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https://www.readbyqxmd.com/read/29150377/urgent-versus-post-stabilisation-antiretroviral-treatment-in-hospitalised-hiv-infected-children-in-kenya-push-a-randomised-controlled-trial
#1
Irene N Njuguna, Lisa M Cranmer, Vincent O Otieno, Cyrus Mugo, Hellen M Okinyi, Sarah Benki-Nugent, Barbra Richardson, Joshua Stern, Elizabeth Maleche-Obimbo, Dalton C Wamalwa, Grace C John-Stewart
BACKGROUND: Urgent antiretroviral therapy (ART) among hospitalised HIV-infected children might accelerate recovery or worsen outcomes associated with immune reconstitution. We aimed to compare urgent versus post-stabilisation ART among hospitalised HIV-infected children in Kenya. METHODS: In this unmasked randomised controlled trial, we randomly assigned (1:1) HIV-infected, ART-naive children aged 0-12 years who were eligible for treatment to receive ART within 48 h (urgent group) or in 7-14 days (post-stabilisation group) at four hospitals in Kenya (two in Nairobi and two in western Kenya)...
November 14, 2017: Lancet HIV
https://www.readbyqxmd.com/read/29147612/low-dose-post-transplant-cyclophosphamide-can-mitigate-gvhd-and-enhance-the-g-csf-atg-induced-gvhd-protective-activity-and-improve-haploidentical-transplant-outcomes
#2
Yu Wang, Ying-Jun Chang, Lu Chen, Lan-Ping Xu, Zhi-Lei Bian, Xiao-Hui Zhang, Chen-Hua Yan, Kai-Yan Liu, Xiao-Jun Huang
Use of high-dose, post-transplant cyclophosphamide (PTCy) results in low rates of graft-versus-host-disease (GVHD) and favorable immune reconstitution, although with higher rates of relapse and somewhat high rates of graft failure. We hypothesized that permissible dose reduction of PTCy might be feasible. The current study attempts to establish a murine model and focus on regulatory T cells (Tregs) to clarify the immunological mechanisms for GVHD prevention by low-dose PTCy. In addition, a prospective, clinical cohort study in haploidentical, T-cell replete transplantation is initiated to support the rational...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29142146/inflammatory-natalizumab-associated-pml-baseline-characteristics-lesion-evolution-and-relation-with-pml-iris
#3
Mike P Wattjes, Martijn T Wijburg, Jeroen van Eijk, Stephan Frequin, Bernard M J Uitdehaag, Frederik Barkhof, Clemens Warnke, Joep Killestein
BACKGROUND AND OBJECTIVE: Natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) patients may show imaging signs suggestive of inflammation at diagnosis ('inflammatory PML'), reminiscent of PML-immune reconstitution inflammatory syndrome (PML-IRIS). We investigated the imaging characteristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating and overlapping features. METHODS: We scored the presence, localisation and pattern of imaging characteristics of inflammation on brain MRI scans of inflammatory NTZ-PML patients...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29137845/enumeration-of-bone-marrow-plasmacytoid-dendritic-cells-by-multiparameter-flow-cytometry-as-a-prognostic-marker-following-allogeneic-hematopoietic-stem-cell-transplantation
#4
Ruijun Jeanna Su, Ralph Green, Mingyi Chen
Plasmacytoid dendritic cells (pDCs) promote tolerance in solid organ transplants and hematopoietic stem cell transplantation (HSCT). pDCs originate from CD34(+) hematopoietic progenitors. Following allogeneic hematopoietic stem cell transplant (allo-HSCT), pDC reconstitution in the BM and PB gradually attain levels similar to those in healthy individuals. We have investigated the recovery of pDC following allo-HSCT as a means to predict successful marrow engraftment. We retrospectively studied immune reconstitution of pDC in the BM of 48 patients following allo-HSCT for initial diagnoses of leukemia or other malignancies...
October 31, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29135655/neutrophil-activation-and-enhanced-release-of-granule-products-in-hiv-tb-immune-reconstitution-inflammatory-syndrome
#5
Justine K Nakiwala, Naomi F Walker, Collin R Diedrich, William Worodria, Graeme Meintjes, Robert J Wilkinson, Harriet Mayanja-Kizza, Robert Colebunders, Luc Kestens, Katalin A Wilkinson, David M Lowe
BACKGROUND: Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and in particular the role of neutrophils. SETTING: Two observational, prospective cohort studies in HIV/TB co-infected patients starting antiretroviral therapy, one to analyze gene expression and subsequently one to explore neutrophil biology...
November 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29128672/long-term-immune-reconstitution-after-matched-unrelated-hematopoietic-stem-cell-transplantation-for-immunodeficiency
#6
Vy Hong-Diep Kim, Brenda Reid, Adelle Atkinson, Julia Upton, Eyal Grunebaum, Chaim M Roifman
No abstract text is available yet for this article.
November 8, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29109290/sea-anemone-model-has-a-single-toll-like-receptor-that-can-function-in-pathogen-detection-nf-%C3%AE%C2%BAb-signal-transduction-and-development
#7
Joseph J Brennan, Jonathan L Messerschmidt, Leah M Williams, Bryan J Matthews, Marinaliz Reynoso, Thomas D Gilmore
In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway. We have characterized the single N...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29104735/tracing-and-targeting-cancer-stem-cells-new-venture-for-personalized-molecular-cancer-therapy
#8
REVIEW
Ramin Radpour
Tumors consist of a mixture of heterogeneous cell types. Cancer stem cells (CSCs) are a minor sub-population within the bulk cancer fraction which has been found to reconstitute and propagate the disease and to be frequently resistant to chemotherapy, irradiation, cytotoxic drugs and probably also against immune attack. CSCs are considered as the seeds of tumor recurrence, driving force of tumorigenesis and metastases. This underlines the urgent need for innovative methods to identify and target CSCs. However, the role and existence of CSCs in therapy resistance and cancer recurrence remains a topic of intense debate...
October 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/29104460/construction-and-identification-of-recombinant-hek293t-cell-lines-expressing-non-structural-protein-1-of-zika-virus
#9
Jun Liu, Pengfei Wan, Qingqing Li, Xiaoxin Li, Andrew Li, Huangyao Chen, Jingjing Li, Wenhan Liang, Haifa Zheng, Weiwang Gu, Hongwei Li
Background: Zika virus (ZIKV) infection has become a major public health problem all around the world. Early diagnosis of Zika infection is important for better management of the disease. Non-structural protein 1 (NS1) is a potential biomarker for ZIKV infections. The purpose of this study was to produce the ZIKV NS1 protein for establishing serological diagnostic methods for ZIKV. Methods: The cDNA fragment encoding a chimeric protein composed of murine Igκ signal peptide, NS1 and histidine tag was synthesized and cloned into the lentiviral expression vector pLV-eGFP...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29099340/humoral-immunity-in-mice-transplanted-with-hematopoietic-stem-cells-derived-from-human-umbilical-cord-blood-recapitulates-that-of-human-infants
#10
Justin A Walker, Raja Vuyyuru, Tim Manser, Kishore R Alugupalli
Immunodeficient mice transplanted with human hematopoietic stem cells (HSCs) have been referred to as "Human Immune System" (HIS) mice and are a translational platform for studying human immune responses in vivo. Human HSC sources used in generating HIS mice include fetal liver (FL), umbilical cord blood (CB), and adult bone marrow (BM). Since HSCs from FL, CB, and BM are produced at various stages of human development, we tested whether mice transplanted with these three HSCs differ in their immune responses...
November 3, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29094807/food-insecurity-may-lead-to-incomplete-hiv-viral-suppression-and-less-immune-reconstitution-among-hiv-hepatitis-c-virus-coinfected-people
#11
W Aibibula, J Cox, A-M Hamelin, Eem Moodie, A I Naimi, T McLinden, M B Klein, P Brassard
OBJECTIVES: The aim of this study was to determine the impact of food insecurity (FI) on HIV viral load and CD4 count among people coinfected with HIV and hepatitis C virus (HCV). METHODS: This study was conducted using data from the Food Security & HIV-HCV Sub-Study of the Canadian Co-Infection Cohort study. FI was measured using the adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food security, moderate food insecurity and severe food insecurity...
November 2, 2017: HIV Medicine
https://www.readbyqxmd.com/read/29079575/hiv-1-vpr-protein-directly-loads-helicase-like-transcription-factor-hltf-onto-the-crl4-dcaf1-e3-ubiquitin-ligase
#12
Xiaohong Zhou, Maria Delucia, Caili Hao, Kasia Hrecka, Christina Monnie, Jacek Skowronski, Jinwoo Ahn
The Vpr protein is an accessory virulence factor of HIV-1 that facilitates infection in immune cells. Cellular functions of Vpr are tied to its interaction with DCAF1, a substrate receptor component of the CRL4 E3 ubiquitin ligase. Recent proteomic approaches suggested that Vpr degrades HLTF DNA helicase in a proteasome-dependent manner by redirecting the CRL4-DCAF1 E3 ligase. However, the precise molecular mechanism of Vprdependent HLTF depletion is not known. Here, using in vitro reconstitution assays, we show that Vpr mediates polyubiquitination of HLTF, by directly loading it onto the C-terminal WD40 domain of DCAF1 in complex with the CRL4 E3 ubiquitin ligase...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29079107/dissecting-antigen-processing-and-presentation-routes-in-dermal-vaccination-strategies
#13
Anouk C M Platteel, Sandrine Henri, Dietmar M Zaiss, Alice J A M Sijts
The skin is an attractive site for vaccination due to its accessibility and presence of immune cells surveilling this barrier. However, knowledge of antigen processing and presentation upon dermal vaccination is sparse. In this study we determined antigen processing routes that lead to CD8(+) T cell activation following dermal DNA tattoo immunization, exploiting a model antigen that contains an immunoproteasome-dependent epitope. In agreement with earlier reports, we found that DNA tattoo immunization of wild type (WT) mice triggered vigorous responses to the immunoproteasome-dependent model epitope, whereas gene-deficient mice lacking the immunoproteasome subunits β5i/LMP7 and β2i/MECL1 failed to respond...
October 24, 2017: Vaccine
https://www.readbyqxmd.com/read/29078283/humanized-mouse-model-supports-development-function-and-tissue-residency-of-human-natural-killer-cells
#14
Dietmar Herndler-Brandstetter, Liang Shan, Yi Yao, Carmen Stecher, Valerie Plajer, Melanie Lietzenmayer, Till Strowig, Marcel R de Zoete, Noah W Palm, Jie Chen, Catherine A Blish, Davor Frleta, Cagan Gurer, Lynn E Macdonald, Andrew J Murphy, George D Yancopoulos, Ruth R Montgomery, Richard A Flavell
Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (IL15) and human signal regulatory protein alpha (SIRPA) knock-in mouse on a Rag2(-/-)Il2rg(-/-) background (SRG-15)...
October 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29075540/immune-reconstitution-inflammatory-syndrome-and-cytomegalovirus-pneumonia-case-report-highlights-and-missing-links-in-classification-criteria-and-standardized-treatment
#15
Stefania Petarra-Del Río, Adrian Rodriguez-Hernandez, Luis Anguiano-Landa, Georgina Aguilar-Portillo, Isidro Zavala-Trujillo, Arnulfo Hernan Nava-Zavala, Maria G Zavala-Cerna
BACKGROUND: Cytomegalovirus (CMV) pulmonary involvement is rarely associated with IRIS; therefore, limited information is available. CASE PRESENTATION: Here, we describe the case of a 43-year-old HIV-infected male who developed an unusual case of IRIS after cytomegalovirus (CMV) pneumonia. Clinically there was a progressive and paradoxical worsening of respiratory distress, despite being treated for CMV after initiation with antiretroviral therapy. Chest X-ray revealed disseminated infiltrates in both lungs; chest CT-scan showed generalized lung involvement and mediastinal adenopathy...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/29075267/pd-1-controls-tonic-signaling-and-lymphopenia-induced-proliferation-of-t-lymphocytes
#16
Kristofor K Ellestad, Jiaxin Lin, Louis Boon, Colin C Anderson
Recovery of the T lymphocyte compartment within a lymphopenic host by lymphopenia-induced proliferation (LIP) is regulated by inter- and intraclonal competition for limited resources, including homeostatic cytokines and peptide:MHC (pMHC) complexes with which the TCR can interact at least weakly to yield a tonic signal. Importantly, the process of LIP can synergize with other factors that promote T cell activation to drive inflammatory disease. While reconstitution of the lymphoid compartment of immune deficient Rag(-/-) mice by transfer of wild-type hematopoietic stem cells (HSC) does not generally result in an overt disease phenotype, transfer of HSC deficient in expression of the co-inhibitory molecule PD-1 results in severe systemic autoimmunity driven by newly generated T cells that emerge from the thymus into the periphery and undergo LIP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29058697/viral-specific-t-cell-transfer-from-hsct-donor-for-the-treatment-of-viral-infections-or-diseases-after-hsct
#17
REVIEW
C Qian, Y Wang, L Reppel, M D'aveni, A Campidelli, V Decot, D Bensoussan
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT...
October 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29055444/progressive-multifocal-leukoencephalopathy-immune-reconstitution-inflammatory-syndrome-pml-iris-in-liver-transplant-recipient
#18
J Avsenik, A Horvat Ledinek, K Šurlan Popovič
65-year-old liver transplant recipient presented with progressive neurologic dysfunction. CSF analysis revealed high JC virus load and MRI findings suggested the diagnosis of progressive multifocal leukoencephalopathy (PML). Cidofovir and mirtazapine were initiated and patient's regular immunosuppressants were reduced. Subsequently patient developed left sided hemiplegia, drowsiness and severe neglect syndrome. MRI revealed enlargement of PML lesions with contrast enhancement and worsening of oedema, consistent with immune reconstitution inflammatory syndrome (IRIS)...
October 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29055014/protein-acyltransferase-dhhc3-regulates-breast-tumor-growth-oxidative-stress-and-senescence
#19
Martin E Hemler, Chandan Sharma, Hong-Xing Wang, Qinglin Li, Konstantin Knoblich, Emily S Reisenbichler, Andrea L Richardson
DHHC-type protein acyltransferases may regulate the localization, stability and/or activity of their substrates. In this study, we show that the protein palmitoyltransferase DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlated with diminished patient survival in breast cancer and six other human cancer types. ZDHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduced the sizes of both the primary tumor and metastatic lung colonies. Gene array data and fluorescence dye assays documented increased oxidative stress and senescence in ZDHHC3-ablated cells...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29048509/plasma-but-not-cerebrospinal-fluid-interleukin-7-and-interleukin-5-levels-pre-antiretroviral-therapy-commencement-predict-cryptococcosis-associated-immune-reconstitution-inflammatory-syndrome
#20
Ngomu Akeem Akilimali, Christina C Chang, Daniel M Muema, Tarylee Reddy, Mahomed-Yunus S Moosa, Sharon R Lewin, Martyn A French, Thumbi Ndung'u
Background: Patients with human immunodeficiency virus/AIDS-associated cryptococcal meningitis (CM) frequently experience clinical deterioration, known as cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS), upon initiation of antiretroviral therapy (ART). The immunological mechanisms underlying C-IRIS are incompletely defined and no reliable predictive biomarkers exist. We investigated whether plasma or cerebrospinal fluid (CSF) levels of cytokines and chemokines predicted C-IRIS and are potential predictive biomarkers...
October 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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