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https://www.readbyqxmd.com/read/29440406/chimeric-antigen-receptor-t-cells-form-nonclassical-and-potent-immune-synapses-driving-rapid-cytotoxicity
#1
A J Davenport, R S Cross, K A Watson, Y Liao, W Shi, H M Prince, P A Beavis, J A Trapani, M H Kershaw, D S Ritchie, P K Darcy, P J Neeson, M R Jenkins
Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29427149/phase-i-trial-of-dasatinib-lenalidomide-and-temozolomide-in-children-with-relapsed-or-refractory-central-nervous-system-tumors
#2
Nathan J Robison, Kee Kiat Yeo, Adrian P Berliner, Jemily Malvar, Michael A Sheard, Ashley S Margol, Robert C Seeger, Teresa Rushing, Jonathan L Finlay, Richard Sposto, Girish Dhall
Single agent studies targeting the tumor microenvironment in central nervous system (CNS) tumors have largely been disappointing. Combination therapies targeting various pathways and cell types may be a more effective strategy. In this phase I study, we evaluated the combination of dasatinib, lenalidomide, and temozolomide in children with relapsed or refractory primary CNS tumors. Patients 1-21 years old with relapsed or refractory CNS tumors were eligible. Starting doses of dasatinib and lenalidomide were 65 mg/m 2 /dose twice daily and 55 mg/m 2 once daily, respectively, while temozolomide was constant at 75 mg/m 2 daily...
February 9, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29140757/new-insights-into-lymphoma-pathogenesis
#3
Kojo S J Elenitoba-Johnson, Megan S Lim
Lymphomas represent clonal proliferations of lymphocytes that are broadly classified based upon their maturity (peripheral or mature versus precursor) and lineage (B cell, T cell, and natural killer cell). Insights into the pathogenetic mechanisms involved in lymphoma impact the classification of lymphoma and have significant implications for the diagnosis and clinical management of patients. Serial scientific and technologic advances over the last 30 years in immunology, cytogenetics, molecular biology, gene expression profiling, mass spectrometry-based proteomics, and, more recently, next-generation sequencing have contributed to greatly enhance our understanding of the pathogenetic mechanisms in lymphoma...
November 15, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/29090365/cd56-immune-cell-infiltration-and-mica-are-decreased-in-breast-lobules-with-fibrocystic-changes
#4
Daniel Kerekes, Daniel W Visscher, Tanya L Hoskin, Derek C Radisky, Rushin D Brahmbhatt, Alvaro Pena, Marlene H Frost, Muhammad Arshad, Melody Stallings-Mann, Stacey J Winham, Linda Murphy, Lori Denison, Jodi M Carter, Keith L Knutson, Amy C Degnim
PURPOSE: While the role of natural killer (NK) cells in breast cancer therapy has been investigated, little information is known about NK cell function and presence in nonmalignant and premalignant breast tissue. Here, we investigate and quantify NK cell marker CD56 and activating ligand MICA in breast tissue with benign breast disease. METHODS: Serial tissue sections from 88 subjects, 44 with benign breast disease (BBD) who remained cancer-free, and 44 with BBD who later developed cancer, were stained with H&E, anti-MICA, and anti-CD56...
November 1, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29055395/the-neural-signature-of-emotional-memories-in-serial-crimes
#5
Philippe Chassy
Neural plasticity is the process whereby semantic information and emotional responses are stored in neural networks. It is hypothesized that the neural networks built over time to encode the sexual fantasies that motivate serial killers to act should display a unique, detectable activation pattern. The pathological neural watermark hypothesis posits that such networks comprise activation of brain sites that reflect four cognitive components: autobiographical memory, sexual arousal, aggression, and control over aggression...
October 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28945556/-hepatitis-c-the-serial-killer-pictured-more-than-25-years-after-his-indictment
#6
Eric Piver, Anne Bull, Philippe Roingeard, Jean-Christophe Meunier
No abstract text is available yet for this article.
August 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28735365/an-update-on-the-use-of-immunotherapy-in-the-treatment-of-lymphoma
#7
REVIEW
Thomas U Marron, Matko Kalac, Joshua Brody
PURPOSE OF REVIEW: Throughout the field of oncology, immunotherapy is moving further towards the first-line setting, and there is encouraging data for the use of these novel therapies in the management of lymphomas, utilizing treatments approved for both solid and hematologic malignancies. Herein, we review promising advances in this rapidly moving field from the past year. RECENT FINDINGS: In the last year, we have seen promising clinical data on engineered antibody therapies for the treatment of lymphomas, as well as further optimization of engineered antibody fragments fused onto linkers or chimeric T cell receptors, both of the modalities capable of transforming non-specific T cells into tumor-specific, serial killer cells...
August 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28465386/medea-a-mythological-case-of-familial-serial-killer-psychiatry-in-literature
#8
Philippe Charlier, Saudamini Deo, Michel De Grèce, Anne-Sophie Wecker
No abstract text is available yet for this article.
May 2017: British Journal of Psychiatry: the Journal of Mental Science
https://www.readbyqxmd.com/read/28433723/elimination-of-the-cryptic-plasmid-in-leuconostoc-citreum-by-crispr-cas9-system
#9
Ye-Ji Jang, Seung-Oh Seo, Seul-Ah Kim, Ling Li, Tae-Jip Kim, Sun Chang Kim, Yong-Su Jin, Nam Soo Han
Leuconostoc spp. are important lactic acid bacteria for the fermentation of foods. In particular, L. citreum strains isolated from various foods have been used as host strains for genetic and metabolic engineering studies. In order to develop a food-grade genetic engineering system, L. citreum CB2567 was isolated from Kimchi. However, the isolated bacterium contained a cryptic plasmid which was difficult to eliminate. As the existence of the plasmid might hinder strain engineering, we eliminated the plasmid using an RNA-guided DNA endonuclease CRISPR/Cas9 system...
April 19, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28394281/was-jack-the-ripper-a-slaughterman-human-animal-violence-and-the-world-s-most-infamous-serial-killer
#10
Andrew Knight, Katherine D Watson
Hundreds of theories exist concerning the identity of "Jack the Ripper". His propensity for anatomical dissection with a knife-and in particular the rapid location and removal of specific organs-led some to speculate that he must have been surgically trained. However, re-examination of a mortuary sketch of one of his victims has revealed several aspects of incisional technique highly inconsistent with professional surgical training. Related discrepancies are also apparent in the language used within the only letter from Jack considered to be probably authentic...
April 10, 2017: Animals: An Open Access Journal From MDPI
https://www.readbyqxmd.com/read/28343680/the-medical-itineraries-of-blaise-cendrars-neuropsychiatry-marks-life-and-literature
#11
L Tatu, J Bogousslavsky
Neuropsychiatry had a profound impact on the life and work of one of the most influential French writers of the 20th century, Frédéric Sauser, better known by his pen name Blaise Cendrars (1887-1961). Cendrars, whose right writing hand was amputated after a battlefield wound in 1915, described with acuity his stump pain and phantom limb syndrome. He became a left-handed writer. Between 1956 and his death in 1961, he also suffered two strokes that progressively paralyzed his left side and greatly diminished his ability to speak...
March 2017: Revue Neurologique
https://www.readbyqxmd.com/read/27990636/factitious-disorder-in-a-patient-claiming-to-be-a-sexually-sadistic-serial-killer
#12
Christopher A Fischer, Mace Beckson, Park Dietz
Factitious disorder involves the conscious simulation of psychological or physiological symptoms of illness, for the purpose of fulfilling the unconscious desire to be taken care of or to assume the "sick role." Typically patients with factitious disorder simulate conditions that are designed to arouse feelings of empathy in care providers with the intention to engage them in caretaking. However, patients might also simulate conditions that arouse revulsion or rejection and still meet full diagnostic criteria for factitious disorder...
May 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/27896824/patients-with-the-worst-outcomes-after-paracetamol-acetaminophen-induced-liver-failure-have-an-early-monocytopenia
#13
J K Moore, A C MacKinnon, T Y Man, J R Manning, S J Forbes, K J Simpson
BACKGROUND: Acute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome. AIM: To investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome. METHODS: In a prospective case-control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non-paracetamol causes of ALF and 16 controls were recruited...
February 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27830183/human-cytomegalovirus-infection-enhances-nk-cell-activity-in-vitro
#14
Astrid Tschan-Plessl, Martin Stern, Laurent Schmied, Christelle Retière, Hans H Hirsch, Christian Garzoni, Christian van Delden, Katia Boggian, Nicolas J Mueller, Christoph Berger, Jean Villard, Oriol Manuel, Pascal Meylan, Grzegorz Terszowski
BACKGROUND: Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive. METHODS: We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant...
July 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27810924/single-cell-imaging-of-normal-and-malignant-cell-engraftment-into-optically-clear-prkdc-null-scid-zebrafish
#15
John C Moore, Qin Tang, Nora Torres Yordán, Finola E Moore, Elaine G Garcia, Riadh Lobbardi, Ashwin Ramakrishnan, Dieuwke L Marvin, Anthony Anselmo, Ruslan I Sadreyev, David M Langenau
Cell transplantation into immunodeficient mice has revolutionized our understanding of regeneration, stem cell self-renewal, and cancer; yet models for direct imaging of engrafted cells has been limited. Here, we characterize zebrafish with mutations in recombination activating gene 2 (rag2), DNA-dependent protein kinase (prkdc), and janus kinase 3 (jak3). Histology, RNA sequencing, and single-cell transcriptional profiling of blood showed that rag2 hypomorphic mutant zebrafish lack T cells, whereas prkdc deficiency results in loss of mature T and B cells and jak3 in T and putative Natural Killer cells...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27563682/effects-of-invariant-nkt-cells-on-parasite-infections-and-hygiene-hypothesis
#16
REVIEW
Jun-Qi Yang, Yonghua Zhou, Ram Raj Singh
Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic "hygiene hypothesis," has not been clearly defined yet...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27527597/endocytosis-of-cytotoxic-granules-is-essential-for-multiple-killing-of-target-cells-by-t-lymphocytes
#17
Hsin-Fang Chang, Hawraa Bzeih, Claudia Schirra, Praneeth Chitirala, Mahantappa Halimani, Emmanuelle Cordat, Elmar Krause, Jens Rettig, Varsha Pattu
CTLs are serial killers that kill multiple target cells via exocytosis of cytotoxic granules (CGs). CG exocytosis is tightly regulated and has been investigated in great detail; however, whether CG proteins are endocytosed following exocytosis and contribute to serial killing remains unknown. By using primary CTLs derived from a knock-in mouse of the CG membrane protein Synaptobrevin2, we show that CGs are endocytosed in a clathrin- and dynamin-dependent manner. Following acidification, endocytosed CGs are recycled through early and late, but not recycling endosomes...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27505426/the-cytotoxic-t-lymphocyte-immune-synapse-at-a-glance
#18
REVIEW
Nele M G Dieckmann, Gordon L Frazer, Yukako Asano, Jane C Stinchcombe, Gillian M Griffiths
The immune synapse provides an important structure for communication with immune cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs) highlight the dynamic changes and specialised mechanisms required to facilitate focal signalling and polarised secretion in immune cells. In this Cell Science at a Glance article and the accompanying poster, we illustrate the different steps that reveal the specialised mechanisms used to focus secretion at the CTL immune synapse and allow CTLs to be such efficient and precise serial killers...
August 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27375156/post-transplantation-natural-killer-cell-count-a-predictor-of-acute-graft-versus-host-disease-and-survival-outcomes-after-allogeneic-hematopoietic-stem-cell-transplantation
#19
Seo Yeon Kim, Hyewon Lee, Mi-Soon Han, Hyoeun Shim, Hyeon-Seok Eom, Boram Park, Sun-Young Kong
BACKGROUND: Reconstitution of the immune system after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in post-transplant outcomes. However, the clinical relevance of the lymphocyte subset (LST) counts to transplant-related complications and survival outcomes after allo-HSCT has not been fully elucidated. PATIENTS AND METHODS: A total of 70 patients who had undergone allo-HSCT from 2007 to 2013, with LST results both 7 days before conditioning and 30 or 90 days after allo-HSCT were included...
September 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27177676/noninvasive-imaging-of-natural-killer-cell-mediated-apoptosis-in-a-mouse-tumor-model
#20
Thoudam Debraj Singh, Jaetae Lee, Yong Hyun Jeon
Natural killer (NK) cells are cytotoxic lymphocytes that induce apoptosis in cancer cells infected with viruses and bacteria through a caspase-3-dependent pathway. Effective NK cell-based immunotherapy requires highly sensitive imaging tools for in vivo monitoring of the dynamic events involved in apoptosis. Here, we describe a noninvasive bioluminescence imaging approach to determine the antitumor effects of NK cell-based therapy by serial imaging of caspase-3-dependent apoptosis in a mouse model of human glioma...
2016: Methods in Molecular Biology
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