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https://www.readbyqxmd.com/read/28346597/association-of-risk-of-viremia-immunosuppression-serious-clinical-events-and-mortality-with-increasing-age-in-perinatally-human-immunodeficiency-virus-infected-youth
#1
Anne M Neilan, Brad Karalius, Kunjal Patel, Russell B Van Dyke, Mark J Abzug, Allison L Agwu, Paige L Williams, Murli Purswani, Deborah Kacanek, James M Oleske, Sandra K Burchett, Andrew Wiznia, Miriam Chernoff, George R Seage, Andrea L Ciaranello
Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status...
March 27, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28346319/effect-of-combination-antiretroviral-therapy-on-hiv-1-specific-antibody-dependent-cellular-cytotoxicity-responses-in-subtype-b-and-subtype-c-infected-cohorts
#2
Vijaya Madhavi, Archana Kulkarni, Ashwini Shete, Wen Shi Lee, Milla R Mclean, Anne B Kristensen, Manisha Ghate, Bruce D Wines, P Mark Hogarth, Matthew S Parsons, Anthony Kelleher, David A Cooper, Janaki Amin, Sean Emery, Madhuri Thakar, Stephen J Kent
BACKGROUND: There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC) and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored. METHODS: The effect of cART on HIV-1- and influenza-specific ADCC was analyzed in two cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after two years of cART...
March 23, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28346229/clinical-efficacy-of-gene-modified-stem-cells-in-adenosine-deaminase-deficient-immunodeficiency
#3
Kit L Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S Abraham, Andrew Scharenberg, Otto O Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B Kohn
BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS: Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346011/various-plus-unique-viral-protein-u-as-a-plurifunctional-protein-for-hiv-1-replication
#4
Andrew Soper, Guillermo Juarez-Fernandez, Hirofumi Aso, Miyu Moriwaki, Eri Yamada, Yusuke Nakano, Yoshio Koyanagi, Kei Sato
Human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, encodes four accessory genes, one of which is viral protein U (Vpu). Recently, the study of Vpu has been of great interest. For instance, various cellular proteins are degraded (e.g. CD4) and down-modulated (e.g. tetherin) by Vpu. Vpu also antagonizes the function of tetherin and inhibits NF-κB. Moreover, Vpu is a viroporin forming ion channels and may represent a promising target for anti-HIV-1 drugs. In this review, we summarize the domains/residues that are responsible for Vpu's functions, describe the current understanding of the role of Vpu in HIV-1-infected cells, and review the effect of Vpu on HIV-1 in replication and pathogenesis...
April 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#5
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344988/inspiired-quantification-and-visualization-tools-for-analyzing-integration-site-distributions
#6
Charles C Berry, Christopher Nobles, Emmanuelle Six, Yinghua Wu, Nirav Malani, Eric Sherman, Anatoly Dryga, John K Everett, Frances Male, Aubrey Bailey, Kyle Bittinger, Mary J Drake, Laure Caccavelli, Paul Bates, Salima Hacein-Bey-Abina, Marina Cavazzana, Frederic D Bushman
Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to genomic features and that support numerous user-defined statistical tests...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344987/safe-and-effective-gene-therapy-for-murine-wiskott-aldrich-syndrome-using-an-insulated-lentiviral-vector
#7
Swati Singh, Iram Khan, Socheath Khim, Brenda Seymour, Karen Sommer, Matthew Wielgosz, Zachary Norgaard, Hans-Peter Kiem, Jennifer Adair, Denny Liggitt, Arthur Nienhuis, David J Rawlings
Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28342223/ritonavir-and-ixazomib-kill-bladder-cancer-cells-by-causing-ubiquitinated-protein-accumulation
#8
Akinori Sato, Takako Asano, Kazuki Okubo, Makoto Isono, Tomohiko Asano
There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress is a novel approach to cancer treatment. The human immunodeficiency virus protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell. If the proteasome functions normally, however, they are rapidly degraded. We postulated that the novel proteasome inhibitor ixazomib combined with ritonavir would kill bladder cancer cells effectively by inhibiting degradation of these unfolded proteins and thereby causing ubiquitinated proteins to accumulate...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28339041/tanshinone-iia-increases-protein-expression-levels-of-perk-atf6-ire1%C3%AE-chop-caspase%C3%A2-3-and-caspase%C3%A2-12-in-pancreatic-cancer-bxpc%C3%A2-3-cell%C3%A2-derived-xenograft-tumors
#9
Tsung-Lang Chiu, Chin Cheng Su
Tanshinone (Tan)-IIA is a derivative of phenanthrenequinone and the main active ingredient isolated from Salviae miltiorrhizae radix (Danshen). Previous studies have demonstrated that Tan‑IIA increased the protein expressions levels of protein kinase RNA‑like endoplasmic reticulum kinase (PERK), activating transcription factor (ATF) 6, caspase‑12 and CCAAT‑enhancer‑binding protein homologous protein (CHOP), to induce endoplasmic reticulum (ER) stress and apoptosis in human pancreatic cancer BxPC‑3 cells...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28337575/a-novel-modeling-approach-for-estimating-patterns-of-migration-into-and-out-of-san-francisco-by-hiv-status-and-race-among-men-who-have-sex-with-men
#10
Alison J Hughes, Yea-Hung Chen, Susan Scheer, H Fisher Raymond
In the early 1980s, men who have sex with men (MSM) in San Francisco were one of the first populations to be affected by the human immunodeficiency virus (HIV) epidemic, and they continue to bear a heavy HIV burden. Once a rapidly fatal disease, survival with HIV improved drastically following the introduction of combination antiretroviral therapy in 1996. As a result, the ability of HIV-positive persons to move into and out of San Francisco has increased due to lengthened survival. Although there is a high level of migration among the general US population and among HIV-positive persons in San Francisco, in- and out-migration patterns of MSM in San Francisco have, to our knowledge, never been described...
March 23, 2017: Journal of Urban Health: Bulletin of the New York Academy of Medicine
https://www.readbyqxmd.com/read/28337084/therapeutic-drug-monitoring-of-continuous-infusion-doripenem-in-a-pediatric-patient-on-continuous-renal-replacement-therapy
#11
Jeffrey J Cies, Wayne S Moore, Susan B Conley, Paul Shea, Adela Enache, Arun Chopra
An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. By day 7 the patient (24.7 kg) had a positive fluid balance of 6925 mL (28% FO), and on days 7 into 8 developed acute kidney injury evidenced by an elevated serum creatinine of 0...
January 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28333304/further-insights-into-the-impact-of-mouse-follicle-stage-on-graft-outcome-in-an-artificial-ovary-environment
#12
M C Chiti, M M Dolmans, C M Lucci, F Paulini, J Donnez, C A Amorim
STUDY QUESTION: Are mouse preantral follicles differently affected by isolation, encapsulation and/or grafting procedures according to stage? SUMMARY ANSWER: Isolated secondary follicles showed superior ability to survive and grow after transplantation, which was not related to a particular effect of the isolation and/or grafting procedure, but rather to their own ability to induce neoangiogenesis. WHAT IS KNOWN ALREADY: Isolated and encapsulated mouse preantral follicles can survive (6-27%) and grow (80-100%) in a fibrin matrix with a low concentration of fibrinogen and thrombin (F12...
March 17, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333133/fidelity-of-classwide-resistant-hiv-2-reverse-transcriptase-and-differential-contribution-of-k65r-to-the-accuracy-of-hiv-1-and-hiv-2-reverse-transcriptases
#13
Mar Álvarez, Alba Sebastián-Martín, Guillermo García-Marquina, Luis Menéndez-Arias
Nucleoside reverse transcriptase (RT) inhibitors constitute the backbone of current therapies against human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2, respectively). However, mutational pathways leading to the development of nucleoside analogue resistance are different in both types of HIV. In HIV-2, resistance to all approved nucleoside analogues is conferred by the combination of RT substitutions K65R, Q151M and M184V. Nucleotide incorporation kinetic analyses of mutant and wild-type (WT) HIV-2 RTs show that the triple-mutant has decreased catalytic efficiency due to the presence of M184V...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331055/reticular-dysgenesis-international-survey-on-clinical-presentation-transplantation-and-outcome
#14
Manfred Hoenig, Chantal Lagresle-Peyrou, Ulrich Pannicke, Luigi D Notarangelo, Fulvio Porta, Andrew R Gennery, Mary Slatter, Morton J Cowan, Polina Stepensky, Hamoud Al-Mousa, Daifulah Al-Zahrani, Sung-Yun Pai, Waleed Al Herz, Hubert B Gaspar, Paul Veys, Koichi Oshima, Kohsuke Imai, Hiromasa Yabe, Lenora M Noroski, Nico M Wulffraat, Karl-Walter Sykora, Pere Soler-Palacin, Hideki Muramatsu, Mariam Al Hilali, Despina Moshous, Klaus-Michael Debatin, Catharina Schuetz, Eva-Maria Jacobsen, Ansgar S Schulz, Klaus Schwarz, Alain Fischer, Wilhelm Friedrich, Marina Cavazzana
Reticular Dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis and sensorineural deafness. Mutations in the gene encoding Adenylate Kinase 2 (AK2) were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics and outcome of HSCT were collected from centers in Europe, Asia and North America for a total of 32 patients born between 1982 and 2011...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28329393/virological-outcomes-of-second-line-protease-inhibitor-based-treatment-for-human-immunodeficiency-virus-type-1-in-a-high-prevalence-rural-south-african-setting-a-competing-risks-prospective-cohort-analysis
#15
Dami Collier, Collins Iwuji, Anne Derache, Tulio de Oliveira, Nonhlanhla Okesola, Alexandra Calmy, Francois Dabis, Deenan Pillay, Ravindra K Gupta
Background.: Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative. Methods.: This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa...
March 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329053/sofosbuvir-plus-ribavirin-without-interferon-for-treatment-of-acute-hepatitis-c-virus-infection-in-hiv-1-infected-individuals-swift-c
#16
Susanna Naggie, Kristen M Marks, Michael Hughes, Daniel S Fierer, Christine Macbrayne, Arthur Kim, Kimberly Hollabaugh, Jhoanna Roa, Bill Symonds, Diana M Brainard, John G McHutchison, Marion G Peters, Jennifer J Kiser, Raymond Chung
Background.: Historically, acute hepatitis C virus (HCV) infection was treated with shorter durations of interferon-containing therapies. In the era of direct-acting antivirals (DAAs), it is unclear whether the efficacy of treatment achieved in chronic infection can be maintained with abbreviated courses of therapy during the acute phase. Methods.: The sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals (SWIFT-C) is an open-label, 2-cohort clinical trial in which the first cohort assessed for the safety and efficacy of 12 weeks of sofosbuvir plus ribavirin for the treatment of acute HCV infection in participants with chronic human immunodeficiency virus type 1 (HIV-1) infection...
February 27, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28325276/limiting-thymic-precursor-supply-increases-the-risk-of-lymphoid-malignancy-in-murine-x-linked-severe-combined-immunodeficiency
#17
Samantha L Ginn, Claus V Hallwirth, Sophia H Y Liao, Erdahl T Teber, Jonathan W Arthur, Jianmin Wu, Hong Ching Lee, Szun S Tay, Min Hu, Roger R Reddel, Matthew P McCormack, Adrian J Thrasher, Marina Cavazzana, Stephen I Alexander, Ian E Alexander
In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28324594/polymers-in-the-delivery-of-sirna-for-the-treatment-of-virus-infections
#18
REVIEW
Nicholas Reynolds, Megan Dearnley, Tracey M Hinton
Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a "magic bullet", due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28319446/good-laboratory-practice-preclinical-safety-studies-for-gsk2696273-mlv-vector-based-ex-vivo-gene-therapy-for-adenosine-deaminase-deficiency-severe-combined-immunodeficiency-in-nsg-mice
#19
Nicola Carriglio, Jan Klapwijk, Raisa Jofra Hernandez, Michela Vezzoli, Franck Chanut, Rhiannon Lowe, Draghici Elena, Melanie Nord, Paola Albertini, Patrizia Cristofori, Jane Richards, Hazel Staton, Jonathan Appleby, Alessandro Aiuti, Aisha V Sauer
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28317804/a-survey-on-undiagnosed-active-pulmonary-tuberculosis-among-pregnant-mothers-in-mekelle-and-surrounding-districts-in-tigray-ethiopia
#20
Dawit Gebreegziabiher, Kelemework Adane, Markos Abebe
OBJECTIVE/BACKGROUND: To determine the prevalence of undiagnosed active pulmonary tuberculosis (PTB) cases and sensitivity, specificity, and positive and negative predictive values of symptom combinations for undiagnosed TB infection in human immunodeficiency virus (HIV)-positive and HIV-negative pregnant mothers attending antenatal care (ANC) clinics. Mycobacterium TB and HIV are the leading causes of death among women of reproductive age worldwide. Symptom screening is the first step in the World Health Organization (WHO)-recommended TB intensified case finding algorithm for people living with HIV...
January 2017: International Journal of Mycobacteriology
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