38 research outputs found
Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia
No full textTo develop a therapy for drug-resistant B-lineage acute lymphoblastic leukemia (ALL), we transduced T lymphocytes with anti-CD19 chimeric receptors, consisting of an anti-CD19 single-chain variable domain (reactive with most ALL cases), the hinge and transmembrane domains of CD8alpha, and the signaling domain of CD3zeta. We compared the antileukemic activity mediated by a novel receptor ('anti-CD19-BB-zeta') containing the signaling domain of 4-1BB (CD137; a crucial molecule for T-cell antitumor activity) to that of a receptor lacking costimulatory molecules. Retroviral transduction produced efficient and durable receptor expression in human T cells. Lymphocytes expressing anti-CD19-BB-zeta receptors exerted powerful and specific cytotoxicity against ALL cells, which was superior to that of lymphocytes with receptors lacking 4-1BB. Anti-CD19-BB-zeta lymphocytes were remarkably effective in cocultures with bone marrow mesenchymal cells, and against leukemic cells from patients with drug-resistant ALL: as few as 1% anti-CD19-BB-zeta-transduced T cells eliminated most ALL cells within 5 days. These cells also expanded and produced interleukin-2 in response to ALL cells at much higher rates than those of lymphocytes expressing equivalent receptors lacking 4-1BB. We conclude that anti-CD19 chimeric receptors containing 4-1BB are a powerful new tool for T-cell therapy of B-lineage ALL and other CD19+ B-lymphoid malignancies.C Imai, K Mihara, M Andreansky, I C Nicholson, C-H Pui, T L Geiger and D Campan
Euryparyphes flexuosus Uvarov 1927
No full textEuryparyphes flexuosus Uvarov, 1927 Material examined. MOROCCO: Azrou, 1600 m, 5.1924, 1♂ (Holotype), 1♀ (Paratype) (NHMUK); Marokko, Azrou, 12–1400 m, 28.5– 1.6.1930, 2♂, 3♀ (leg. et det. Ebner); Azru, 5.1925, 2♂ (leg. A. Weldholz); Ost Marokko, Taza, 17- 21.5.1930, 1♀ (leg. Andreansky); Fez, Zalagh, 23.5.1930, 1♀ (leg. R. Ebner) (NMW).Published as part of Ünal, Mustafa, 2016, Pamphagidae (Orthoptera: Acridoidea) from the Palaearctic Region: taxonomy, classification, keys to genera and a review of the tribe Nocarodeini I. Bolívar, pp. 1-223 in Zootaxa 4206 (1) on page 82, DOI: 10.11646/zootaxa.4206.1.1, http://zenodo.org/record/20826
Busulfan and melphalan as preparative therapy for stem cell transplantation in pediatric patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS)
No full textRecommended from our members
Analysis of Autoprocessing of Mason-Pfizer Monkey Virus Proteinase in Vitro Three Active Forms of Proteinase
No full textMason-Pfizer Monkey Virus (M-PMV, also called SRV-3) is a primate retrovirus that was first isolated from a spontaneous breast carcinoma of a female rhesus monkey Macaca mulatta.1,2 Infection of macaque species with M-PMV causes an AIDS-like disease.3,6 M-PMV is characterized by the self-assembly of the Gag, Gag-Pro and Gag-Pro-Pol precursors into intracytoplasmic particles (procapsids) within the infected cell cytoplasm. These morphogenetic properties of the virus are typical for D-type retrovirus.7,
Intra‐Arterial Platelet Infusion for Intractable Hemorrhage and Refractory
No full textAcute gastrointestinal graft‐versus‐host disease (GVHD) refractory to first‐line treatment with systemic corticosteroids results in increased morbidity and potential mortality. We retrospectively assessed the feasibility and efficacy of catheter‐directed intra‐arterial platelet infusion (IAPI) in two pediatric patients with steroid and transfusion refractory gastrointestinal GVHD causing intractable lower gastrointestinal hemorrhage and refractory thrombocytopenia, that were referred for salvage therapy. Immediate angiographic response was noted with a resolution of hemorrhage and decreased blood requirements. We reviewed the literature regarding this treatment modality and compared it to the available minimally invasive transcatheter techniques to control gastrointestinal hemorrhage. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc
Recommended from our members
The Hypoxia Inducible Factor 1 Alpha is Required for Optimal GammaHerpes Virus Lytic Replication and Reactivation from Latency
No full textLytic replication of Kaposi's Sarcoma Associated Herpes Virus (KSHV) exacerbates Kaposi's sarcoma (KS) progression, an angiogenic spindle‐cell sarcoma associated with AIDS. Current antiviral therapy targeting lytic replication can prevent KS in seropositive patients. KSHV lytic infection is not manifested in vitro, and currently there are no animal models that display pathogenic phenotypes. In this study, we employed a biological and genetically mouse pathogen similar to KSHV, the murine gammaherpes virus (gHV) 68 (MHV68), that readily infects laboratory mice providing a valuable small animal model. Moreover, MHV68 in vitro infection exhibits a default lytic infection. Several studies have shown that during infection KSHV employs several viral proteins to de‐regulate the host transcription factor hypoxia inducible factor 1 alpha (HIF1α) and KSHV‐induced activation of HIF1α is necessary for viral persistence and KS progression. However, little is known about the role of HIF1 α in gHV replication and pathogenesis. To further investigate the role of this host factor, we induced transcriptional inactivation of HIF1α in MHV68 virus‐specific cells in vivo. Conditional knock out of HIF1α was achieved by infecting transgenic mice with Cre‐recombinase (Cre) LoxP specific site within the functional domain of HIF1α gene using a recombinant MHV68 that expressing a CMV driven Cre expression.
Our data demonstrated for the first time that HIF1α inactivation during gammaherpes virus infection in vivo affects viral gene transcription resulting in impaired virus expansion and early clearance of acute infection in a mouse model. In addition, our results from in vitro MHV68 lytic infection of mouse fibroblasts lacking HIF1α showed that lytic virus production and transcription is decreased. During latency establishment in vivo, the frequency of MHV68 latent splenocytes undergoing latent to lytic replication was largely decreased as well. Our data suggest that HIF1α is required for sustained acute infection since it's deletion in virus‐infected cells resulted in early clearance of productive infection and impairment in reactivation. Moreover, HIF1α is required for mRNA upregulation of glycolytic enzymes during MHV68 lytic infection suggesting a role for HIF1a as a modulator of cell energetics and viral gene expression. We conclude that gammaherpes viruses required the function of the cellular host factor HIF1α in order to effectively replicate and establish latency within its host.
Support or Funding Information
National Cancer Institute 3R01CA136387‐08S1
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal
Direct pulmonary instillation of recombinant factor VII (rFVIIa) for treatment of diffuse alveolar hemorrhage (DAH) in a 2 year old: the youngest pediatric case reported
No full text236: Busulfan and Single-Dose Melphalan as Preparative Therapy for Infants and Young Children Undergoing Stem Cell Transplantation for Leukemia: A Single Center Experience
No full textRecommended from our members
Effect of Chronic Thoracic Spinal Cord Injury (SCI) on the Peripheral Immune System in Mice
No full textPatients with chronic spinal cord injury (SCI) are at higher risk than the general population of developing infections and their prognosis is often much poorer. The disruption of the normal balance between central nervous system and immune system following SCI induces immunodepression, leading to a compromised capacity to combat infections such as influenza virus in patients with SCI. Using a contusion model of SCI at thoracic level 9, we analyzed the chronic effect of SCI on the peripheral immune system in mice, with a focus on T-cell immunity. We found that although the splenic T-cell number was not changed during chronic SCI, their function as measured in cytokine production, upon ex vivo stimulation, was diminished. We further explored the mechanisms of SCI-induced T-cell dysfunction and demonstrated that chronic SCI increased sympathetic nervous system (SNS) activity and elevated norepinephrine level in the spleen. Higher splenic norepinephrine level correlates with a T-cell exhaustion phenotype as shown by higher expression of exhaustion marker PD-1 on T-cells. Up-regulated PD-1 expression contributes to the CD8+ T-cell functional deficiency in chronic SCI mice, as blocking PD-1 signaling in vitro restored the CD8+ T-cell function. We next investigated how chronic SCI affects the antiviral immunity in mice using a well-established influenza virus mouse model. Virus specific immunity was analyzed in chronically injured mice at different times post-infection in comparison to uninjured controls. The data indicates that chronic SCI injury impairs the ability of the animals to mount an antiviral immunity. While all the control mice cleared the virus from the lungs 10 days post-infection, significant number of SCI mice did not clear the virus. This was attributed to severe deficit in both virus-specific antibody and CD8+ T-cell response in injured mice. Taken together, our study indicates that the alteration of sympathetic activity following chronic SCI induces T-cell exhaustion, which in turn impairs T-cell function and contributes to immune depression. Moreover, we demonstrate that the antiviral immunity against influenza virus infection is compromised in mice with chronic SCI. Our results highlight the important role of central nervous system and neurotransmitters in regulation of immune cell function. Our study also suggests that blockade of PD-1 pathway is a potential therapeutic strategy to restore immunity in patients with chronic SCI.</p
Effect of Chronic Thoracic Spinal Cord Injury (SCI) on the Peripheral Immune System in Mice
No full textPatients with chronic spinal cord injury (SCI) are at higher risk than the general population of developing infections and their prognosis is often much poorer. The disruption of the normal balance between central nervous system and immune system following SCI induces immunodepression, leading to a compromised capacity to combat infections such as influenza virus in patients with SCI. Using a contusion model of SCI at thoracic level 9, we analyzed the chronic effect of SCI on the peripheral immune system in mice, with a focus on T-cell immunity. We found that although the splenic T-cell number was not changed during chronic SCI, their function as measured in cytokine production, upon ex vivo stimulation, was diminished. We further explored the mechanisms of SCI-induced T-cell dysfunction and demonstrated that chronic SCI increased sympathetic nervous system (SNS) activity and elevated norepinephrine level in the spleen. Higher splenic norepinephrine level correlates with a T-cell exhaustion phenotype as shown by higher expression of exhaustion marker PD-1 on T-cells. Up-regulated PD-1 expression contributes to the CD8+ T-cell functional deficiency in chronic SCI mice, as blocking PD-1 signaling in vitro restored the CD8+ T-cell function. We next investigated how chronic SCI affects the antiviral immunity in mice using a well-established influenza virus mouse model. Virus specific immunity was analyzed in chronically injured mice at different times post-infection in comparison to uninjured controls. The data indicates that chronic SCI injury impairs the ability of the animals to mount an antiviral immunity. While all the control mice cleared the virus from the lungs 10 days post-infection, significant number of SCI mice did not clear the virus. This was attributed to severe deficit in both virus-specific antibody and CD8+ T-cell response in injured mice. Taken together, our study indicates that the alteration of sympathetic activity following chronic SCI induces T-cell exhaustion, which in turn impairs T-cell function and contributes to immune depression. Moreover, we demonstrate that the antiviral immunity against influenza virus infection is compromised in mice with chronic SCI. Our results highlight the important role of central nervous system and neurotransmitters in regulation of immune cell function. Our study also suggests that blockade of PD-1 pathway is a potential therapeutic strategy to restore immunity in patients with chronic SCI.</p
