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Elisabeth Salzer, Deniz Cagdas, Miroslav Hons, Emily M Mace, Wojciech Garncarz, Özlem Yüce Petronczki, René Platzer, Laurène Pfajfer, Ivan Bilic, Sol A Ban, Katharina L Willmann, Malini Mukherjee, Verena Supper, Hsiang Ting Hsu, Pinaki P Banerjee, Papiya Sinha, Fabienne McClanahan, Gerhard J Zlabinger, Winfried F Pickl, John G Gribben, Hannes Stockinger, Keiryn L Bennett, Johannes B Huppa, Loïc Dupré, Özden Sanal, Ulrich Jäger, Michael Sixt, Ilhan Tezcan, Jordan S Orange, Kaan Boztug
RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1...
October 24, 2016: Nature Immunology
Brennan S Dirk, Logan R Van Nynatten, Jimmy D Dikeakos
Viruses must continuously evolve to hijack the host cell machinery in order to successfully replicate and orchestrate key interactions that support their persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of viral persistence within the host, having plagued the human population for decades. In recent years, advances in cellular imaging and molecular biology have aided the elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis. Super-resolution imaging techniques such as stimulated emission depletion (STED) and photoactivation and localization microscopy (PALM) have been instrumental in studying viral assembly and release through both cell-cell transmission and cell-free viral transmission...
October 19, 2016: Viruses
Jason Gandhi, Gautam Dagur, Kelly Warren, Noel Smith, Sardar Ali Khan
BACKGROUND: Diabetes mellitus is a vastly prevalent metabolic disorder with escalating global health concerns. Particularly when mismanaged, chronic micro- and macrovascular complications may highly impair physiological systems while immunodeficiency disposes us to infection. OBJECTIVE: We investigate infections, localized complications, and neoplasms of the genitourinary system secondary to the chronic complications of diabetes mellitus in males and females. METHOD: A comprehensive MEDLINE® search was guided using key words relevant to diabetes mellitus and the genitourinary system...
October 19, 2016: Current Diabetes Reviews
Athanasios Tsiouris, Lynn Wilson, Rajesh B Sekar, Abeel A Mangi, James J Yun
BACKGROUND: A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. METHODS: All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed...
October 23, 2016: Journal of Cardiac Surgery
Chiara Vendramin, Siobhan McGuckin, Ferras Alwan, John-Paul Westwood, Mari Thomas, Marie Scully
BACKGROUND: Patients presenting with acute episodes of thrombotic microangiopathies (TMAs) require urgent access to plasma exchange (PEX). OctaplasLG, a solvent/detergent fresh-frozen plasma product that has undergone viral inactivation and prion reduction step, has been used in our institution since 2013, replacing Octaplas. STUDY DESIGN AND METHODS: We prospectively reviewed 981 PEX procedures where OctaplasLG was the replacement fluid in 90 patients admitted acutely with a TMA presentation within our institution from January 1, 2013, to December 31, 2015...
October 23, 2016: Transfusion
Xuewu Liang, Jie Zang, Mengyuan Zhu, Qianwen Gao, Binghe Wang, Wenfang Xu, Yingjie Zhang
Abnormalities in the JAK/STAT signaling pathway lead to many diseases such as immunodeficiency, inflammation, and cancer. Herein, we designed and synthesized a series of 4-amino-(1H)-pyrazole derivatives as potent JAKs inhibitors for cancer treatment. Results from in vitro protein kinase inhibition experiments indicated that compounds 3a-f and 11b are potent JAKs inhibitors. For example, the IC50 values of compound 3f against JAK1, JAK2, and JAK3 were 3.4, 2.2, and 3.5 nM, respectively. In cell culture experiments, compound 3f showed potent antiproliferative activity against various cell lines (PC-3, HEL, K562, MCF-7, and MOLT4) at low micromolar levels, while compound 11b showed selective cytotoxicity at submicromolar levels against HEL (IC50: 0...
October 13, 2016: ACS Medicinal Chemistry Letters
Daisuke Ikeda, Makiko Sugawa, Kazuo Kawahara
Nucleic acid amplification test (NAT), which was introduced by the Japanese Red Cross Society in October 1999, began to be performed for screening of blood transfusion formulations in Japan in August 2014. In this study, the precision of immunological screenings of hepatitis B (HBsAg, HBcAb, and HBsAb), hepatitis C (HCVAb), and human immunodeficiency (HIVAb) virus antigens in donated blood were evaluated. In addition, the sensitivity of the alanine aminotransferase (ALT) test for detection of the hepatitis B and C viruses was re-evaluated...
2016: Journal of Medical and Dental Sciences
Juan Sebastián Saavedra, Sebastián Urrego, María Eugenia Toro, Carlos Santiago Uribe, Jenny García, Olga Hernández, Juan Carlos Arango, Ángela Beatriz Pérez, Andrés Franco, Isabel Cristina Vélez, Helena Del Corral
OBJECTIVE: To determine the diagnostic accuracy of Thwaites Index (TI) in a Colombian population to distinguish meningeal tuberculosis (MTB) from bacterial meningitis (BM) and from non-tuberculous meningitis. Exploratory analyses were conducted to assess the TI's validity for patients with human immunodeficiency virus (HIV) and children above six-years-old. METHODS: The study included 527 patients, the TI was calculated and results compared with those of a reference standard established by expert neurologists...
November 15, 2016: Journal of the Neurological Sciences
Kathleen O Degnan, Emily A Blumberg
Patients infected with human immunodeficiency virus (HIV) are living longer, healthier lives on highly active antiretroviral therapy and, as a result, interest in kidney transplantation for HIV-infected patients with end-stage renal disease has increased. HIV is no longer considered a contraindication to solid-organ transplantation and the number of kidney transplants performed in HIV-infected patients each year is increasing steadily. HIV-infected kidney transplant recipients have had excellent outcomes overall, but there are still significant challenges, including high rates of acute rejection, drug-drug interactions, and poor outcomes in patients co-infected with hepatitis C virus...
September 2016: Seminars in Nephrology
D Mantas, C Damaskos, P Dailiani, M Samarkos, P Korkolopoulou
INTRODUCTION: Castleman's disease (CD), also known as giant or angiofolicular lymphoid hyperplasia or lymphoid hamartoma, is a group of atypical lymphoproliferative disorders that share common lymph node histological features and may be localized either to a single lymph node (unicentric) or occur systemically (multicentric). PATIENT AND METHOD: Herein, we present a rare case of a of 75-year-old female patient who was referred to our department and after a thorough work-up, underwent splenectomy with synchronous resection of an accessory spleen, splenic artery lymph nodes, and splenic hilar lymph nodes due to splenic involvement in a multicentric CD...
October 24, 2016: Acta Chirurgica Belgica
David M Stoff, Deborah Colosi, Anna Rubtsova, Gina Wingood
This paper reviews some background issues as a foundation to place the ensuing supplement papers of this special issue section in context. The articles in this special supplement issue deepen and expand our understanding of biomedical, neurocognitive, and psychosocial aspects involved in human immunodeficiency virus (HIV) of older women, primarily through the use of the Women's Interagency HIV Study (WIHS) prospective cohort study. As it relates to research on the intersection between HIV and aging in women, we discuss (i) epidemiology as introduction, (ii) the cohort study design featuring the WIHS, (iii) definitions, (iv) models, and (v) section articles...
October 22, 2016: Current HIV/AIDS Reports
Tian Loon Lee, Rupesh Agrawal, Jackie Yu-Ling Tan, Kiat Hoe Ong, Chen Seong Wong, Su Ling Ho
BACKGROUND: Nontuberculous mycobacteria (NTM) are found ubiquitously in the environment. Since exposure to NTM is universal, infection likely represents underlying host susceptibility factors. Anti-IFN-ɣ autoantibodies have been described previously in patients with NTM. Up to 88 % of patients with disseminated NTM or other opportunistic infections have high-titer anti-IFN-ɣ autoantibodies, compared with 2 % of patients with TB and healthy controls. FINDINGS: We report a unique presentation of a patient with anti-IFN-ɣ autoantibodies with disseminated NTM infection who presents with panuveitis with multifocal retinitis and vasculitis...
December 2016: Journal of Ophthalmic Inflammation and Infection
Rafael Conceição de Souza, Gabriela de Medeiros Muniz, Andrei Santos Siqueira, Adonis de Melo Lima, Alessandra Pereira da Silva, Evonnildo Costa Gonçalves, João Lídio da Silva Gonçalves Vianez Júnior
Human immunodeficiency virus (HIV) infections continue to exert an enormous impact on global human health. This led experts to emphasize the importance of new measures for preventing HIV infections, including the development of vaccines and novel drugs. In this context, a promising approach involves the use of lectins that can bind the surface envelope glycoprotein gp120 of HIV with high affinity, preventing viral entry. The cyanobacterial lectin microvirin (MVN) has been proposed as a candidate for development as a topical microbicide because of its ability to bind to high mannose-type glycans, potently inhibiting HIV-1 entry...
November 2016: Journal of Molecular Modeling
Shakil Shaikh, Ira Shah
No abstract text is available yet for this article.
September 8, 2016: Indian Pediatrics
Goran Cuturilo, Danijela Drakulic, Ida Jovanovic, Aleksandar Krstic, Milan Djukic, Dejan Skoric, Marija Mijovic, Igor Stefanovic, Milena Milivojevic, Milena Stevanovic
OBJECTIVE: The incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome. DESIGN: Prospective study. SETTING: University Childrens Hospital in Belgrade, Serbia between 2005 and 2014. PARTICIPANTS: 57 patients with clinical characteristics of 22q11.2 deletion syndrome. METHODS: Standard G-banding cytogenetic analysis was performed in all children, and the 22q11...
September 8, 2016: Indian Pediatrics
Deepti Suri, Sagar Bhattad, Anju Gupta, Amita Trehan, Deepak Bansal, Arvind Rajwanshi, Ashim Das, Amit Rawat, Surjit Singh
BACKGROUND: With improved survival in children living with human immunodeficiency virus (HIV) infection (CLHIV), malignancies are being increasingly recognized. PATIENTS AND METHODS: Among the CLHIV registered at our institute from January 1994 to March 2015, children with malignancy were analysed in detail. RESULTS: In total, 734 children affected by HIV were registered. Out of these, 11 children (9 boys, 2 girls) were diagnosed to have malignancy...
October 22, 2016: Journal of Tropical Pediatrics
Ameya R Kirtane, Robert Langer, Giovanni Traverso
The human immunodeficiency virus has infected millions of people and the epidemic continues to grow rapidly in some parts of the world. Antiretroviral (ARV) therapy has provided improved treatment and prolonged the life expectancy of patients. Moreover, there is growing interest in using ARVs to protect against new infections. Hence, ARVs have emerged as our primary strategy in combating the virus. Unfortunately, several challenges limit the optimal performance of these drugs. First, ARVs often require life-long use and complex dosing regimens...
October 19, 2016: Journal of Pharmaceutical Sciences
Wai Jia Tam, Philip Yap
Approximately two-thirds of the world's older adults live in developing nations. By 2050, as many as 80% of such older people will live in low- and middle-income countries. In sub-Saharan Africa alone, the number of individuals aged 60 and older is projected to reach 163 million. Despite this demographic wave, the majority of Africa has limited access to qualified geriatric health care.(3) Although foreign aid and capacity-building efforts can help to close this gap over time, it is likely that failure to understand the unique context of Africa's older adults, many of whom are marginalized, will lead to inadequacies in service delivery and poor health outcomes...
October 22, 2016: Journal of the American Geriatrics Society
Sofia Morfopoulou, Edward T Mee, Sarah M Connaughton, Julianne R Brown, Kimberly Gilmour, W K 'Kling' Chong, W Paul Duprex, Deborah Ferguson, Mike Hubank, Ciaran Hutchinson, Marios Kaliakatsos, Stephen McQuaid, Simon Paine, Vincent Plagnol, Christopher Ruis, Alex Virasami, Hong Zhan, Thomas S Jacques, Silke Schepelmann, Waseem Qasim, Judith Breuer
Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines...
October 21, 2016: Acta Neuropathologica
Mark E Westman, Richard Malik, Evelyn Hall, Matthew Harris, Margaret J Hosie, Jacqueline M Norris
OBJECTIVES: Recently, two point-of-care (PoC) feline immunodeficiency virus (FIV) antibody test kits (Witness and Anigen Rapid) were reported as being able to differentiate FIV-vaccinated from FIV-infected cats at a single time point, irrespective of the gap between testing and last vaccination (0-7 years). The aim of the current study was to investigate systematically anti-FIV antibody production over time in response to the recommended primary FIV vaccination series. METHODS: First, residual plasma from the original study was tested using a laboratory-based ELISA to determine whether negative results with PoC testing were due to reduced as opposed to absent antibodies to gp40...
October 21, 2016: Journal of Feline Medicine and Surgery
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