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Malibu, CA, United States

HRL Laboratories , was the research arm of Hughes Aircraft. It is a dedicated research center, established in 1960, in Malibu. Currently owned by General Motors Corporation and Boeing, the research facility is housed in two large, white multi-story buildings overlooking the Pacific Ocean. Wikipedia.

Sciascia S.,Thrombosis and Haemophilia Center | Sciascia S.,University of Turin | Branch D.W.,University of Utah | Levy R.A.,State University of Rio de Janeiro | And 10 more authors.
Thrombosis and Haemostasis | Year: 2016

The use of low-dose aspirin and heparinoids has improved the pregnancy outcome in obstetric antiphospholipid syndrome (APS). However, current treatment fails in 20–30% of APS pregnancies, raising the need to explore other treatments to improve obstetrical outcome. Hydroxychloroquine (HCQ) is widely used in patients with autoimmune diseases, mainly systemic lupus erythematous (SLE), due to its anti-inflammatory, anti-aggregant and immune-regulatory properties. Evidence from in vitro and animal models suggests a potential protective effect of HCQ in obstetric APS. Pending the availability of prospective trials, we aimed to systematically review the available evidence and to assess the clinical judgment of a panel of experts regarding the use of HCQ in improving pregnancy outcome in women with antiphospholipid antibodies (aPL). Clinical data on the ability of HCQ to improve pregnancy outcome in women with aPL are very limited in the available literature. Only one cohort study evaluating maternal and fetal outcome of pregnancy in patients with SLE who were exposed to HCQ was identified. Four of 14 (29%) treated with HCQ patients had pregnancy failure, compared with six of 24 (25%) of patients not treated with HCQ. However, the effect of HCQ was not adjusted for the use of other medications such as aspirin, heparins or steroids. Selected experts were contacted by e-mail and asked to review the summary of the evidence provided by the working group and to briefly answer each of the proposed questions. Overall, the panel of experts agreed that adding HCQ could be considered in selected cases or after failure of standard treatment with aspirin and a heparin agent. Specifically, the majority of experts considered adding HCQ in specific scenarios, such as women with previous thrombosis (either arterial and/or venous), and/or with previous ischaemic placenta-mediated complications. Prospective studies are necessary before the use of HCQ during pregnancy in women with aPL should be routinely recommended for clinical practice. © Schattauer 2016. Source

Uthman I.,American University of Beirut | Noureldine M.H.A.,Lebanese American University | Berjawi A.,Lebanese American University | Skaf M.,Lebanese American University | And 3 more authors.
Lupus | Year: 2015

Multiple sclerosis (MS) and antiphospholipid syndrome (APS) share common clinical, laboratory and radiological features. We reviewed all the English papers on MS and APS published in the literature from 1965 to 2014 using PubMed and Google Scholar. We found that APS can mimic antiphospholipid antibodies (aPL)-positive MS in many ways in its clinical presentation. Nevertheless, APS diagnosis, clinical manifestations and management differ from those of MS. aPL were found in MS patients with titers ranging from 2% to 88%. The distribution and volume of lesions on magnetic resonance imaging (MRI) may help to differentiate MS from primary APS. In addition, atypical MS presentation can guide physicians toward an alternative diagnosis, especially when features of thrombosis and/or history of connective tissue disease are present. In that case, an anticoagulation trial could be worthwhile. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. Source

Punnialingam S.,Guys and St. Thomas Hospital | Khamashta M.A.,Hughes Research Laboratory
Current Rheumatology Reports | Year: 2013

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia for which anti-thrombotic medication is necessary for long-term management to reduce thrombotic risk or pregnancy morbidity. Choosing the type of pharmacological treatment, i.e. The intensity and duration of anticoagulation, depends on the severity of an individual's APS and the risk of bleeding. This article reviews the current literature on anticoagulation therapy, provides recommendations on when to initiate therapy, and suggests possible alternatives for optimisation of management. © Springer Science+Business Media New York 2013. Source

Martinez E.M.,Hughes Research Laboratory | Yoshida M.C.,Hughes Research Laboratory | Candelario T.L.T.,Hughes Research Laboratory | Hughes-Fulford M.,Hughes Research Laboratory | Hughes-Fulford M.,University of California at San Francisco
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2015

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (µg) conditions. Scientists on the ground use two models of simulated µg (sµg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true µg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true µg and sµg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sµg models provide an excellent test bed for scientists to develop baseline studies and augment true µg in spaceflight experiments. Ultimately, sµg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. © 2015 the American Physiological Society. Source

Chang T.T.,University of California at San Francisco | Walther I.,ETH Zurich | Li C.-F.,Hughes Research Laboratory | Li C.-F.,Veterans Affairs Medical Center | And 8 more authors.
Journal of Leukocyte Biology | Year: 2012

This study tested the hypothesis that transcription of immediate early genes is inhibited in T cells activated in μg. Immunosuppression during spaceflight is a major barrier to safe, long-term human space habitation and travel. The goals of these experiments were to prove that μg was the cause of impaired T cell activation during spaceflight, as well as understand the mechanisms controlling early T cell activation. T cells from four human donors were stimulated with Con A and anti-CD28 on board the ISS. An on-board centrifuge was used to generate a 1g simultaneous control to isolate the effects of μg from other variables of spaceflight. Microarray expression analysis after 1.5 h of activation demonstrated that μg- and 1g-activated T cells had distinct patterns of global gene expression and identified 47 genes that were significantly, differentially down-regulated in μg. Importantly, several key immediate early genes were inhibited in μg. In particular, transactivation of Rel/NF-κB, CREB, and SRF gene targets were downregulated. Expression of cREL gene targets were significantly inhibited, and transcription of cREL itself was reduced significantly in μg and upon anti-CD3/anti-CD28 stimulation in simulated μg. Analysis of gene connectivity indicated that the TNF pathway is a major early downstream effector pathway inhibited in μg and may lead to ineffective proinflammatory host defenses against infectious pathogens during spaceflight. Results from these experiments indicate that μg was the causative factor for impaired T cell activation during spaceflight by inhibiting transactivation of key immediate early genes. © Society for Leukocyte Biology. Source

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