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BIOLOGY (1423 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 1720 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 20)
Achievements in the Life Sciences     Open Access   (Followers: 4)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 21)
Acta Biologica Colombiana     Open Access   (Followers: 7)
Acta Biologica Hungarica     Full-text available via subscription   (Followers: 4)
Acta Biologica Sibirica     Open Access  
Acta Biomaterialia     Hybrid Journal   (Followers: 25)
Acta Biotheoretica     Hybrid Journal   (Followers: 5)
Acta Chiropterologica     Full-text available via subscription   (Followers: 6)
acta ethologica     Hybrid Journal   (Followers: 4)
Acta Limnologica Brasiliensia     Open Access   (Followers: 3)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Musei Silesiae, Scientiae Naturales : The Journal of Silesian Museum in Opava     Open Access  
Acta Parasitologica     Hybrid Journal   (Followers: 9)
Acta Scientiarum. Biological Sciences     Open Access   (Followers: 2)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
Actualidades Biológicas     Open Access   (Followers: 1)
Advanced Health Care Technologies     Open Access   (Followers: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Bioinformatics     Open Access   (Followers: 18)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4)
Advances in Biology     Open Access   (Followers: 8)
Advances in Biosensors and Bioelectronics     Open Access   (Followers: 6)
Advances in Cell Biology     Open Access   (Followers: 23)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Ecological Research     Full-text available via subscription   (Followers: 41)
Advances in Ecology     Open Access   (Followers: 16)
Advances in Environmental Sciences - International Journal of the Bioflux Society     Open Access   (Followers: 20)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in High Energy Physics     Open Access   (Followers: 19)
Advances in Human Biology     Open Access   (Followers: 1)
Advances in Life Science and Technology     Open Access   (Followers: 14)
Advances in Life Sciences     Open Access   (Followers: 4)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 22)
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3)
Advances in Regenerative Biology     Open Access   (Followers: 1)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Virus Research     Full-text available via subscription   (Followers: 5)
African Journal of Range & Forage Science     Hybrid Journal   (Followers: 6)
AFRREV STECH : An International Journal of Science and Technology     Open Access   (Followers: 1)
Ageing Research Reviews     Hybrid Journal   (Followers: 8)
Aging Cell     Open Access   (Followers: 10)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Agrokreatif Jurnal Ilmiah Pengabdian kepada Masyarakat     Open Access  
AJP Cell Physiology     Full-text available via subscription   (Followers: 13)
AJP Endocrinology and Metabolism     Full-text available via subscription   (Followers: 22)
AJP Lung Cellular and Molecular Physiology     Full-text available via subscription   (Followers: 3)
Al-Kauniyah : Jurnal Biologi     Open Access  
Alasbimn Journal     Open Access   (Followers: 1)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Biology Teacher     Full-text available via subscription   (Followers: 12)
American Fern Journal     Full-text available via subscription   (Followers: 1)
American Journal of Agricultural and Biological Sciences     Open Access   (Followers: 10)
American Journal of Bioethics     Hybrid Journal   (Followers: 10)
American Journal of Biostatistics     Open Access   (Followers: 9)
American Journal of Human Biology     Hybrid Journal   (Followers: 12)
American Journal of Medical and Biological Research     Open Access   (Followers: 5)
American Journal of Plant Sciences     Open Access   (Followers: 19)
American Journal of Primatology     Hybrid Journal   (Followers: 15)
American Malacological Bulletin     Full-text available via subscription   (Followers: 3)
American Naturalist     Full-text available via subscription   (Followers: 65)
Amphibia-Reptilia     Hybrid Journal   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4)
Analytical Methods     Full-text available via subscription   (Followers: 7)
Anatomical Science International     Hybrid Journal   (Followers: 2)
Animal Cells and Systems     Hybrid Journal   (Followers: 4)
Annales de Limnologie - International Journal of Limnology     Hybrid Journal   (Followers: 1)
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3)
Annales UMCS, Biologia     Open Access   (Followers: 1)
Annals of Applied Biology     Hybrid Journal   (Followers: 8)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18)
Annals of Human Biology     Hybrid Journal   (Followers: 4)
Annual Review of Biomedical Engineering     Full-text available via subscription   (Followers: 17)
Annual Review of Biophysics     Full-text available via subscription   (Followers: 25)
Annual Review of Cancer Biology     Full-text available via subscription  
Annual Review of Cell and Developmental Biology     Full-text available via subscription   (Followers: 38)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 14)
Annual Review of Genomics and Human Genetics     Full-text available via subscription   (Followers: 19)
Annual Review of Phytopathology     Full-text available via subscription   (Followers: 10)
Anthropological Review     Open Access   (Followers: 25)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antibiotics     Open Access   (Followers: 8)
Antioxidants     Open Access   (Followers: 4)
Antioxidants & Redox Signaling     Hybrid Journal   (Followers: 8)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apidologie     Hybrid Journal   (Followers: 4)
Apmis     Hybrid Journal   (Followers: 1)
APOPTOSIS     Hybrid Journal   (Followers: 8)
Applied Bionics and Biomechanics     Open Access   (Followers: 8)
Applied Vegetation Science     Full-text available via subscription   (Followers: 9)
Aquaculture Environment Interactions     Open Access   (Followers: 2)
Aquaculture International     Hybrid Journal   (Followers: 22)
Aquaculture Reports     Open Access   (Followers: 3)
Aquaculture, Aquarium, Conservation & Legislation - International Journal of the Bioflux Society     Open Access   (Followers: 6)
Aquatic Biology     Open Access   (Followers: 4)
Aquatic Ecology     Hybrid Journal   (Followers: 30)
Aquatic Ecosystem Health & Management     Hybrid Journal   (Followers: 13)
Aquatic Science and Technology     Open Access   (Followers: 3)
Aquatic Toxicology     Hybrid Journal   (Followers: 19)
Archaea     Open Access   (Followers: 3)
Archiv für Molluskenkunde: International Journal of Malacology     Full-text available via subscription   (Followers: 3)
Archives of Biomedical Sciences     Open Access   (Followers: 7)
Archives of Microbiology     Hybrid Journal   (Followers: 8)
Archives of Natural History     Hybrid Journal   (Followers: 7)
Archives of Oral Biology     Hybrid Journal   (Followers: 2)
Archives of Virology     Hybrid Journal   (Followers: 5)
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2)
Arid Ecosystems     Hybrid Journal   (Followers: 3)
Arquivos do Instituto Biológico     Open Access   (Followers: 1)
Arquivos do Museu Dinâmico Interdisciplinar     Open Access  
Arthropod Structure & Development     Hybrid Journal   (Followers: 2)
Arthropods     Open Access   (Followers: 1)
Artificial DNA: PNA & XNA     Hybrid Journal   (Followers: 2)
Artificial Photosynthesis     Open Access   (Followers: 1)
Asian Bioethics Review     Full-text available via subscription   (Followers: 1)
Asian Journal of Biodiversity     Open Access   (Followers: 5)
Asian Journal of Biological Sciences     Open Access   (Followers: 3)
Asian Journal of Cell Biology     Open Access   (Followers: 5)
Asian Journal of Developmental Biology     Open Access   (Followers: 2)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 2)
Asian Journal of Nematology     Open Access   (Followers: 3)
Asian Journal of Poultry Science     Open Access   (Followers: 4)
Australian Life Scientist     Full-text available via subscription   (Followers: 2)
Australian Mammalogy     Hybrid Journal   (Followers: 5)
Autophagy     Hybrid Journal   (Followers: 2)
Avian Biology Research     Full-text available via subscription   (Followers: 4)
Avian Conservation and Ecology     Open Access   (Followers: 10)
Bacteriology Journal     Open Access   (Followers: 2)
Bacteriophage     Full-text available via subscription   (Followers: 3)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Plant Taxonomy     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Berita Biologi     Open Access   (Followers: 1)
Between the Species     Open Access   (Followers: 1)
Bio Tribune Magazine     Hybrid Journal  
BIO Web of Conferences     Open Access  
BIO-Complexity     Open Access  
Bio-Grafía. Escritos sobre la Biología y su enseñanza     Open Access  
Bioanalytical Reviews     Hybrid Journal   (Followers: 2)
Biocatalysis and Biotransformation     Hybrid Journal   (Followers: 6)
Biochemistry and Cell Biology     Hybrid Journal   (Followers: 14)
Biochimie     Hybrid Journal   (Followers: 7)
BioControl     Hybrid Journal   (Followers: 5)
Biocontrol Science and Technology     Hybrid Journal   (Followers: 5)
Biodemography and Social Biology     Hybrid Journal   (Followers: 1)
Biodiversidad Colombia     Open Access  
Biodiversity : Research and Conservation     Open Access   (Followers: 26)
Biodiversity and Natural History     Open Access   (Followers: 5)
Biodiversity Data Journal     Open Access   (Followers: 3)
Biodiversity Informatics     Open Access  
Bioedukasi : Jurnal Pendidikan Biologi FKIP UM Metro     Open Access  
Bioeksperimen : Jurnal Penelitian Biologi     Open Access  
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 1)
Bioenergy Research     Hybrid Journal   (Followers: 2)
Bioengineering and Bioscience     Open Access   (Followers: 1)
BioEssays     Hybrid Journal   (Followers: 10)
Bioethics     Hybrid Journal   (Followers: 14)
BioéthiqueOnline     Open Access  
Biofabrication     Hybrid Journal   (Followers: 3)
Biogeosciences (BG)     Open Access   (Followers: 10)
Biogeosciences Discussions (BGD)     Open Access   (Followers: 1)
Bioinformatics     Hybrid Journal   (Followers: 293)
Bioinformatics and Biology Insights     Open Access   (Followers: 15)
Bioinspiration & Biomimetics     Hybrid Journal   (Followers: 6)
Biointerphases     Open Access   (Followers: 1)
Biojournal of Science and Technology     Open Access  
Biologia     Hybrid Journal  
Biologia on-line : Revista de divulgació de la Facultat de Biologia     Open Access  
Biological Bulletin     Partially Free   (Followers: 4)
Biological Control     Hybrid Journal   (Followers: 5)
Biological Invasions     Hybrid Journal   (Followers: 16)
Biological Journal of the Linnean Society     Hybrid Journal   (Followers: 15)
Biological Letters     Open Access   (Followers: 4)
Biological Procedures Online     Open Access  
Biological Psychiatry     Hybrid Journal   (Followers: 42)
Biological Psychology     Hybrid Journal   (Followers: 6)
Biological Research     Open Access  
Biological Rhythm Research     Hybrid Journal   (Followers: 2)
Biological Theory     Hybrid Journal   (Followers: 1)
Biological Trace Element Research     Hybrid Journal  
Biologicals     Full-text available via subscription   (Followers: 9)
Biologics: Targets & Therapy     Open Access   (Followers: 1)
Biologie Aujourd'hui     Full-text available via subscription  
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42)
Biologija     Open Access  
Biology     Open Access   (Followers: 5)
Biology and Philosophy     Hybrid Journal   (Followers: 16)
Biology Bulletin     Hybrid Journal   (Followers: 1)
Biology Bulletin Reviews     Hybrid Journal  
Biology Direct     Open Access   (Followers: 7)
Biology Letters     Full-text available via subscription   (Followers: 35)

        1 2 3 4 5 6 7 8 | Last

Journal Cover Apmis
  [SJR: 0.855]   [H-I: 73]   [1 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0903-4641 - ISSN (Online) 1600-0463
   Published by John Wiley and Sons Homepage  [1576 journals]
  • Hyaluronate effect on bacterial biofilm in ENT district infections: a
    • Authors: Alberto Vito Marcuzzo; Margherita Tofanelli, Francesca Boscolo Nata, Annalisa Gatto, Giancarlo Tirelli
      Abstract: Bacterial resistance is a growing phenomenon which led the scientific community to search for new therapeutic targets, such as biofilm. A bacterial biofilm is a surface-associated agglomerate of microorganisms embedded in a self-produced extracellular polymeric matrix made of polysaccharides, nucleic acids, and proteins. Scientific literature offers several reports on a biofilm's role in infections regarding various body districts. The presence of a bacterial biofilm is responsible for poor efficacy of antibiotic therapies along with bacterial infections in ear, nose, and throat (ENT) districts such as the oral cavity, ear, nasal cavities, and nasal sinuses. In particular, bacterial biofilms are associated with recalcitrant and symptomatically more severe forms of chronic rhinosinusitis. As of today, there are no therapeutic options for the eradication of bacterial biofilm in ENT districts. Hyaluronic acid is a glycosaminoglycan composed of glucuronic acid and N-acetylglucosamine disaccharide units. Its efficacy in treating rhinosinusitis, whether or not associated with polyposis, is well documented, as well as results from its effects on mucociliary clearance, free radical production and mucosal repair. This review's aim is to evaluate the role of bacterial biofilms and the action exerted on it by hyaluronic acid in ENT pathology, with particular attention to the rhinosinusal district. In conclusion, this paper underlines how the efficacy of hyaluronate as an anti-bacterial biofilm agent is well demonstrated by in vitro studies; it is, however, only preliminarily demonstrated by clinical studies.
      PubDate: 2017-07-24T02:41:03.403452-05:
      DOI: 10.1111/apm.12728
  • CXCL8 promotes the invasion of human osteosarcoma cells by regulation of
           PI3K/Akt signaling pathway
    • Authors: Hai Jiang; Xiaowei Wang, Wusheng Miao, Bing Wang, Yusheng Qiu
      Abstract: Chemokine cysteine-X-cysteine motif ligand 8 (CXCL8) is up-regulated in many malignancies, indicating that CXCL8 takes part in tumor progression. However, the expression and function of CXCL8 in osteosarcoma remained not fully elucidated. In this study, expressions of 12 cytokines and chemokines were measured in the serum from 12 of normal controls (NCs) and 25 of osteosarcoma patients. The human osteosarcoma cell line MG-63 was stimulated by recombinant CXCL8 to further analyze invasion, proliferation, apoptosis, cell cycles, cytokine secretions, and signaling pathways. We found that serum concentrations of CXCL8 and vascular endothelial growth factor were elevated in osteosarcoma patients in comparison with those in NCs. CXCL8 stimulation led to enhancement of invasion and suppression of late stage apoptosis in MG-63 cells. Moreover, secretions of MMPs by MG-63 cells were also increased upon stimulation. However, early stage apoptosis, proliferation, and cell cycles were not affected by CXCL8 treatment. Furthermore, CXCL8 stimulation induced elevations of phosphorylated PI3K and Akt, but not PKC or FAK. In conclusion, our findings suggested that CXCL8 enhanced the invasion and suppressed late stage apoptosis of osteosarcoma cells probably via influencing PI3K/Akt signaling pathway and elevating the expression of MMPs. CXCL8 may promote disease progression of osteosarcoma as a protumorigenic molecule, and may be served as a new therapeutic target for osteosarcoma.
      PubDate: 2017-07-24T02:36:49.718966-05:
      DOI: 10.1111/apm.12721
  • No associations established between single nucleotide polymorphisms in
           human Toll-like receptor 2 and Toll-interacting protein and Staphylococcus
           aureus bloodstream infections
    • Authors: Tom Eirik Smeland; Fredrik Müller, Anita Blomfeldt, Knut Stavem, Hege Vangstein Aamot
      Abstract: Staphylococcus aureus bloodstream infections (SABSI) are associated with high morbidity and mortality. The Toll-like receptor 2 (TLR2) and Toll-interacting protein (TOLLIP) are important in recognition and regulation of human innate immunity response to S. aureus. Single nucleotide polymorphisms (SNPs) in the TLR2 and TOLLIP encoding genes have been associated with disease, including BSI. The aim of this study was to examine potential associations between a selection of SNPs in the genes encoding TLR2 and TOLLIP, and predisposition, severity, and outcome of SABSI. All patients ≥18 years of age with at least one S. aureus positive blood culture collected from March 2011 through February 2014 at Akershus University Hospital, Lørenskog, Norway, were considered for inclusion. Patients attending elective orthopaedic surgery (total hip and knee replacements, lumbar surgery) served as a control group. The TLR2 Arg753Gln, TLR2 Pro631His, TOLLIP rs5743942, and rs5743867 polymorphisms were analysed using TaqMan SNP Genotyping Assays. A total of 209 SABSI patients and 295 controls were included. The TLR2 Arg753Gln and TLR2 Pro631His polymorphisms were infrequent with no homozygotes and
      PubDate: 2017-07-24T02:25:18.306074-05:
      DOI: 10.1111/apm.12734
  • Testing for high-risk HPV in cervical and tonsillar paraffin-embedded
           tissue using a cartridge-based assay
    • Authors: Elina Virtanen; Pekka Laurila, Jaana Hagström, Pekka Nieminen, Eeva Auvinen
      Abstract: This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin-fixed paraffin-embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining. Among valid cervical LC samples 46.8% were hrHPV positive using Xpert test and 55.3% with HC2. The sensitivity of Xpert was 84.6% as compared to HC2, and overall test concordance was 91.5%. Test concordance between valid Xpert results from biopsies and LC samples was 84.6%. Among valid tonsillar samples 70.4% were hrHPV positive, and concordance of 96.3% was found between Xpert and p16 staining. To conclude, Xpert HPV test cartridge provides a convenient platform to test individual samples, including FFPE samples. Further studies are needed to establish whether test sensitivity is sufficient to reliably differentiate between hrHPV positive and hrHPV negative head and neck carcinomas.
      PubDate: 2017-07-24T01:30:23.360573-05:
      DOI: 10.1111/apm.12727
  • BMP-7 ameliorates cobalt alloy particle-induced inflammation by
           suppressing Th17 responses
    • Authors: Fengrong Chen; Ruisong Chen, Haoyuan Liu, Rupeng Sun, Jianming Huang, Zheyuan Huang, Guojian Jian
      Abstract: Metal wear debris has been shown to activate an aseptic osteolytic process that causes failure in total joint arthroplasty (TJA). This osteolysis is characterized by a proinflammatory, self-propagating immune response involving primarily macrophages, dendritic cells, and activated osteoclasts, as well as T cells and B cells. The human bone morphogenic protein (BMP)-7, on the other hand, was shown to promote osteoblast survival, and reversed the downregulation of anabolic Smad proteins and Runx2 following cobalt injury. Therefore, we investigated the effect and mechanism of BMP-7 on the proinflammatory immune responses in osteoarthritis patients with previous TJA. Cobalt-treated monocytes/macrophages presented significantly elevated levels of interleukin 6 (IL-6) and tumor necrosis factor (TNF), both of which were suppressed by the addition of exogenous BMP-7. In patients with TJA, the serum BMP-7 level was inversely associated with the level of IL-6 and TNF secreted by monocytes/macrophages. Cobalt-treated monocytes/macrophages effectively supported Th17 inflammation, by an IL-6-dependent but not TNF-dependent mechanism. BMP-7, however, significantly suppressed cobalt-induced Th17 inflammation. In patients with TJA, the risk of osteolysis development was positively associated with the frequency of Th17 cells and negatively associated with the level of BMP-7. Together, these results demonstrated that BMP-7 could serve as a therapeutic agent in treating patients with metal wear debris-induced inflammation.
      PubDate: 2017-07-24T01:21:07.925308-05:
      DOI: 10.1111/apm.12730
  • Cytokine expression associated with Helicobacter pylori and Epstein-Barr
           virus infection in gastric carcinogenesis
    • Authors: Jung Yeon Kim; Byung-Noe Bae, Guhyun Kang, Hyun-Jung Kim, Kyeongmee Park
      Abstract: Helicobacter pylori and Epstein-Barr virus (EBV) infection, and associated cytokines are involved in gastric carcinogenesis. We investigated the expression of these cytokines and their relationship with clinicopathological characteristics. The study included specimens from 207 patients with gastric adenocarcinoma, 56 with chronic gastritis, 32 with metaplasia, and 30 with low-grade epithelial dysplasia. Tissue microarrays were constructed and immunohistochemical staining for IL-1β, IL-6, IL-10, IL-17, p16, p21, TNF-α, and TNFR1 was performed. EBV and H. pylori infection status was determined. IL-1β, IL-6, IL-17, p16, and p21 protein expression was significantly higher in adenocarcinoma cases than in the other cases (p < 0.05). EBV was only noted in adenocarcinoma (13 cases, 6.3%). The H. pylori infection rate in adenocarcinoma was significantly higher than that in the other cases (p < 0.005). IL-6 expression was associated with improved survival (p < 0.05), whereas IL-17 expression was associated with decreased survival (p < 0.05). IL-6 expression was inversely associated with angioinvasion, and disease stage (p < 0.05), whereas IL-17 expression was associated with disease stage (p < 0.05). IL-10 expression was correlated with IL-1β and TNF-α expression, and p16 expression was correlated with IL-17 and EBV status. Our results indicate that IL-6 and IL-17 are associated with gastric carcinogenesis and may be considered prognostic factors.
      PubDate: 2017-07-24T01:10:43.475814-05:
      DOI: 10.1111/apm.12725
  • Tim-1+ B cells suppress T cell interferon-gamma production and promote
           Foxp3 expression, but have impaired regulatory function in coronary artery
    • Authors: Xiao-Long Gu; Huan He, Lin Lin, Guo-Xin Luo, Yan-Fei Wen, Ding-Cheng Xiang, Jian Qiu
      Abstract: Atherosclerosis and its associated coronary artery disease (CAD) represent another chronic low-grade inflammatory disorder. Regulatory B cells (Bregs) possess essential functions in maintaining peripheral tolerance and inhibiting pathogenic inflammation through IL-10. Here, we investigated one subset of Bregs, Tim-1+ B cell, and its role in atherosclerosis and CAD patients. In healthy individuals, IL-10-producing B cells were predominantly found in the Tim-1+ B cells. Upon stimulation of the B cell receptor (BCR) and Toll-like receptor 9 (TLR-9) by anti-BCR antibodies and CpG, respectively, the Tim-1+ B cells could further upregulate IL-10 expression. In contrast, the Tim-1+ B cells were present at normal frequency in CAD patients, but showed impaired capacity to upregulate IL-10 with or without BCR + CpG stimulation. The stimulated Tim-1+ B cells from healthy individuals also suppressed expression of interferon gamma (IFN-γ), an atherogenic cytokine in T cells, in an IL-10-dependent fashion, and strongly promoted the expression of Foxp3 in naive CD4+CD45RO− T cells. In contrast, the Tim-1+ B cells from CAD patients were unable to suppress IFN-γ secretion, and only minimally increased the expression of Foxp3 in naive CD4+CD45RO− T cells. Despite this, the frequency of Tim-1+ B cells in the atherosclerotic lesions from CAD patients was inversely correlated with the frequency of IFN-γ-expressing T cells. Together, these results demonstrated that CAD patients presented an inflammatory disorder in regulatory B cells, which could be used as a therapeutic target.
      PubDate: 2017-07-24T01:00:25.166733-05:
      DOI: 10.1111/apm.12729
  • Molecular characterization of nasal methicillin resistant Staphylococcus
           aureus isolates from workers of an automaker company in southeast Iran
    • Authors: Mohammad Hossein Sobhanipoor; Roya Ahmadrajabi, Afsaneh Karmostaji, Fereshteh Saffari
      Abstract: Colonization of methicillin resistant Staphylococccus aureus (MRSA) can occur more commonly in healthy people who live in close together or are in close physical contact with each other. Having knowledge about the molecular characteristics of these strains provides considerable discernment into the epidemiology of this important microorganism. A total of 806 nasal swabs were collected from healthy workers of an automaker company in the southeast of Iran and were analyzed to detect MRSA isolates. Multilocus sequence typing (MLST), spa typing, and detection of staphylococcal cassette chromosome mec (SCCmec) were performed. The presence of genes encoding Panton-Valentine Leukocidin (PVL) and Arginine Catabolic Mobile Element (ACME) were also investigated. Carriage rate of S. aureus was 20%. Among 10 identified MRSA, no acme was found while high prevalence of pvl (60%) was of great concern. Seven different spa types including five new ones were identified. The most frequent sequence type was the novel one; ST 3373 (n = 3), followed by each of ST22, ST88, ST859 (n = 2) and ST1955 (n = 1). MRSA isolates were clustered into two main clonal complexes; CC22 (n = 6) and CC88 (n = 4). Low genetic diversity with the dominance of CC22, SCCmecIV was found. Distribution of previously found hospital-associated MRSA was demonstrated among our isolates.
      PubDate: 2017-07-24T00:50:19.245313-05:
      DOI: 10.1111/apm.12732
  • Regulatory T cell subsets in peripheral blood of celiac disease patients
           and TLR2 expression: correlation with oxidative stress
    • Authors: Sanjay Kumar; Sadhna Lal, Archana Bhatnagar
      Abstract: The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon-γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls. On the other hand, inducible Tregs were much lower in GFD patients as compared to CD patients. Expression of TLR2 on iTregs was elevated in CD and GFD, however, expression on nTregs was unaltered in all the three groups. The inflammatory cytokine IFN-γ positive Treg cells were found to be elevated in CD as compared to control group. Oxidative stress was elevated in CD as compared to healthy controls while that in GFD samples was lower in comparison to CD. The levels of LPO, activities of enzymes SOD and Catalase were higher in CD and GFD samples when compared to controls. However, enzyme Glutathione peroxidase and reduced glutathione levels declined in both CD and GFD groups as compared to controls. This report highlights the effect of elevated oxidative stress in CD on reduced traffic of iTregs toward periphery. A strong correlation was observed between the cytokine IFN-γ and TLR2 expression in movement of iTregs in CD patients.
      PubDate: 2017-07-24T00:20:33.765895-05:
      DOI: 10.1111/apm.12735
  • Unrecognized viral infections and chromosome abnormalities as a cause of
           fetal death – examination with fluorescence in situ hybridization,
           immunohistochemistry and polymerase chain reaction
    • Authors: Bente Ediassen Opsjøn; Svein Arne Nordbø, Christina Vogt
      Abstract: Fifteen to 50% of fetal deaths remain unexplained after post-mortem examination depending on inclusion criteria and classification systems. Our aim was to examine a selection of unexplained fetal deaths in order to investigate whether any common chromosome aberrations or viral infections were present. Reports from 351 fetal autopsies performed at the Department of Pathology and Medical Genetics at St. Olavs University Hospital from 2001 through 2010 were reviewed. Of these, 105 fetal deaths were classified as unexplained. Tissue samples from 30 cases were further examined with fluorescence in situ hybridization (FISH) to detect abnormalities in chromosomes 13, 18, and 21. The samples were also examined with immunohistochemistry (IHC) and polymerase chain reaction (PCR) to detect infections with cytomegalovirus, parvovirus B19, herpes simplex virus 1 and 2, enterovirus, and parechovirus. In two cases, a possible trisomy 13 mosaicism was found. No viruses were detected. In our selection of 30 unexplained cases, possible trisomy 13 mosaicism was found in two cases, and no viruses were detected. High degree of maceration and missing placental examination often complicate the investigation of fetal death, and extensive ancillary examinations do not necessarily contribute to a more specific diagnosis.
      PubDate: 2017-07-24T00:07:59.350074-05:
      DOI: 10.1111/apm.12726
  • First environmental sample containing plasmid-mediated colistin-resistant
           ESBL-producing Escherichia coli detected in Norway
    • Authors: Silje Bakken Jørgensen; Arne Søraas, Lotte Stenfors Arnesen, Truls Leegaard, Arnfinn Sundsfjord, Pål A. Jenum
      Abstract: We hereby report a detection of the plasmid borne mcr-1 gene conferring colistin resistance in an extended-spectrum β-lactamase (ESBL) producing Escherichia coli ST10 strain retrieved from seawater at a public beach in Norway. The sample was collected in September 2010 and was investigated by whole-genome sequencing in 2016. This report illustrates that E. coli strains carrying plasmid-mediated colistin resistance genes have also reached areas where this drug is hardly used at all. Surveillance of colistin resistance in environmental, veterinary, and human strains is warranted also in countries where colistin resistance is rare in clinical settings.
      PubDate: 2017-06-22T08:20:19.937934-05:
      DOI: 10.1111/apm.12720
  • Trichomonas vaginalis is very rare among women with vaginal discharge in
           Podlaskie province, Poland
    • Authors: Agnieszka Beata Serwin; Violetta Bulhak-Koziol, Marianna Sokolowska, Daniel Golparian, Magnus Unemo
      Abstract: Trichomonas vaginalis is the most common curable sexually transmitted pathogen globally. However, in the European Union (EU), trichomoniasis appears to be a rare condition. The aim of this study was to examine the prevalence of T. vaginalis among females attending an STI centre in Bialystok, Poland, using the highly sensitive and specific APTIMA T. vaginalis assay. Consecutive females, referred by gynaecologists mainly because of abnormal vaginal discharge, were diagnosed using wet mount microscopy, culture and APTIMA T. vaginalis assay. Among 272 women studied, 82% were pre- and 18% postmenopausal. The average age was 36.0 ± 13.9 (range: 18–86) years. Abnormal discharge (alone or accompanied by itch or vulvovaginal burning) was the most frequent complain in both groups (66.2% and 48.0%). Erythema and discharge were the most frequent abnormal signs (58.6% and 56.0%). Not a single T. vaginalis-positive sample was detected using wet mount microscopy, culture or APTIMA T. vaginalis assay. Despite using the highly sensitive APTIMA T. vaginalis assay for detection, the pathogen could not be identified in females in the studied setting, similar to results from other EU settings. The need for general screening using NAAT for this pathogen while diagnosing vulvovaginal symptoms in females in Poland appears to be low.
      PubDate: 2017-06-14T02:30:38.276966-05:
      DOI: 10.1111/apm.12713
  • Blood donor Borrelia burgdorferi sensu lato seroprevalence and history of
           tick bites at a northern limit of the vector distribution
    • Authors: Dag Hvidsten; Liisa Mortensen, Bjørn Straume, Mirjana Grujic Arsenovic, Anne-Berit Pedersen, Gro Lyngås, Jeremy S. Gray, Nils Grude
      Abstract: In order to study the antibody seroprevalence of the causal agent of Lyme borreliosis, Borrelia burgdorferi sensu lato (s.l.), and the history of tick bites at a geographical distribution limit of Ixodes ricinus, we compared healthy blood donors in geographically extreme regions: the borreliosis-endemic Vestfold County (59°N) and the region of northern Norway. Blood samples were screened using IgG/VlsE ELISA, and positive/borderline samples were confirmed using C6 ELISA and immunoblot assays. Also, donors completed a questionnaire consisting of several items including the places they have lived, and whether they owned any pets. The seroprevalence was 0.48% (5/1048) in northern Norway and 9.25% (48/519) in Vestfold County. Seven donors (of 1048) had experienced a single tick bite in the southern part of Nordland County (65°N) in northern Norway. This first study on B. burgdorferi s.l. antibody seroprevalence and tick bites on humans and pets in northern Norway showed that the seroprevalence of B. burgdorferi s.l. infection and the risk of tick bite in northern Norway are insignificant; the fact that only five positive IgG samples were detected underscores the very low background seroprevalence. These results suggest that so far I. ricinus has not expanded north of the previously established geographical distribution limit.
      PubDate: 2017-06-14T02:25:24.03867-05:0
      DOI: 10.1111/apm.12708
  • Use of the optical disector in canine mammary simple and complex
    • Authors: Marta Santos; Patrícia Dias-Pereira, Carla Correia-Gomes, Ricardo Marcos, Augusto Matos, Eduardo Rocha, Carlos Lopes
      Abstract: Grading of canine mammary carcinomas (CMC) is associated to subjective assessments made by the pathologists. Due to its unbiased nature, stereology can be used to objectively quantify morphological parameters associated with grading and malignancy. However, the use of stereology in CMC has not been fully disclosed. The nuclear numerical density [NV (nuclei, tumor)] is a cellularity-associated parameter that can be estimated by the optical disector. Herein, it was estimated in 44 CMC and its association with clinicopathologic factors – such as tumor size, histological subtype and grade, vascular/lymph node invasion, nuclear pleomorphism, and survival – was evaluated. Considering all the cases, the mean NV (nuclei, tumor) was 1.6 × 106 ± 0.5 × 106 nuclei/mm3. Lower values were attained in complex carcinomas, comparing to simple carcinomas, in tumors smaller than 5 cm, with low mitotic activity and in those with high nuclear pleomorphism. No statistically significant association with grade or vascular/lymph node invasion was observed, but tumors with disease progression had lower nuclear densities. The NV (nuclei, tumor) and the correlated parameters mirror to some extension those in human breast cancer, suggesting an interesting interspecies agreement. This first estimation of the nuclear numerical density in CMC highlights the feasibility of the optical disector and their utility for objective morphological assessments in CMC. The association between nuclear numerical density and disease progression warrants future studies.
      PubDate: 2017-06-06T07:55:30.670407-05:
      DOI: 10.1111/apm.12717
  • A DNA hypermethylation profile reveals new potential biomarkers for the
           evaluation of prognosis in urothelial bladder cancer
    • Authors: Jose I. López; Javier C. Angulo, Ana Martín, Manuel Sánchez-Chapado, Ana González-Corpas, Begoña Colás, Santiago Ropero
      Abstract: DNA hypermethylation has emerged as a molecular biomarker for the evaluation of cancer diagnosis and prognosis. We define a methylation signature of bladder cancer and evaluate whether this profile assesses prognosis of patients. Genome-wide methylation analysis was performed on 70 tumor and 10 normal bladder samples. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Thirty-three genes were significantly hypermethylated in ≥10% of the tumors. Three clusters of patients were characterized by their DNA methylation profile, one at higher risk of dead of disease (p = 0.0012). Association between cluster distribution and stage (p = 0.02) or grade (p = 0.02) was demonstrated. Hypermethylation of JAK3 and absence of hypermethylation of EYA4, GAT6, and SOX1 were associated with low-grade non-invasive disease. On the other hand, in high-grade invasive disease hypermethylation of CSPG2, HOXA11, HOXA9, HS3ST2, SOX1, and TWIST1 was associated with muscle invasiveness. A panel of hypermethylated genes including APC, CSPG2, EPHA5, EYA4, HOXA9, IPF1, ISL1, JAK3, PITX2, SOX1, and TWIST1 predicted cancer-specific survival and SOX1 (HR = 3.46), PITX2 (HR = 4.17), CSPG2 (HR = 5.35), and JAK3 hypermethylation (HR = 0.19) did so independently. Silencing of genes by hypermethylation is a common event in bladder cancer and could be used to develop diagnostic and prognostic markers. Combined hypermethylation of SOX1, PITX2, or CSPG2 signals patients at higher risk of death from bladder cancer.
      PubDate: 2017-06-06T06:56:47.64749-05:0
      DOI: 10.1111/apm.12719
  • Circulation and diagnostics of Puumala virus in Norway: nephropatia
           epidemica incidence and rodent population dynamics
    • Authors: Natacha Milhano; Lars Korslund, Magnus Evander, Clas Ahlm, Kirsti Vainio, Susanne G. Dudman, Åshild Andreassen
      Abstract: Hantaviruses pose a public health concern worldwide causing haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Puumala virus (PUUV) is the most prevalent hantavirus in Central and Northern Europe, and causes a mild form of HFRS, also known as nephropathia epidemica (NE). In nature, the main host of PUUV is the bank vole (Myodes glareolus), and transmission to humans occurs through inhalation of aerosols from rodent excreta. Nephropathia epidemica is particularly prevalent in Nordic countries, however, few studies of PUUV have been performed in Norway. The aim of this study was to analyse the dynamics of PUUV in Norway and compare with bank vole population dynamics, and also to complement the current diagnostic methodology of NE in Norway. Our results showed a significant seasonal and geographical variation of NE, and a general parallel peak trend between bank vole population densities and human NE incidence. A real-time and a nested PCR were successfully established as an invaluable diagnostic tool, with detection and sequencing of PUUV in a human serum sample for the first time in Norway. Phylogenetic analysis showed clustering of the obtained human sample with previous Norwegian bank vole isolates.
      PubDate: 2017-06-06T03:50:33.605986-05:
      DOI: 10.1111/apm.12712
  • TFE3-rearranged hepatic epithelioid hemangioendothelioma—a case report
           with immunohistochemical and molecular study
    • Authors: Fang-Ying Kuo; Hsuan-Ying Huang, Chao-Long Chen, Hock-Liew Eng, Chao-Cheng Huang
      Abstract: A recurrent YAP1-TFE3 gene fusion has been identified in WWTR1-CAMTA1-negative epithelioid hemangioendotheliomas arising in soft tissue, bone, and lung, but not in liver. We present the first case of TFE3-rearranged hepatic epithelioid hemangioendothelioma in a 39-year-old Taiwanese woman. Computed tomography scan revealed multifocal, ill-defined nodules involving both hepatic lobes. She then underwent deceased donor liver transplantation. Histologically, the tumors in the liver explant showed a biphasic growth pattern. One component was composed of dilated and well-formed blood vessels lined by epithelioid cells with abundant eosinophilic cytoplasm, mimicking an alveolar pattern, whereas the other component was composed of cords and single cells, featuring intracytoplasmic vacuoles, separated by a myxoid stroma. The tumor cells showed vesicular nuclei and small indistinct nucleoli with mild to moderate cytologic atypia. Most tumor cells showed factor VIII, CD34, CD31, and TFE3 positivity in immunohistochemical study. Fluorescence in situ hybridization analysis for the tumor cells exhibited TFE3 gene rearrangement. The patient is currently alive, and no post-operative tumor recurrence developed during a 13-year follow-up. Awareness of this rare vasoformative variant and identification of the gene rearrangement would be helpful on differential diagnosis with other high-grade carcinoma and angiosarcoma of liver.
      PubDate: 2017-06-06T03:42:04.773799-05:
      DOI: 10.1111/apm.12716
  • Inadequate adherence to Swedish guidelines for uncomplicated lower urinary
           tract infections among adults in general practice
    • Authors: Heidi Lindbäck; Johan Lindbäck, Åsa Melhus
      Abstract: In a primary care study of urinary tract infections (UTIs) performed 2008 in Uppsala County, Sweden, 43% of the patients were culture negative. In order to investigate the background to the observed overdiagnosis of UTI, study invitations were sent to the previously included patients. A total of 256 patients (88% women) approved to participate. Patient charts and recorded laboratory data were reviewed. Two or more of the cardinal symptoms were reported in 53% of the women and in 19% of the men. A dipstick test was performed in 93% of the consultations. The highest positive predicted values in women had a positive nitrite test (95%, 95% CI 87; 99) and dysuria in combination with urgency (81%, 95% CI 72; 88). Seventy-one percent of the women who fulfilled the symptom criteria received an antibiotic prescription directly, 87% of these had a positive culture. The drug of choice was pivmecillinam for women (51%) and quinolones (50%) for men. The treatment duration was too long for the women; 68% were treated for ≥7 days. In conclusion, the adherence to national guidelines/recommendations was inadequate. To reduce the selection of multiresistant bacteria, an improvement of the use of diagnostic criteria/tools and antibiotic drugs in primary care is necessary.
      PubDate: 2017-06-06T03:38:53.415026-05:
      DOI: 10.1111/apm.12718
  • Epithelial–mesenchymal transition markers in malignant ovarian germ
           cell tumors
    • Authors: Olesya Solheim; Mette Førsund, Claes G. Tropé, Sigrid Marie Kraggerud, Jahn M. Nesland, Ben Davidson
      Abstract: The purpose of this study was to determine the expression and potential clinical role of epithelial-to-mesenchymal transition (EMT)-related factors in malignant ovarian germ cell tumors (MOGCT). Protein expression of E-cadherin, N-cadherin, P-cadherin, Zeb1, HMGA2, and vimentin by immunohistochemistry was analyzed in 42 MOGCT from patients treated in Norway during the period 1981–2001. Expression was analyzed for association with clinicopathologic parameters. E-cadherin (p = 0.016) and HMGA2 (p = 0.002) expression was significantly higher in immature teratomas and yolk sac tumors compared with dysgerminomas. Vimentin (p < 0.001) and Zeb1 (p = 0.029) staining was significantly higher in immature teratomas compared with yolk sac tumors and dysgerminomas, whereas no significant differences were observed for N-cadherin and P-cadherin. EMT-associated markers were not significantly related to clinicopathologic parameters including age, tumor diameter, and FIGO stage. In conclusion, based on this limited series, EMT-associated markers are not associated with clinical parameters in MOGCT, in contrast to ovarian carcinoma. EMT-related proteins are differentially expressed among various MOGCT subtypes, suggesting differences in biological characteristics associated with invasion and metastasis.
      PubDate: 2017-06-06T03:20:44.937692-05:
      DOI: 10.1111/apm.12715
  • Prognostic value of p21-activated kinase 4 in resected pancreatic cancer
    • Authors: Sehhoon Park; Jin Won Kim, Haeryoung Kim, Ji-Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Jai Hwan Kim, Jin-Hyeok Hwang, Young Rok Choi, Jai Young Cho, Yoo-Seok Yoon, Ho-Seong Han
      Abstract: Resectable pancreatic cancer has a high recurrence rate after curative surgery. Biomarkers are needed for distinguishing patients who may benefit from curative resection. In this study, we sought to analyze the prognostic value of p21-activated kinase 1 (PAK1), p21-activated kinase 4 (PAK4), human equilibrative nucleoside transporter 1 (hENT1), and thymidylate synthase (TS) in surgically resected pancreatic ductal adenocarcinomas. A total of 160 pancreatic cancer patients who underwent surgery with curative intent were retrospectively reviewed. Tissue microarrays were constructed and immunohistochemical stains were performed for PAK1, PAK4, hENT1, and TS. The absence of PAK4 expression in pancreatic adenocarcinomas was associated with poorer histologic differentiation (p < 0.001), shorter overall survival [hazard ratio (HR) = 2.86, 95% confidence interval (CI) 1.43–5.71; p = 0.003], and disease-free survival (HR = 2.29, 95% CI: 1.11–4.74; p = 0.025) on univariate analyses. In addition, more frequent venous invasion and lymph node metastases were seen in PAK4-negative tumors although not statistically significant. PAK1, hENT1, and TS expression status did not have significant influences on patient survival. In conclusion, PAK4 of the markers tested in this study may be a potential prognostic biomarker for pancreatic adenocarcinomas.
      PubDate: 2017-05-30T03:10:35.537693-05:
      DOI: 10.1111/apm.12705
  • Liposomes or traditional adjuvants: induction of bactericidal activity by
           the macrophage infectivity potentiator protein (Mip) of Neisseria
    • Authors: Liliana Costoya; Juan Marzoa, Carlos Ferreirós, Maria Teresa Criado
      Abstract: Currently, one of the main approaches to achieve a vaccine for serogroup B Neisseria meningitidis is based on outer membrane proteins with low antigenic variability among strains. Since these proteins tend to be minor components of the outer membrane, recombinant production is required to obtain them in sufficient amounts for evaluation and development of vaccines. In this study, we analysed the ability of recombinant macrophage infectivity potentiator (rMip) protein to induce protective bactericidal activity in mice. The rMip protein was cloned from N. meningitidis strain H44/76 and was used to immunise mice, and the sera obtained were tested against the homologous and several heterologous N. meningitidis strains. The sera were obtained using the rMip alone, with adjuvant Al(OH)3, or after inclusion into liposomes. Bactericidal activity was variable depending on the strain, although high titres were seen against strains H44/76 and NmP27. Liposomes enhanced fourfold the reactivity against the homologous strain. The results presented suggest that the rMip protein should be considered a promising candidate for the improvement of future protein-based vaccines.
      PubDate: 2017-05-25T05:06:12.852213-05:
      DOI: 10.1111/apm.12709
  • A unique case of bilateral ovarian splenosis and review of the literature
    • Authors: Maria Giulia Disanto; Francesca Mercalli, Andrea Palicelli, Alberto Arnulfo, Renzo Boldorini
      Abstract: Splenosis is an acquired anomaly related to heterotopic auto-transplantation of splenic tissue following abdominal trauma or splenectomy. We report the first definitive bilateral ovarian case in a 65-year-old woman who underwent splenectomy following a motor vehicle accident 44 years prior to presentation. We review the literature and discuss the main differential diagnoses. Gross examination revealed a 1-cm well-circumscribed dark nodule on the surface of each ovary. Paraffin-embedded, formalin-fixed blocks were sectioned and stained with hematoxylin–eosin and immunostains (CK5/6, Calretinin, WT1, Vimentin). The histological presence of both red and white splenic pulp, delimitation from ovarian tissue and ovarian origin of blood supply, as well as medical history, led us to the correct diagnosis. The outer nodular surface was covered by mesothelium (WT1+, CK5/6+, Calretinin+, Vimentin+), which was in continuity with the ovarian surface epithelium. To our knowledge, only six previous cases of ovarian splenosis are reported. Our patient is the oldest, with a very long interval from splenectomy to presentation. Clinically, splenosis may mimic malignancy, and a correct diagnosis avoids unnecessary overtreatment. The differential diagnosis includes an accessory spleen, spleno-gonadal fusion, and splenic hamartoma: they should be excluded to come to the correct diagnosis.
      PubDate: 2017-05-25T05:05:28.745787-05:
      DOI: 10.1111/apm.12714
  • NUT carcinoma presenting in the palate – a case report
    • Authors: Libana Raffoul Bjornstrup; Jesper Reibel, Katalin Kiss, Morten Schioedt
      Abstract: NUT carcinomas (NC) are rare and aggressive tumours characterized by chromosomal rearrangements of the gene encoding for nuclear protein of the testis (NUT) located on chromosome 15q14. This article presents a case of a 60-year-old woman diagnosed with NC presenting as a fast growing primary tumour in the right palate. Further evaluation revealed a tumour mass in the lungs and widespread metastases. A review of the literature did not reveal earlier cases presenting in the palate. In order to improve early diagnosis it is suggested to perform immunohistochemical testing for NUT in all poorly differentiated carcinomas without glandular differentiation arising in the chest, and head and neck (Clin Cancer Res, 18, 2012, 5773).
      PubDate: 2017-05-25T05:00:32.194266-05:
      DOI: 10.1111/apm.12710
  • Polymorphism of TLR5 rs5744174 is associated with disease progression in
           Chinese patients with chronic HBV infection
    • Authors: Lina Cao; Tong Zhang, Junping Zhu, Aixin Li, Kai Zheng, Nan Zhang, Bin Su, Wei Xia, Hao Wu, Ning Li, Qiushui He
      Abstract: Toll-like receptors (TLRs) play a crucial role in innate and adaptive immunity, protecting the host from viral pathogens. Studies have implicated that TLR5 is associated with various diseases such as autoimmune and inflammation related diseases. However, little is known about the relationship between TLR5 and hepatitis B virus (HBV) infection. We studied the effect of TLR5 gene polymorphisms on susceptibility to and disease progression of chronic hepatitis B (CHB) infection in Chinese. Blood samples were taken from 636 patients with CHB, HBV-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 273 controls. Polymorphisms of TLR5 (1775A>G rs2072493 and 1846T>C rs5744174) were analyzed by PCR-based sequencing. No difference in genotypic and allelic frequencies of TLR5 rs2072493 and rs5744174 was observed between patients and controls. Significant difference was found in frequency of TLR5 rs5744174 TT genotype between men with CHB and LC (p = 0.035). Frequency of TT genotype of TLR5 rs5744174 in patients positive for HBeAg was increased from 53.2% in patients with CHB to 74.1% in those with HCC (p = 0.024). Our results indicate that in Chinese genetic variation of TLR5 may be not a determinant of susceptibility to HBV-related diseases but may play a role in development of HBV-related severe liver diseases.
      PubDate: 2017-05-25T03:55:59.778718-05:
      DOI: 10.1111/apm.12707
  • HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less
           cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor
    • Authors: Fanzhi Meng; Shoumei Zhen, Bin Song
      Abstract: In East Asia and sub-Saharan Africa, chronic infection is the main cause of the development of hepatocellular carcinoma, an aggressive cancer with low survival rate. Cytotoxic T cell-based immunotherapy is a promising treatment strategy. Here, we investigated the possibility of using HBV-specific CD4+ cytotoxic T cells to eliminate tumor cells. The naturally occurring HBV-specific cytotoxic CD4+ and CD8+ T cells were identified by HBV peptide pool stimulation. We found that in HBV-induced hepatocellular carcinoma patients, the HBV-specific cytotoxic CD4+ T cells and cytotoxic CD8+ T cells were present at similar numbers. But compared to the CD8+ cytotoxic T cells, the CD4+ cytotoxic T cells secreted less cytolytic factors granzyme A (GzmA) and granzyme B (GzmB), and were less effective at eliminating tumor cells. In addition, despite being able to secrete cytolytic factors, CD4+ T cells suppressed the cytotoxicity mediated by CD8+ T cells, even when CD4+CD25+ regulator T cells were absent. Interestingly, we found that interleukin 10 (IL-10)-secreting Tr1 cells were enriched in the cytotoxic CD4+ T cells. Neutralization of IL-10 abrogated the suppression of CD8+ T cells by CD4+CD25− T cells. Neither the frequency nor the absolute number of HBV-specific CD4+ cytotoxic T cells were correlated with the clinical outcome of advanced stage hepatocellular carcinoma patients. Together, this study demonstrated that in HBV-related hepatocellular carcinoma, CD4+ T cell-mediated cytotoxicity was present naturally in the host and had the potential to exert antitumor immunity, but its capacity was limited and was associated with immunoregulatory properties.
      PubDate: 2017-05-11T04:45:26.057918-05:
      DOI: 10.1111/apm.12704
  • STAT3 promotes bone fracture healing by enhancing the FOXP3 expression and
           the suppressive function of regulatory T cells
    • Authors: Guojing Sun; Zhen Wang, Yunfan Ti, Yicun Wang, Jun Wang, Jianning Zhao, Hongbo Qian
      Abstract: Signal transducer and activator of transcription 3 (STAT3) is a key signaling protein in the skeletal system as well as in the immune system. Accumulating evidence demonstrates that the inflammatory response is deeply involved in the healing process of bone fractures, but how the immune system is regulated during this process is unclear. In this study, we examined STAT3-mediated regulation of immunity in adult patients with closed tibia fracture. In all patients, the expression and activation of STAT3 peaked at around day 7 to day 14 after surgery, and gradually decreased during the rest of the healing period. At day 7 (peak STAT3 expression and phosphorylation), the CD4+CD25+ T cells from bone fracture patients presented the highest level of STAT3 activation among lymphocyte subsets. Therefore, we investigated the role of STAT3 in CD4+CD25+ T cells. The level of FOXP3 expression by CD4+CD25+ T cells was directly correlated with the level of STAT3 phosphorylation in these cells. The level of STAT3 phosphorylation in CD4+CD25+ T cells was also inversely correlated with the level of IFN-γ and TNF-α secretion in peripheral blood mononuclear cells. Inhibition of STAT3 significantly suppressed FOXP3 and IL-10 expression by CD4+CD25+ T cells, as well as the ability of CD4+CD25+ T cells to suppress T-cell IFN-γ and TNF-α secretion. Furthermore, early healers patients presented significantly higher STAT3 expression and phosphorylation than late healers, possibly due to the higher IL-6 and IL-10 levels in the serum of early healing patients. Together, these data demonstrated that STAT3 was beneficial to bone fracture healing, possibly by enhancing Treg-mediated suppression of counteracting inflammations, and suggested that STAT3 could be used as a prognostic marker to identify otherwise undistinguishable patients at risk of developing delayed union or nonunion.
      PubDate: 2017-05-11T04:40:33.401053-05:
      DOI: 10.1111/apm.12706
  • Expression and prognostic significance of programmed death protein 1 and
           programmed death ligand-1, and cytotoxic T lymphocyte-associated
           molecule-4 in hepatocellular carcinoma
    • Authors: Hyeyoon Chang; Wonkyung Jung, Aeree Kim, Han Kyeom Kim, Wan Bae Kim, Ji Hoon Kim, Baek-hui Kim
      Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001 and r = 0.149, p = 0.012). Only high Edmondson–Steiner grade was statistically related to high PD-1 expression. High PD-L1 expression was demonstrated as an independent poor prognostic factor for disease-free survival in addition to previous known factors, size>5 cm and serum albumin ≤3.5 g/dL in high CD8+ TILs group. We have demonstrated that the combined high expression of PD-L1 and CD8+ TIL is an important prognostic factor related to the immune checkpoint pathway in HCC and furthermore, there is a possibility that it could be used as a predictor of therapeutic response. Also, this result would be helpful in evaluating the applicable group of PD-1/PD-L1 blocking agent for HCC patients.
      PubDate: 2017-05-11T02:15:35.180269-05:
      DOI: 10.1111/apm.12703
  • Clinicopathologic features and immunohistochemical spectrum of 11 cases of
           epithelioid malignant peripheral nerve sheath tumors, including
           INI1/SMARCB1 results and BRAF V600E analysis
    • Authors: Bharat Rekhi; Kemal Kosemehmetoglu, Gaye Guler Tezel, Sergulen Dervisoglu
      Abstract: Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare, relatively less chemosensitive sarcoma. We report clinicopathologic features of 11 epithelioid MPNSTs, including rare forms, along with INI1 immunostaining and BRAF V600E mutation results. BRAF V600E mutation was tested by Real-time polymerase chain reaction (PCR) technique. Eleven tumors occurred in six men and five women (M:F ratio = 0.85:1) within an age range of 5–73 years (average = 44), mostly in lower limbs (five), followed by upper limbs (four). Tumor size (n = 6), varied from 3.1 to 15 cm (average = 8.3). Histopathologically, most tumors were multilobular, characterized by epithelioid to round-shaped, malignant cells, along with spindle cells (three cases), “rhabdoid-like” cells (seven cases) and pleomorphic giant cells (single case). By immunohistochemistry, tumor cells were positive for S100 protein (11/11) (100%), EMA (3/7) (42.8%), pan CK(2/7) (28.5%), and HMB45 (1/11) (9%), while these were negative for Melan A (0/11) and INI1 (3/11), including a single tumor, displaying HMB45 positivity. BRAF V600E mutation was positive in 1/8 cases, that lacked melanocytic marker expression. All patients (n = 5) were treated by surgical resection. During follow-up (n = 8, median duration = 23 months), four patients developed tumor recurrences and four developed metastasis, mostly to lymph nodes (3). Finally, four patients were alive with disease, two were alive with no evidence of disease, and two patients died of disease. Epithelioid MPNSTs have a diverse histopathologic spectrum. Loss of INI1 is useful, including in identifying rare forms of epithelioid MPNST, displaying melanocytic differentiation. Most tumors are treated by surgical resection. Loss of INI1 and the presence of BRAF V600E mutation in some cases raises future possibility of exploring targeted therapy in those, rare epithelioid MPNSTs.
      PubDate: 2017-04-27T19:18:10.167578-05:
      DOI: 10.1111/apm.12702
  • Issue Information
    • Pages: 677 - 678
      PubDate: 2017-07-18T21:18:43.291734-05:
      DOI: 10.1111/apm.12617
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