Malibu, CA, United States

Hughes Research Laboratory

www.hrl.com
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.

SEARCH FILTERS
Time filter
Source Type

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.


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.


Hughes-Fulford M.,Veterans Affairs Medical Center | Hughes-Fulford M.,University of California at San Francisco | Hughes-Fulford M.,Hughes Research Laboratory | Li C.,Hughes Research Laboratory
Journal of Orthopaedic Surgery and Research | Year: 2011

Introduction: The difficulty in re-growing and mineralizing new bone after severe fracture can result in loss of ambulation or limb. Here we describe the sequential roles of FGF-2 in inducing gene expression, cell growth and BMP-2 in gene expression and mineralization of bone.Materials and methods: The regulation of gene expression was determined using real-time RTPCR (qRTPCR) and cell proliferation was measured by thymidine incorporation or fluorescent analysis of DNA content in MC3T3E1 osteoblast-like cells. Photomicroscopy was used to identify newly mineralized tissue and fluorescence was used to quantify mineralization.Results: Fibroblast growth factor-2 (FGF-2) had the greatest ability to induce proliferation after 24 hours of treatment when compared to transforming growth factor beta (TGFβ, insulin-like growth factor-1 (IGF-1), bone morphogenic protein (BMP-2), platelet derived growth factor (PDGF) or prostaglandin E2(PGE2). We found that FGF-2 caused the most significant induction of expression of early growth response-1 (egr-1), fgf-2, cyclo-oxygenase-2 (cox-2), tgfβ and matrix metalloproteinase-3 (mmp-3) associated with proliferation and expression of angiogenic genes like vascular endothelial growth factor A (vegfA) and its receptor vegfr1. We found that FGF-2 significantly reduced gene expression associated with mineralization, e.g. collagen type-1 (col1a1), fibronectin (fn), osteocalcin (oc), IGF-1, noggin, bone morphogenic protein (bmp-2) and alkaline phosphatase (alp). In contrast, BMP-2 significantly stimulated expression of the mineralization associated genes but had little or no effect on gene expression associated with growth.Conclusions: The ability of FGF-2 to re-program a mineralizing gene expression profile to one of proliferation suggests that FGF-2 plays a critical role of osteoblast growth in early fracture repair while BMP-2 is instrumental in stimulating mineralization. © 2011 Hughes-Fulford and Li; licensee BioMed Central Ltd.


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.


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.


Sciascia S.,Hughes Research Laboratory | Sciascia S.,University of Turin | Khamashta M.A.,Hughes Research Laboratory | Khamashta M.A.,St Thomas Hospital | D'Cruz D.P.,St Thomas Hospital
Current Opinion in Rheumatology | Year: 2014

PURPOSE OF REVIEW: To review novel therapeutic targets that are currently under investigation to develop safer, targeted therapies for antiphsopholipid antibody (aPL)-mediated clinical manifestations. RECENT FINDINGS: Novel therapeutic options potentially available include anti-CD20 monoclonal antibodies and new-generation anticoagulants (such as direct thrombin and anti-Xa inhibitors). Research focusing on interfering with aPL-mediated cell activation, targeting complement components and the innovative concept of blocking the pathogenic subpopulation of aPL with tailored peptides are currently being explored. SUMMARY: Antiphospholipid syndrome is an autoimmune disease characterized by thrombosis and pregnancy morbidity occurring in patients persistently positive for aPL. Current therapeutic options remain confined to long-term anticoagulation with vitamin K antagonists. The future holds much promise with the identification of novel potential targets, many of which are currently under investigation. The challenge will be to design prospective randomized controlled clinical trials to provide the evidence necessary to support integration of these therapies into clinical practice. © 2014 Wolters Kluwer Health.


Sciascia S.,Hughes Research Laboratory | Sciascia S.,University of Turin | Bertolaccini M.L.,Hughes Research Laboratory | Roccatello D.,University of Turin | And 4 more authors.
Journal of Neurology | Year: 2014

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most important manifestations of SLE, and includes a variety of clinical manifestations, classified by the American College of Rheumatology in 19 different neuropsychiatric syndromes. To date, more than 116 antibodies have been reported in SLE and at least 20 of them, including 11 brain-specific and 9 systemic antibodies, have been controversially associated with NPSLE. To systematically review the available evidence, to define the association between the above antibodies and NPSLE as a whole and with the 19 neuropsychiatric syndromes associated with SLE, by strictly applying the American College Rheumatology case definitions. Medline reports published between 1999 and 2013 investigating the association between antibodies and NPSLE were included. Whenever possible, associations between antibodies and both NPSLE as a whole and with the 19 syndromes were analysed. This systematic review is based on available data from more than 8,000 patients and controls from 42 studies analysing antibodies and NPSLE. Nineteen studies analysed the role of antiphospholipid antibodies (aPL), 11 focused on anti-ribosomal-P protein antibodies and 5 on anti-N-Methyl-d-Aspartate receptor antibodies. Two studies analysed, respectively, antibodies to aquaporin-4 and VH4-34 encoded antibodies. Given the multitude of clinical manifestations related to NPSLE, a single biomarker failed to be reliably associated with all neuropsychiatric events. Our findings provide evidence that aPL, mainly the lupus anticoagulant, and anti-ribosomal P antibodies are significantly associated with specific manifestations of neuropsychiatric disease attributed to SLE, namely, cerebrovascular events and psychosis, respectively. © 2014, Springer-Verlag Berlin Heidelberg.


Sangle S.R.,Hughes Research Laboratory | Lutalo P.M.K.,Hughes Research Laboratory | Davies R.J.,Hughes Research Laboratory | Khamashta M.A.,Hughes Research Laboratory | D'Cruz D.P.,Hughes Research Laboratory
Journal of Autoimmunity | Year: 2013

Objective: To study the pregnancy outcome following Rituximab treatment before conception in patients with refractory autoimmune rheumatic diseases. Methodology: Five women with systemic lupus erythematosus (SLE) and 1 woman with ANCA positive vasculitis fulfilling the respective ACR classification criteria were studied retrospectively when they became pregnant following rituximab treatment for refractory disease. Rituximab was given as a 1g infusion together with 500mg Methylprednisolone, on day 1 and day 15 after written informed consent. Results: The median age was 34 (range 32-39) years and median disease duration was 10 (range 5-16) years. All the patients achieved complete B-cell depletion<1cell/μL at 1 month and <5cells/μL at 6 months with prolonged B-cell depletion. Four women had successful pregnancies with median gestational age of 38 (range 31-40) weeks; median weight of the new born was 3.25 (range1.17-3.3) kg with no documented adverse neonatal events. One patient with lupus nephritis (LN) had a premature delivery and increasing proteinuria in the third trimester. One other patient with LN had a premature delivery and the new born had oesophageal atresia. Conclusion: We report a child with oesophageal atresia born to a mother with lupus nephritis who hadreceived Rituximab 12 months prior to conception, while four other pregnancies in women with SLEresulted in morphologically normal children. We also describe the first report, to our knowledge, ofasuccessful pregnancy outcome in a woman with granulomatosis with polyangiitis treated with rituximab. © 2013.


PubMed | Hughes Research Laboratory
Type: | Journal: Journal of autoimmunity | Year: 2013

To study the pregnancy outcome following Rituximab treatment before conception in patients with refractory autoimmune rheumatic diseases.Five women with systemic lupus erythematosus (SLE) and 1 woman with ANCA positive vasculitis fulfilling the respective ACR classification criteria were studied retrospectively when they became pregnant following rituximab treatment for refractory disease. Rituximab was given as a 1g infusion together with 500mg Methylprednisolone, on day 1 and day 15 after written informed consent.The median age was 34 (range 32-39) years and median disease duration was 10 (range 5-16) years. All the patients achieved complete B-cell depletion<1cell/L at 1 month and <5cells/L at 6 months with prolonged B-cell depletion. Four women had successful pregnancies with median gestational age of 38 (range 31-40) weeks; median weight of the new born was 3.25 (range1.17-3.3) kg with no documented adverse neonatal events. One patient with lupus nephritis (LN) had a premature delivery and increasing proteinuria in the third trimester. One other patient with LN had a premature delivery and the new born had oesophageal atresia.We report a child with oesophageal atresia born to a mother with lupus nephritis who hadreceived Rituximab 12 months prior to conception, while four other pregnancies in women with SLEresulted in morphologically normal children. We also describe the first report, to our knowledge, ofasuccessful pregnancy outcome in a woman with granulomatosis with polyangiitis treated with rituximab.


PubMed | American University of Beirut, Hughes Research Laboratory, Lebanese American University and The Royal London Hospital
Type: Journal Article | Journal: 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.

Loading Hughes Research Laboratory collaborators
Loading Hughes Research Laboratory collaborators