsen BE, Platt JL, Nath KA, Knutson KL, Brunn GJ, Grande JP Abstract Systemic inflammation remains a major cause of morbidity and mortality in the United States, across many disease processes. One classic murine model to study this syndrome is lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4)-dependent systemic inflammation. Although most studies have focused on inflammatory cell TLR4 responses, parenchymal cells also express TLR4. Our objective was to define the in vivo role of parenchymal- versus marrow-derived cell activation via TLR4 during LPS-induced inflammation. Mice bearing TLR4 on parenchymal cells only, marrow-derived cells only, both, or neither were generated using bone marrow transplantation. Mortality occurred only in mice that h... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430391 Sat, 05 Nov 2011 04:00:00 +0100 5430391 http://www.medworm.com/index.php?rid=5430390&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067910%26dopt%3DAbstract Authors: Caccamo A, Majumder S, Oddo S Abstract Transactive response DNA-binding protein 43 (TDP-43) is the pathological signature protein in several neurodegenerative disorders, including the majority of frontotemporal lobar degeneration cases (FTLD-TDP), motor neuron disease, and amyotrophic lateral sclerosis. Pathological TDP-43 is mislocalized from its nuclear location to the cytoplasm, where it accumulates and is proteolytically cleaved to form C-terminal fragments. Although the 25-kDa C-terminal fragment of TDP-43 (TDP-25) accumulates in affected brain regions, its role in the disease pathogenesis remains elusive. To address this problem, we have generated a novel transgenic mouse that selectively expresses TDP-25 in neurons. We show that transgenic mice expressing TDP-25 dev... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430390 Sat, 05 Nov 2011 04:00:00 +0100 5430390 http://www.medworm.com/index.php?rid=5430389&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067911%26dopt%3DAbstract Authors: Kessler M, Zielecki J, Thieck O, Mollenkopf HJ, Fotopoulou C, Meyer TF Abstract The obligate intracellular pathogen Chlamydia trachomatis (Ctr) is a major cause of sexually transmitted disease and infertility worldwide. Ascending genital infections cause inflammation of fallopian tubes and subsequent scarring and occlusion. The cellular basis for such sequelae remains undetermined. We used confocal immunofluorescence microscopy to show that Ctr disrupts epithelial homeostasis in an ex vivo infection model of human fallopian tubes. Ctr triggered loss of polarity of inclusion harboring cells and of neighboring uninfected cells, as shown by subcellular redistribution of adhesion and polarity (occludin) markers. β-catenin (a component of the adherens junction and a Wnt signal... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430389 Sat, 05 Nov 2011 04:00:00 +0100 5430389 http://www.medworm.com/index.php?rid=5430388&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067912%26dopt%3DAbstract Authors: McKenzie JA, Fruttiger M, Abraham S, Lange C, Stone J, Gandhi P, Wang X, Bainbridge J, Moss SE, Greenwood J Abstract Retinal pathologies are frequently accompanied by retinal vascular responses, including the formation of new vessels by angiogenesis (neovascularization). Pathological vascular changes may also include less well characterized traits of vascular remodeling that are non-neovascular, such as vessel pruning and the emergence of dilated and tortuous vessel phenotypes (telangiectasis). The molecular mechanisms underlying neovascular growth versus non-neovascular remodeling are poorly understood. We therefore undertook to identify novel regulators of non-neovascular remodeling in the retina by using the dystrophic Royal College of Surgeons (RCS) rat and the retinal... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430388 Sat, 05 Nov 2011 04:00:00 +0100 5430388 http://www.medworm.com/index.php?rid=5430387&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067913%26dopt%3DAbstract Authors: Hofmann U, Bonz A, Frantz S, Hu K, Waller C, Roemer K, Wolf J, Gattenlöhner S, Bauersachs J, Ertl G Abstract Collagen breakdown and de novo synthesis are important processes during early wound healing after myocardial infarction (MI). We tested the hypothesis that collagen I, the main constituent of the extracellular matrix, affects wound healing after MI. The osteogenesis imperfecta mouse (OIM), lacking pro-α2(I) collagen expression, represents a model of the type III form of the disease in humans. Homozygous (OIM/OIM), heterozygous (OIM/WT), and wild-type (WT/WT) mice were subjected to a permanent myocardial infarction protocol or sham surgery. Baseline functional and geometrical parameters determined by echocardiography did not differ between genotypes. After MI but n... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430387 Sat, 05 Nov 2011 04:00:00 +0100 5430387 http://www.medworm.com/index.php?rid=5430386&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067914%26dopt%3DAbstract Authors: Ishimaru N, Yamada A, Nitta T, Arakaki R, Lipp M, Takahama Y, Hayashi Y Abstract Forkhead box p3-positive (Foxp3(+)) regulatory T cells (T(reg) cells) participate in maintaining peripheral immune tolerance and suppressing autoimmunity. We recently reported that in situ patrolling by C-C-chemokine receptor 7 (CCR7)(+) T(reg) cells in target organs is essential for controlling autoimmune lesions in Sjögren's syndrome. In the present study, the molecular mechanism underlying CCR7-mediated T(reg) cell migration was investigated in a mouse model. The impaired migratory response of Ccr7(-/-) T(reg) cells to sphingosine 1-phosphate (S1P) occurred because of defective association of S1P receptor 1 (S1P(1)) with a G coupled-protein. In addition, T-cell receptor (TCR)- and S1P(1)-m... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5430386 Sat, 05 Nov 2011 04:00:00 +0100 5430386 http://www.medworm.com/index.php?rid=5385562&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22062220%26dopt%3DAbstract Authors: Yang HZ, Wang JP, Mi S, Liu HZ, Cui B, Yan HM, Yan J, Li Z, Liu H, Hua F, Lu W, Hu ZW Abstract Pulmonary fibrosis is an inflammation-driven lung disease with a poor prognosis and no cure. Here we report that basal toll-like receptor 4 (TLR4) activity is critical for the resolution of acute and chronic inflammation and pulmonary fibrosis in mouse models of lung injury. We found that genetic or pharmacologic inhibition of TLR4 exacerbates bleomycin-induced pulmonary inflammation, fibrosis, dysfunction, and animal death through promoting formation of an immunosuppressive tissue microenvironment and attenuating autophagy-associated degradation of collagen and cell death in the fibrotic lung tissues. In contrast, pharmacologic activation of TLR4 resulted in a quick resolution o... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385562 Fri, 04 Nov 2011 04:00:00 +0100 5385562 http://www.medworm.com/index.php?rid=5385561&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22062221%26dopt%3DAbstract Authors: Choi B, Chun E, Kim SY, Kim M, Lee KY, Kim SJ Abstract Ex vivo expansion of CD34(+) stem cells in contact culture between hCD34(+)CD38(-)Lin(-) cord blood stem cells and human delta-like-expressing AFT024 feeder cells revealed increased amounts of stemness-related proteins such as HoxB4, GATA2, Bmi-1, and p21 and anti-apoptotic proteins such as Bcl-2, Bcl-xL, Mcl-1, and Bad, when compared with control or noncontact culture. Production of human IL-6 (hIL-6) was markedly elevated in the culture, but was profoundly inhibited by treatment with γ-secretase inhibitor. In addition, Notch-induced activation of STAT3 was directly involved in gene expression of hIL-6 and soluble hIL-6Rα, indicating the close linkage between Notch signaling and hIL-6 production. Furthermore, deplet... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385561 Fri, 04 Nov 2011 04:00:00 +0100 5385561 http://www.medworm.com/index.php?rid=5385560&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22062222%26dopt%3DAbstract In this study, we used an IL-6 blocking antibody and IL-6 knockout (IL-6KO) mice to examine the role of IL-6 in the bleomycin-induced mouse model of scleroderma. Bleomycin was administered to C57BL/6 and IL-6KO mice to induce dermal sclerosis. Bleomycin-treated and control phosphate-buffered saline (PBS)-treated mice were treated with IL-6 receptor-specific monoclonal antibody (MR16-1). Disease severity was evaluated by measuring dermal thickness and skin hardness, by counting the numbers of α-smooth muscle actin (α-SMA)-positive cells and mast cells, and by examining the cutaneous draining lymph nodes. C57BL/6 mice with bleomycin-induced scleroderma had elevated serum IL-6 levels and more severe dermal sclerosis than IL-6KO mice. Weekly administration of MR16-1, but not control antibody... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385560 Fri, 04 Nov 2011 04:00:00 +0100 5385560 http://www.medworm.com/index.php?rid=5385559&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22063298%26dopt%3DAbstract In conclusion, fibroblasts, and not epithelial cells, appear to be the defective cell type in nitrofen-induced hypoplastic lungs due to a decreased ability to undergo apoptosis and maintain overall proliferation. This may explain the characteristic pulmonary interstitial thickening and hypoplasia observed in both nitrofen-induced hypoplastic lungs as well as human hypoplastic CDH lungs. PMID: 22063298 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385559 Thu, 03 Nov 2011 04:00:00 +0100 5385559 http://www.medworm.com/index.php?rid=5385558&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22063299%26dopt%3DAbstract Authors: Mommert S, Gschwandtner M, Koether B, Gutzmer R, Werfel T Abstract The histamine H4 receptor is functionally expressed on CD4(+) T cells and in particular on human CD4(+) Th2-polarized T cells. Interleukin (IL)-17-producing T cells (Th17 cells) represent a newly defined major CD4(+) T-cell subset, having been identified in psoriatic plaques and in acute skin lesions of atopic dermatitis where histamine is also present in high concentrations. To elucidate the role of the histamine H4 receptor (H4R) on these effector T cells, we polarized human memory T cells into Th17 cells. Further, we investigated H4R expression and assessed its function by real-time PCR, by a cytokine secretion assay of IL-17, and by electrophoretic mobility shift assay of activating protein-1 (AP-1). We... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385558 Thu, 03 Nov 2011 04:00:00 +0100 5385558 http://www.medworm.com/index.php?rid=5385568&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056358%26dopt%3DAbstract Authors: Mori N, Kuwamura M, Tanaka N, Hirano R, Nabe M, Ibuki M, Yamate J Abstract Cortical heterotopia, a malformation of the developing cortex, are a major cause of epilepsy and mental retardation in humans. Hemorrhagic hydrocephalus (hhy) mutation on mouse chromosome 12 results in subcortical heterotopia and nonobstructive hydrocephalus with frequent brain hemorrhage. Here, we show that coiled-coil domain-containing 85C (Ccdc85c), consisting of 6 exons that encode a 420 amino acid protein, is disrupted by replacement of a 3.2-kb sequence, including exon 2 in Ccdc85c by a 1.5-kb retrotransposon-like repeat sequence in the hhy mutant. Immunoreactivity to Ccdc85C was detected predominantly at the apical junctions of radial glia in the wall of lateral ventricles of the developing b... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385568 Wed, 02 Nov 2011 04:00:00 +0100 5385568 http://www.medworm.com/index.php?rid=5385567&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056359%26dopt%3DAbstract Authors: Woo DK, Green PD, Santos JH, D'Souza AD, Walther Z, Martin WD, Christian BE, Chandel NS, Shadel GS Abstract Alterations in mitochondrial oxidative phosphorylation have long been documented in tumors. Other types of mitochondrial dysfunction, including altered reactive oxygen species (ROS) production and apoptosis, also can contribute to tumorigenesis and cancer phenotypes. Furthermore, mitochondria contain mtDNA, mutation and altered amounts of which have been observed in cancer cells. However, how mtDNA instability per se contributes to cancer remains largely undetermined. The transcription factor and mtDNA-packaging protein (Tfam) is required for expression and maintenance of mtDNA. Tfam heterozygous knock-out (Tfam(+/-)) mice show mild mtDNA depletion, but have no overt... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385567 Wed, 02 Nov 2011 04:00:00 +0100 5385567 http://www.medworm.com/index.php?rid=5385566&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056360%26dopt%3DAbstract In this study, we determined the effect of EGCG on the development of experimental autoimmune encephalomyelitis, an animal model for human multiple sclerosis, and the underlying mechanisms. Female C57BL/6 mice were fed EGCG (0%, 0.15%, 0.3%, and 0.6% in diet) for 30 days and then immunized with specific antigen myelin oligodendrocyte glycoprotein 35-55. EGCG dose dependently attenuated clinical symptoms and pathological features (leukocyte infiltration and demyelination) in the central nervous system and inhibited antigen-specific T-cell proliferation and delayed-type hypersensitivity skin response. We further showed that EGCG reduced production of interferon-γ, IL-17, IL-6, IL-1β, and tumor necrosis factor-α; decreased types 1 and 17 helper T cells (Th1 and Th17, respectively); and inc... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385566 Wed, 02 Nov 2011 04:00:00 +0100 5385566 http://www.medworm.com/index.php?rid=5385565&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056361%26dopt%3DAbstract Authors: Fröhlich JD, Huppertz B, Abuja PM, König J, Desoye G Abstract Pregestational diabetes retards early embryonic growth. Placental and fetal growth are closely associated, suggesting that placental growth is also impaired. During the first trimester of gestation, oxygen tension rises steeply, leading to excessive production of reactive oxygen species (ROS), which is exacerbated in diabetes and may affect placental development. We hypothesized that oxygen modifies hyperglycemic effects on ROS formation, resulting in decreased first-trimester trophoblast growth. This was tested using a first-trimester trophoblast-derived cell line (ACH-3P). Normoglycemia did not alter ACH-3P proliferation at 2.5%, 8%, and 21% oxygen. Hyperglycemic conditions for up to 3 days reduced cell numb... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385565 Wed, 02 Nov 2011 04:00:00 +0100 5385565 http://www.medworm.com/index.php?rid=5385564&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056910%26dopt%3DAbstract Authors: Ok CY, Singh RR, Vega F Abstract The hedgehog (HH) signaling pathway is a highly regulated signaling pathway that is important not only for embryonic development, tissue patterning, and organogenesis but also for tissue repair and the maintenance of stem cells in adult tissues. In the adult hematopoietic system, HH signaling regulates intrathymic T-cell development, and it is one of the survival signals provided by follicular dendritic cells to prevent apoptosis in germinal center B cells. HH signaling is required for primitive hematopoiesis; however, conflicting data have been reported regarding the role of the HH pathway in adult hematopoiesis. Inappropriate activation of the HH signaling pathway occurs in several human cancers, including hematopoietic neoplasms. Emergin... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385564 Tue, 01 Nov 2011 04:00:00 +0100 5385564 http://www.medworm.com/index.php?rid=5385563&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056911%26dopt%3DAbstract We report herein that MKlp2 transiently accumulates in vivo during mouse liver regeneration after partial hepatectomy and is strongly overexpressed in preneoplastic and neoplastic mouse liver. In vitro in mitogen-stimulated primary hepatocytes, MKlp2 accumulated in the nucleus during the G2 phase of the cell cycle coincident with the mitotic kinase Aurora B. Human hepatoma cell lines exhibited high levels of MKlp2; however, it was undetectable in normal human hepatocytes. RNAi-mediated MKlp2 knockdown in hepatoma cells induced polyploidization consistent with its essential function in promoting cytokinesis and inhibited cell proliferation without inducing apoptosis. KIF20A mRNA was strongly accumulated in a large series of human hepatocellular carcinomas, with the highest expression observ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385563 Tue, 01 Nov 2011 04:00:00 +0100 5385563 http://www.medworm.com/index.php?rid=5385571&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051773%26dopt%3DAbstract In this study, we found that acute ethanol administration increased AQP4 expression after TBI, leading to severe brain edema in rats. Rats were pretreated with ethanol (3 g/kg) or dl-buthionine-(S,R)-sulfoximine (BSO; 100 mg/kg), an oxidative stressor, before TBI. Acetazolamide, an AQP4 inhibitor, was administered to ethanol-pretreated rats 3 or 12 hours after TBI. Brain edema was increased 24 hours after TBI in both the ethanol- and BSO-pretreated groups. Ethanol pretreatment induced lipid peroxidation 24 hours after TBI. Transcription factors, NF-κB and hypoxia-inducible factor-1α, were activated 3 and 24 hours after TBI in the BSO- and ethanol-pretreated groups, respectively. In the ethanol-pretreated group, AQP4 was accumulated, particularly in astrocyte end feet, 24 hours after TBI.... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385571 Mon, 31 Oct 2011 04:00:00 +0100 5385571 http://www.medworm.com/index.php?rid=5385570&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051774%26dopt%3DAbstract Authors: Torzewski M, Wenzel P, Kleinert H, Becker C, El-Masri J, Wiese E, Brandt M, Pautz A, Twardowski L, Schmitt E, Münzel T, Reifenberg K Abstract We recently described a model of inflammatory cardiomyopathy in signaling lymphocyte activation molecule-associated protein (SAP)-interferon (IFN)-γ transgenic mice stably circulating IFN-γ in the serum. SAP-IFN-γ transgenic mice show cardiac infiltration by mononuclear leukocytes, culminating in dilated cardiomyopathy. characterized by an increase of left ventricular end diastolic/systolic diameter and reduction of fractional shortening. We hypothesized that the pathological mechanism underlying SAP-IFN-γ cardiomyopathy might be mediated by (auto)immune processes or tumor necrosis factor (TNF)-α synthesis from IFN-γ-activated... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385570 Mon, 31 Oct 2011 04:00:00 +0100 5385570 http://www.medworm.com/index.php?rid=5385569&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051775%26dopt%3DAbstract Authors: Sato Y, Harada K, Sasaki M, Yasaka T, Nakanuma Y Abstract Cholangiocarcinoma often is diagnosed at an advanced stage. Thus, it is necessary to establish sensitive screening methods that would allow cholangiocarcinoma and preferably its precursor lesion [biliary intraepithelial neoplasia (BilIN)] to be detected. We sought to clarify the usefulness of heat shock protein (HSP) 27 and HSP70 as biomarkers of cholangiocarcinoma and have used immunohistochemical analyses of hepatolithiatic livers to characterize HSP27 and HSP70 expression during the multistep cholangiocarcinogenesis process. HSP27 and HSP70 were measured in serum and bile samples via enzyme-linked immunosorbent assay. In hepatolithiatic tissue, the expression of HSP27 and HSP70 was increased in BilIN as well as i... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385569 Mon, 31 Oct 2011 04:00:00 +0100 5385569 http://www.medworm.com/index.php?rid=5385572&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22040583%26dopt%3DAbstract Authors: Abstract The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. PMID: 22040583 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385572 Sat, 29 Oct 2011 04:00:00 +0100 5385572 http://www.medworm.com/index.php?rid=5385574&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035642%26dopt%3DAbstract Authors: Pennock S, Rheaume MA, Mukai S, Kazlauskas A Abstract Proliferative vitreoretinopathy (PVR) thwarts the repair of rhegmatogenous retinal detachments. Currently, there is no effective prevention for PVR. Platelet-derived growth factor receptor α (PDGFRα) is associated with PVR in humans and strongly promotes experimental PVR driven by multiple vitreal growth factors outside the PDGF family. We sought to identify vitreal factors required for experimental PVR and to establish a potential approach to prevent PVR. Vitreous was obtained from normal rabbits or those in which PVR was either developing or stabilized. Normal vitreous contained substantial levels of growth factors and cytokines, which changed quantitatively and/or qualitatively as PVR progressed and stabilized. Neu... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385574 Thu, 27 Oct 2011 04:00:00 +0100 5385574 http://www.medworm.com/index.php?rid=5385573&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22037251%26dopt%3DAbstract Authors: Nakasone Y, Fujimoto M, Matsushita T, Hamaguchi Y, Huu DL, Yanaba M, Sato S, Takehara K, Hasegawa M Abstract Leukocytic infiltration into malignant melanoma lesions is tightly regulated by chemokines. To assess the role of the CC chemokines monocyte chemotactic protein (MCP)-1/chemokine ligand 2 and macrophage inflammatory protein (MIP)-1α/chemokine ligand 3 in this process, s.c. primary and metastatic B16 F10 melanoma tumor growth levels were examined in mice lacking MCP-1 or MIP-1α. Primary s.c. B16 F10 melanoma growth was augmented by loss of MCP-1 or MIP-1α. Similarly, lung metastasis was enhanced by the deficiency of MCP-1 or MIP-1α. Enhanced tumor outgrowth was associated with decreased percentages of infiltrating CD4(+) T cells, CD8(+) T cells, and natural kille... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385573 Wed, 26 Oct 2011 04:00:00 +0100 5385573 http://www.medworm.com/index.php?rid=5385575&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033229%26dopt%3DAbstract Authors: Moore CS, Crocker SJ Abstract Tissue inhibitors of metalloproteinases (TIMPs) are pleiotropic extracellular proteins. TIMPs are recognized as endogenous regulators of matrix metalloproteinases (MMPs), a large family of extracellular enzymes with proteolytic activities that participate in cellular homeostasis, adaptation, and tissue remodeling. In addition to their roles as endogenous potent MMP inhibitors, accumulating evidence indicates important physiological roles for TIMPs that are independent of their ability to block MMP activities. For instance, MMP-independent actions of TIMP-1 in the central nervous system have been implicated in synaptic plasticity, neuroprotection, oncogenesis, and oligodendrocyte differentiation. Expression of TIMP-1 is dramatically increased i... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385575 Tue, 25 Oct 2011 04:00:00 +0100 5385575 http://www.medworm.com/index.php?rid=5385578&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019896%26dopt%3DAbstract In conclusion, loss of DDR2 promotes chronic liver fibrosis after CCl(4) injury. The fibrogenic sinusoidal milieu generated in chronic DDR2(-/-) livers recruits more HSCs to injured regions, which enhances fibrosis. Together, these findings suggest that normally DDR2 orchestrates gene programs and paracrine interactions between HSCs and macrophages that together attenuate chronic hepatic fibrosis. PMID: 22019896 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385578 Wed, 19 Oct 2011 04:00:00 +0100 5385578 http://www.medworm.com/index.php?rid=5385577&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019897%26dopt%3DAbstract Authors: Tsujimoto I, Moriya K, Sakai K, Dickneite G, Sakai T Abstract The transglutaminase-mediated, covalent cross-linking of proteins is an essential step in tissue remodeling after injury. This process provides tissues with extra rigidity and resistance against proteolytic degradation. Plasma coagulation factor XIII (FXIII) is a transglutaminase that promotes cross-linking of the extracellular matrix (ECM) components fibrin and fibronectin to form a provisional matrix in response to tissue damage. However, the functional requirement for this FXIII-mediated cross-linked provisional matrix in adult tissue remodeling remains to be defined. Although it has been proposed that the formation FXIII-mediated fibrin-fibronectin provisional matrix is a critical step for ECM remodeling, we... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385577 Wed, 19 Oct 2011 04:00:00 +0100 5385577 http://www.medworm.com/index.php?rid=5385576&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019898%26dopt%3DAbstract Authors: Zhang J, Hu W, Xing W, You T, Xu J, Qin X, Peng Z Abstract Hepatic ischemia-reperfusion injury (IRI) is a major factor influencing graft outcome in liver transplantation, but its mechanism is not well defined. Although complement, including the membrane attack complex (MAC), a terminal product of complement activation, is thought to be involved in the multiple reactions subsequent to the ischemia-reperfusion (IR) process, the role of MAC in the pathogenesis of hepatic IRI requires further investigation. We used a warm ischemia-reperfusion injury model in mice and a syngeneic orthotopic liver transplantation model in rats to define the role of complement, including MAC, in hepatic IR. CD59-deficient mice had more severe liver dysfunction, evidenced by increased aspartate am... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385576 Wed, 19 Oct 2011 04:00:00 +0100 5385576 http://www.medworm.com/index.php?rid=5385583&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22005277%26dopt%3DAbstract Authors: Kenyon N, Liu FT PMID: 22005277 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385583 Tue, 18 Oct 2011 04:00:00 +0100 5385583 http://www.medworm.com/index.php?rid=5385582&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015457%26dopt%3DAbstract In conclusion, oxidized LDL-mediated PGIS nitration and associated thromboxane receptor stimulation might be important in the initiation and progression of diabetic retinopathy. PMID: 22015457 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385582 Tue, 18 Oct 2011 04:00:00 +0100 5385582 http://www.medworm.com/index.php?rid=5385579&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015460%26dopt%3DAbstract Authors: Aldrich A, Kielian T Abstract Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow-derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow-derived cells were capable of acquiring fibrotic characteristics during brain a... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385579 Tue, 18 Oct 2011 04:00:00 +0100 5385579 http://www.medworm.com/index.php?rid=5385581&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015458%26dopt%3DAbstract Authors: Ren XS, Sato Y, Harada K, Sasaki M, Yoneda N, Lin ZH, Nakanuma Y Abstract Cholangitis arising from biliary infection dominates the prognosis in Caroli's disease. To clarify the influences of bacterial infection on the biliary cystogenesis, in vivo and in vitro studies were performed using the polycystic kidney (PCK) rat as an animal model of Caroli's disease. Cholangitis became a frequent histological finding in aged PCK rats, and neovascularization around the bile ducts also increased in aged PCK rats. Immunohistochemistry revealed that expression of vascular endothelial growth factor (VEGF) was increased in PCK rat biliary epithelium. In vitro, PCK cholangiocytes overexpressed VEGF, and the supernatant of cultured PCK cholangiocytes significantly increased the proliferat... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385581 Mon, 17 Oct 2011 04:00:00 +0100 5385581 http://www.medworm.com/index.php?rid=5385580&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015459%26dopt%3DAbstract Authors: Balluff B, Rauser S, Meding S, Elsner M, Schöne C, Feuchtinger A, Schuhmacher C, Novotny A, Jütting U, Maccarrone G, Sarioglu H, Ueffing M, Braselmann H, Zitzelsberger H, Schmid RM, Höfler H, Ebert MP, Walch A Abstract Proteomics-based approaches allow us to investigate the biology of cancer beyond genomic initiatives. We used histology-based matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to identify proteins that predict disease outcome in gastric cancer after surgical resection. A total of 181 intestinal-type primary resected gastric cancer tissues from two independent patient cohorts were analyzed. Protein profiles of the discovery cohort (n = 63) were directly obtained from tumor tissue sections by MALDI imaging. A seven-protein signat... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385580 Mon, 17 Oct 2011 04:00:00 +0100 5385580 http://www.medworm.com/index.php?rid=5385584&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001698%26dopt%3DAbstract Authors: Damjanovic D, Divangahi M, Kugathasan K, Small CL, Zganiacz A, Brown EG, Hogaboam CM, Gauldie J, Xing Z Abstract Lung immunopathology is the main cause of influenza-mediated morbidity and death, and much of its molecular mechanisms remain unclear. Whereas tumor necrosis factor-α (TNF-α) is traditionally considered a proinflammatory cytokine, its role in influenza immunopathology is unresolved. We have investigated this issue by using a model of acute H1N1 influenza infection established in wild-type and TNF-α-deficient mice and evaluated lung viral clearance, inflammatory responses, and immunopathology. Whereas TNF-α was up-regulated in the lung after influenza infection, it was not required for normal influenza viral clearance. However, TNF-α deficiency led, not only... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385584 Fri, 14 Oct 2011 04:00:00 +0100 5385584 http://www.medworm.com/index.php?rid=5385590&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001177%26dopt%3DAbstract Authors: Ricciardelli C, Frewin KM, Tan ID, Williams ED, Opeskin K, Pritchard MA, Ingman WV, Russell DL Abstract A disintegrin and metalloprotease with thrombospondin motifs protein 1 (ADAMTS1) is a protease commonly up-regulated in metastatic carcinoma. Its overexpression in cancer cells promotes experimental metastasis, but whether ADAMTS1 is essential for metastatic progression is unknown. To address this question, we investigated mammary cancer progression and spontaneous metastasis in the MMTV-PyMT mouse mammary tumor model in Adamts1 knockout mice. Adamts1(-/-)/PyMT mice displayed significantly reduced mammary tumor and lung metastatic tumor burden and increased survival, compared with their wild-type and heterozygous littermates. Histological examination revealed an increase... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385590 Wed, 12 Oct 2011 04:00:00 +0100 5385590 http://www.medworm.com/index.php?rid=5385589&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001178%26dopt%3DAbstract Authors: Ikeda Y, Inagi R, Miyata T, Nagai R, Arai M, Miyashita M, Itokawa M, Fujita T, Nangaku M Abstract Although kidney functions deteriorate with age, little is known about the general morphological alterations and mechanisms of renal senescence. We hypothesized that carbonyl stress causes senescence and investigated the possible role of glyoxalase I (GLO1), which detoxifies precursors of advanced glycation end products in the aging process of the kidney. We observed amelioration of senescence in GLO1-transgenic aged rats (assessed by expression levels of senescence markers such as p53, p21(WAF1/CIP1), and p16(INK4A)) and a positive rate of senescence-associated β-galactosidase (SABG) staining, associated with reduction of renal advanced glycation end product accumulation (est... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385589 Wed, 12 Oct 2011 04:00:00 +0100 5385589 http://www.medworm.com/index.php?rid=5385588&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001346%26dopt%3DAbstract We examined the expression pattern of versican in skin tumors from wild-type mice and UVB-treated Ogg1 knockout mice, and also analyzed 157 sun-related human skin tumors. Versican was strongly expressed in malignant skin tumors in both mice and humans, and especially in Ogg1 knockout mice. Additionally, infiltrating neutrophils strongly colocalized with versican in UVB-treated Ogg1 knockout mouse skin. These data demonstrate that inflammatory responses, particularly neutrophil infiltration and versican up-regulation, are closely involved in UVB/ROS-induced skin tumorigenesis. PMID: 22001346 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385588 Tue, 11 Oct 2011 04:00:00 +0100 5385588 http://www.medworm.com/index.php?rid=5385587&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001347%26dopt%3DAbstract Authors: Sangaletti S, Tripodo C, Cappetti B, Casalini P, Chiodoni C, Piconese S, Santangelo A, Parenza M, Arioli I, Miotti S, Colombo MP Abstract Fibrosis results from inflammatory tissue damage and impaired regeneration. In the context of bleomycin-induced pulmonary fibrosis, we demonstrated that the matricellular protein termed secreted protein acidic and rich in cysteine (SPARC) distinctly regulates inflammation and collagen deposition, depending on its cellular origin. Reciprocal Sparc(-/-) and wild-type (WT) bone marrow chimeras revealed that SPARC expression in host fibroblasts is required and sufficient to induce collagen fibrosis in a proper inflammatory environment. Accordingly, Sparc(-/-) WT chimeras showed exacerbated inflammation and fibrosis due to the inability of Sp... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385587 Tue, 11 Oct 2011 04:00:00 +0100 5385587 http://www.medworm.com/index.php?rid=5385586&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001348%26dopt%3DAbstract In this study, biochemical and genetic approaches identified a role for Ccr5, a chemokine receptor, in transducing the signals of EMCV infection that result in the expression of inflammatory genes in macrophages. Antibody neutralization and gene knockout strategies were used to show that the presence of Ccr5 is required for EMCV-stimulated mitogen-activated protein (MAP) kinase and nuclear factor-kappa B (NF-κB) activation, and the subsequent expression of the inflammatory gene-inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Ccr5 appears to participate in the early control of virus replication: EMCV mRNA accumulates to sevenfold higher levels in Ccr5-deficient mice when compared to wild-type controls. These findings support a regulatory role for Ccr5 in the antiviral ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385586 Tue, 11 Oct 2011 04:00:00 +0100 5385586 http://www.medworm.com/index.php?rid=5385585&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001349%26dopt%3DAbstract Authors: Li S, Zhou Y, Fan J, Cao S, Cao T, Huang F, Zhuang S, Wang Y, Yu X, Mao H Abstract Peritoneal dialysis-related peritonitis causes the denudation of mesothelial cells and, ultimately, membrane integrity alterations and peritoneal dysfunction. Because heat shock protein 72 (HSP72) confers protection against apoptosis and because autophagy mediates survival in response to cellular stresses, we examined whether autophagy contributes to HSP72-mediated cytoprotection in lipopolysaccharide (LPS)-induced peritonitis. Exposure of cultured peritoneal mesothelial cells to LPS resulted first in autophagy and later, apoptosis. Inhibition of autophagy by 3-methyladenine or Beclin-1 small-interfering RNA sensitized cells to apoptosis and abolished the antiapoptotic effect of HSP72, sugge... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5385585 Tue, 11 Oct 2011 04:00:00 +0100 5385585 http://www.medworm.com/index.php?rid=5321897&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21996676%26dopt%3DAbstract Authors: Shirai YT, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, Miyazono K Abstract A relationship exists between defects in bone morphogenetic protein (BMP) signaling and formation of hamartoma and adenoma in the gastric epithelium; however, the role of BMP signaling in the progression of diffuse-type gastric carcinoma remains unknown. We investigated whether BMP functions as a tumor suppressor in human diffuse-type gastric carcinoma using three different human diffuse-type gastric carcinoma cell lines (OCUM-12, HSC-39, and OCUM-2MLN). Overexpression of the dominant-negative form of BMP-2/4-specific type I receptor (ALK-3) in OCUM-12 and HSC-39 cells accelerated their growth in vivo. BMP-4 induced cell cycle arrest in these cells via p21 induction through the SMAD pathway. Moreo... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321897 Mon, 10 Oct 2011 04:00:00 +0100 5321897 http://www.medworm.com/index.php?rid=5321896&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21996677%26dopt%3DAbstract We report evidence that the effects of hypoxia on melanoma cells are mediated through activation of Snail1. Hypoxia increased melanoma cell migration and drug resistance, and these changes were accompanied by increased Snail1 and decreased E-cadherin expression. Snail1 expression was regulated by HIF-2α in melanoma. Snail1 overexpression led to more aggressive tumor phenotypes and features associated with stem-like melanoma cells in vitro and increased metastatic capacity in vivo. In addition, we found that knockdown of endogenous Snail1 reduced melanoma proliferation and migratory capacity. Snail1 knockdown also prevented melanoma metastasis in vivo. In summary, hypoxia up-regulates Snail1 expression and leads to increased metastatic capacity and drug resistance in melanoma cells. Our fi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321896 Mon, 10 Oct 2011 04:00:00 +0100 5321896 http://www.medworm.com/index.php?rid=5321895&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21996678%26dopt%3DAbstract Authors: Ramachandran A, Gong EM, Pelton K, Ranpura SA, Mulone M, Seth A, Gomez P, Adam RM Abstract Fibroproliferative remodeling in smooth muscle-rich hollow organs is associated with aberrant extracellular matrix (ECM) production. Although mechanical stimuli regulate ECM protein expression, the transcriptional mediators of this process remain poorly defined. Previously, we implicated AP-1 as a mediator of smooth muscle cell (SMC) mechanotransduction; however, its role in stretch-induced ECM regulation has not been explored. Herein, we identify a novel role for the AP-1 subunit FosB in stretch-induced ECM expression in SMCs. The DNA-binding activity of AP-1 increased after stretch stimulation of SMCs in vitro. In contrast to c-jun and c-fos, which are also activated by the SMC mit... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321895 Mon, 10 Oct 2011 04:00:00 +0100 5321895 http://www.medworm.com/index.php?rid=5321898&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21986443%26dopt%3DAbstract This study investigates the influence of food deprivation on Paneth cell function in a mouse starvation model. Quantitative PCR showed significant decreases in mRNA expression of typical Paneth cell antimicrobials, lysozyme, cryptdin, and RegIIIγ, in ileal tissue after 48 hours of food deprivation. Protein expression levels of lysozyme and RegIIIγ precursor were also significantly diminished, as shown by using Western blot analysis and IHC. Late degenerative autophagolysosomes and aberrant Paneth cell granules in starved mice were evident by electron microscopy, Western blot analysis, and quantitative PCR. Furthermore, increased bacterial translocation to mesenteric lymph nodes coincided with Paneth cell abnormalities. The current study demonstrates the occurrence of Paneth cell abnormal... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321898 Fri, 07 Oct 2011 04:00:00 +0100 5321898 http://www.medworm.com/index.php?rid=5321905&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983632%26dopt%3DAbstract Authors: Notomi S, Hisatomi T, Kanemaru T, Takeda A, Ikeda Y, Enaida H, Kroemer G, Ishibashi T Abstract Stressed cells release ATP, which participates in neurodegenerative processes through the specific ligation of P2RX7 purinergic receptors. Here, we demonstrate that extracellular ATP and the more specific P2RX7 agonist, 2'- and 3'-O-(4-benzoylbenzoyl)-ATP, both induce photoreceptor cell death when added to primary retinal cell cultures or when injected into the eyes from wild-type mice, but not into the eyes from P2RX7(-/-) mice. Photoreceptor cell death was accompanied by the activation of caspase-8 and -9, translocation of apoptosis-inducing factor from mitochondria to nuclei, and TUNEL-detectable chromatin fragmentation. All hallmarks of photoreceptor apoptosis were prevented ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321905 Thu, 06 Oct 2011 04:00:00 +0100 5321905 http://www.medworm.com/index.php?rid=5321904&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983633%26dopt%3DAbstract Authors: Rino Tulone C, Giorgini A, Freeley S, Coughlan A, Gregory Robson M Abstract To explore the role of antigen-specific CD4(+) T cells in glomerulonephritis, we administered ovalbumin 323-339 peptide conjugated to glomerular-binding polyclonal antibody and induced disease in RAG1(-/-) mice with CD4(+) T cells from OT2 × RAG1(-/-) mice. These OT2 × RAG1(-/-) mice have a transgenic T-cell receptor specific for this peptide. When CD4(+) T cells were primed in vivo, crescentic glomerulonephritis developed after 21 days in mice given peptide-conjugated glomerular-binding antibody but not unconjugated antibody control. We then investigated the relative roles of T(H)1 and T(H)17 cells, using Fab(2) fragments of glomerular-binding antibody to exclude a role for antibody in this mode... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321904 Thu, 06 Oct 2011 04:00:00 +0100 5321904 http://www.medworm.com/index.php?rid=5321903&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983634%26dopt%3DAbstract Authors: Gorowiec MR, Catalano RD, Norman JE, Denison FC, Jabbour HN Abstract The infiltration of human myometrium and cervix with leukocytes and the formation of a pro-inflammatory environment within the uterus have been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labor. The expression of PROK1 receptor remains unchanged during labor and is abundantly expressed in the myometrium. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines, including IL-1β, chemokine C-C motif ligand 3, and colony-stimulating fact... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321903 Thu, 06 Oct 2011 04:00:00 +0100 5321903 http://www.medworm.com/index.php?rid=5321902&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983635%26dopt%3DAbstract Authors: Massoner P, Ladurner Rennau M, Heidegger I, Kloss-Brandstätter A, Summerer M, Reichhart E, Schäfer G, Klocker H Abstract The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGF1 receptor (IGF1R) in different tumors, including prostate cancer, are under way. Although studies on the IGF axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGF axis in microdissected tissue specimens of local prostate cancer using quantitative PCR. All members of the IGF axis, including IGF1, IGF2, IGF binding proteins 1 through ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321902 Thu, 06 Oct 2011 04:00:00 +0100 5321902 http://www.medworm.com/index.php?rid=5321901&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983636%26dopt%3DAbstract Authors: Krause K, Prawitt S, Eszlinger M, Ihling C, Sinz A, Schierle K, Gimm O, Dralle H, Steinert F, Sheu SY, Werner Schmid K, Fuhrer D Abstract Benign hypofunctional cold thyroid nodules (CTNs) are a frequent scintiscan finding and need to be distinguished from thyroid carcinomas. The origin of CTNs with follicular morphologic features is unresolved. The DNA damage response might act as a physiologic barrier, inhibiting the progression of preneoplastic lesions to neoplasia. We investigated the following in hypofunctional follicular adenoma (FA) and follicular thyroid cancer (FTC): i) the mutation rate of frequently activated oncogenes, ii) the activation of DNA damage response checkpoints, and iii) the differential proteomic pattern between FA and FTC. Both FTC and FA, which did... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321901 Thu, 06 Oct 2011 04:00:00 +0100 5321901 http://www.medworm.com/index.php?rid=5321900&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983637%26dopt%3DAbstract Authors: Sawane M, Kidoya H, Muramatsu F, Takakura N, Kajiya K Abstract Apelin, the ligand of the G protein-coupled receptor APJ, is involved in the regulation of cardiovascular functions, fluid homeostasis, and vessel formation. Recent reports indicate that apelin secreted from endothelial cells mediates APJ regulation of blood vessel caliber size; however, the function of apelin in lymphatic vessels is unclear. Here we report that APJ was expressed by human lymphatic endothelial cells and that apelin induced migration and cord formation of lymphatic endothelial cells dose-dependently in vitro. Furthermore, permeability assays demonstrated that apelin stabilizes lymphatic endothelial cells. In vivo, transgenic mice harboring apelin under the control of keratin 14 (K14-apelin) exhi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321900 Thu, 06 Oct 2011 04:00:00 +0100 5321900 http://www.medworm.com/index.php?rid=5321899&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983638%26dopt%3DAbstract Authors: Clark PE, Polosukhina D, Love H, Correa H, Coffin C, Perlman EJ, de Caestecker M, Moses HL, Zent R Abstract Wilms' tumor (WT) is the most common childhood renal cancer. Although mutations in known tumor-associated genes (WT1, WTX, and CATNB) occur only in a third of tumors, many tumors show evidence of activated β-catenin-dependent Wnt signaling, but the molecular mechanism by which this occurs is unknown. A key obstacle to understanding the pathogenesis of WT is the paucity of mouse models that recapitulate its features in humans. Herein, we describe a transgenic mouse model of primitive renal epithelial neoplasms that have high penetrance and mimic the epithelial component of human WT. Introduction of a stabilizing β-catenin mutation restricted to the kidney is suffici... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321899 Thu, 06 Oct 2011 04:00:00 +0100 5321899 http://www.medworm.com/index.php?rid=5321907&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983071%26dopt%3DAbstract In this study, we demonstrate enhanced myofibroblast contraction in bleomycin-induced lung fibrosis in mice and in fibroblastic foci of human subjects with IPF, using phosphorylation of the regulatory myosin light chain (MLC(20)) as a biomarker of in vivo cellular contractility. Compared with wild-type mice, relaxin knockout mice express higher lung levels of phospho-MLC(20) and develop more severe bleomycin-induced lung fibrosis. Exogenous relaxin inhibits MLC(20) phosphorylation and bleomycin-induced lung fibrosis in both relaxin knockout and wild-type mice. Ex vivo studies of IPF lung myofibroblasts demonstrate decreases in MLC(20) phosphorylation and reduced contractility in response to relaxin. Characterization of the signaling pathway reveals that relaxin regulates MLC(20) dephosphor... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321907 Wed, 05 Oct 2011 04:00:00 +0100 5321907 http://www.medworm.com/index.php?rid=5321906&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983072%26dopt%3DAbstract Authors: Shen N, Shao Y, Lai SS, Qiao L, Yang RL, Xue B, Pan FY, Chen HQ, Li CJ Abstract Cigarette smoke activates the extracellular signal-regulated kinase (ERK) 1/2 mitogen activated-protein kinase pathway, which, in turn, is responsible for early growth response gene-1 (EGR-1) activation. Here we provide evidence that EGR-1 activation can also reactivate ERK 1/2 mitogen activated-protein kinase through a positive feedback loop through its target gene (geranylgeranyl diphosphate synthase) ggpps. For the first time, the ggpps gene is identified as a target of EGR-1, as EGR-1 can directly bind to the predicted consensus-binding site in the ggpps promoter and regulate its transcription. Long-term observations show that there are two ERK 1/2 phosphorylation peaks after cigarette smok... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321906 Wed, 05 Oct 2011 04:00:00 +0100 5321906 http://www.medworm.com/index.php?rid=5321909&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982831%26dopt%3DAbstract Authors: Qin Y, Alderliesten MC, Stokman G, Pennekamp P, Bonventre JV, de Heer E, Ichimura T, de Graauw M, Price LS, Water BV Abstract Renal ischemia/reperfusion (I/R) injury is associated with cell matrix and focal adhesion remodeling. Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase that localizes at focal adhesions and regulates their turnover. Here, we investigated the role of FAK in renal I/R injury, using a novel conditional proximal tubule-specific FAK-deletion mouse model. Tamoxifen treatment of FAK(loxP/loxP)//γGT-Cre-ER(T2) mice caused renal-specific fak recombination (FAK(ΔloxP/ΔloxP)) and reduction of FAK expression in proximal tubules. In FAK(ΔloxP/ΔloxP) mice compared with FAK(loxP/loxP) controls, unilateral renal ischemia followed by reperfus... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321909 Tue, 04 Oct 2011 04:00:00 +0100 5321909 http://www.medworm.com/index.php?rid=5321908&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982832%26dopt%3DAbstract Authors: Bhan U, Newstead MJ, Zeng X, Ballinger MN, Standiford LR, Standiford TJ Abstract Hypersensitivity pneumonitis (HP), an inflammatory lung disease, develops after repeated exposure to inhaled particulate antigen and is characterized by a vigorous T helper type 1-mediated immune response, resulting in the release of IL-12 and interferon (IFN)-γ. These T helper type 1 cytokines may participate in the pathogenesis of HP. Stachybotrys chartarum (SC) is a dimorphic fungus implicated in a number of respiratory illnesses, including HP. Here, we have developed a murine model of SC-induced HP that reproduces pathology observed in human HP and hypothesized that toll receptor-like 9 (TLR9)-mediated dendritic cell responses are required for the generation of granulomatous inflammation ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321908 Tue, 04 Oct 2011 04:00:00 +0100 5321908 http://www.medworm.com/index.php?rid=5321911&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975022%26dopt%3DAbstract Authors: Finnberg NK, Hart LS, Dolloff NG, Rodgers ZB, Dicker DT, El-Deiry WS Abstract Bone marrow-derived cells (BMDCs) participate in the growth and spread of tumors of the breast, brain, lung, and stomach. To date, there are limited reports of bone marrow involvement in colon cancer pathogenesis, but such findings would have the potential to generate novel treatments for colon cancer patients. We have established a mouse model for imaging BMDCs from whole tumor to single-cell resolution, whereby the bone marrow of lethally irradiated host animals is reconstituted with EGFP-expressing bone marrow cells from matched TgActb(EGFP) donors. The BM transplants yield mice with fluorescently labeled bone marrow, and so BMDCs can subsequently be monitored within a tumor through optical im... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321911 Mon, 03 Oct 2011 04:00:00 +0100 5321911 http://www.medworm.com/index.php?rid=5321910&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21978492%26dopt%3DAbstract Authors: Uddin S, Hussain AR, Ahmed M, Al-Sanea N, Abduljabbar A, Ashari LH, Alhomoud S, Al-Dayel F, Bavi P, Al-Kuraya KS Abstract Dysregulated overexpression of hepatocyte growth factor and its receptor, c-Met, has been reported in various cancers, but its role in colorectal carcinoma (CRC) has not been elucidated. Therefore, we investigated the role of phosphorylated Met (p-Met) in Middle Eastern CRC patient samples and cell lines. The p-Met was overexpressed in 80.8% of CRCs and strongly associated with the expression of p-AKT, DR5, and Ki-67 by IHC. Coexpression of p-Met and DR5 was seen in 53.1% of CRC cases and was associated with a less aggressive phenotype, characterized by a histological subtype of adenocarcinomas, well-differentiated tumors, and was an independent prognos... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5321910 Mon, 03 Oct 2011 04:00:00 +0100 5321910 http://www.medworm.com/index.php?rid=5270157&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21819957%26dopt%3DAbstract Authors: Roy D, Dittmer DP Abstract Primary effusion lymphoma (PEL) is a non-Hodgkin's B-cell lymphoma driven by Kaposi's sarcoma-associated herpesvirus. It is uniquely sensitive to mTOR, PI3K, and Akt inhibitors; however, the basis of this requirement for the mTOR pathway remains to be elucidated. The phosphatase and tensin homolog gene (PTEN) on chromosome 10 controls the first step in the phosphatidylinositol 3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway and is genetically inactivated in many solid tumors. We find an absence of PTEN deletions, mutations, or protein mislocalization in PEL. However, we find consistent hyperphosphorylation at serine 380 of PTEN, which is an inactivating modification, in PEL cell lines and in tumor xenografts. We also evaluated a ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270157 Sat, 01 Oct 2011 04:00:00 +0100 5270157 http://www.medworm.com/index.php?rid=5270156&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21835157%26dopt%3DAbstract Authors: PMID: 21835157 [PubMed - in process] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270156 Sat, 01 Oct 2011 04:00:00 +0100 5270156 http://www.medworm.com/index.php?rid=5270155&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839062%26dopt%3DAbstract Authors: Tian H, Lu Y, Shah SP, Hong S Abstract Impaired macrophage functions imposed by diabetic complications and the suppressed formation of 14S,21R-dihydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA) in wounds contribute significantly to deficient wound healing in diabetics, but how are macrophage functions and 14S,21R-diHDHA formation associated? We studied 14S,21R-diHDHA generation from macrophages using liquid chromatography/mass spectrometry. The role in macrophage-mediated wound healing functions was determined using a murine splinted excisional wound healing model and in vitro assays. 14S,21R-diHDHA acts as a macrophage-generated autacoid, and its attenuated formation in macrophages of diabetic db/db mice was accompanied by impairment of macrophage prohe... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270155 Sat, 01 Oct 2011 04:00:00 +0100 5270155 http://www.medworm.com/index.php?rid=5270154&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839716%26dopt%3DAbstract Authors: Horbinski C, Hobbs J, Cieply K, Dacic S, Hamilton RL Abstract Epidermal growth factor receptor (EGFR) expression and signaling contribute to glioma biological features and, thus, are a target for new drug development. The role, if any, of EGFR in routine surgical neuropathological diagnostics is less clear. Herein, we describe prospective EGFR IHC analysis in an adult cohort comprising 750 infiltrative gliomas. EGFR expression increased with World Health Organization grade but did not significantly differ between grade-matched astrocytic and oligodendroglial tumors. Survival did not significantly differ by EGFR expression among astrocytic tumors adjusted for World Health Organization grade. However, grade II oligodendrogliomas with strong EGFR expression and 1p/19q codelet... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270154 Sat, 01 Oct 2011 04:00:00 +0100 5270154 http://www.medworm.com/index.php?rid=5270153&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843497%26dopt%3DAbstract Authors: Zhang X, Chen W, De Paiva CS, Volpe EA, Gandhi NB, Farley WJ, Li DQ, Niederkorn JY, Stern ME, Pflugfelder SC Abstract We investigated the role of CD4(+) T-cell-produced interferon (IFN)-γ on corneal epithelial apoptosis in a murine desiccating stress (DS) model that resembles Sjögren's syndrome. The DS model was generated in C57BL/6 (B6) and B6 IFN-γ-knockout (B6γKO) mice. Adoptive transfer of CD4(+) T cells from DS-exposed donor to recombination activating gene (RAG)-1(-/-) recipient mice and topical neutralization of IFN-γ were performed to determine whether IFN-γ produced by pathogenic CD4(+) T cells promotes corneal epithelial apoptosis. Apoptosis in corneal epithelia was assessed by evaluating the expression and activity of caspases 3, 8, and 9. The activation o... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270153 Sat, 01 Oct 2011 04:00:00 +0100 5270153 http://www.medworm.com/index.php?rid=5270152&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21854739%26dopt%3DAbstract Authors: Hempel C, Combes V, Hunt NH, Kurtzhals JA, Grau GE Abstract Cerebral malaria (CM) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. To assess the role of cerebral hypoxia, we used two experimental models of CM, Plasmodium berghei ANKA in CBA and C57BL/6 mice, and two models of malaria without neurologic signs, P. berghei K173 in CBA mice and P. berghei ANKA in BALB/c mice. Hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining with hypoxia-inducible factor-1α-specific antibody. Cytopathic hypoxia was studied using poly (ADP-ribose) polymerase-1 (PARP-1) gene knockout mice. The effect of erythropoietin, an oxygen-sensitive cytokine that mediates ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270152 Sat, 01 Oct 2011 04:00:00 +0100 5270152 http://www.medworm.com/index.php?rid=5270151&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21854742%26dopt%3DAbstract Authors: Mazzanti CM, Al Hamad M, Fanelli G, Scatena C, Zammarchi F, Zavaglia K, Lessi F, Pistello M, Naccarato AG, Bevilacqua G Abstract A viral etiology of human breast cancer (HBC) has been postulated for decades since the identification of mouse mammary tumor virus (MMTV). The detection of MMTV env-like exogenous sequences (MMTVels) in 30% to 40% of invasive HBCs increased attention to this hypothesis. Looking for MMTVels during cancer progression may contribute to a better understanding of their role in HBC. Herein, we analyzed HBC preinvasive lesions for the presence of MMTVels. Samples were obtained by laser microdissection of FFPE tissues: 20 usual-type ductal hyperplasias, 22 atypical ductal hyperplasias (ADHs), 49 ductal carcinomas in situ (DCISs), 20 infiltrating ductal ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270151 Sat, 01 Oct 2011 04:00:00 +0100 5270151 http://www.medworm.com/index.php?rid=5270150&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21854745%26dopt%3DAbstract This study indicated that some dysregulated signaling proteins could be selected as useful biomarkers for tumor classification and predicting outcome in gastric cancer patients. PMID: 21854745 [PubMed - in process] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270150 Sat, 01 Oct 2011 04:00:00 +0100 5270150 http://www.medworm.com/index.php?rid=5270149&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21854751%26dopt%3DAbstract Authors: Kopeikina KJ, Carlson GA, Pitstick R, Ludvigson AE, Peters A, Luebke JI, Koffie RM, Frosch MP, Hyman BT, Spires-Jones TL Abstract Neurofibrillary tangles (NFT), intracellular inclusions of abnormal fibrillar forms of microtubule associated protein tau, accumulate in Alzheimer's disease (AD) and other tauopathies and are believed to cause neuronal dysfunction, but the mechanism of tau-mediated toxicity are uncertain. Tau overexpression in cell culture impairs localization and trafficking of organelles. Here we tested the hypothesis that, in the intact brain, changes in mitochondrial distribution occur secondary to pathological changes in tau. Array tomography, a high-resolution imaging technique, was used to examine mitochondria in the reversible transgenic (rTg)4510, a reg... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270149 Sat, 01 Oct 2011 04:00:00 +0100 5270149 http://www.medworm.com/index.php?rid=5270148&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21854752%26dopt%3DAbstract Authors: Van Hul N, Lanthier N, Español Suñer R, Abarca Quinones J, van Rooijen N, Leclercq I Abstract Activation of myofibroblasts (MF) and extracellular matrix (ECM) deposition predispose the expansion and differentiation of liver progenitor cells (LPC) during chronic liver injury. Because Kupffer cells (KC) are active modulators of tissue response and fibrosis, we analyzed their role in a model of LPC proliferation. A choline-deficient diet, supplemented by ethionine (CDE) was administrated to C57Bl/6J mice that were depleted of KC by repeated injections of clodronate (CLO) and compared to PBS-injected mice. On CDE, massive KC activation was observed in the PBS group, but this was blunted in CLO-treated mice. The depletion of KC did not influence LPC proliferation but reduced ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270148 Sat, 01 Oct 2011 04:00:00 +0100 5270148 http://www.medworm.com/index.php?rid=5270147&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21854754%26dopt%3DAbstract In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome. PMID: 21854754 [PubMed - in process] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270147 Sat, 01 Oct 2011 04:00:00 +0100 5270147 http://www.medworm.com/index.php?rid=5270146&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864493%26dopt%3DAbstract We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270146 Sat, 01 Oct 2011 04:00:00 +0100 5270146 http://www.medworm.com/index.php?rid=5270145&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871425%26dopt%3DAbstract Authors: Kumar D, Salhan D, Magoon S, Torri DD, Sayeneni S, Sagar A, Bandhlish A, Malhotra A, Chander PN, Singhal PC Abstract In the present study, we hypothesized that HIV-1-induced occult HIV-associated nephropathy (HIVAN) would become apparent in the presence of adverse host factors. To test our hypothesis, Vpr mice (which display doxycycline-dependent Vpr expression in podocytes) with two, three, and four copies of the angiotensinogen (Agt) gene (Vpr-Agt-2, Vpr-Agt-3, and Vpr-Agt-4) were administered doxycycline for 3 weeks (to develop clinically occult HIVAN) followed by doxycycline-free water during the next 3 weeks. Subsequently, renal biomarkers were measured, and kidneys were harvested for renal histology. Vpr-Agt-2 developed neither proteinuria nor elevated blood pressure... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270145 Sat, 01 Oct 2011 04:00:00 +0100 5270145 http://www.medworm.com/index.php?rid=5270144&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871426%26dopt%3DAbstract Authors: Proust A, Rincé P, Creidy R, Lazure T, Joab I, Garçon L, Fabre M, Guettier C, Raphael M Abstract Posttransplantation lymphoproliferative disorders (PTLD) are associated with Epstein-Barr virus (EBV) and activate the NF-κB pathway. B-cell activating factor (BAFF) modulates cell growth and survival in non-Hodgkin's lymphomas. However, there are few studies of EBV, BAFF/BAFF-R signaling, and NF-κB1 and NF-κB2 pathway activation in PTLD. Diffuse large B-cell lymphomas (DLBCL) in two different clinical contexts, immunocompetent patients (DLBCL/IC; n = 30) or posttransplantation solid-organ recipients (DLBCL/PTLD; n = 21), were characterized histogenically as germinal center (GC) or non-germinal center (NGC). Expression of BAFF, BAFF-R, and NF-κB proteins p50 and p52 and t... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270144 Sat, 01 Oct 2011 04:00:00 +0100 5270144 http://www.medworm.com/index.php?rid=5270143&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871427%26dopt%3DAbstract Authors: Yamashita CM, Dolgonos L, Zemans RL, Young SK, Robertson J, Briones N, Suzuki T, Campbell MN, Gauldie J, Radisky DC, Riches DW, Yu G, Kaminski N, McCulloch CA, Downey GP Abstract Idiopathic pulmonary fibrosis (IPF) may be triggered by epithelial injury that results in aberrant production of growth factors, cytokines, and proteinases, leading to proliferation of myofibroblasts, excess deposition of collagen, and destruction of the lung architecture. The precise mechanisms and key signaling mediators responsible for this aberrant repair process remain unclear. We assessed the importance of matrix metalloproteinase-3 (MMP-3) in the pathogenesis of IPF through i) determination of MMP-3 expression in patients with IPF, ii) in vivo experiments examining the relevance of MMP-3 in... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270143 Sat, 01 Oct 2011 04:00:00 +0100 5270143 http://www.medworm.com/index.php?rid=5270142&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871428%26dopt%3DAbstract Authors: Cheunsuchon P, Zhou Y, Zhang X, Lee H, Chen W, Nakayama Y, Rice KA, Tessa Hedley-Whyte E, Swearingen B, Klibanski A Abstract DLK1-MEG3 is an imprinted locus consisting of multiple maternally expressed noncoding RNA genes and paternally expressed protein-coding genes. The expression of maternally expressed gene 3 (MEG3) is selectively lost in clinically nonfunctioning adenomas (NFAs) of gonadotroph origin; however, expression status of other genes at this locus in human pituitary adenomas has not previously been reported. Using quantitative real-time RT-PCR, we evaluated expression of 24 genes from the DLK1-MEG3 locus in 44 human pituitary adenomas (25 NFAs, 7 ACTH-secreting, 7 GH-secreting, and 5 PRL-secreting adenomas) and 10 normal pituitaries. The effects on cell prolif... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270142 Sat, 01 Oct 2011 04:00:00 +0100 5270142 http://www.medworm.com/index.php?rid=5270141&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871429%26dopt%3DAbstract Authors: Thompson KA, Cherry CL, Bell JE, McLean CA Abstract We detected HIV-1 DNA in pure populations of perivascular macrophages, parenchymal microglia, and astrocytes, isolated using laser microdissection from brain tissue of five untreated individuals who died in the presymptomatic stage of infection from non-HIV causes. HIV-1 DNA was detected in the three cell populations, most consistently in perivascular macrophages, without evidence of productive infection. The percentage of PCR reactions detecting HIV-1 DNA in perivascular macrophages correlated inversely with peripheral blood CD4 counts. These findings demonstrate that brain cell reservoirs of latent HIV-1 exist before pathological HIV encephalitis and suggest that perivascular macrophage trafficking of latent virus into ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270141 Sat, 01 Oct 2011 04:00:00 +0100 5270141 http://www.medworm.com/index.php?rid=5270133&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872562%26dopt%3DAbstract Authors: Hvilsted Nielsen H, Toft-Hansen H, Lambertsen KL, Owens T, Finsen B Abstract In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early after induction via axonal transection, resulting in a 25% increase in the numbers of oligodendrocytes. In con... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270133 Sat, 01 Oct 2011 04:00:00 +0100 5270133 http://www.medworm.com/index.php?rid=5270131&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872563%26dopt%3DAbstract We examined the function of Interleukin-34 (IL-34), a newly discovered cytokine, on microglia because it reportedly induces proliferation of monocytes and macrophages. We observed that the neuronal cells primarily produce IL-34 and that microglia express its receptor, colony-stimulating factor 1 receptor. IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-β (oAβ), which mediates synaptic dysfunction and neuronal damage in AD. IL-34 increased the expression of insulin-degrading enzyme, aiding the clearance of oAβ, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules. Consequently, microglia treated with IL-34 attenuated oAβ neurotoxicity in primary neuron-microglia co-cultures... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270131 Sat, 01 Oct 2011 04:00:00 +0100 5270131 http://www.medworm.com/index.php?rid=5270130&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872564%26dopt%3DAbstract Authors: Inui S, Shono F, Nakajima T, Hosokawa K, Itami S Abstract To elucidate pathogenic molecules in keloids, microarray analysis was performed using RNAs extracted from keloid-derived fibroblasts and normal skin-derived fibroblasts from the same patient with a typical keloid. Among 11 up-regulated extracellular matrix genes, cartilage oligomeric matrix protein (COMP) was most prominently increased. Up-regulation of COMP mRNA and protein was confirmed in the keloid tissue by quantitative RT-PCR and Western blot. Using immunohistochemistry, we compared 15 keloids and 6 control normal tissues using a COMP-specific antibody and found that COMP stained positively in 10 keloids (66.7%), whereas no staining was observed in normal tissues, demonstrating the ectopic expression of COMP i... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270130 Sat, 01 Oct 2011 04:00:00 +0100 5270130 http://www.medworm.com/index.php?rid=5270129&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21884676%26dopt%3DAbstract Authors: Mason AL, Gilady SY, Mackey JR PMID: 21884676 [PubMed - in process] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270129 Sat, 01 Oct 2011 04:00:00 +0100 5270129 http://www.medworm.com/index.php?rid=5270128&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21888887%26dopt%3DAbstract Authors: Heaphy CM, Subhawong AP, Hong SM, Goggins MG, Montgomery EA, Gabrielson E, Netto GJ, Epstein JI, Lotan TL, Westra WH, Shih IeM, Iacobuzio-Donahue CA, Maitra A, Li QK, Eberhart CG, Taube JM, Rakheja D, Kurman RJ, Wu TC, Roden RB, Argani P, De Marzo AM, Terracciano L, Torbenson M, Meeker AK Abstract Approximately 10% to 15% of human cancers lack detectable telomerase activity, and a subset of these maintain telomere lengths by the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres (ALT). The ALT phenotype, relatively common in subtypes of sarcomas and astrocytomas, has rarely been reported in epithelial malignancies. However, the prevalence of ALT has not been thoroughly assessed across all cancer types. We therefore comprehensi... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270128 Sat, 01 Oct 2011 04:00:00 +0100 5270128 http://www.medworm.com/index.php?rid=5270127&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21944279%26dopt%3DAbstract Authors: Han G, Li F, Ten Dijke P, Wang XJ Abstract The expression of Smad7, a tumor growth factor-β (TGFβ) antagonist, is increased during cutaneous wound healing. To assess this significance, we temporally induced Smad7 transgene expression in wounded skin in gene-switch-Smad7 transgenic (Smad7 tg) mice. Smad7 induction in epidermal keratinocytes caused an increase in keratinocyte proliferation with reduced Smad2 activation, indicating that Smad7 abrogated TGFβ-mediated growth inhibition. Additionally, wounded skin from Smad7 tg mice exhibited accelerated re-epithelialization, with increased activation of extracellular signal-regulated kinase (Erk), and an in vitro migration assay revealed that Erk activation contributed to Smad7-mediated keratinocyte migration. Notably, epide... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270127 Sat, 01 Oct 2011 04:00:00 +0100 5270127 http://www.medworm.com/index.php?rid=5270120&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945803%26dopt%3DAbstract Authors: Koon HW, Shih DQ, Hing TC, Chen J, Ho S, Zhao D, Targan SR, Pothoulakis C Abstract We have shown that substance P (SP) and its neurokinin-1 receptor (NK-1R) regulate intestinal angiogenesis by increasing expression of protein CYR61 (the cysteine-rich angiogenic inducer 61, or CCN1) in colonic epithelial cells. However, the mechanism involved in SP-induced CCN1 expression has not been studied, and the outcome of increased CCN1 expression in the development of colitis is not fully understood. Because histone deacetylase (HDAC) modulates transcription of several genes involved in inflammation, we investigated participation of HDAC in SP-induced CCN1 expression in human colonic epithelial NCM460 cells overexpressing NK-1R (NCM460-NK-1R) and in primary colonocytes. SP increased... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270120 Fri, 23 Sep 2011 04:00:00 +0100 5270120 http://www.medworm.com/index.php?rid=5270119&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945804%26dopt%3DAbstract Authors: Jimenez-Mateos EM, Bray I, Sanz-Rodriguez A, Engel T, McKiernan RC, Mouri G, Tanaka K, Sano T, Saugstad JA, Simon RP, Stallings RL, Henshall DC Abstract When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepti... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270119 Fri, 23 Sep 2011 04:00:00 +0100 5270119 http://www.medworm.com/index.php?rid=5270118&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945805%26dopt%3DAbstract Authors: Fukasawa H, Obayashi H, Schmieder S, Lee J, Ghosh P, Farquhar MG Abstract Podocalyxin (PC) is a polysialylated, anti-adhesin that is essential for maintaining foot process architecture and the integrity of the glomerular filtration barrier. We showed previously that PC is firmly attached to the actin cytoskeleton through ezrin, that in puromycin aminonucleoside (PAN)-mediated nephrosis the PC-ezrin-actin complex is disrupted, and that PC is uncoupled from actin. However, the precise mechanisms involved remained unknown. Here we show that detachment of PC from actin is regulated by phosphorylation of PC. PC is hyperphosphorylated at serines in puromycin aminonucleoside (PAN)- and protamine sulfate (PS)-treated rat glomeruli. We determined that PC is a substrate of PKC and t... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270118 Fri, 23 Sep 2011 04:00:00 +0100 5270118 http://www.medworm.com/index.php?rid=5270117&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945902%26dopt%3DAbstract Authors: Vana L, Kanaan NM, Ugwu IC, Wuu J, Mufson EJ, Binder LI Abstract Tau is a microtubule-associated protein that forms neurofibrillary tangles (NFTs) in the vulnerable long projection neurons of the cholinergic basal forebrain (CBF) in Alzheimer's disease (AD). Although CBF neurodegeneration correlates with cognitive decline during AD progression, little is known about the temporal changes of tau accumulation in this region. We investigated tau posttranslational modifications during NFT evolution within the CBF neurons of the nucleus basalis (NB) using tissue from subjects with no cognitive impairment, mild cognitive impairment, and AD. The pS422 antibody was used as an early tau pathology marker that labels tau phosphorylated at Ser422; the TauC3 antibody was used to detect ... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270117 Fri, 23 Sep 2011 04:00:00 +0100 5270117 http://www.medworm.com/index.php?rid=5270116&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945903%26dopt%3DAbstract Authors: Masterson JC, McNamee EN, Jedlicka P, Fillon S, Ruybal J, Hosford L, Rivera-Nieves J, Lee JJ, Furuta GT Abstract Intestinal remodeling and stricture formation is a complication of inflammatory bowel disease (IBD) that often requires surgical intervention. Although eosinophils are associated with mucosal remodeling in other organs and are increased in IBD tissues, their role in IBD-associated remodeling is unclear. Histological and molecular features of ileitis and remodeling were assessed using immunohistochemical, histomorphometric, flow cytometric, and molecular analysis (real-time RT-PCR) techniques in a murine model of chronic eosinophilic ileitis. Collagen protein was assessed by Sircol assay. Using a spontaneous eosinophilic Crohn's-like mouse model, we demonstrate a... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270116 Fri, 23 Sep 2011 04:00:00 +0100 5270116 http://www.medworm.com/index.php?rid=5270121&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945411%26dopt%3DAbstract Authors: Tassi E, McDonnell K, Gibby KA, Tilan JU, Kim SE, Kodack DP, Schmidt MO, Sharif GM, Wilcox CS, Welch WJ, Gallicano GI, Johnson MD, Riegel AT, Wellstein A Abstract Fibroblast growth factors (FGFs) participate in embryonic development, in maintenance of tissue homeostasis in the adult, and in various diseases. FGF binding proteins (FGFBP) are secreted proteins that chaperone FGFs stored in the extracellular matrix to their receptor, and can thus modulate FGF signaling. FGFBP1 (alias BP1, FGF-BP1, or HBp17) expression is required for embryonic survival, can modulate FGF-dependent vascular permeability in embryos, and is an angiogenic switch in human cancers. To determine the function of BP1 in vivo, we generated tetracycline-regulated conditional BP1 transgenic mice. BP1-expr... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270121 Wed, 21 Sep 2011 04:00:00 +0100 5270121 http://www.medworm.com/index.php?rid=5270125&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945321%26dopt%3DAbstract Authors: Béréziat V, Cervera P, Le Dour C, Verpont MC, Dumont S, Vantyghem MC, Capeau J, Vigouroux C, Abstract Some LMNA mutations responsible for insulin-resistant lipodystrophic syndromes are associated with peripheral subcutaneous lipoatrophy and faciocervical fat accumulation. Their pathophysiologic characteristics are unknown. We compared histologic, immunohistologic, ultrastructural, and protein expression features of enlarged cervical subcutaneous adipose tissue (scAT) obtained during plastic surgery from four patients with LMNA p.R482W, p.R439C, or p.H506D mutations versus cervical fat from eight control subjects, buffalo humps from five patients with HIV infection treated or not with protease inhibitors, and dorsocervical lipomas from two patients with mitochondrial DNA... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270125 Tue, 20 Sep 2011 04:00:00 +0100 5270125 http://www.medworm.com/index.php?rid=5270124&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945322%26dopt%3DAbstract In conclusion, chronic inflammation induces transdifferentiation of intestinal mucosal microvascular cells into mesenchymal cells, suggesting that the intestinal microvasculature contributes to IBD-associated fibrosis through the novel process of EndoMT. PMID: 21945322 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology) The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270124 Tue, 20 Sep 2011 04:00:00 +0100 5270124 http://www.medworm.com/index.php?rid=5270123&cid=s_37399_32_f&fid=37399&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945323%26dopt%3DAbstract Authors: Wang F, Li Y, Zhou J, Xu J, Peng C, Ye F, Shen Y, Lu W, Wan X, Xie X Abstract Pelvic lymph node metastases are regarded as the most important risk factor and a predictor of poor prognosis for patients with cervical cancer. Exploration of metastasis-related molecules is helpful toward improving the prognosis in cervical cancer. To identify the role of miR-375 in metastasis and progression of cervical cancer, we examined the expression of miR-375 in 170 cervical cancer tissues and 68 normal cervical tissues, using stem-loop quantitative PCR, and found that the expression of miR-375 in cervical cancer tissues was significantly decreased by 4.454-fold, compared with 68 normal tissues. A significant correlation existed between miR-375 expression and clinicopathologic parameters... The American Journal of Pathology journals http://www.medworm.com/rss/comments.php?id=5270123 Tue, 20 Sep 2011 04:00:00 +0100 5270123