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https://www.readbyqxmd.com/read/28081260/comparative-genome-sequencing-reveals-within-host-genetic-changes-in-neisseria-meningitidis-during-invasive-disease
#1
Johanna Klughammer, Marcus Dittrich, Jochen Blom, Vera Mitesser, Ulrich Vogel, Matthias Frosch, Alexander Goesmann, Tobias Müller, Christoph Schoen
Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation...
2017: PloS One
https://www.readbyqxmd.com/read/28075410/is-toxoplasma-gondii-a-trigger-of-bipolar-disorder
#2
REVIEW
Claudia Del Grande, Luca Galli, Elisa Schiavi, Liliana Dell'Osso, Fabrizio Bruschi
Toxoplasma gondii, a ubiquitous intracellular parasite, has a strong tropism for the brain tissue, where it forms intracellular cysts within the neurons and glial cells, establishing a chronic infection. Although latent toxoplasmosis is generally assumed to be asymptomatic in immunocompetent individuals, it is now clear that it can induce behavioral manipulations in mice and infected humans. Moreover, a strong relation has emerged in recent years between toxoplasmosis and psychiatric disorders. The link between T...
January 10, 2017: Pathogens
https://www.readbyqxmd.com/read/28073774/temporally-distinct-pd-l1-expression-by-tumor-and-host-cells-contributes-to-immune-escape
#3
Takuro Noguchi, Jeffrey P Ward, Matthew M Gubin, Cora D Arthur, Sang Hun Lee, Jasreet Hundal, Mark Selby, Robert F Graziano, Elaine R Mardis, Alan J Korman, Robert D Schreiber
Antibody blockade of Programmed Death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically-related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28068342/neuropathogenesis-of-zika-virus-in-a-highly-susceptible-immunocompetent-mouse-model-after-antibody-blockade-of-type-i-interferon
#4
Darci R Smith, Bradley Hollidge, Sharon Daye, Xiankun Zeng, Candace Blancett, Kyle Kuszpit, Thomas Bocan, Jeff W Koehler, Susan Coyne, Tim Minogue, Tara Kenny, Xiaoli Chi, Soojin Yim, Lynn Miller, Connie Schmaljohn, Sina Bavari, Joseph W Golden
Animal models are needed to better understand the pathogenic mechanisms of Zika virus (ZIKV) and to evaluate candidate medical countermeasures. Adult mice infected with ZIKV develop a transient viremia, but do not demonstrate signs of morbidity or mortality. Mice deficient in type I or a combination of type I and type II interferon (IFN) responses are highly susceptible to ZIKV infection; however, the absence of a competent immune system limits their usefulness for studying medical countermeasures. Here we employ a murine model for ZIKV using wild-type C57BL/6 mice treated with an antibody to disrupt type I IFN signaling to study ZIKV pathogenesis...
January 9, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28068178/cetuximab-plus-chemoradiotherapy-in-immunocompetent-patients-with-anal-carcinoma-a-phase-ii-eastern-cooperative-oncology-group-american-college-of-radiology-imaging-network-cancer-research-group-trial-e3205
#5
Madhur K Garg, Fengmin Zhao, Joseph A Sparano, Joel Palefsky, Richard Whittington, Edith P Mitchell, Mary F Mulcahy, Karin I Armstrong, Nassim H Nabbout, Shalom Kalnicki, Bassel F El-Rayes, Adedayo A Onitilo, Daniel J Moriarty, Thomas J Fitzgerald, Al B Benson
Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab...
January 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28063344/reducing-persistent-polyomavirus-infection-increases-functionality-of-virus-specific-memory-cd8-t-cells
#6
Qingsong Qin, Matthew Lauver, Saumya Maru, Eugene Lin, Aron E Lukacher
Mouse polyomavirus (MuPyV) causes a smoldering persistent infection in immunocompetent mice. To lower MuPyV infection in acutely and persistently infected mice, and study the impact of a temporal reduction in viral loads on the memory CD8 T cell response, we created a recombinant MuPyV in which a loxP sequence was inserted into the A2 strain genome upstream of the early promoter and another loxP sequence was inserted in cis into the intron shared by all three T antigens. Using mice transgenic for tamoxifen-inducible Cre recombinase, we demonstrated that reduction in MuPyV load during persistent infection was associated with differentiation of virus-specific CD8 T cells having a superior recall response...
January 4, 2017: Virology
https://www.readbyqxmd.com/read/28063238/aspergillus-awamori-fermented-mung-bean-seed-coats-enhance-the-antioxidant-and-immune-responses-of-weaned-pigs
#7
D N Lee, Y S Hung, T S Yang, J H Lin, C F Weng
The potential benefits of Aspergillus-fermented mung bean seed coats (FMSC) for weaned pigs remain unexplored. Both in vitro and in vivo experiments were employed to evaluate the potential of FMSC supplement on the growth, antioxidant and immune responses of weaned pigs. The total polyphenols and DPPH scavenging capability of ethanol extract of FMSC exhibited a greater (p < 0.01) increase than those of pre-fermentation. With the addition of the polyphenol of FMSC extract, an increase in phagocytosis by neutrophils and proliferation of peripheral blood mononuclear cells (PBMC) were found...
January 7, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28061034/delayed-diagnosis-of-a-nasal-type-lymphoma-misdiagnosed-as-persistent-sinusitis
#8
Antonio Celentano, Massimo Mascolo, Nicola Cirillo, Gaetano De Rosa, Michele Davide Mignogna
Nasal Type T/natural killer (NK)-cell lymphomas are rare clinical entities, highly aggressive with a very poor prognosis. We present a case of a 37-year-old immunocompetent man presenting with deep palatal ulceration and a 3-month history of symptoms, which appear to have been misdiagnosed by physicians. The final diagnosis was achieved by a 15-day diagnostic algorithm, during which time the clinical status of the patient worsened severely. In this article, we also provide a succinct update on the clinical and histopathological findings of Peripheral T/NK-cell lymphomas and propose that symptoms that are consistent with these clinical entities should be considered from the early stages to inform a suitable diagnostic pathway Because of their highly aggressive behavior, we suggest that early therapy of T/NK-cell lymphomas may be started before completing the specific diagnostic investigations...
January 6, 2017: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/28059607/influences-of-obesity-on-the-immunogenicity-of-hepatitis-b-vaccine
#9
Fang Liu, Zhirong Guo, Chen Dong
OBJECTIVE: Hepatitis B vaccine is regarded as the most effective method for the prevention of hepatitis B virus (HBV) infection. However, several factors such as age, body mass index and immunocompetent state have been reported to be associated with reduced immunization responses. The present commentary was aimed to discuss the influences of obesity on the immunogenicity of hepatitis B vaccines. DATA SOURCES: Available peer-reviewed literatures, practice guidelines, and statistics published on hepatitis B vaccine in obesity between 1973 and 2015...
January 6, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28045576/combination-therapy-with-l-arginine-and-%C3%AE-pd-l1-antibody-boosts-immune-response-against-osteosarcoma-in-immunocompetent-mice
#10
Xiaojun He, Haiqing Lin, Li Yuan, Binghao Li
L-arginine supplementation was recently proved to promote the function of immune cells, especially T-cells, by facilitating T-cell proliferation, differentiation and survival in vivo. Cytotoxic CD8(+) plays a crucial role in modulating anti-cancer response mediated by the immune system, but was restricted by exhaustion. Thus, we hypothesized that L-arginine, in combination with α-PD-L1 antibody, may provide a favored environment for T-cell response against osteosarcoma. Immunocompetent BALB/c mouse models bearing orthotopic and metastatic osteosarcoma were established to validate this conjecture...
January 3, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28041663/potent-immunomodulatory-activity-of-a-highly-selective-cannabinoid-cb2-agonist-on-immune-cells-from-healthy-subjects-and-patients-with-multiple-sclerosis
#11
Pasquale Annunziata, Chiara Cioni, Claudia Mugnaini, Federico Corelli
COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects and patients with relapsing-remitting multiple sclerosis (MS). In MS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanism involving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines...
December 23, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28039407/cryptosporidium-parvum-infection-attenuates-the-ex%C3%A2-vivo-propagation-of-murine-intestinal-enteroids
#12
Xin-Tian Zhang, Ai-Yu Gong, Yang Wang, Xiqiang Chen, Sheng-Yau S Lim, Courtney E Dolata, Xian-Ming Chen
Cryptosporidium, a ubiquitous coccidian protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces, is an important opportunistic pathogen for immunocompromised individuals and a common cause of diarrhea in young children in the developing countries. One of the pathological hallmarks of intestinal cryptosporidiosis is villous atrophy, which results in a shorter height of intestinal villi. Here, we investigated the effects of Cryptosporidium infection on intestinal epithelial growth, using an ex vivo model of intestinal cryptosporidiosis employing enteroids from mice...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/28039358/stromal-senescence-by-prolonged-cdk4-6-inhibition-potentiates-tumor-growth
#13
Xiangnan Guan, Kyle M LaPak, Rebecca C Hennessey, Christina Y Yu, Reena Shakya, Jianying Zhang, Christin E Burd
: Senescent cells within the tumor microenvironment (TME) adopt a pro-inflammatory, senescence-associated secretory phenotype (SASP) that promotes cancer initiation, progression and therapeutic resistance. Here, exposure to Palbociclib (PD-0332991), a CDK4/6 inhibitor, induces senescence and a robust SASP in normal fibroblasts. Senescence caused by prolonged CDK4/6 inhibition is DNA damage-independent and associated with Mdm2 downregulation, whereas the SASP elicited by these cells is largely reliant upon NF-kappaB activation...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28038706/hepatosplenic-t-cell-lymphoma-arising-in-patients-with-immunodysregulatory-disorders-a-study-of-7-patients-who-did-not-receive-tumor-necrosis-factor-%C3%AE-inhibitor-therapy-and-literature-review
#14
Mariko Yabe, L Jeffrey Medeiros, Yahya Daneshbod, Masoud Davanlou, Carlos E Bueso-Ramos, Elisa J Moran, Ken H Young, Roberto N Miranda
Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that can arise in patients with underlying immune disorders. Others have suggested that tumor necrosis factor (TNF)-α inhibitor therapy for immune disorders increases the risk of HSTCL. To assess for a potential relationship between HSTCL and the use of TNF-α inhibitors, we searched for patients with HSTCL and underlying immune disorders at our institution. We identified 7 patients with a median age of 38 years. Five patients had Crohn disease, 1 ulcerative colitis, and 1 rheumatoid arthritis...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28031361/severe-symptomatic-primary-hcmv-infection-despite-effective-innate-and-adaptive-immune-responses
#15
Raphaëlle Riou, Céline Bressollette-Bodin, David Boutoille, Katia Gagne, Audrey Rodallec, Maeva Lefebvre, François Raffi, David Senitzer, Berthe-Marie Imbert-Marcille, Christelle Retière
: Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. Some rare severe clinical cases have however been reported without investigation of host immune responses or viral virulence. In this present study, we investigate, for the first time, phenotypic and functional features together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty PHIP were enrolled as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28028895/characterization-of-sox9-overexpressing-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-based-engineered-cartilage-both-in-vitro-and-in-vivo
#16
Xiao-Li Li, Jun Zhang, Hua-Nan Luo, Xiaoyan Zhao, A-Ling Zhang, Zheng-Hui Wang
The source of seed cells is a critical factor for tissue engineering . The goal of this study was to evaluate the chondrogenesis of Sox9-overexpressing human umbilical cord mesenchymal stem cells (hUCMSCs) seeded onto bone matrix gelatin (BMG)/fibrin hybrid scaffolds both in vitro and in vivo. hUCMSCs were stably transfected with Sox9-expressing plasmid and grown on the three-dimensional BMG/fibrin hybrid scaffold for 8 weeks. Scanning electron microscopy and histochemistry were performed. The hUCMSC-loaded scaffolds were implanted into the subcutaneous layer of immunocompetent rats and chondrogenesis and host immune responses were monitored for 8 weeks...
December 28, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28027646/protein-nanocage-mediated-fibroblast-activation-protein-targeted-photoimmunotherapy-to-enhance-cytotoxic-t-cell-infiltration-and-tumor-control
#17
Zipeng Zhen, Wei Tang, Mengzhe Wang, Shiyi Zhou, Hui Wang, Zhanhong Wu, Zhonglin Hao, Zibo Li, Lin Liu, Jin Xie
Carcinoma-associated fibroblasts (CAFs) are found in many types of cancer and play an important role in tumor growth and metastasis. Fibroblast-activation protein (FAP), which is overexpressed on the surface of CAFs, has been proposed as a universal tumor targeting antigen. However, recent studies show that FAP is also expressed on multipotent bone marrow stem cells. A systematic anti-FAP therapy may lead to severe side effects and even death. Hence, there is an urgent need of a therapy that can selectively kill CAFs without causing systemic toxicity...
January 4, 2017: Nano Letters
https://www.readbyqxmd.com/read/28025425/virus-and-host-events-in-squamous-carcinogenesis
#18
Nicholas Coleman
Our group investigates early and late stages in the development of squamous cell carcinomas (SCCs), in order to identify new approaches to diagnosis and therapy. The principal themes are:1. Transcriptional deregulation of high-risk human papillomavirus (HRHPV)We study mechanisms of HRHPV transcriptional deregulation and competitive cell selection during SCC progression, focussing on the causes and effects of integration of HPV16 into the host genome. We showed that HPV16 integration does not necessarily lead to a competitive growth advantage or increased levels of virus oncogenes...
2016: Keio Journal of Medicine
https://www.readbyqxmd.com/read/28011506/distant-bystander-effect-of-reic-dkk3-gene-therapy-through-immune-system-stimulation-in-thoracic-malignancies
#19
Ken Suzawa, Kazuhiko Shien, Huang Peng, Masakiyo Sakaguchi, Masami Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Shuta Tomida, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi, Shinichi Toyooka
BACKGROUND: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. MATERIALS AND METHODS: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/28008866/antiviral-potential-and-mode-of-action-of-indigofera-heterantha-against-hsv-2-by-targeting-the-early-stages-of-infection
#20
Natasha Kapoor Kaushik, Rupa Guha, Becky M Thomas
BACKGROUND: The development of antivirals against herpes simplex virus 2 (HSV-2) has a major public health importance because of the wide spectrum of associated clinical disease in both immunocompetent and immunocompromised populations. Even with the extensive use of acyclovir, issues such as emergence of drug resistant strains, poor oral bioavailability, and low effectiveness in recurrent infections have highlighted the requirement for alternate therapies. Plants, which are rich in metabolites and active against viruses, are being explored as one such source...
December 23, 2016: Antiviral Therapy
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