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https://www.readbyqxmd.com/read/28544366/enumeration-of-wt1-specific-cd8-t-cells-for-clinical-application-using-an-mhc-streptamer-based-no-wash-single-platform-flow-cytometric-assay
#1
Sarah Matko, Madeleine Teichert, Antje Tunger, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
The advent of novel strategies to generate leukemia-associated-antigen (LAA)-specific T cells for adoptive immunotherapies creates a demand for standardized good laboratory practice (GLP)-compliant enumeration assays to provide a secure clinical environment-whether it is to identify potential donors, define therapeutic doses for transplantation, or monitor clinical success. Here, we introduce a no-wash assay based on single-platform cell enumeration and Streptamer staining to determine the Wilms' tumor antigen 1 (WT1)-specific T cell immunity in clinical samples...
May 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28544101/belatacept-combined-with-transient-calcineurin-inhibitor-therapy-prevents-rejection-and-promotes-improved-long-term-renal-allograft-function
#2
A B Adams, J Goldstein, C Garrett, R Zhang, R E Patzer, K A Newell, N A Turgeon, A S Chami, A Guasch, A D Kirk, S O Pastan, T C Pearson, C P Larsen
Belatacept, a T cell costimulation-blocker demonstrated superior renal function, lower cardiovascular risk, and improved graft/patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011 we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n=535) to a historical cohort receiving a tacrolimus-based protocol (n=205)...
May 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28533400/the-pentameric-complex-drives-immunologically-covert-cell-cell-transmission-of-wild-type-human-cytomegalovirus
#3
Isa Murrell, Carmen Bedford, Kristin Ladell, Kelly L Miners, David A Price, Peter Tomasec, Gavin W G Wilkinson, Richard J Stanton
Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop susceptibility to natural killer cells. To permit experimentation with a virus that retained a clinically relevant phenotype, we reconstructed a wild-type (WT) HCMV genome using bacterial artificial chromosome technology. Like clinical virus, this genome proved to be unstable in cell culture; however, propagation of intact virus was achieved by placing the RL13 and UL128 genes under conditional expression...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532344/pre-transplantation-thymic-function-is-associated-with-the-risk-of-acute-graft-versus-host-disease-and-cytomegalovirus-viremia-after-allogeneic-hematopoietic-stem-cell-transplantation
#4
Xin Yang, Yuanxin Sun, Sudong Zhang, Hui Yang, Jialin Wei, Yi He, Donglin Yang, Erlie Jiang, Mingzhe Han, Xuemei Qin, Sizhou Feng
OBJECTIVES: To analyze the kinetics of T-cell subsets and thymic function reconstitution after allogeneic hematopoietic stem cell transplantation (AHSCT); to determine whether sjTREC (signal joint TCR rearrangement excision circle) and CD31-positive recent thymic emigrant (CD31 + RTE) are correlated with acute graft versus host disease (aGVHD) or CMV (cytomegalovirus) viremia after AHSCT. METHODS: Forty-nine patients who underwent AHSCT in our institution were prospectively enrolled...
May 22, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28529540/the-potential-role-of-infectious-agents-and-pelvic-inflammatory-disease-in-ovarian-carcinogenesis
#5
REVIEW
Kasper Ingerslev, Estrid Hogdall, Tine Henrichsen Schnack, Wojciech Skovrider-Ruminski, Claus Hogdall, Jan Blaakaer
BACKGROUND: The etiological cause of ovarian cancer is poorly understood. It has been theorized that bacterial or viral infection as well as pelvic inflammatory disease could play a role in ovarian carcinogenesis. AIM: To review the literature on studies examining the association between ovarian cancer and bacterial or viral infection or pelvic inflammatory disease. METHODS: Database search through MEDLINE, applying the medical subject headings: "Ovarian neoplasms", AND "Chlamydia infections", "Neisseria gonorrhoeae", "Mycoplasma genitalium", "Papillomaviridae", or "pelvic inflammatory disease"...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28503279/incidence-and-risk-factors-for-cytomegalovirus-in-kidney-transplant-patients-in-babol-northern-iran
#6
Arefeh Babazadeh, Mostafa Javanian, Farshid Oliaei, Roghayeh Akbari, Abazar Akbarzadepasha, Ali Bijani, Mahmoud Sadeghi
BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of death and possibly transplant rejection in kidney transplant (KT) patients. This study was conducted to investigate the incidence and risk factors of CMV disease in kidney transplant patients. METHODS: All end-stage renal disease (ESRD) patients who underwent kidney transplantation during 1998-2014 and their donors were assessed. All samples were followed-up for approximately 70 months. CMV was identified by polymerase chain reaction (PCR) and/or PP65 antigen in peripheral blood leukocytes along with clinical manifestations...
2017: Caspian Journal of Internal Medicine
https://www.readbyqxmd.com/read/28501424/ro0504985-is-an-inhibitor-of-cmgc-kinase-proteins-and-has-anti-human-cytomegalovirus-activity
#7
Blair L Strang
Public-private partnerships allow many previously unavailable compounds to be screened for antiviral activity. Here a screening method was used to identify an oxindole compound, RO0504985, from a Roche kinase inhibitor library that inhibited human cytomegalovirus (HCMV) protein production. RO0504985 was previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2). However, using kinase selectivity assays it was found that RO0504985 was an inhibitor of several CMGC group kinase proteins, including CDK2...
May 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28500691/an-interventional-study-using-cell-mediated-immunity-to-personalize-therapy-for-cytomegalovirus-infection-after-transplantation
#8
Deepali Kumar, Muhtashim Mian, Lianne Singer, Atul Humar
Cell mediated immune responses predict clinical CMV events but have not been adopted into routine practice due to lack of interventional studies. Our objective was to demonstrate the safety and feasibility of early discontinuation of antivirals based on the real-time measurement of CMV-specific CMI in patients with CMV viremia. Transplant patients were enrolled at the onset of CMV viremia requiring antiviral therapy. CD8 T-cell responses were determined using the Quantiferon-CMV assay, and results were used to guide subsequent management...
May 13, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28477135/lentiviral-reprogramming-of-a-t-patient-fibroblasts-to-induced-pluripotent-stem-cells
#9
Sam Nayler, Sergei V Kozlov, Martin F Lavin, Ernst Wolvetang
Reprogramming of cells enables generation of pluripotent stem cells and resulting progeny through directed differentiation, making this technology an invaluable tool for the study of human development and disease. Reprogramming occurs with a wide range of efficiency, a culmination of intrinsic and extrinsic factors including the tissue of origin, the passage number and culture history of the target cells. Another major factor affecting reprogramming is the methodology used and the quality of the reprogramming process itself, including for conventional viral-based approaches viral titer and subsequent viral transduction efficiency, including downstream transgene insertion and stoichiometry...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28473657/human-cytomegalovirus-immediate-early-protein-promotes-survival-of-glioma-cells-through-interacting-and-acetylating-atf5
#10
Ming Hu, Bin Wang, Dongmeng Qian, Mengyuan Wang, Rui Huang, Li Wei, Ling Li, Li Zhang, David X Liu
Human cytomegalovirus (HCMV), a widespread beta-herpes virus, infects a high percentage of gliomas. HCMV is specifically detected in human gliomas at a low level of expression raises the possibility that it may regulate the malignant phenotype in a chronic manner. Although HCMV is not recognized as an oncogenic virus, it might dysregulate signaling pathways involved in initiation and promotion of malignancy.Here, our immunohistochemical staining reveals that nucleus staining of the HCMV 86-kDa immediate-early protein (IE86) is markedly increased in GBM (58...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468758/two-alternate-strategies-for-innate-immunity-to-epstein-barr-virus-one-using-nk-cells-and-the-other-nk-cells-and-%C3%AE-%C3%AE-t-cells
#11
Zakia Djaoud, Lisbeth A Guethlein, Amir Horowitz, Tarik Azzi, Neda Nemat-Gorgani, Daniel Olive, David Nadal, Paul J Norman, Christian Münz, Peter Parham
Most humans become infected with Epstein-Barr virus (EBV), which then persists for life. Infrequently, EBV infection causes infectious mononucleosis (IM) or Burkitt lymphoma (BL). Type I EBV infection, particularly type I BL, stimulates strong responses of innate immune cells. Humans respond to EBV in two alternative ways. Of 24 individuals studied, 13 made strong NK and γδ T cell responses, whereas 11 made feeble γδ T cell responses but stronger NK cell responses. The difference does not correlate with sex, HLA type, or previous exposure to EBV or cytomegalovirus...
May 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28459662/clinical-outcomes-with-antiviral-prophylaxis-or-preemptive-therapy-for-cytomegalovirus-disease-after-liver-transplantation-a-systematic-review-and-meta-analysis
#12
Yang Hui, Cui Xiangli, Wang Xin, Qiu Shuang, Liu Lihong
Objectives:We conducted a systematic review and meta-analysis to compare the clinical outcomes of patients after liver transplantation accepting antiviral prophylaxis (AP) or preemptive therapy (PT) for preventing cytomegalovirus (CMV) disease. METHODS: A literature search of PubMed, Cochrane, Embase was conducted up to June 1, 2016. References of the retrieved articles were also reviewed and relevant studies were included. The primary outcomes were incidence of CMV infection, incidence of CMV disease, mortality and opportunistic infection...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28457046/gastrointestinal-histoplasmosis-and-cmv-co-infection-in-an-immunocompetent-host
#13
Mukesh Nasa, Nisharg Patel, Lipika Lipi, Randhir Sud
A middle aged male with no known comorbidities presented with history of colicky abdominal pain, low grade fever and weight loss. Laboratory parameters were normal except low albumin. Imaging showed multiple areas of mural thickening with enhancement in jejunum & ileum. On Colonoscopy there was a thickened and deformed ileum with multiple ulcers. The biopsy showed co-infection of CMV and histoplasma, urine antigen for histoplasma was positive and CMV DNA detected in blood. He was successfully treated with combination of Valgancyclovir and Amphotericin-B followed by itraconazole...
February 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28437539/safety-and-efficacy-of-antiviral-therapy-for-prevention-of-cytomegalovirus-reactivation-in-immunocompetent-critically-ill-patients-a-randomized-clinical-trial
#14
Nicholas J Cowley, Andrew Owen, Sarah C Shiels, Joanne Millar, Rebecca Woolley, Natalie Ives, Husam Osman, Paul Moss, Julian F Bion
Importance: Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness. Objective: To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients. Design, Setting, and Participants: A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014...
April 24, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28419213/risks-factors-for-congenital-cmv-infection-following-primary-and-non-primary-maternal-infection-a-prospective-neonatal-screening-study-using-pcr-in-saliva
#15
Marianne Leruez-Ville, Jean-François Magny, Sophie Couderc, Christine Pichon, Marine Parodi, Laurence Bussières, Tiffany Guilleminot, Idir Ghout, Yves Ville
Background: The design of diagnostic and preventive strategies have been prevented by gaps in knowledge of the epidemiology of congenital CMV (cCMV) with the type of maternal infection as well as the lack of large-scale neonatal screening tools. Methods: 11,715 consecutive newborns were screened for cCMV by PCR in saliva. Prevalence, type of maternal infection, socio-demographic, obstetrical and serological data were analyzed. Results: Positive predictive value of CMV PCR in saliva was 59%, false positive results were associated with lower viral loads (p<0...
April 17, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28407149/determination-of-the-biological-form-of-human-cytomegalovirus-dna-in-the-plasma-of-solid-organ-transplant-recipients
#16
Yupin Tong, Xiaoli L Pang, Curtis Mabilangan, Jutta K Preiksaitis
Background: Whether cytomegalovirus (CMV) DNA exists in plasma as virion-associated or free DNA is uncertain. Methods: An assay combining DNase I digestion and CMV quantitative polymerase chain reaction (DNase-CMV-qPCR) was developed to differentiate free naked DNA from virion DNA. One hundred three frozen and 10 fresh CMV DNA-positive plasma samples from solid-organ transplant recipients (SOTRs) were tested. Three sets of paired qPCR (P-qPCR) assays with amplicons of variable length were used to study CMV DNA fragmentation in 20 SOTR plasma samples, viral stocks (Towne, Merlin, AD169) and the first World Health Organization (WHO) international standard (IS) for CMV DNA...
April 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28400201/inhibitors-of-dual-specificity-tyrosine-phosphorylation-regulated-kinases-dyrk-exert-a-strong-anti-herpesviral-activity
#17
Corina Hutterer, Jens Milbradt, Stuart Hamilton, Mirko Zaja, Johann Leban, Christophe Henry, Daniel Vitt, Mirjam Steingruber, Eric Sonntag, Isabel Zeitträger, Hanife Bahsi, Thomas Stamminger, William Rawlinson, Stefan Strobl, Manfred Marschall
Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of (val)ganciclovir therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy of antiviral treatment is based on the exploitation of cell-directed signaling, e. g. pathways with a known relevance for carcinogenesis and tumor drug development. Here we describe a principle for putative antiviral drugs based on targeting dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs)...
April 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28393254/antitumor-effects-of-a-dual-specific-lentiviral-vector-carrying-the-escherichia-coli-purine-nucleoside-phosphorylase-gene
#18
Xiaolong Wang, Lei Sun, Xuejun Sun, Junhui Yu, Kai Wang, Yunhua Wu, Qi Gao, Jianbao Zheng
The Escherichia coli purine nucleoside phosphorylase/Fludarabine phosphate (ePNP/Fludara) suicide system has several drawbacks, such as side-effects and the low efficiency of ePNP expression. In this study, we evaluated the antitumor effects of the dual-specific 8HSEs-hTERTp-ePNP/Fludara suicide system under hyperthermia in vitro and in vivo. Luciferase activities from the 8HSEs‑hTERT and CMV promoters were compared using the dual luciferase assay in SW480 (high hTERT expression) and MKN74 cells (hTERT-negative) in the presence and absence of hyperthermia...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28391502/genomic-analysis-of-chimeric-human-cytomegalovirus-vaccine-candidates-derived-from-strains-towne-and-toledo
#19
Nicolás M Suárez, Betty Lau, George M Kemble, Ronzo Lee, Edward S Mocarski, Gavin W G Wilkinson, Stuart P Adler, Michael A McVoy, Andrew J Davison
Human cytomegalovirus (HCMV) is an important opportunistic pathogen in immunocompromised patients and a major cause of congenital birth defects when acquired in utero. In the 1990s, four chimeric viruses were constructed by replacing genome segments of the high passage Towne strain with segments of the low passage Toledo strain, with the goal of obtaining live attenuated vaccine candidates that remained safe but were more immunogenic than the overly attenuated Towne vaccine. The chimeras were found to be safe when administered to HCMV-seronegative human volunteers, but to differ significantly in their ability to induce seroconversion...
April 8, 2017: Virus Genes
https://www.readbyqxmd.com/read/28389165/cytomegalovirus-retinitis-followed-by-immune-recovery-uveitis-in-an-elderly-patient-with-rheumatoid-arthritis-undergoing-administration-of-methotrexate-and-tofacitinib-combination-therapy
#20
Kunio Yanagisawa, Yoshiyuki Ogawa, Mayumi Hosogai, Daisuke Todokoro, Takeki Mitsui, Akihiko Yokohama, Shoji Kishi, Hiroshi Handa
Cytomegalovirus (CMV) retinitis is an opportunistic ocular infection most commonly observed in patients infected with human immunodeficiency virus (HIV). We present a rare case of CMV retinitis that developed in a non-HIV patient with rheumatoid arthritis (RA). Over the preceding 5 months, a family doctor had been treating the 78-year-old male patient with a combination therapy of methotrexate (MTX) and tofacitinib (TOF). CMV retinitis occurred when the patient's CD4+ T cells were low (196 cells/μl), and preceded the onset of Pneumocystis pneumonia...
April 4, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
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