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https://www.readbyqxmd.com/read/28216187/recombinant-proteins-of-zaire-ebolavirus-induce-potent-humoral-and-cellular-immune-responses-and-protect-against-live-virus-infection-in-mice
#1
Axel T Lehrer, Teri-Ann S Wong, Michael M Lieberman, Tom Humphreys, David E Clements, Russell R Bakken, Mary Kate Hart, William D Pratt, John M Dye
Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death...
February 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28214184/-systemic-lupus-erythematosus-and-lymphopenia-clinical-and-pathophysiological-features
#2
M Martin, A Guffroy, X Argemi, T Martin
Lymphopenia is frequent in systemic lupus erythematosus (SLE) and profound (<500/mm(3)) in 10% of cases. T lymphocytes, especially CD4+, are more affected than B cells. The pathophysiological mechanisms are complex, involving lymphocytotoxic antibodies, excess of apoptosis, increased susceptibility of T cells to complement mediated cytolysis, as well as lymphopoiesis impairment and lymphocyte sequestration. Lymphopenia in SLE is independent from other cytopenia and immunosuppressive drug regiments, and associated with disease activity, risk of flare and damage scores...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28204914/salvage-therapy-with-bendamustine-for-temozolomide-refractory-recurrent-anaplastic-gliomas-a-prospective-phase-ii-trial
#3
Marc C Chamberlain, Howard Colman, Bryan T Kim, Jeffrey Raizer
There is no standard therapy for recurrent anaplastic glioma (AG). Salvage therapies include alkylator-based chemotherapy, re-resection with or without carmustine implants, re-irradiation and bevacizumab. Bendamustine is a novel bifunctional alkylator with CNS penetration never previously evaluated in AG. Assess response and toxicity of bendamustine in recurrent AG in a phase II trial. Adults with radiation and temozolomide refractory recurrent AG were treated with bendamustine. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m(2)/day) administered once every 4 weeks...
February 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28181505/parp-1-parp-2-double-deficiency-in-mouse-t-cells-results-in-faulty-immune-responses-and-t-lymphomas
#4
Judith Navarro, Beatriz Gozalbo-López, Andrea C Méndez, Françoise Dantzer, Valérie Schreiber, Carlos Martínez, David M Arana, Jordi Farrés, Beatriz Revilla-Nuin, María F Bueno, Coral Ampurdanés, Miguel A Galindo-Campos, Philip A Knobel, Sandra Segura-Bayona, Juan Martin-Caballero, Travis H Stracker, Pedro Aparicio, Margarita Del Val, José Yélamos
The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4(+) and CD8(+) T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179378/the-human-immune-response-to-respiratory-syncytial-virus-infection
#5
REVIEW
Clark D Russell, Stefan A Unger, Marc Walton, Jürgen Schwarze
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8)...
April 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28178716/invasive-haemophilus-influenzae-infection-in-patients-with-cancer
#6
Vivek Singh, Sowmya Nanjappa, Smitha Pabbathi, John N Greene
A major cause of morbidity and mortality in patients with cancer is infection. Since the introduction of the Haemophilus influenzae type b (Hib) vaccine in the United States in the 1990s, invasive H influenzae infection has become less common. We report on 5 patients with cancer and invasive H influenzae infection. A literature review was also performed of the dominant Haemophilus subtype and the clinical features associated with the infection and concomitant cancer. Of the 17 cases found in the literature, had hematological malignancies and 1 case each had thymoma, schwannoma, teratoma, and pancreatic, Merkel cell, pharyngeal, laryngeal, and rectal carcinomas...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28173871/characterization-and-pathogenesis-of-aerosolized-eastern-equine-encephalitis-in-the-common-marmoset-callithrix-jacchus
#7
Aimee I Porter, Rebecca A Erwin-Cohen, Nancy Twenhafel, Taylor Chance, Steven B Yee, Steven J Kern, David Norwood, Laurie J Hartman, Michael D Parker, Pamela J Glass, Luis DaSilva
BACKGROUND: Licensed antiviral therapeutics and vaccines to protect against eastern equine encephalitis virus (EEEV) in humans currently do not exist. Animal models that faithfully recapitulate the clinical characteristics of human EEEV encephalitic disease, including fever, drowsiness, anorexia, and neurological signs such as seizures, are needed to satisfy requirements of the Food and Drug Administration (FDA) for clinical product licensing under the Animal Rule. METHODS: In an effort to meet this requirement, we estimated the median lethal dose and described the pathogenesis of aerosolized EEEV in the common marmoset (Callithrix jacchus)...
February 7, 2017: Virology Journal
https://www.readbyqxmd.com/read/28160213/a-multicenter-single-arm-phase-ii-clinical-trial-of-bendamustine-monotherapy-in-patients-with-chronic-lymphocytic-leukemia-in-japan
#8
Yoshiaki Ogawa, Koji Izutsu, Toru Kiguchi, Ilseung Choi, Yoshifusa Takatsuka, Kiyoshi Ando, Junji Suzumiya
The present study was intended to examine the efficacy and safety of bendamustine monotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL) for whom treatment with fludarabine (FLU) was not suitable, and in FLU-naïve patients with relapsed/refractory CLL. We intravenously administered bendamustine 100 mg/m(2)/day on days 1 and 2 of each 28-day cycle to 10 patients (eight previously untreated; two relapsed/refractory) up to six cycles. The primary endpoint was overall response rate (ORR: partial remission or better) according to the 2008 International Workshop on the CLL guidelines...
February 3, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28159165/viral-pneumonia-in-patients-with-hematologic-malignancy-or-hematopoietic-stem-cell-transplantation
#9
REVIEW
Erik Vakil, Scott E Evans
Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses...
March 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28154551/prolonged-activation-of-invariant-natural-killer-t-cells-and-th2-skewed-immunity-in-stroke-patients
#10
Connie H Y Wong, Craig N Jenne, Patrick P Tam, Caroline Léger, Andres Venegas, Karla Ryckborst, Michael D Hill, Paul Kubes
BACKGROUND: Infection is highly prevalent and contribute significantly to mortality of stroke patients. In addition to the well described robust systemic lymphocytopenia and skewed T helper 2 (TH2)-immunity after stroke, emerging experimental evidence demonstrate that the development of infection poststroke is attributed by the activation of invariant natural killer T (iNKT) cells. In this prospective study, we examined the levels of a broad spectrum of inflammatory mediators, the activation status of iNKT cell in the blood of patients with various degree of stroke severity, and investigate whether these parameters differ in patients who later develop poststroke infections...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28153824/brincidofovir-is-highly-efficacious-in-controlling-adenoviremia-in-pediatric-recipients-of-hematopoietic-cell-transplant
#11
Prashant Hiwarkar, Persis Amrolia, Ponni Sivaprakasam, Su Han Lum, Hemalatha Doss, Ciara O'Rafferty, Toni Petterson, Katharine Patrick, Juliana Silva, Mary Slatter, Sarah Lawson, Kanchan Rao, Colin Steward, Adam Gassas, Paul Veys, Robert Wynn
Cidofovir is pre-emptively used for controlling adenoviremia and preventing disseminated viral disease in hematopoietic cell transplant (HCT) recipients but does not lead to resolution of viremia without T-cell immune-reconstitution. The lipid conjugated prodrug of Cidofovir, Brincidofovir, has improved oral bioavailability and achieves higher intracellular concentrations of active drug. We present retrospective multicentre data comparing the kinetics of viremia and toxicities following pre-emptive treatment with Cidofovir and Brincidofovir in children and adolescents diagnosed with HCT-related adenoviremia...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/28137643/mlf1-is-a-proapoptotic-antagonist-of-hop-complex-mediated-survival
#12
Yi Sun, Jyh-Rong Chao, Wu Xu, Alan Pourpak, Kelli Boyd, Simon Moshiach, Guo-Yan Qi, Amina Fu, Hua-Rong Shao, Stanley Pounds, Stephan W Morris
In the HAX1/HtrA2-OMI/PARL (HOP) mitochondrial protein complex, anti-apoptotic signals are generated by cleavage and activation of the serine protease HtrA2/OMI by the rhomboid protease PARL upon recruitment of both proteases to inner mitochondrial membrane protein HAX1 (HS1-associated protein X-1). Here we report the negative regulation of the HOP complex by human leukemia-associated myeloid leukemia factor 1 (MLF1). We demonstrate that MLF1 physically and functionally associates with HAX1 and HtrA2. Increased interaction of MLF1 with HAX1 and HtrA2 displaces HtrA2 from the HOP complex and inhibits HtrA2 cleavage and activation, resulting in the apoptotic cell death...
January 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28128086/vesicular-contact-reaction-may-progress-into-erythema-multiforme
#13
Magdalena Czarnecka-Operacz, Dorota Jenerowicz, Joanna Szulczyńska-Gabor, Ewa Teresiak-Mikołajczak, Joanna Szyfter-Harris, Monika Bowszyc-Dmochowska
Dear Editor, Erythema multiforme is considered an acute skin condition, characterized by a self-limiting and sometimes recurrent course. It is regarded as a type IV hypersensitivity reaction associated with certain infections, medications, and other various triggers. Allergic contact dermatitis is in turn a delayed type of induced allergy as a result of cutaneous contact with a specific allergen to which the patient develops specific sensitivity. This type of cutaneous reaction is associated with inflammation manifesting with erythema, edema, and vesicles...
December 2016: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28120567/lower-respiratory-tract-diseases-caused-by-common-respiratory-viruses-among-stem-cell-transplantation-recipients-a-single-center-experience-in-korea
#14
Kyung Wook Hong, Su Mi Choi, Dong Gun Lee, Sung Yeon Cho, Hyo Jin Lee, Jae Ki Choi, Si Hyun Kim, Sun Hee Park, Jung Hyun Choi, Jin Hong Yoo, Jong Wook Lee
PURPOSE: To describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (LRDs) caused by common respiratory viruses (CRVs) in stem cell transplantation (SCT) recipients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 1038 patients who received SCT between January 2007 and August 2011 at a single center in Korea. RESULTS: Seventy-one CRV-LRDs were identified in 67 (6...
March 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28120234/ataxia-telangiectasia-in-turkey-multisystem-involvement-of-91-patients
#15
Hacer Akturk, Murat Sutcu, Ayper Somer, Sanem Piskin, Manolya Acar, Meral Ozmen, Umut Altinoglu, Burak Tatli, Nuran Salman
BACKGROUND: Ataxia telangiectasia (AT) is a genetically based multisystemic disorder. We aimed to make a comprehensive evaluation of multisystem involvement in AT by describing clinical features and outcome of 91 patients. METHODS: Medical records of the patients who were diagnosed and followed by a multidisciplinary approach during a 27-year period (1988-2015) were reviewed retrospectively. RESULTS: Forty six female and 45 male patients with a mean follow-up period of 39...
January 25, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28118538/peficitinib-a-jak-inhibitor-in-combination-with-limited-conventional-synthetic-dmards-in-the-treatment-of-moderate-to-severe-rheumatoid-arthritis
#16
Mark C Genovese, Maria Greenwald, Christine Codding, Anna Zubrzycka-Sienkiewicz, Alan J Kivitz, Annie Wang, Kathyjo Shay, Xuegong Wang, Jay P Garg, Mario H Cardiel
OBJECTIVE: To evaluate the efficacy and safety of orally administered once-daily peficitinib in patients with moderate-to-severe rheumatoid arthritis (RA) in combination with limited conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). METHODS: In this double-blind, randomized, phase IIb trial, patients with RA (N=289) were treated with peficitinib 25 mg, 50 mg, 100 mg, 150 mg, or matching placebo once daily for 12 weeks. Primary endpoint was the percentage of patients achieving an American College of Rheumatology (ACR) 20% response at Week 12...
January 24, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28109627/a-final-report-of-a-phase-i-study-of-veliparib-abt-888-in-combination-with-low-dose-fractionated-whole-abdominal-radiation-therapy-ldfwar-in-patients-with-advanced-solid-malignancies-and-peritoneal-carcinomatosis-with-a-dose-escalation-in-ovarian-and-fallopian
#17
Kim A Reiss, Joseph M Herman, Deborah Armstrong, Marianna Zahurak, Anthony Fyles, Anthony Brade, Michael Milosevic, Laura A Dawson, Angela Scardina, Patricia Fischer, Amy Hacker-Prietz, Robert J Kinders, Lihua Wang, Alice Chen, Sarah Temkin, Naomi Horiba, Lee-Anne Stayner, Lillian L Siu, Nilofer S Azad
BACKGROUND: The combination of low-dose radiation therapy with PARP inhibition enhances anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with ABT-888 in patients with peritoneal carcinomatosis with a dose escalation in ovarian and fallopian cancer patients (OV). METHODS: Patients were treated with veliparib, 40-400mg orally BID on days 1-21 of 3 28-day cycles on 6 dose levels. Dose levels 5 and 6 included only OV patients...
January 18, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28109013/investigation-of-genetic-defects-in-severe-combined-immunodeficiency-patients-from-turkey-by-targeted-sequencing
#18
Baran Erman, Ivan Bilic, Tatjana Hirschmugl, Elisabeth Salzer, Heidrun Boztug, Özden Sanal, Deniz Çağdaş Ayvaz, Ilhan Tezcan, Kaan Boztug
Primary immunodeficiencies (PIDs) represent a large group of disorders with an increased susceptibility to infections. Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) with marked T-cell lymphopenia. Investigation of the genetic etiology using classical Sanger sequencing is associated with considerable diagnostic delay. We here established a custom-designed, next generation sequencing-based panel to efficiently identify disease-causing genetic defects in PID patients and applied this method in SCID patients of Turkish origin with previously undefined genetic etiology...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28095350/progressive-multifocal-leukoencephalopathy-in-a-patient-with-systemic-mastocytosis-treated-with-cladribine
#19
Karl B Alstadhaug, Randi Fykse Halstensen, Francis Odeh
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the human polyomavirus JC (JCPyV). A particular problem with the drug cladribine seems to be prolonged suppression of the CD4+ T-cells, a well-known risk factor for PML. CASE DESCRIPTION: A 67-year-old male presented with a 3-weeks history of unsteady gait, dysarthria and a dysfunctional right arm. Seven years earlier, he had been diagnosed with urticaria pigmentosa, and 2 years later aggressive systemic mastocytosis...
March 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28093780/subacute-demyelinating-polyradiculoneuropathy-complicating-epstein-barr-virus-infection-in-gata2-haploinsufficiency
#20
Mohamed Kazamel, Christopher J Klein, Eduardo E Benarroch, Mrinal M Patnaik, Jennifer A Tracy
INTRODUCTION: Autosomal dominant haploinsufficiency of GATA2 causes monocytopenia and natural killer cell lymphopenia, resulting in predisposition to mycobacterial, fungal, and viral infections. METHODS: We report clinical, serologic, electrophysiologic, and pathologic evaluation of a 29-year-old woman with GATA2 haploinsufficiency and active Epstein-Barr virus (EBV) infection complicated by subacute painful neuropathy. RESULTS: Nerve conduction and electromyography studies showed predominantly demyelinating sensorimotor polyradiculoneuropathy...
January 17, 2017: Muscle & Nerve
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