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https://www.readbyqxmd.com/read/28527887/mst1-deficiency-promotes-b-cell-responses-by-cd4-t-cell-derived-il-4-resulting-in-hypergammaglobulinemia
#1
Eunchong Park, Myun Soo Kim, Ju Han Song, Kyung Min Cho, Kyung-Hye Roh, Rana Lee, Tae Sung Kim
MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production. Recent studies have shown that the autoimmune responses observed in MST1-deficient patients were most likely attributable to defective regulatory T (Treg) cells instead of intrinsic signals in MST1-lacking B cells. Nevertheless, it is not determined how MST1 deficiency in T cells breaks B cell tolerance and causes systemic autoimmune-like phenotypes...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526178/late-onset-progressive-multifocal-leukoencephalopathy-in-hodgkin-lymphoma
#2
Whitley W Aamodt, James E Siegler, Angela N Viaene, Michael N Rubenstein
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from infection of oligodendrocytes in the central nervous system with John Cunningham virus. Although PML is commonly diagnosed in immunocompromised patients with human immunodeficiency virus, it can also arise in other immunodeficient states. In this report, we present an unusual case of PML occurring 40years after chemoradiation therapy for Hodgkin lymphoma in a patient with normal total lymphocyte counts on annual surveillance...
May 16, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28514722/the-interventional-effect-of-new-drugs-combined-with-the-stupp-protocol-on-glioblastoma-a-network-meta-analysis
#3
Mei Li, Xiangqi Song, Jun Zhu, Aijun Fu, Jianmin Li, Tong Chen
OBJECTIVE: New therapeutic agents in combination with the standard Stupp protocol (a protocol about the temozolomide combined with radiotherapy treatment with glioblastoma was research by Stupp R in 2005) were assessed to evaluate whether they were superior to the Stupp protocol alone, to determine the optimum treatment regimen for patients with newly diagnosed glioblastoma. PATIENTS AND METHODS: We implemented a search strategy to identify studies in the following databases: PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang, and VIP, and assessed the quality of extracted data from the trials included...
May 11, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28512628/dysplasia-of-granulocytes-in-a-patient-with-hpv-disease-recurrent-infections-and-b-lymphopenia-a-novel-variant-of-whim-syndrome
#4
Giusella M F Moscato, Erica Giacobbi, Lucia Anemona, Silvia Di Cesare, Gigliola Di Matteo, Massimo Andreoni, Alessandro Mauriello, Viviana Moschese
WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28507545/clinical-and-molecular-heterogeneity-of-rtel1-deficiency
#5
Carsten Speckmann, Sushree Sangita Sahoo, Marta Rizzi, Shinsuke Hirabayashi, Axel Karow, Nina Kathrin Serwas, Marc Hoemberg, Natalja Damatova, Detlev Schindler, Jean-Baptiste Vannier, Simon J Boulton, Ulrich Pannicke, Gudrun Göhring, Kathrin Thomay, J J Verdu-Amoros, Holger Hauch, Wilhelm Woessmann, Gabriele Escherich, Eckart Laack, Liliana Rindle, Maximilian Seidl, Anne Rensing-Ehl, Ekkehart Lausch, Christine Jandrasits, Brigitte Strahm, Klaus Schwarz, Stephan R Ehl, Charlotte Niemeyer, Kaan Boztug, Marcin W Wlodarski
Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28497777/phase-i-ii-clinical-trial-to-assess-safety-and-efficacy-of-intratumoral-and-subcutaneous-injection-of-hvj-e-in-castration-resistant-prostate-cancer-patients
#6
K Fujita, Y Nakai, A Kawashima, T Ujike, A Nagahara, T Nakajima, T Inoue, C M Lee, M Uemura, Y Miyagawa, Y Kaneda, N Nonomura
Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, single-arm, phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E...
May 12, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28495790/systemic-inflammatory-response-syndrome-related-lymphopenia-is-associated-with-adenosine-a1-receptor-dysfunction
#7
Reut Riff, Yair Cohen, Hadar Eini-Rider, Oshri Naamani, Julia Mazar, Yosef S Haviv, Cidio Chaimovitz, Amos Douvdevani
SIRS is associated with lymphopenia, and prolonged lymphopenia of septic patients has been associated with increased mortality risk. We hypothesize that elevated adenosine during SIRS down-regulates Gi-coupled A1R, which signals an effect that sensitizes a cAMP-dependent lymphotoxic response. In this study, we evaluate the role of adenosine in SIRS-mediated lymphopenia and impaired IL-15 production. Cecal ligation and puncture was used to induce sepsis-associated SIRS in mice. BMDCs were cultured and used to measure the effect of adenosine on IL-15...
May 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28495639/safety-and-tolerability-of-the-first-in-class-agent-cpi-613-in-combination-with-modified-folfirinox-in-patients-with-metastatic-pancreatic-cancer-a-single-centre-open-label-dose-escalation-phase-1-trial
#8
Angela Alistar, Bonny B Morris, Rodwige Desnoyer, Heidi D Klepin, Keyanoosh Hosseinzadeh, Clancy Clark, Amy Cameron, John Leyendecker, Ralph D'Agostino, Umit Topaloglu, Lakmal W Boteju, Asela R Boteju, Rob Shorr, Zuzana Zachar, Paul M Bingham, Tamjeed Ahmed, Sandrine Crane, Riddhishkumar Shah, John J Migliano, Timothy S Pardee, Lance Miller, Gregory Hawkins, Guangxu Jin, Wei Zhang, Boris Pasche
BACKGROUND: Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells...
May 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28491220/a-primary-intestinal-lymphangiectasia-hiding-the-diagnosis-of-pleural-and-pericardial-tuberculosis-a-clinical-observation
#9
Sanaa Hammi, Hajar Berrani, Thami Benouchen, Naima Lamlami, Imane Elkhiyat, Jamal Eddine Bourkadi
Primary intestinal lymphangiectasia (Waldmann's disease) is an exudative enteropathy characterized by lymph leakage into the small bowel lumen leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia (particularly T-cell). The diagnosis is based on viewing the duodenal lymphangiectasia. A 20 years old female patient, treated for a primary intestinal lymphangiectasia, has consulted for anasarca. Etiological work-up reveals pleural and pericardial tuberculosis. The clinical aggravation of an enteropathy, particularly in adulthood, requires a search for a secondary etiology...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28488066/a-phase-i-trial-of-concurrent-sorafenib-and-stereotactic-radiosurgery-for-patients-with-brain-metastases
#10
Kyle Arneson, Joshua Mondschein, Mark Stavas, Anthony J Cmelak, Albert Attia, Leora Horn, Kenneth Niermann, Igor Puzanov, A Bapsi Chakravarthy, Fen Xia
We hypothesized that sorafenib (BAY 43-9006), an oral multi-kinase inhibitor, used in combination with SRS will improve overall intracranial control. This Phase I study assesses the safety, tolerability, and maximal tolerated dose of sorafenib administered with SRS to treat 1-4 brain metastases. This was an open label phase I dose escalation study with an expansion cohort. Eligible adults had 1-4 brain metastases from solid malignancies. Sorafenib was begun 5-7 days prior to SRS and continued for 14 days thereafter...
May 9, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28484088/radium-223-for-primary-bone-metastases-in-patients-with-hormone-sensitive-prostate-cancer-after-radical-prostatectomy
#11
Vera Wenter, Annika Herlemann, Wolfgang P Fendler, Harun Ilhan, Natalia Tirichter, Peter Bartenstein, Christian G Stief, Christian la Fougère, Nathalie L Albert, Axel Rominger, Christian Gratzke
Radium-223 dichloride (Ra-223) is the first bone-targeting agent showing improvement in overall survival in patients with castration-resistant prostate cancer (CRPC) and bone metastases. We aimed to assess feasibility of Ra-223 treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ten patients with primary bone metastases received Ra-223 following radical prostatectomy (RP). Changes in alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were recorded, while pain intensity was evaluated using the self-reporting Brief Pain Inventory (BPI) questionnaire...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28481926/delineating-morbillivirus-entry-dissemination-and-airborne-transmission-by-studying-in-vivo-competition-of-multicolor-canine-distemper-viruses-in-ferrets
#12
Rory D de Vries, Martin Ludlow, Alwin de Jong, Linda J Rennick, R Joyce Verburgh, Geert van Amerongen, Debby van Riel, Peter R W A van Run, Sander Herfst, Thijs Kuiken, Ron A M Fouchier, Albert D M E Osterhaus, Rik L de Swart, W Paul Duprex
Identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis. However, specific aspects of viral entry, dissemination and transmission remain difficult to recapitulate in animal models. Here, we used three virologically identical but phenotypically distinct recombinant (r) canine distemper viruses (CDV) expressing different fluorescent reporter proteins for in vivo competition and airborne transmission studies in ferrets (Mustela putorius furo)...
May 8, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28480897/antigen-inexperienced-memory-cd8-t-cells-where-they-come-from-and-why-we-need-them
#13
REVIEW
Jason T White, Eric W Cross, Ross M Kedl
Memory-phenotype CD8(+) T cells exist in substantial numbers within hosts that have not been exposed to either foreign antigen or overt lymphopenia. These antigen-inexperienced memory-phenotype T cells can be divided into two major subsets: 'innate memory' T cells and 'virtual memory' T cells. Although these two subsets are nearly indistinguishable by surface markers alone, notable developmental and functional differences exist between the two subsets, which suggests that they represent distinct populations...
May 8, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28480794/dimethyl-fumarate-induces-changes-in-b-and-t-lymphocyte-function-independent-of-the-effects-on-absolute-lymphocyte-count
#14
Erin E Longbrake, Claudia Cantoni, Salim Chahin, Francesca Cignarella, Anne H Cross, Laura Piccio
BACKGROUND: Dimethyl fumarate (DMF) is used to treat relapsing multiple sclerosis and causes lymphopenia in a subpopulation of treated individuals. Much remains to be learned about how the drug affects B- and T-lymphocytes. OBJECTIVES: To characterize changes in B- and T-cell phenotype and function induced by DMF and to investigate whether low absolute lymphocyte count (ALC) is associated with unique functional changes. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from DMF-treated patients, untreated patients, and healthy controls...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28476145/disseminated-bacillus-calmette-gu%C3%A3-rin-bcg-infections-in-infants-with-immunodeficiency
#15
Suleiman Al-Hammadi, Ahmed R Alsuwaidi, Eman T Alshamsi, Ghassan A Ghatasheh, Abdul-Kader Souid
BACKGROUND: The Bacillus Calmette-Guérin (BCG) preparations are live-attenuated derivatives of Mycobacterium bovis. These products are used to vaccinate infants at birth, a practice that may result in a disseminated infection in those patients who have an unidentified immunodeficiency. CASE PRESENTATION: Patients who were immunized at birth with BCG and who developed a disseminated infection are reported here to emphasize the importance of taking an extensive medical history before ‎giving the BCG vaccine...
May 5, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28471727/safety-and-clinical-activity-of-the-programmed-death-ligand-1-inhibitor-durvalumab-in-combination-with-poly-adp-ribose-polymerase-inhibitor-olaparib-or-vascular-endothelial-growth-factor-receptor-1-3-inhibitor-cediranib-in-women-s-cancers-a-dose-escalation
#16
Jung-Min Lee, Ashley Cimino-Mathews, Cody J Peer, Alexandra Zimmer, Stanley Lipkowitz, Christina M Annunziata, Liang Cao, Maria I Harrell, Elizabeth M Swisher, Nicole Houston, Dana-Adriana Botesteanu, Janis M Taube, Elizabeth Thompson, Aleksandra Ogurtsova, Haiying Xu, Jeffers Nguyen, Tony W Ho, William D Figg, Elise C Kohn
Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition and/or reduced vascular endothelial growth factor signaling by vascular endothelial growth factor receptor inhibition may complement antitumor activity of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. Patients and Methods This phase I study tested durvalumab doublets in parallel 3 + 3 dose escalations...
May 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28471626/idiopathic-cd4-lymphopenia-severe-cd4-lymphopenia-in-the-absence-of-human-immunodeficiency-virus-infection
#17
REVIEW
Ilan Asher, Keren Mahlab-Guri, Daniel Elbirt, Shira Ezalel-Rosenberg, Zev Sthoeger
No abstract text is available yet for this article.
October 2016: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28466551/functionality-testing-of-stem-cell-grafts-to-predict-infectious-complications-after-allogeneic-hematopoietic-stem-cell-transplantation
#18
J Nilsson, I Granrot, J Mattsson, B Omazic, M Uhlin, S Thunberg
BACKGROUND AND OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is a routine clinical procedure performed to treat patients with haematological malignancies, primary immune deficiencies or metabolic disorders. Infections during lymphopenia after allogeneic HSCT are associated with high mortality and morbidity. Typical infectious agents are Epstein-Barr virus, cytomegalovirus, herpes simplex virus, varicella-zoster virus and fungi. The study aim was to evaluate whether measurement of the responses of antigen-specific T-cells, recognizing infectious pathogens would correlate to protective functions in the stem cell recipient post-transplant...
May 2, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28459367/glioblastoma-synthesized-g-csf-and-gm-csf-contribute-to-growth-and-immunosuppression-potential-therapeutic-benefit-from-dapsone-fenofibrate-and-ribavirin
#19
Richard E Kast, Quentin A Hill, Didier Wion, Håkan Mellstedt, Daniele Focosi, Georg Karpel-Massler, Tim Heiland, Marc-Eric Halatsch
Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28456447/antithymocyte-globulins-in-renal-transplantation-from-lymphocyte-depletion-to-lymphocyte-activation-the-doubled-edged-sword
#20
REVIEW
Jamal Bamoulid, Thomas Crépin, Cécile Courivaud, Jean-Michel Rebibou, Philippe Saas, Didier Ducloux
Compelling data suggest that lymphocyte depletion following T cell depleting therapy may induce prolonged CD4 T cell lymphopenia and trigger lymphocyte activation in some patients. These profound and non-reversible immune changes in T cell pool subsets are the consequence of both impaired thymic renewal and peripheral homeostatic proliferation. Chronic viral challenges by CMV play a major role in these immune alterations. Even when the consequences of CD4 T cell lymphopenia have been now well described, recent studies shed new light on the clinical consequences of immune activation...
February 17, 2017: Transplantation Reviews
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