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https://www.readbyqxmd.com/read/27896824/patients-with-the-worst-outcomes-after-paracetamol-acetaminophen-induced-liver-failure-have-an-early-monocytopenia
#1
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...
November 28, 2016: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27830183/human-cytomegalovirus-infection-enhances-nk-cell-activity-in-vitro
#2
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
#3
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
#4
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
#5
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
#6
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/27177676/noninvasive-imaging-of-natural-killer-cell-mediated-apoptosis-in-a-mouse-tumor-model
#7
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
https://www.readbyqxmd.com/read/27092139/microchip-screening-platform-for-single-cell-assessment-of-nk-cell-cytotoxicity
#8
Karolin Guldevall, Ludwig Brandt, Elin Forslund, Karl Olofsson, Thomas W Frisk, Per E Olofsson, Karin Gustafsson, Otto Manneberg, Bruno Vanherberghen, Hjalmar Brismar, Klas Kärre, Michael Uhlin, Björn Önfelt
Here, we report a screening platform for assessment of the cytotoxic potential of individual natural killer (NK) cells within larger populations. Human primary NK cells were distributed across a silicon-glass microchip containing 32,400 individual microwells loaded with target cells. Through fluorescence screening and automated image analysis, the numbers of NK and live or dead target cells in each well could be assessed at different time points after initial mixing. Cytotoxicity was also studied by time-lapse live-cell imaging in microwells quantifying the killing potential of individual NK cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27013443/decitabine-enhances-anti-cd33-monoclonal-antibody-bi-836858-mediated-natural-killer-adcc-against-aml-blasts
#9
Sumithira Vasu, Shun He, Carolyn Cheney, Bhavani Gopalakrishnan, Rajeswaran Mani, Gerard Lozanski, Xiaokui Mo, Veronica Groh, Susan P Whitman, Renate Konopitzky, Christian Kössl, Donna Bucci, David M Lucas, Jianhua Yu, Michael A Caligiuri, William Blum, Paul J Adam, Eric Borges, Bjoern Rueter, Karl-Heinz Heider, Guido Marcucci, Natarajan Muthusamy
Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML. Here, we report the in vitro efficacy of BI 836858, a fully human, Fc-engineered, anti-CD33 antibody using AML cell lines and primary AML blasts as targets...
June 9, 2016: Blood
https://www.readbyqxmd.com/read/27009223/prairie-dogs-increase-fitness-by-killing-interspecific-competitors
#10
John L Hoogland, Charles R Brown
Interspecific competition commonly selects for divergence in ecology, morphology or physiology, but direct observation of interspecific competition under natural conditions is difficult. Herbivorous white-tailed prairie dogs (Cynomys leucurus) employ an unusual strategy to reduce interspecific competition: they kill, but do not consume, herbivorous Wyoming ground squirrels (Urocitellus elegans) encountered in the prairie dog territories. Results from a 6-year study in Colorado, USA, revealed that interspecific killing of ground squirrels by prairie dogs was common, involving 47 different killers; 19 prairie dogs were serial killers in the same or consecutive years, and 30% of female prairie dogs killed at least one ground squirrel over their lifetimes...
March 30, 2016: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/26772545/effects-of-stimulating-interleukin-2-anti-interleukin-2-antibody-complexes-on-renal-cell-carcinoma
#11
Kyu-Hyun Han, Ki Won Kim, Ji-Jing Yan, Jae-Ghi Lee, Eun Mi Lee, Miyeon Han, Eun Jin Cho, Seong Sik Kang, Hye Jin Lim, Tai Yeon Koo, Curie Ahn, Jaeseok Yang
BACKGROUND: Current therapies for advanced renal cell carcinoma (RCC) have low cure rates or significant side effects. It has been reported that complexes composed of interleukin (IL)-2 and stimulating anti-IL-2 antibody (IL-2C) suppress malignant melanoma growth. We investigated whether it could have similar effects on RCC. METHODS: A syngeneic RCC model was established by subcutaneously injecting RENCA cells into BALB/c mice, which were administered IL-2C or phosphate-buffered saline every other day for 4 weeks...
January 16, 2016: BMC Urology
https://www.readbyqxmd.com/read/26670998/mother-centriole-distal-appendages-mediate-centrosome-docking-at-the-immunological-synapse-and-reveal-mechanistic-parallels-with-ciliogenesis
#12
Jane C Stinchcombe, Lyra O Randzavola, Karen L Angus, Judith M Mantell, Paul Verkade, Gillian M Griffiths
Cytotoxic T lymphocytes (CTLs) are highly effective serial killers capable of destroying virally infected and cancerous targets by polarized release from secretory lysosomes. Upon target contact, the CTL centrosome rapidly moves to the immunological synapse, focusing microtubule-directed release at this point [1-3]. Striking similarities have been noted between centrosome polarization at the synapse and basal body docking during ciliogenesis [1, 4-8], suggesting that CTL centrosomes might dock with the plasma membrane during killing, in a manner analogous to primary cilia formation [1, 4]...
December 21, 2015: Current Biology: CB
https://www.readbyqxmd.com/read/26587330/car-t-cells-are-serial-killers
#13
Alexander J Davenport, Misty R Jenkins, David S Ritchie, H Miles Prince, Joseph A Trapani, Michael H Kershaw, Phillip K Darcy, Paul J Neeson
Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours...
December 2015: Oncoimmunology
https://www.readbyqxmd.com/read/26468266/toward-identification-of-the-sexual-killer-a-comparison-of-sexual-killers-engaging-in-post-mortem-sexual-interference-and-non-homicide-sexual-aggressors
#14
Tamsin Higgs, Adam J Carter, Ewa B Stefanska, Emily Glorney
Establishing a model of sexual assault reflecting psychosocial and behavioral characteristics of perpetrators of sexual killing and rape is necessary for development in risk assessment and intervention. Methodological variations in defining sexual killing have amalgamated serial and non-serial offenders and perpetrators with direct and indirect associations between killing and sexual arousal. This study defined sexual killing specifying that killing should be directly linked to sexual arousal, and sampled 48 sexual killers, operationalized to include only those engaging in post-mortem sexual interference, with one or two known female victims (non-serial), from prison service national (England and Wales) databases...
October 14, 2015: Sexual Abuse: a Journal of Research and Treatment
https://www.readbyqxmd.com/read/26463110/m-by-fritz-lang-germany-1931-phenomenology-of-evil-a-serial-killer-and-his-social-group
#15
Cesare Secchi
In 1931 an unknown murderer of little girls (Peter Lorre) is terrorizing the city of Berlin. We see him entice a new victim, the little Elsie Beckmann, who is coming home from school: whistling a tune by Grieg, he buys her a balloon from a blind beggar. When her corpse is discovered, the police undertake a major mobilization aimed at seeking the serial killer in the criminal underworld; meanwhile, the ever more terrified population starts to see the dangerous murderer in everyone. Since the roundups and incursions into the seediest parts of town disturb the gangsters' activities, the leaders of organized crime, headed by Schränker (Gustav Gründgens), take it upon themselves also to hunt down the solitary child-killer, engaging the community of beggars...
October 2015: International Journal of Psycho-analysis
https://www.readbyqxmd.com/read/26320254/microchip-based-single-cell-imaging-reveals-that-cd56dimcd57-kir-nkg2a-nk-cells-have-more-dynamic-migration-associated-with-increased-target-cell-conjugation-and-probability-of-killing-compared-to-cd56dimcd57-kir-nkg2a-nk-cells
#16
Elin Forslund, Ebba Sohlberg, Monika Enqvist, Per E Olofsson, Karl-Johan Malmberg, Björn Önfelt
NK cells are functionally educated by self-MHC specific receptors, including the inhibitory killer cell Ig-like receptors (KIRs) and the lectin-like CD94/NKG2A heterodimer. Little is known about how NK cell education influences qualitative aspects of cytotoxicity such as migration behavior and efficacy of activation and killing at the single-cell level. In this study, we have compared the behavior of FACS-sorted CD56(dim)CD57(-)KIR(-)NKG2A(+) (NKG2A(+)) and CD56(dim)CD57(-)KIR(-)NKG2A(-) (lacking inhibitory receptors; IR(-)) human NK cells by quantifying migration, cytotoxicity, and contact dynamics using microchip-based live cell imaging...
October 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26292843/-am-i-becoming-a-serial-killer-a-case-study-of-cognitive-behavioral-therapy-for-mental-illness-anxiety
#17
Bethany L Gelinas, Heather Hadjistavropoulos
BACKGROUND: Although mental illness anxiety is described in the literature, there is very little information on which to draw when treating individuals who present with fears and worries about mental health. In fact, we identified no previous case descriptions focused on this form of anxiety and treated from a cognitive behavioral perspective. AIMS: The current case study aims to advance the understanding of the clinical picture of mental illness anxiety, and facilitate the understanding of how cognitive behavioral techniques for health anxiety can be effectively adapted and implemented for such a case...
May 2016: Behavioural and Cognitive Psychotherapy
https://www.readbyqxmd.com/read/26259153/attempted-serial-neonaticides-case-report-and-a-brief-review-of-the-literature
#18
Alcina Juliana Soares Barros, Regis Goulart Rosa, Lisieux Elaine de Borba Telles, José Geraldo Vernet Taborda
Neonaticide is an infant murder occurring on the day of birth. The case reports found in the literature are often focused on the mother as the agent in the context of pregnancy denial, dissociative symptoms, or psychosis. However, this report describes a rare case of attempted serial neonaticides, in which the acts were committed by a nurse at the nursery of a referral hospital in Brazil. The authors describe a forensic psychiatric evaluation for criminal responsibility and correlate the information from this particular case with relevant forensic themes, namely neonaticide, Munchausen by proxy syndrome, and serial healthcare killers...
January 2016: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/26246369/reframing-serial-murder-within-empirical-research-offending-and-adjudication-patterns-of-male-female-and-partnered-serial-killers
#19
Elizabeth A Gurian
Empirical research on serial murder is limited due to the lack of consensus on a definition, the continued use of primarily descriptive statistics, and linkage to popular culture depictions. These limitations also inhibit our understanding of these offenders and affect credibility in the field of research. Therefore, this comprehensive overview of a sample of 508 cases (738 total offenders, including partnered groups of two or more offenders) provides analyses of solo male, solo female, and partnered serial killers to elucidate statistical differences and similarities in offending and adjudication patterns among the three groups...
August 5, 2015: International Journal of Offender Therapy and Comparative Criminology
https://www.readbyqxmd.com/read/26215372/establishment-of-a-heterotypic-3d-culture-system-to-evaluate-the-interaction-of-treg-lymphocytes-and-nk-cells-with-breast-cancer
#20
Tanya N Augustine, Thérèse Dix-Peek, Raquel Duarte, Geoffrey P Candy
Three-dimensional (3D) culture approaches to investigate breast tumour progression are yielding information more reminiscent of the in vivo microenvironment. We have established a 3D Matrigel system to determine the interactions of luminal phenotype MCF-7 cells and basal phenotype MDA-MB-231 cells with regulatory T lymphocytes and Natural Killer cells. Immune cells were isolated from peripheral blood using magnetic cell sorting and their phenotype validated using flow cytometry both before and after activation with IL-2 and phytohaemagglutinin...
November 2015: Journal of Immunological Methods
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