Ecole d’été de probabilités de Saint-Flour XXXII

CERN Document Server

2004-01-01

This is yet another indispensable volume for all probabilists and collectors of the Saint-Flour series, and is also of great interest for mathematical physicists. It contains two of the three lecture courses given at the 32nd Probability Summer School in Saint-Flour (July 7-24, 2002). Boris Tsirelson's lectures introduce the notion of nonclassical noise produced by very nonlinear functions of many independent random variables, for instance singular stochastic flows or oriented percolation. Two examples are examined (noise made by a Poisson snake, the Brownian web). A new framework for the scaling limit is proposed, as well as old and new results about noises, stability, and spectral measures. Wendelin Werner's contribution gives a survey of results on conformal invariance, scaling limits and properties of some two-dimensional random curves. It provides a definition and properties of the Schramm-Loewner evolutions, computations (probabilities, critical exponents), the relation with critical exponents of planar...

Epidemiologi ved systemisk lupus erythematosus (SLE

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Inge-Margrethe Gilboe

2009-10-01

Full Text Available Det er utført få epidemiologiske studier av SLE i Norge. De studier som er utført viser liknende hyppighet og forekomst av SLE i Norge som i de øvrige nordiske land og forekomst av mild sykdom med en lav andel av alvorlig indre organ manifestasjoner. Insidens og prevalens er kartlagt i Nord-Norge visende en lavere insidens enn i de øvrige nordiske land, mens prevalensen er sammenliknbar. Tall fra Sverige tyder på stabil insidens, men økende prevalens, forenelig med økt overlevelse. Norske og nordiske studier viser høy kvinneandel og sammenliknbar alder ved diagnose. Studiene tyder på en høyere alder ved diagnose i Skandinavia enn i USA og England. Ut fra de nordiske studier er overlevelsen ved SLE god, selv om den er lavere enn i den generelle befolkningen. Overlevelse i de nordiske og europeiske land er sammenliknbare.Selv om overlevelsen ved SLE er betydelig bedret over tid utgjorde aktiv SLE og infeksjoner 50% av dødsårsakene i den danske mortalitetsstudien. Aterosklerotisk hjerte-karsykdom var en hyppig dødsårsak i alle studiene. Kardiovaskulær sykdom som hovedårsak til død ved SLE er påvist i den store internasjonale studien hvor pasienter fra Island og Sverige deltok og i andre europeiske og internasjonale studier. Betydelig økt risiko for hjerteinfarkt hos unge SLE-kvinner i Sverige er også påvist tidligere i internasjonale studier og styrker teorien om at SLE per ce er en selvstendig risikofaktor for aterosklerose. Det er ønskelig med flere epidemiologiske studier av SLE i Norge.There has been few studies on the epidemiology of SLE in Norway. The studies that have been conducted show similar frequency and occurence of SLE in Norway in comparison to the other Nordic countries, and mainly occurence of mild disease with only a low proportion suffering severe internal organ involvement. Studies on incidence and prevalence in the northern part of Norway show a lower incidence than in other Nordic countries, but a

Dimension of the SLE Light Cone, the SLE Fan, and SLE_κ(ρ) for κ \\in (0,4) and ρ \\in \\big[{κ/2}-4,-2\\big

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Miller, Jason

2018-02-01

Suppose that h is a Gaussian free field (GFF) on a planar domain. Fix {κ \\in (0,4)} . The {SLE_κ} light cone L {(θ)} of h with opening angle {θ \\in [0,π]} is the set of points reachable from a given boundary point by angle-varying flow lines of the (formal) vector field {e^{ih/χ}} , {χ = {2}/{√{κ}} - {√{κ}}/{2}} , with angles in [-{θ}/{2},{θ}/{2}]. We derive the Hausdorff dimension of L {(θ)} . If {θ =0} then L {(θ)} is an ordinary {SLE_{κ}} curve (with {κ 4} ). In these extremes, this leads to a new proof of the Hausdorff dimension formula for {SLE} . We also consider {SLE_κ(ρ)} processes, which were originally only defined for {ρ > - 2} , but which can also be defined for {ρ ≤ -2} using Lévy compensation. The range of an {SLE_κ(ρ)} is qualitatively different when {ρ ≤ -2} . In particular, these curves are self-intersecting for {κ fan is the same as that of ordinary {SLE_κ}.

Hypothyroidism among SLE patients: Case-control study.

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Watad, Abdulla; Mahroum, Naim; Whitby, Aaron; Gertel, Smadar; Comaneshter, Doron; Cohen, Arnon D; Amital, Howard

2016-05-01

The prevalence of hypothyroidism in SLE patients varies considerably and early reports were mainly based on small cohorts. To investigate the association between SLE and hypothyroidism. Patients with SLE were compared with age and sex-matched controls regarding the proportion of hypothyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. The study included 5018 patients with SLE and 25,090 age and sex-matched controls. The proportion of hypothyroidism in patients with SLE was increased compared with the prevalence in controls (15.58% and 5.75%, respectively, Phypothyroidism (odds ratio 2.644, 95% confidence interval 2.405-2.908). Patients with SLE have a greater proportion of hypothyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of the possibility of thyroid dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

Dicty_cDB: SLE232 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SL (Link to library) SLE232 (Link to dictyBase) - - - Contig-U16255-1 SLE232F (Link... to Original site) SLE232F 614 - - - - - - Show SLE232 Library SL (Link to library) Clone ID SLE232 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16255-1 Original site URL http://dict...PSSGFTDFIPSNATCSSLNCNAQQMSCKYVQQACHETSCCPDIPQC QIPATGGGPATGSATGQGTSGGTPGSCDKVNCPNGYICTIVNQLAVCVSPSSSSSSSSST ...CHETSCCPDIPQC QIPATGGGPATGSATGQGTSGGTPGSCDKVNCPNGYICTIVNQLAVCVSPSSSSSSSSST TGSHTTTGGSTTGSHTTTGGSTTGSHTTTGGSA

Psychiatric disorders in systemic lupus erythematosus (SLE: a serious SLE-related crime

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Gabriele Nicolosi

2013-04-01

Full Text Available Introduction: Systemic lupus erythematosus (SLE is associated with CNS disorders in 50-90% of all cases. Thus far 19 neuropsychiatric syndromes have been reported in association with SLE, and many others will be added to this list in the future. Long-term observation and use of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (Text Revision is the solution for a correct diagnosis. Case report: The patient was an 18-year-old woman who had been charged with the attempted murder of an elderly woman in the latter’s home. According to the victim’s testimony, the young woman had entered the victim’s home under pretence and suddently attacked her with a hammer. The young woman denied all knowledge of the event. A few days after her arrest the patient was hospitalized for attempted suicide. The work-up that began with this hospitalization led to the diagnosis of an intermittent explosive disorder secondary to SLE. The authors analyze this case from the psychiatric, medical, and legal points of view. Conclusions: This is the first report of this type of disorder is a patient with SLE. The authors suggest that intermittent explosive disorder should be added to the list of neuropsychiatric syndromes associated with this disease.

Dicty_cDB: SLE110 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SL (Link to library) SLE110 (Link to dictyBase) - - - Contig-U16520-1 SLE110E (Link... to Original site) - - - - - - SLE110E 237 Show SLE110 Library SL (Link to library) Clone ID SLE110 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16520-1 Original site URL http://dict...NLSEDVNLEEFVMSKDDLSGADIKAICTESGLLALRERRMRVTYXDFKKAKEKVLYR KTAGAPEGLYM*kkknqnq Translated Amino Acid sequence... (All Frames) Frame A: AKMNLSEDVNLEEFVMSKDDLSGADIKAICTESGLLALRERRMRVTYXDFKKAKEKVL

The Spaces of Functions of Two Variables of Bounded κΦ-Variation in the Sense of Schramm-Korenblum

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A. Azócar

2015-01-01

Full Text Available The purpose of this paper is twofold. Firstly, we introduce the concept of bounded κΦ-variation in the sense of Schramm-Korenblum for real functions with domain in a rectangle of R2. Secondly, we study some properties of these functions and we prove that the space generated by these functions has a structure of Banach algebra.

Haemorrhagic SLE In A Young Male

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Rajagopal R

2002-01-01

Full Text Available Systemic lupus erythematous (SLE is a systemic autoimmune disease that tends to occur in early adult life. The peak age of onset of the first symptom or sign in females is about 38 years and later in men, at about 44 years. Females outnumber men in this illness in a ratio of about 8 : 1. Cutaneous lesions in male have not been properly investigated and some studies in male with SLE have shown that the illness may present with atypical skin lesions. A case of SLE in a 20 year male who developed sudden onset of haemorrhagic vesiculobullous butterfly rash is described.

Multi-User Space Link Extension (SLE) System

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Perkins, Toby

2013-01-01

The Multi-User Space (MUS) Link Extension system, a software and data system, provides Space Link Extension (SLE) users with three space data transfer services in timely, complete, and offline modes as applicable according to standards defined by the Consultative Committee for Space Data Systems (CCSDS). MUS radically reduces the schedule, cost, and risk of implementing a new SLE user system, minimizes operating costs with a lights-out approach to SLE, and is designed to require no sustaining engineering expense during its lifetime unless changes in the CCSDS SLE standards, combined with new provider implementations, force changes. No software modification to MUS needs to be made to support a new mission. Any systems engineer with Linux experience can begin testing SLE user service instances with MUS starting from a personal computer (PC) within five days. For flight operators, MUS provides a familiar-looking Web page for entering SLE configuration data received from SLE. Operators can also use the Web page to back up a space mission's entire set of up to approximately 500 SLE service instances in less than five seconds, or to restore or transfer from another system the same amount of data from a MUS backup file in about the same amount of time. Missions operate each MUS SLE service instance independently by sending it MUS directives, which are legible, plain ASCII strings. MUS directives are usually (but not necessarily) sent through a TCP-IP (Transmission Control Protocol Internet Protocol) socket from a MOC (Mission Operations Center) or POCC (Payload Operations Control Center) system, under scripted control, during "lights-out" spacecraft operation. MUS permits the flight operations team to configure independently each of its data interfaces; not only commands and telemetry, but also MUS status messages to the MOC. Interfaces can use single- or multiple-client TCP/IP server sockets, TCP/IP client sockets, temporary disk files, the system log, or standard in

A case of brain SLE: MRI findings

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Kim, Myung Soon; Kim, Seung Min [Wonju College of Medicine, Yonsei University, Wonju (Korea, Republic of)

1992-01-15

Systemic lupus erythematosus(SLE) is an autoimmune disease characterized by multisystem involvement including central nervous system and various neurologic symptoms. The authors experienced a case of brain SLE and report MRI and other neuroimaging findings.

Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

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das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

2016-04-01

The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality. © The Author(s) 2015.

The SLE heart in scintigraphic diagnostics

International Nuclear Information System (INIS)

Rottensteiner, J.

2001-01-01

Investigation of SLE-heart of 14 patients with 201Ti-SPECT and 18 FDG-SPECT and comparison with clinical and laboratory parameters. Results: SLE-patients with unspecific heart symptoms show in spite of sufficiently perfusion in 201Ti-SPECT considerable defects in 18-FDG. Interpretation: cause of the defects in FDG in a disturbed glucose metabolism independent of perfusion. (boteke)

Disease characterization of systemic lupus erythematosus (SLE) patients in Quebec.

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Ng, R; Bernatsky, S; Rahme, E

2017-08-01

Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an array of organ manifestations that can appear during flares and disappear during remissions. The objectives of this study were: (i) to examine SLE manifestation groups longitudinally in an SLE cohort; and (ii) to assess the association between early antimalarial treatment and renal manifestations. Methods Seven SLE manifestation groups-cutaneous, hematologic, lung, musculoskeletal, neuropsychiatric, serositis, renal-were tracked using Kaplan-Meier survival curves in an incident SLE cohort from Quebec health administrative data ( n = 2010). A subgroup with provincial drug insurance coverage was followed over time to examine the association between early antimalarial treatment (within three months after SLE diagnosis) and renal manifestations using a Cox proportional hazards survival model. Results Cutaneous manifestations was the most common manifestation at SLE diagnosis (30.0%, 95% CI: 27.7-32.2%). About two-thirds (66.2%, 95% CI: 63.4-68.9%) of patients had evidence of at least one SLE manifestation at diagnosis, which increased to 87.2% (95% CI: 84.2-90.3%) by the end of follow-up. After adjusting for age, sex, early concomitant systemic steroid therapy, Charlson comorbidity index, primary care visits in the year prior and other SLE manifestations at baseline, no statistically significant association was established between antimalarial therapy and renal manifestations. Conclusion This study provides insight regarding organ manifestations within a population-based sample. Most patients identified with SLE had other diagnostic evidence that supports an underlying diagnosis of SLE. No protective effects for antimalarial agents against renal manifestations could be established in this population-based cohort.

Baseline Retinal Examinations among SLE Patients Newly Initiating Hydroxychloroquine in a U.S. Medicaid SLE Population, 2000-2010.

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Lin, Tzu-Chieh; Marmor, Michael F; Barbhaiya, Medha; Guan, Hongshu; Chen, Sarah K; Feldman, Candace H; Costenbader, Karen H

2018-02-06

Baseline retinal examination has long been recommended at hydroxychloroquine (HCQ) initiation, but it is unknown how well this guideline is followed. We investigated baseline eye examinations among U.S. Medicaid SLE patients initiating HCQ. Using billing codes, we identified SLE patients aged 18-65 enrolled in Medicaid, residing in the 29 most populated U.S. states from 2000-2010. New HCQ users were identified by filling a prescription, with none in the preceding 12 months. Baseline retinal exams were identified within 30 days before to one year after this index prescription. We examined proportions of patients receiving retinal exams over the study years and compared characteristics of those who did and did not receive exams using bivariable and multivariable logistic regression models. Of 12,755 SLE patients newly starting HCQ, 32.5% received baseline dilated eye exams. The proportions of individuals receiving baseline eye exams did not significantly change during these years (31.0% to 34.4%, p for trend 0.12). Factors associated with increased likelihood of examinations included female sex, Asian versus White race, and receiving a higher number of laboratory tests during the preceding year. Lower proportions of Black and Native American versus White SLE patients had baseline retinal exams. Only one third of Medicaid SLE patients newly initiating HCQ received recommended baseline retinal examinations and this proportion did not significantly increase during these years. The sociodemographic variation in this indicated care has been observed for other recommended medical care for SLE and requires both further investigation and interventions to address it. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

School and conference on probability theory

International Nuclear Information System (INIS)

Lawler, G.F.

2004-01-01

very difficult area. It has been conjectured for a long time that in two dimensions many models in statistical physics have limits that are in some sense conformal invariant. There has been much activity recently proving such results. Richard Kenyon's lecture focuses on the dimer model where conformal invariance can be used at the discrete level. The continuum limit of many models is now understood with the aid of the stochastic Loewner evolution (SLE), developed by Oded Schramm. Gregory Lawler describes some of these recent results, including applications to percolation and path properties of planar Brownian motion

General constraints on the age and chemical evolution of the Galaxy

International Nuclear Information System (INIS)

Meyer, B.S.; Schramm, D.N.

1986-05-01

The formalism of Schramm and Wasserburg (1970) for determining the mean age of the elements is extended. Model-independent constraints (constraints that are independent of a specific form for the effective nucleosynthesis rate and Galactic chemical evolution over time) are derived on the first four terms in the expansion giving the mean age of the elements, and from these constraints limits are derived on the total duration of nucleosynthesis. These limits require only input of the Schramm-Wasserburg parameter Δ/sup max/ and of the ratio of the mean time for formation of the elements to the total duration of nucleosynthesis, t/sub nu//T. The former quantity is a function of nuclear input parameters. Limits on the latter are obtained from constraints on the relative rate of nucleosynthesis derived from the 232 Th/ 238 U, 235 U/ 238 U, and shorter-lived chronometric pairs. 65 refs

A framework for remission in SLE : Consensus findings from a large international task force on definitions of remission in SLE (DORIS)

NARCIS (Netherlands)

van Vollenhoven, Ronald F.; Voskuyl, Alexandre E.; Bertsias, George K.; Aranow, Cynthia; Aringer, Martin; Arnaud, Laurent; Askanase, Anca; Balazova, Petra; Bonfa, Eloisa; Bootsma, Hendrika; Boumpas, Dimitrios T.; Bruce, Ian N.; Cervera, Ricard; Clarke, Ann; Coney, Cindy; Costedoat-Chalumeau, Nathalie; Czirjak, Laszlo; Derksen, Ronald; Doria, Andrea; Doerner, Thomas; Fischer-Betz, Rebecca; Fritsch-Stork, Ruth; Gordon, Caroline; Graninger, Winfried; Gyori, Noemi; Houssiau, Frederic A.; Isenberg, David A.; Jacobsen, Soren; Jayne, David; Kuhn, Annegret; Le Guern, Veronique; Lerstrom, Kirsten; Levy, Roger; Machado-Ribeiro, Francinne; Mariette, Xavier; Missaykeh, Jamil; Morand, Eric; Mosca, Marta; Inanc, Murat; Navarra, Sandra; Neumann, Irmgard; Olesinska, Marzena; Petri, Michelle; Rahman, Anisur; Rekvig, Ole Petter; Rovensky, Jozef; Shoenfeld, Yehuda; Smolen, Josef S.; Tincani, Angela; Urowitz, Murray; van Leeuw, Bernadette; Vasconcelos, Carlos; Voss, Anne; Werth, Victoria P.; Zakharova, Helena; Zoma, Asad; Schneider, Matthias; Ward, Michael

Objectives Treat-to-target recommendations have identified `remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.

Simulated learning environment (SLE) in audiology education: A systematic review.

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Dzulkarnain, Ahmad Aidil Arafat; Wan Mhd Pandi, Wan Mahirah; Rahmat, Sarah; Zakaria, Nur 'Azzah

2015-01-01

To systematically review the relevant peer-review literature investigating the outcome of simulated learning environment (SLE) training in audiology education. A systematic review research design. Fifteen databases were searched with four studies meeting the inclusion criteria. Three of the four studies revealed positive findings for the use of an SLE (that is, the SLE group showed a higher post-training score compared to the traditional training group or a significantly higher post-training score than the non-training groups). One study revealed negative findings where the traditional training group showed a significantly higher post-training score than the SLE group. In addition, both the studies comparing post- and pre-training scores reported significantly higher post-training scores than the pre-training scores of the participants that underwent SLE training. Overall, this review supports the notions that SLE training is an effective learning tool and can be used for basic clinical training. This conclusion should be treated with caution, considering the limited numbers of studies published in this area and future research should be conducted to cope with the gaps highlighted in this review.

Simultaneous presentation of acute disseminated encephalomyelitis (ADEM) and systemic lupus erythematosus (SLE) after enteroviral infection: can ADEM present as the first manifestation of SLE?

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Kim, J-M; Son, C-N; Chang, H W; Kim, S-H

2015-05-01

Central Nervous System (CNS) involvement of Systemic Lupus Erythematosus (SLE) includes a broad range of neuropsychiatric syndromes. Acute Disseminated Encephalomyelitis (ADEM) is a demyelinating CNS disorder characterized by encephalopathy and multifocal lesions predominantly involving the white matter on brain magnetic resonance imaging. ADEM associated with SLE has been only rarely reported. We report an unusual case of a 17-year-old girl who developed ADEM after enteroviral infection as the first manifestation of SLE. The authors emphasize that the patient's illness was preceded by enteroviral infection and that ADEM occurred before any other symptoms of SLE, which makes this case unique. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Auricular Chondritis in a Postpartum Flare of SLE and APS

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Elodie Ponce

2014-10-01

Full Text Available Introduction: Auricular chondritis has been occasionally described in patients with systemic lupus erythematosus (SLE and antiphospholipid syndrome (APS. Materials and methods: We report the case of a woman with a previous history of APS who presented with auricular chondritis with onset of SLE symptoms during the postpartum period. Conclusion: SLE and APS should be taken into consideration in the differential diagnosis of auricular chondritis.

Hydroxychloroquine in systemic lupus erythematosus (SLE).

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Ponticelli, C; Moroni, G

2017-03-01

Hydroxychloroquine (HCQ) is an alkalinizing lysosomatropic drug that accumulates in lysosomes where it inhibits some important functions by increasing the pH. HCQ has proved to be effective in a number of autoimmune diseases including systemic lupus erythematosus (SLE). Areas covered: In this review the mechanisms of action, the efficacy, and the safety of HCQ in the management of patients with SLE have been reviewed. HCQ may reduce the risk of flares, allow the reduction of the dosage of steroids, reduce organ damage, and prevent the thrombotic effects of anti-phospholipid antibodies. The drug is generally safe and may be prescribed to pregnant women. However, some cautions are needed to prevent retinopathy, a rare but serious complication of the prolonged use of HCQ. Expert opinion: HCQ may offer several advantages not only in patients with mild SLE but can also exert important beneficial effects in lupus patients with organ involvement and in pregnant women. The drug has a low cost and few side effects. These characteristics should encourage a larger use of HCQ, also in lupus patients with organ involvement.

SLE local martingales in logarithmic representations

International Nuclear Information System (INIS)

Kytölä, Kalle

2009-01-01

A space of local martingales of SLE-type growth processes forms a representation of Virasoro algebra, but apart from a few simplest cases, not much is known about this representation. The purpose of this paper is to exhibit examples of representations where L 0 is not diagonalizable—a phenomenon characteristic of logarithmic conformal field theory. Furthermore, we observe that the local martingales bear a close relation to the fusion product of the boundary changing fields. Our examples reproduce first of all many familiar logarithmic representations at certain rational values of the central charge. In particular we discuss the case of SLE κ=6 describing the exploration path in critical percolation and its relation to the question of operator content of the appropriate conformal field theory of zero central charge. In this case one encounters logarithms in a probabilistically transparent way, through conditioning on a crossing event. But we also observe that some quite natural SLE variants exhibit logarithmic behavior at all values of κ, thus at all central charges and not only at specific rational values

RNA-Seq for enrichment and analysis of IRF5 transcript expression in SLE.

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Rivka C Stone

Full Text Available Polymorphisms in the interferon regulatory factor 5 (IRF5 gene have been consistently replicated and shown to confer risk for or protection from the development of systemic lupus erythematosus (SLE. IRF5 expression is significantly upregulated in SLE patients and upregulation associates with IRF5-SLE risk haplotypes. IRF5 alternative splicing has also been shown to be elevated in SLE patients. Given that human IRF5 exists as multiple alternatively spliced transcripts with distinct function(s, it is important to determine whether the IRF5 transcript profile expressed in healthy donor immune cells is different from that expressed in SLE patients. Moreover, it is not currently known whether an IRF5-SLE risk haplotype defines the profile of IRF5 transcripts expressed. Using standard molecular cloning techniques, we identified and isolated 14 new differentially spliced IRF5 transcript variants from purified monocytes of healthy donors and SLE patients to generate an IRF5 variant transcriptome. Next-generation sequencing was then used to perform in-depth and quantitative analysis of full-length IRF5 transcript expression in primary immune cells of SLE patients and healthy donors by next-generation sequencing. Evidence for additional alternatively spliced transcripts was obtained from de novo junction discovery. Data from these studies support the overall complexity of IRF5 alternative splicing in SLE. Results from next-generation sequencing correlated with cloning and gave similar abundance rankings in SLE patients thus supporting the use of this new technology for in-depth single gene transcript profiling. Results from this study provide the first proof that 1 SLE patients express an IRF5 transcript signature that is distinct from healthy donors, 2 an IRF5-SLE risk haplotype defines the top four most abundant IRF5 transcripts expressed in SLE patients, and 3 an IRF5 transcript signature enables clustering of SLE patients with the H2 risk haplotype.

Immunomodulators in SLE: Clinical evidence and immunologic actions.

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Durcan, L; Petri, M

2016-11-01

Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease. Current treatment strategies rely heavily on corticosteroids, which are in turn responsible for a significant burden of morbidity, and immunosuppressives which are limited by suboptimal efficacy, increased infections and malignancies. There are significant deficiencies in our immunosuppressive armamentarium, making immunomodulatory therapies crucial, offering the opportunity to prevent disease flare and the subsequent accrual of damage. Currently available immunomodulators include prasterone (synthetic dehydroeipandrosterone), vitamin D, hydroxychloroquine and belimumab. These therapies, acting via numerous cellular and cytokine pathways, have been shown to modify the aberrant immune responses associated with SLE without overt immunosuppression. Vitamin D is important in SLE and supplementation appears to have a positive impact on disease activity particularly proteinuria. Belimumab has specific immunomodulatory properties and is an effective therapy in those with specific serological and clinical characteristics predictive of response. Hydroxychloroquine is a crucial background medication in SLE with actions in many molecular pathways. It has disease specific effects in reducing flare, treating cutaneous disease and inflammatory arthralgias in addition to other effects such as reduced thrombosis, increased longevity, improved lipids, better glycemic control and blood pressure. Dehydroeipandrosterone is also an immunomodulator in SLE which can have positive effects on disease activity and has bone protective properties. This review outlines the immunologic actions of these drugs and the clinical evidence supporting their use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyperthyroidism association with SLE, lessons from real-life data--A case-control study.

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Watad, Abdulla; Cohen, Arnon D; Comaneshter, Doron; Tekes-Manova, Dorit; Amital, Howard

2016-01-01

Despite the frequently encountered association between thyroid disease and systemic lupus erythematosus (SLE) is well known, it is of surprise that only several reports compromised of small population size support this observation. To investigate the association of comorbid SLE and hyperthyroidism. Using the database of the largest health maintenance organization (HMO) in Israel, the Clalit Health Services, we searched for the co-existence of SLE and hyperthyroidism. Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of hyperthyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study included 5018 patients with SLE and 25,090 age- and sex- matched controls. The prevalence of hyperthyroidism in patients with SLE was increased compared with the prevalence in controls (2.59% and 0.91%, respectively, p hyperthyroidism (odds ratio 2.52, 95% confidence interval 2.028-3.137). Patients with SLE have a greater prevalence of hyperthyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of this possibility of this thyroid dysfunction.

Conformal invariance in hydrodynamic turbulence

International Nuclear Information System (INIS)

Falkovich, Gregory

2007-01-01

This short survey is written by a physicist. It contains neither theorems nor precise definitions. Its main content is a description of the results of numerical solution of the equations of fluid mechanics in the regime of developed turbulence. Due to limitations of computers, the results are not very precise. Despite being neither exact nor rigorous, the findings may nevertheless be of interest for mathematicians. The main result is that the isolines of some scalar fields (vorticity, temperature) in two-dimensional turbulence belong to the class of conformally invariant curves called SLE (Scramm-Loewner evolution) curves. First, this enables one to predict and find a plethora of quantitative relations going far beyond what was known previously about turbulence. Second, it suggests relations between phenomena that seemed unrelated, like the Euler equation and critical percolation. Third, it shows that one is able to get exact analytic results in statistical hydrodynamics. In short, physicists have found something unexpected and hope that mathematicians can help to explain it.

Space Link Extension (SLE) Emulation for High-Throughput Network Communication

Science.gov (United States)

Murawski, Robert W.; Tchorowski, Nicole; Golden, Bert

2014-01-01

As the data rate requirements for space communications increases, significant stress is placed not only on the wireless satellite communication links, but also on the ground networks which forward data from end-users to remote ground stations. These wide area network (WAN) connections add delay and jitter to the end-to-end satellite communication link, effects which can have significant impacts on the wireless communication link. It is imperative that any ground communication protocol can react to these effects such that the ground network does not become a bottleneck in the communication path to the satellite. In this paper, we present our SCENIC Emulation Lab testbed which was developed to test the CCSDS SLE protocol implementations proposed for use on future NASA communication networks. Our results show that in the presence of realistic levels of network delay, high-throughput SLE communication links can experience significant data rate throttling. Based on our observations, we present some insight into why this data throttling happens, and trace the probable issue back to non-optimal blocking communication which is sup-ported by the CCSDS SLE API recommended practices. These issues were presented as well to the SLE implementation developers which, based on our reports, developed a new release for SLE which we show fixes the SLE blocking issue and greatly improves the protocol throughput. In this paper, we also discuss future developments for our end-to-end emulation lab and how these improvements can be used to develop and test future space communication technologies.

Disease activity assessment in SLE: do we have the right instruments?

OpenAIRE

Petri, Michelle

2007-01-01

No new therapy has been approved for systemic lupus erythematosus (SLE) in decades. Interest in SLE by pharmaceutical and biotechnology companies has increased, leading to multiple clinical trials. Unfortunately, we have now compiled quite a long list of “failed” trials. If this was due to the fact that the studied therapy did not work in SLE, we could accept it and move on. Of concern, however, is that many of the “failed” treatments had a strong “signal” of efficacy, often in subgroup analy...

Children born to SLE and APS mothers.

Science.gov (United States)

Nalli, C; Iodice, A; Andreoli, L; Lojacono, A; Motta, M; Fazzi, E; Tincani, A

2014-10-01

Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Pregnancies in these patients carry several complications such as prematurity. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta but they don't generally cause any neonatal thrombotic event. Because of the incompleteness of the fetal blood-brain barrier, aPL could theoretically reach the fetal brain. Whether this can have an effect on brain development is still under investigation. Some studies performed in children of patients with SLE and/or APS showed an increased number of learning disabilities without impairment in intelligence level. The objectives of this article are to evaluate the neurodevelopment outcome in 30 children (median age 9 years) born to mothers with SLE and/or APS with IgG anti-beta2-glycoprotein I during the third trimester of pregnancy and found positive for the same antibodies at birth. A neurological physical exam was performed in all children. We submitted some questionnaires to the mothers: the Child Behavior CheckList (CBCL) and a homemade set of questions obtained by a team composed of rheumatologists and pediatric neurologists. Intellectual functioning was determined by the Wechsler scale for corrected age. In all children neurological physical exam and intelligence levels were found to be normal but mild behavior disorders and history of neurological manifestations were shown in three children. Offspring of patients with SLE and/or APS are generally healthy. We and others observed the occurrence of minor neurological disorders that might be related to maternal disease or to prematurity. The limited number of the available data on this sensitive issue supports the need for further studies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS).

Science.gov (United States)

van Vollenhoven, Ronald; Voskuyl, Alexandre; Bertsias, George; Aranow, Cynthia; Aringer, Martin; Arnaud, Laurent; Askanase, Anca; Balážová, Petra; Bonfa, Eloisa; Bootsma, Hendrika; Boumpas, Dimitrios; Bruce, Ian; Cervera, Ricard; Clarke, Ann; Coney, Cindy; Costedoat-Chalumeau, Nathalie; Czirják, László; Derksen, Ronald; Doria, Andrea; Dörner, Thomas; Fischer-Betz, Rebecca; Fritsch-Stork, Ruth; Gordon, Caroline; Graninger, Winfried; Györi, Noémi; Houssiau, Frédéric; Isenberg, David; Jacobsen, Soren; Jayne, David; Kuhn, Annegret; Le Guern, Veronique; Lerstrøm, Kirsten; Levy, Roger; Machado-Ribeiro, Francinne; Mariette, Xavier; Missaykeh, Jamil; Morand, Eric; Mosca, Marta; Inanc, Murat; Navarra, Sandra; Neumann, Irmgard; Olesinska, Marzena; Petri, Michelle; Rahman, Anisur; Rekvig, Ole Petter; Rovensky, Jozef; Shoenfeld, Yehuda; Smolen, Josef; Tincani, Angela; Urowitz, Murray; van Leeuw, Bernadette; Vasconcelos, Carlos; Voss, Anne; Werth, Victoria P; Zakharova, Helena; Zoma, Asad; Schneider, Matthias; Ward, Michael

2017-03-01

Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes. Published by the BMJ Publishing Group Limited. For

Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE).

Science.gov (United States)

Kozora, E; Erkan, D; West, S G; Filley, C M; Zhang, L; Ramon, G; Duggan, E; Lockshin, M D

2013-01-01

Mild cognitive dysfunction (MCD) is common in patients with systemic lupus erythematosus (MCD-SLE) but few studies have investigated potential site differences. SLE patients from Denver, CO, and New York, NY, were enrolled in two different cognition studies employing similar screening methods. Using the resulting neuropsychological scores, cognitive impairment was calculated using a cognitive impairment index (CII). The rate of MCD-SLE was 24% at the Denver, CO, site and 60% at the New York, NY, site. The mean CII was 2.6 ± 2.3 versus 4.4 ± 2.7, respectively (p = 0.005). The NY participants had a significantly longer disease duration (p = 0.13) and higher American College of Rheumatology SLE criteria scores (p > 0.001). NY participants had a higher frequency of impairment in semantic verbal fluency (p = 0.005), visuomotor speed (p = 0.013), and motor sequencing (p = 0.001). A correlation was found between cognitive impairment and SLE disease duration (p = 0.03). The rate of MCD-SLE was greater in SLE patients from New York, NY, compared to patients in the Denver, CO, area. The greater duration of disease and higher prevalence of medical complications in the NY group might contribute to this difference. Findings suggest that MCD-SLE may differ by site, but future studies that better evaluate site or selection bias are recommended.

Murine Lupus Susceptibility Locus Sle2 Activates DNA-Reactive B Cells through Two Sub-Loci with Distinct Phenotypes

Science.gov (United States)

Zeumer, Leilani; Sang, Allison; Niu, Haitao; Morel, Laurence

2010-01-01

The NZM2410-derived Sle2 lupus susceptibility locus induces an abnormal B cell differentiation which most prominently leads to the expansion of autoreactive B1a cells. We have mapped the expansion of B1a cells to three Sle2 sub-loci, Sle2a, Sle2b, and Sle2c. Sle2 also enhances the breach of B cell tolerance to nuclear antigens in the 56R anti-DNA immunoglobulin transgenic (Tg) model. This study used the Sle2 sub-congenic strains to map the activation of 56R Tg B cells. Sle2c strongly sustained the breach of tolerance and the activation of anti-DNA B cells. The production of Tg-encoded anti-DNA antibodies was more modest in Sle2a expressing mice, but Sle2a was responsible for the recruitment for Tg B cells to the marginal zone, a phenotype that has been found for 56R Tg B cells in mice expressing the whole Sle2 interval. In addition, Sle2a promoted the production of endogenously encoded anti-DNA antibodies. Overall, this study showed that at least two Sle2 genes are involved in the activation of anti-DNA B cells, and excluded more than two-thirds of the Sle2 interval from contributing to this phenotype. This constitutes an important step toward the identification of novel genes that play a critical role in B cell tolerance. PMID:21270826

Study on the relationship between SLE and the related serum hormone

International Nuclear Information System (INIS)

Lu Yun; Deng Shouzhen; Lin Xiangtong; Feng Shufang; Xu Jinhua; He Wanting; Zhang Guangming; Cheng Wei; Gao Quan

1998-01-01

To explore the relationship between PRL, GH(RIA), GH(RRA) serum levels changes and the onset and development of disease in patients with SLE, and to understand the hormonal changes in active and inactive phase of disease, 28 cases and 20 controls were studied. The results showed that anti-ds-DNA serum level in active and inactive phases was higher than those in controls (P 1 2 <0.05). This study indicated that the higher serum level of PRL, GH(RIA), GH(RRA) is correlated with some autoimmune characteristics of SLE, especially in its active phase. Therefore it gives some help for clinical study of SLE

Clinical significance of changes of expression of anti-dsDNA antibody in serum in patients with SLE

International Nuclear Information System (INIS)

Chen Xingguo; Zhang Xiaoli; Liu Chunyan; Cao Jiwei; Du Tongxing; Wang Zizheng

2008-01-01

Objective: To investigate the significance of anti-dsDNA antibody in diagnosis and treatment of SLE through measurement of changes of serum anti-dsDNA antibody expression in patients with SLE. Methods: Serum anti-dsDNA antibody was detected with radioisotope method in 60 patients with SLE and 33 controls (consisted of patients with other collagen diseases including Sjogren syndrome, systemic sclerosis, rheumatoid arthritis, polymyositis, mixed connective tissue disease, ankylosing spondylitis). Clinical manifestation and laboratory findings in the SLE patients were studied in detail. Results: (1) Serum anti-dsDNA antibody was positive in 39 of the 60 SLE patients with only two false positive cases in the 33 controls: a sensitivity of 65% and specificity of 93. 3%. (2) In SLE patients, positivity of anti-dsDNA antibody was not correlated with positivity of anti-Sm antibody (P>0.05), but was correlated with positivity of anti-SSA antibody (P<0.05). (3) Incidences of alopecia, skin rashes, oral mucosal ulcer, proteinuria were significantly higher in SLE patients with positive anti-dsDNA antibody than those in SLE patients with negative anti-dsDNA antibody (P<0.05). (4) Incidences of leukopenia and thrombocytopenia were also significantly higher in SLE patients with positive anti-dsDNA antibody (P<0.05). Conclusion: Anti-dsDNA antibody could be taken as a specific marker of SLE and the serum expression were positively correlated with the activity and severity of the disease. (authors)

Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

Directory of Open Access Journals (Sweden)

Daisuke Sakurai

Full Text Available Immunoregulatory cytokine interleukin-10 (IL-10 is elevated in sera from patients with systemic lupus erythematosus (SLE correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA (P = 2.7×10⁻⁸, OR = 1.30, but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively, and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1 detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane.

Science.gov (United States)

Gutiérrez Nava, Zúlima Jannette; Jiménez-Aparicio, Antonio Ruperto; Herrera-Ruiz, Maribel Lucila; Jiménez-Ferrer, Enrique

2017-05-25

In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana , provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane

Directory of Open Access Journals (Sweden)

Zúlima Jannette Gutiérrez Nava

2017-05-01

Full Text Available In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana, provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol; octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.

Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

DEFF Research Database (Denmark)

Nolsøe, R L; Kelly, J A; Pociot, F

2005-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens and tissue injury. Defective apoptosis of activated immune cells leads to the development of autoantibodies in SLE. FasL initiated apoptosis is central...... for peripheral tolerance. Fas deficiencies in humans and mice predispose toward systemic autoimmunity. SLE is conferred by many genes. The genetic effects may be concentrated by familial clustering or by stratifying of subphenotypes. We have tested polymorphisms and haplotypes in FAS and FASL for association...... to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC(C/T) as well as the FAS-670G>A'-codon214 AC(C/T)' haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE...

Coupling of c  =  ‑2 and c =\\frac{1}{2} and c  =  0 conformal field theories: the geometrical point of view

Science.gov (United States)

Najafi, M. N.

2018-04-01

The coupling of the c  =  ‑2, c=\\frac{1}{2} and c  =  0 conformal field theories are numerically considered in this paper. As the prototypes of the couplings, (c_1=-2)\\oplus (c_2=0) and (c_1=-2)\\oplus (c_2=\\frac{1}{2}) , we consider the Bak–Tang–Weisenfeld (BTW) model on the 2D square critical site-percolation and the BTW model on Ising-correlated percolation lattices respectively. Some geometrical techniques are used to characterize the presumable conformal symmetry of the resultant systems. Based on the numerical analysis of the diffusivity parameter (κ) in the Schramm–Loewner evolution (SLE) theory we propose that the algebra of the central charges of the coupled models is closed. This result is based on the analysis of the conformal loop ensemble (CLE) analysis. The diffusivity parameter in each case is obtained by calculating the fractal dimension of loops (and the corresponding exponent of mean-square root distance), the direct SLE mapping method, the left passage probability and the winding angle analysis. More precisely we numerically show that the coupling (c_1=-2)\\oplus (c_2=\\frac{1}{2}) results to 2D self-avoiding walk (SAW) fixed point corresponding to c  =  0 conformal field theory, whereas the coupling (c_1=-2)\\oplus (c_2=0) results to the 2D critical Ising fixed point corresponding to the c=\\frac{1}{2} conformal field theory.

The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE.

Science.gov (United States)

Hagberg, Niklas; Joelsson, Martin; Leonard, Dag; Reid, Sarah; Eloranta, Maija-Leena; Mo, John; Nilsson, Magnus K; Syvänen, Ann-Christine; Bryceson, Yenan T; Rönnblom, Lars

2018-02-23

Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ + cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs. In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8 + T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8 + and CD4 + T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively. T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protective Role of Ets1 in SLE

Science.gov (United States)

2014-07-01

Purification and differentiation of Th cells were performed according to a published protocol without modi - fication (3). Preparation of Cytoplasmic...RA), systemic lupus erythematosus (SLE), and type 1 diabetes but reduces the risk of Crohn’s disease [7,14-17]. Despite these observations, it is

Women's experience of SLE-related fatigue: a focus group interview study.

Science.gov (United States)

Pettersson, Susanne; Möller, Sonia; Svenungsson, Elisabet; Gunnarsson, Iva; Welin Henriksson, Elisabet

2010-10-01

The aim of this study was to describe women's experience of SLE-related fatigue, how they express the feeling of fatigue, impact on life and strategies developed to manage fatigue in daily living. Seven, semi-structured focus group discussions with 33 women were audio-taped, transcribed verbatim and analysed according to qualitative content analysis. Perceptions of SLE-related fatigue were sorted into four themes. Nature of Fatigue, involved the sensation, occurrence and character. Aspects Affected by Fatigue described emotions that arose together with fatigue as well as aspects of work, family life, social contacts and leisure activities that were affected by fatigue. Striving Towards Power and Control concluded the array of ways used to manage daily life and were categorized into the mental struggle, structure, restrict and provide. Factors Influencing the Perception of Fatigue described understanding from their surroundings and pain as strongly influencing the experience and perception of fatigue. SLE-related fatigue was portrayed as an overwhelming phenomenon with an unpredictable character, resulting in the feeling that fatigue dominates and controls most situations in life. The choice of strategies was described as a balance with implications for how fatigue limited a person's life. Health care professionals are advised to take a more active role to empower people with SLE to find their own balance as a way to achieve a feeling of being in control.

Independent association of glucocorticoids with damage accrual in SLE.

Science.gov (United States)

Apostolopoulos, Diane; Kandane-Rathnayake, Rangi; Raghunath, Sudha; Hoi, Alberta; Nikpour, Mandana; Morand, Eric F

2016-01-01

To determine factors associated with damage accrual in a prospective cohort of patients with SLE. Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual. A total of 162 patients were observed over a median (IQR) 3.6 (2.0-4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p<0.01). Higher glucocorticoid exposure was independently associated with overall damage accrual after controlling for factors including ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone/day; the OR of damage accrual in patients in the highest quartile of cumulative glucocorticoid exposure was over 10. Glucocorticoid exposure was independently associated with damage accrual in glucocorticoid-related and non-glucocorticoid related domains of the SDI. Glucocorticoid use is independently associated with the accrual of damage in SLE, including in non-glucocorticoid related domains.

Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort

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Rufei Lu

2012-01-01

Full Text Available Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE clinical features in a large lupus cohort. Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis. Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use.

The useful application of anti-ds DNA antibody radioimmunoassay in the diagnosis of male SLE patients

Energy Technology Data Exchange (ETDEWEB)

Alshaikhly, A W.A.R. [Al-Rasheed Hospital, Baghdad, (Iraq)

1995-10-01

From the period of 1994 to 1990, the anti double stranded deoxyribonucleic acid radioimmunoassay (Anti-ds DNA RIA) were extensively applied to confirm diagnosis of Systemic Lupus Erythematosus (SLE) disease in male patients. 54 patients sera with definite diagnosis of SLE, 30 patients sera with Rheumatoid Arthritis (RA), 20 patients sera with other Rheumatic or Collagen vascular diseases (ORD), 5 patients sera of non specific arthritis (NSA) and 55 healthy male individual sera were included. The 54 male SLE patients were diagnosed after screening more than 2000 sera from male patients with various Rheumatic diseases who overlapping clinical symptoms with SLE. The results of this study are confirming that the anti-ds DNA RIA is proved to be a simple, sensitive, specific and useful technique among various assays used for diagnosis purposes. The results also pointed out that the prevalence of SLE disease in males is much lower than females. 4 tabs.

The useful application of anti-ds DNA antibody radioimmunoassay in the diagnosis of male SLE patients

International Nuclear Information System (INIS)

Alshaikhly, A.W.A.R.

1995-01-01

From the period of 1994 to 1990, the anti double stranded deoxyribonucleic acid radioimmunoassay (Anti-ds DNA RIA) were extensively applied to confirm diagnosis of Systemic Lupus Erythematosus (SLE) disease in male patients. 54 patients sera with definite diagnosis of SLE, 30 patients sera with Rheumatoid Arthritis (RA), 20 patients sera with other Rheumatic or Collagen vascular diseases (ORD), 5 patients sera of non specific arthritis (NSA) and 55 healthy male individual sera were included. The 54 male SLE patients were diagnosed after screening more than 2000 sera from male patients with various Rheumatic diseases who overlapping clinical symptoms with SLE. The results of this study are confirming that the anti-ds DNA RIA is proved to be a simple, sensitive, specific and useful technique among various assays used for diagnosis purposes. The results also pointed out that the prevalence of SLE disease in males is much lower than females. 4 tabs

Significance of abnormal myocardial perfusion scintigraphy in young adult patients with SLE

International Nuclear Information System (INIS)

Zakavi, S.R.; Kakhki, V.R.D.; Sadeghi, R.; Jokar, M.H.; Khazaei, G.

2009-01-01

Detection of subclinical coronary artery disease (CAD) is a potential challenge in patients with systemic lupus erythematosus (SLE) and it is suggested that myocardial perfusion single photon emission computerized tomography (SPECT) is more sensitive than exercise test in this setting. However, the significance of perfusion abnormalities in SLE patients is not well known. In this study, we evaluated the prognostic significance of myocardial perfusion defects in patients with SLE. Patients with proven diagnosis of SLE admitted to the hospital due to noncardiac problems with no history of CAD were studied. All patients underwent 99m Tc-methoxyisobutylisonitrile (MIBI) myocardial perfusion scan using dipyridamole as pharmacological stress. All patients were followed up by reviewing patients file in lupus clinic and any minor or major cardiac events were recorded. Eighteen female and two male patients with mean age of 28.2±12.05 years were included. Six patients had mild reversible perfusion defects with mean summed difference score of 2.5±1.0. Pattern of reverse redistribution (reverse fill-in) was noted in three patients. Eleven patients had normal myocardial perfusion. Hypokinesia was noted in three patients on gated images. One patient with abnormal perfusion died 21 days after imaging due to on-cardiac cause. Nineteen patients were followed for a mean time of 39.2±16.0 months. No major or minor cardiac events were noted during follow-up. Three patients (one with abnormal perfusion) had at least one readmission during follow-up period. Our study showed that myocardial perfusion abnormalities are fairly frequent in SLE patients but the defects are generally mild and do not advocate an adverse prognosis. (author)

Screening for cognitive impairment in SLE using the Self-Administered Gerocognitive Exam.

Science.gov (United States)

Meara, A; Davidson, N; Steigelman, H; Zhao, S; Brock, G; Jarjour, W N; Rovin, B H; Madhoun, H; Parikh, S; Hebert, L; Ayoub, I; Ardoin, S P

2018-01-01

Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can affect the central nervous system in multiple ways, including causing cognitive dysfunction. Cognitive dysfunction is a common complaint of SLE patients yet diagnosis is challenging, time consuming, and costly. This study evaluated the Self-Administered Gerocognitive Exam (SAGE) as a screening test for cognitive impairment in a cohort of SLE patients. Methods A total of 118 SLE patients completed the SAGE. Providers completed the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborative Clinics Damage Index (SLICC-DI). SAGE scores were grouped into normal (>16) and abnormal (≤16) categories. Univariate and multivariate analyses were performed. Results Of the 118 participants, 21(18%) scored ≤16 on the SAGE instrument. In univariate analysis, race, ethnicity, household income, and SLICC-DI scores were associated with the SAGE ( p SAGE score was independently associated with higher SLICC-DI score (odds ratio (OR) = 1.44, 95% confidence intervals 1.04-1.99, p = 0.03)), Hispanic ethnicity (OR = 43.4, 95% CI 3.1-601, p = 0.005), and lower household income (OR = 11.9 for ≤$15,000 vs >$50,000, 95% CI 2.45-57, p = 0.002). Conclusions In SLE patients, this study demonstrates an independent relationship between neurocognitive impairment (as measured by the SAGE) and higher lupus-related damage, as measured by the SLICC-DI, and lower household income. Abnormal SAGE scores were also associated with Hispanic ethnicity. A language barrier could explain this because the SAGE instrument was conducted in English only. The SAGE was feasible to measure in the clinic setting.

Diagnostic significance of the radiologic appearances of the hands in systemic lupus erythematosus (SLE)

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Winkler, P; Baenkler, H W; Pfuhl, E; Gutmann, W

1980-09-01

40 patients with SLE were assessed, the diagnoses being made according to modified ARA-criteria; the hand films of 25 of these patients were analysed. The most important roentgenologic findings consisted of reducible deformities with mild or absent articular changes in the deformed MCP and PIP joints. As these changes often occur late in the course of SLE, a primary radiological diagnosis was possible in only three cases (8%), whereas hand films provided confirmatory evidence of disease in a further seven patients. These roentgenological characteristics of SLE were found significantly less often in patients with definite RA; this group tended to have positive ANF (antinuclear factors). Antibodies against DNA may be absent, especially in a less active phase of disease. ANF is non-specific, and SLE simulates RA in 10-20% of cases. It is, therefore, very important in individual cases to consider the diagnosis of SLE in the presence of deformity without corresponding articular changes. Direct comparison of both the p.a. and oblique views is essential in the evaluation of reducible deformities, although this point has not been stressed in the literature. Reducible deformities may be overlooked in physical examination, when the patient gives no history of functional disability. The main differential diagnosis is Jaccoud's arthropathy, which is rarely seen in a general hospital. Most of these patients give a history of recurrent rheumatic fever, a minority complain about joint pain or disability, approximately 90% show signs indicating a valvular lesion of the heart, over 75% have a normal ESR and a positive rheumatoid or antinuclear factor is very rarely found. The distinction from SLE or rheumatoid arthritis is therefore easily established on additional non-radiological criteria.

Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

DEFF Research Database (Denmark)

Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E

1984-01-01

Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease g...

Genetic Association of CD247 (CD3ζ) with SLE in a Large-Scale Multiethnic Study

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Martins, Madalena; Williams, Adrienne H.; Comeau, Mary; Marion, Miranda; Ziegler, Julie T.; Freedman, Barry I.; Merrill, Joan T.; Glenn, Stuart B.; Kelly, Jennifer A.; Sivils, Kathy M.; James, Judith A.; Guthridge, Joel M.; Alarcón-Riquelme, Marta E.; Bae, Sang-Cheol; Kim, Jae-Hoon

2015-01-01

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) i...

Cryptogenic Organising Pneumonia As The Initial Presenting Manifestation of SLE

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Neena Mampilly

2015-07-01

Full Text Available Cryptogenic Organising Pneumonia (COP, also called idiopathic Bronchiolitis Obliterans Organising Pneumonia( BOOP, is a distinct entity among the idiopathic interstitial pneumonias defined histopathologically by intraalveolar buds of granulation tissue. The etiology includes idiopathic, infectious, drug induced radiation induced and connective tissue diseases. Organising pneumonia occurs particularly in patients with dermatomyositis-polymyositis where it may be the presenting manifestation, and rarely in SLE, rheumatoid arthritis, scleroderma and other connective tissue diseases. We describe a 30 yr old lady who initially presented with respiratory symptoms, not responding to antibiotics. She was subsequently diagnosed as SLE and HRCT thorax showed consolidation involving both lung fields. A percutaneous lung biopsy revealed features of Cryptogenic Organising Pneumonia.

Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA.

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Khan, Md Asad; Alam, Khursheed; Mehdi, Syed Hassan; Rizvi, M Moshahid A

2017-12-01

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Autoantibodies in SLE: Specificities, Isotypes and Receptors

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Barbara Dema

2016-01-01

Full Text Available Systemic Lupus Erythematosus (SLE is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

Barriers And Motivators for Smoking Cessation in Patients With Systemic Lupus Erythematosus (SLE).

Science.gov (United States)

Terrell, Deirdra R; Stewart, Lauren M; Tolma, Eleni L; McClain, Rebekah; Vesely, Sara K; James, Judith A

2015-11-01

Although studies have shown that smoking is detrimental to the health of patients with systemic lupus erythematosus (SLE), studies regarding barriers and motivators for smoking cessation are lacking. The purpose of this study was to generate hypotheses regarding the barriers and motivators for smoking cessation in SLE patients. This study was based on the theoretical framework of the stages of change model. All participants met SLE classification criteria. Interviews were conducted with 16 current and 10 former smokers. Motivators included: medical reasons, readiness, and concern for others. Barriers included: enjoyment, coping mechanism, and an emotional connection. Participants were unsure of the impact of smoking on their medication and disease, and had mixed feelings regarding the impact on pain. The main motivator for cessation in this population was concern for one's health. Rheumatologists need to include disease specific harms and assess pain management strategies as part of cessation counseling.

A framework for remission in SLE

DEFF Research Database (Denmark)

van Vollenhoven, Ronald; Voskuyl, Alexandre; Bertsias, George

2017-01-01

, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3....... Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg...

The diagnostic significance of the radiologic appearances of the hands in systemic lupus erythematosus (SLE)

International Nuclear Information System (INIS)

Winkler, P.; Baenkler, H.W.; Pfuhl, E.; Gutmann, W.

1980-01-01

40 patients with SLE were assessed, the diagnoses being made according to modified ARA-criteria; the hand films of 25 of these patients were analysed. The most important roentgenologic findings consisted of reducible deformities with mild or absent articular changes in the deformed MCP and PIP joints. As these changes often occur late in the course of SLE, a primary radiological diagnosis was possible in only three cases (8%), whereas hand films provided confirmatory evidence of disease in a further seven patients. These roentgenological characteristics of SLE were found significantly less often in patients with definite RA; this group tended to have positive ANF (antinuclear factors). Antibodies against DNA may be absent, especially in a less active phase of disease. ANF is non-specific, and SLE simulates RA in 10-20% of cases. It is, therefore, very important in individual cases to consider the diagnosis of SLE in the presence of deformity without corresponding articular changes. Direct comparison of both the p.a. and oblique views is essential in the evaluation of reducible deformities, although this point has not been stressed in the literature. Reducible deformities may be overlooked in physical examination, when the patient gives no history of functional disability. The main differential diagnosis is Jaccoud's arthropathy, which is rarely seen in a general hospital. Most of these patients give a history of recurrent rheumatic fever, a minority complain about joint pain or disability, approximately 90% show signs indicating a valvular lesion of the heart, over 75% have a normal ESR and a positive rheumatoid or antinuclear factor is very rarely found. The distinction from SLE or rheumatoid arthritis is therefore easily established on additional non-radiological criteria. (orig./MG) [de

High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.

Science.gov (United States)

Sun, Celi; Molineros, Julio E; Looger, Loren L; Zhou, Xu-Jie; Kim, Kwangwoo; Okada, Yukinori; Ma, Jianyang; Qi, Yuan-Yuan; Kim-Howard, Xana; Motghare, Prasenjeet; Bhattarai, Krishna; Adler, Adam; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Kochi, Yuta; Suzuki, Akari; Kubo, Michiaki; Sumida, Takayuki; Yamamoto, Kazuhiko; Lee, Shin-Seok; Kim, Young Jin; Han, Bok-Ghee; Dozmorov, Mikhail; Kaufman, Kenneth M; Wren, Jonathan D; Harley, John B; Shen, Nan; Chua, Kek Heng; Zhang, Hong; Bae, Sang-Cheol; Nath, Swapan K

2016-03-01

Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.

Decreased SAP expression in T cells from patients with SLE contributes to early signaling abnormalities and reduced IL-2 production

Science.gov (United States)

Karampetsou, Maria P.; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C.; Tsokos, George C.

2016-01-01

T cells from patients with systemic lupus erythematosus (SLE) display a number of functions including increased early signaling events following engagement of the T cell receptor (TCR). Signaling lymphocytic activation molecule family (SLAMF) cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating immune response. Here we present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and 3 men with SLE independently of disease activity. In SLE T cells the SAP protein is also subject to increased degradation by a caspase-3. Forced expression of SAP in SLE T cells simultaneously heightened IL-2 production, calcium (Ca2+) responses and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR antibodies, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

Association of anti C1q and ds-DNA levels with the pathogenesis of Lupus Nephritis among SLE patients

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Zara Sohail

2018-02-01

Full Text Available Background: Lupus nephritis (LN is the most common and serious complication associated with SLE and it results in significant morbidity and mortality. It is known by several studies that patients of LN have higher levels of anti-dsDNA and anti-C1q compared with SLE patients without renal involvement. The current study was designed to determine and compare the level of anti-dsDNA and anti-C1q in patients of SLE with and without lupus nephritis in the Pakistani population. This current study was also aimed at providing proof that anti-C1q levels are more prominent in LN/non-LN SLE as compared to anti-dsDNA. This project may help in the determination of results in Pakistan and contribute to the further confirmation of the sensitivity of anti-C1q. Method: The patient samples were collected from Sheikh Zayed hospital, Lahore. These patients were clinically diagnosed by the Rheumatologists as SLE and LN positive on the basis of ACR and SLEDAI scoring criteria. This study was performed and samples were analyzed in the Department of Medical and Laboratory Sciences, Imperial College of Business Study, Lahore on the patient’s serum by ELISA technique. Result: About 38% (12 patients with LN were positive for anti-dsDNA and 31% (9 SLE patients without LN were positive whereas about 38.7% (12 were anti-dsDNA negative in LN cases and 58.6% (17 in SLE without LN. In case of anti-C1q 100% (31 of these LN patients were positive and 93.1% (27 patients SLE without LN showed positive anti C1q results. Only 6.9% (2 patients showed negative results for anti-C1q in LN negative patients Conclusion: The higher levels of anti-C1q suggest that it may be a better diagnostic marker for LN than that of anti-dsDNA and that it can be helpful in the prognosis of SLE patients.

Endovascular repair as a sole treatment in multiple aneurysms in patient with SLE

International Nuclear Information System (INIS)

Dineva, S.; Al-Amin, M.; Demetriou, S.; Tsetis, D.

2013-01-01

Full text: Introduction: Most aneurysms are local manifestations of systemic disease. For patients over 65 years the incidence of aneurysm of the abdominal aorta (AAA) is approximately 5-6% in men and 1-2 % for women. The presence of both the AAA and aneurysms in other location is even rarer, and this percentage is likely increase further in patients with systemic lupus erythematosus (SLE). What you will learn: We present a rare clinical case of endovascular treatment of multifocal aneurysm including post catheterization pseudoaneurysm. The patient is a 73 years old woman with a history of SLE and age-related comorbidity. Originally an endovascular treatment of aneurysms of the abdominal aorta and right common iliac artery was used. Two years later a successfully endovascular treatment of aneurysm of the right renal artery was conducted, which however is complicated by the formation of a pseudoaneurysm in access through the left femoral artery. The late one is again treated endovascular by placement of a covered stent after failure of percutaneous injection of 1000 UI thrombin. Discussion: Adult patients with a long history of SLE are unsuitable candidates for surgical treatment of aneurysmal disease, especially in its multifocal form. In our case we have taken multistep successful endovascular procedures, including technically hard placing of the stent at the site of the right renal aneurysms, and post catheterization pseudoaneurysm. Conclusion: Multifocal aneurysmal vascular changes due to macroangiopathia in SLE can be treated alone by endovascular means in multi-stages procedures

Identification of MAMDC1 as a candidate susceptibility gene for systemic lupus erythematosus (SLE.

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Anna Hellquist

2009-12-01

Full Text Available Systemic lupus erythematosus (SLE is a complex autoimmune disorder with multiple susceptibility genes. We have previously reported suggestive linkage to the chromosomal region 14q21-q23 in Finnish SLE families.Genetic fine mapping of this region in the same family material, together with a large collection of parent affected trios from UK and two independent case-control cohorts from Finland and Sweden, indicated that a novel uncharacterized gene, MAMDC1 (MAM domain containing glycosylphosphatidylinositol anchor 2, also known as MDGA2, MIM 611128, represents a putative susceptibility gene for SLE. In a combined analysis of the whole dataset, significant evidence of association was detected for the MAMDC1 intronic single nucleotide polymorphisms (SNP rs961616 (P -value = 0.001, Odds Ratio (OR = 1.292, 95% CI 1.103-1.513 and rs2297926 (P -value = 0.003, OR = 1.349, 95% CI 1.109-1.640. By Northern blot, real-time PCR (qRT-PCR and immunohistochemical (IHC analyses, we show that MAMDC1 is expressed in several tissues and cell types, and that the corresponding mRNA is up-regulated by the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha and interferon gamma (IFN-gamma in THP-1 monocytes. Based on its homology to known proteins with similar structure, MAMDC1 appears to be a novel member of the adhesion molecules of the immunoglobulin superfamily (IgCAM, which is involved in cell adhesion, migration, and recruitment to inflammatory sites. Remarkably, some IgCAMs have been shown to interact with ITGAM, the product of another SLE susceptibility gene recently discovered in two independent genome wide association (GWA scans.Further studies focused on MAMDC1 and other molecules involved in these pathways might thus provide new insight into the pathogenesis of SLE.

Chinese SLE Treatment and Research group (CSTAR) registry VII: prevalence and clinical significance of serositis in Chinese patients with systemic lupus erythematosus.

Science.gov (United States)

Zhao, J; Bai, W; Zhu, P; Zhang, X; Liu, S; Wu, L; Ma, L; Bi, L; Zuo, X; Sun, L; Huang, C; Tian, X; Li, M; Zhao, Y; Zeng, X

2016-05-01

To investigate both the prevalence and clinical characteristics of serositis in Chinese patients with systemic lupus erythematosus (SLE) in a large cohort in the Chinese SLE Treatment and Research group (CSTAR) database. A prospective cross-sectional study of patients with SLE was conducted based on the data from the CSTAR registry. Serositis was defined according to the 1999 revised American College of Rheumatology (ACR) criteria for SLE - that is, pleuritis/pleural effusion and/or pericarditis/pericardial effusion detected by echocardiography, chest X-ray or chest computerized tomography (CT) scan. Peritonitis/peritoneal effusion were confirmed by abdominal ultrasonography. We analysed the prevalence and clinical associations of serositis with demographic data, organ involvements, laboratory findings and SLE disease activity. Of 2104 patients with SLE, 345 were diagnosed with serositis. The prevalence of lupus nephritis (LN), interstitial lung disease and pulmonary arterial hypertension, as well as the presence of leukocytopenia, thrombocytopenia, hypocomplementemia and anti-dsDNA antibodies was significantly higher in patients with serositis (P Lupus-related peritonitis had similar clinical manifestations and laboratory profiles as serositis caused by SLE. There is a significant association of nephropathy, interstitial lung disease, pulmonary arterial hypertension, hypocomplementemia, leukocytopenia, thrombocytopenia and elevated anti-dsDNA antibodies with serositis. The results suggest that higher SLE disease activity contributes to serositis development, and should be treated aggressively. © The Author(s) 2016.

Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis.

Science.gov (United States)

Negi, Vir S; Devaraju, Panneer; Gulati, Reena

2015-09-01

SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40-75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian

Surface complement C3 fragments and cellular binding of microparticles in patients with SLE

DEFF Research Database (Denmark)

Winberg, Line Kjær; Nielsen, Claus Henrik; Jacobsen, Søren

2017-01-01

Objectives: To examine microparticles (MPs) from patients with SLE and healthy controls (HCs) by determining the cellular origin of the MPs, quantifying attached fragments of complement component 3 (C3) and assessing the ability of MPs to bind to circulating phagocytes and erythrocytes. These fea......Objectives: To examine microparticles (MPs) from patients with SLE and healthy controls (HCs) by determining the cellular origin of the MPs, quantifying attached fragments of complement component 3 (C3) and assessing the ability of MPs to bind to circulating phagocytes and erythrocytes...

Sex influences eQTL effects of SLE and Sjögren's syndrome-associated genetic polymorphisms.

Science.gov (United States)

Lindén, Magdalena; Ramírez Sepúlveda, Jorge I; James, Tojo; Thorlacius, Gudny Ella; Brauner, Susanna; Gómez-Cabrero, David; Olsson, Tomas; Kockum, Ingrid; Wahren-Herlenius, Marie

2017-10-25

Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects. We used genome-wide genotype and gene expression data from primary B cells from 125 males and 162 females. The MatrixEQTL R package was used to identify eQTLs within a genomic window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex interaction term. We found ten SNPs affecting the expression of 16 different genes (FDR rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D, rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune compartment and B cells. By analyzing the SNP * sex interaction terms, we identified six genes with differentially regulated expression in females compared to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1 locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus), and DHX9 (NCF2 locus). We identified several unknown sex-specific eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel insight into how gene-sex interactions may contribute to the sex bias in systemic autoimmune diseases.

Depression and ways of coping in SLE induced arthritis patient: a case study

International Nuclear Information System (INIS)

Farah, D.; Nezam, N.; Naz, H.

2012-01-01

Systemic lupus erythematosus is a systemic autoimmune disease (autoimmune connective tissue disease) that most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system. One of the outcomes of SLE is arthritis which is a group of conditions involving damage to the joints of the body. One of the most common types is rheumatoid arthritis which is an autoimmune immune disease. This SLE induced arthritis has many impacts on every aspect of life including biological, psychological, social and - financial domains. In most of the cases arthritis is associated With depression and anxiety. It is envisaged that people with arthritis suffer more from depression as compared to general population. The present study was designed to evaluate depression using lung Self Rating Scale and coping using two scales: Ways of Coping and Coping Self Efficacy in a 27 years old female participant with SLE induced Arthritis. The results of the two paradigms and detailed case history revealed that the level of depression lies in the normal range that coincides with the use of effective coping strategies. Thus the participant's positive outlook enabled to improve the quality of life. (author)

Localization of radiolabeled anti-DNA monoclonal antibodies in murine systemic lupus erythematosus (SLE)

International Nuclear Information System (INIS)

Wahl, R.; Hahn, B.; Ebling, F.

1984-01-01

The diagnosis of SLE can be extremely difficult. This multi-system disease is characterized by the deposition of DNA-anti-DNA antibody (Ab) complexes in many tissues, producing glomerulonephritis and systemic vasculitis. This study evaluates an IGG monoclonal (Mo) Ab directe3d against DNA (MrSSl) for potential radioimmunodiagnosis of SLE. Six 15 wk. old F-1 female hybrids of NZB+NZW mice (an animal SLE model that develops vasculitis and nephritis) were injected with 50 μCl of I-131 MrSSl and 15 μCl of I-125 isotype-matched control mouse myeloma (LPC-1) (non-reactive with DNA). Imaging and tissue distribution were studied. Two animals were also imaged using I-131 LPC Ab. Images at 2 and 9 days showed no clear differences in scan patterns using MrSSl or LPC-1 Ab. Tissue distribution studies at six days, however, showed a significantly higher accumulation of MrSSl in the kidneys vs. control Ab (2.7% vs. 1.8% of injected dose) (p < .04). Similarly, higher levels of MrSS were also seen in the spleen, liver and lungs (p < .03). Blood levels tended to be higher with the specific antibody as well. These differences were not apparent at 3 days post injection. The increased concentration of MrSSl present at 9 days in several organs may be secondary to MrSSl binding to DNA containing immune complexes present in diseased tissues. Blocked clearance by immune complexes or DNA, or differences in electrical charges of the antibodies could be contributing to the higher MrSSl levels seen. Images did not suggest deiodination as responsible. Further studies are necessary to determine if the amount of MrSSl retained by diseased animals is indicative of SLE disease activity

Outcome of lupus nephritis in childhood onset SLE in North and Central India: single-centre experience over 25 years.

Science.gov (United States)

Srivastava, P; Abujam, B; Misra, R; Lawrence, A; Agarwal, V; Aggarwal, A

2016-04-01

Childhood SLE (cSLE) has a higher prevalence of lupus nephritis (LN), and there are ethnic variations in response to treatment as well as outcome of LN. There are limited data on long-term outcome of LN in cSLE from the Indian subcontinent. Retrospective analysis of case records of patients with cSLE (satisfying revised American College of Rheumatology (ACR) 1997 criteria for diagnosis) and age of onset Collaborating Clinics (SLICC)/ACR damage score was 0.79 ± 1.13. Actuarial ESRD-free survival at five, 10 and 15 years was 91.1%, 79% and 76.2%, and five-, 10- and 15-year renal survival was 93.8%, 87.1% and 84%, respectively. Although multiple factors individually predicted poor outcome (death/ESRD), only raised serum creatinine at onset (R square = 0.65, p ≤ 0.0001) and damage accrual (R square = 0.62, p ≤ 0.0001) remained significant on multivariate analysis. Eleven (8.2%) children died during the follow-up period, and infections were the leading cause of mortality. Long-term outcome of LN in cSLE in our cohort was better than previous reports from India. However, a high rate of major infection still remains the leading cause of mortality. © The Author(s) 2015.

3rd international software language engineering conference (SLE) : pre-proceedings, October 12-13, 2010, Eindhoven, the Netherlands

OpenAIRE

Brand, van den, M.G.J.; Malloy, B.; Staab, S.

2010-01-01

We are pleased to present the proceedings of the Third International Conference on Software Language Engineering (SLE 2010). The conference will be held in Eindhoven, the Netherlands during October 12-13, 2010 and will be co-located with The Ninth International Conference on Generative Programming and Component Engineering (GPCE'10), and The Workshop on Feature-Oriented Software Development (FOSD). An important goal of SLE is to integrate the different sub-communities of the software-language...

Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort

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Willis, R; Seif, AM; McGwin, G; Martinez-Martinez, LA; González, EB; Dang, N; Papalardo, E; Liu, J; Vilá, LM; Reveille, JD; Alarcón, GS; Pierangeli, SS

2013-01-01

Objective We sought to determine the effect of hydroxychloroquine therapy on the levels proinflammatory/prothrombotic markers and disease activity scores in patients with systemic lupus erythematosus (SLE) in a multiethnic, multi-center cohort (LUMINA). Methods Plasma/serum samples from SLE patients (n=35) were evaluated at baseline and after hydroxychloroquine treatment. Disease activity was assessed using SLAM-R scores. Interferon (IFN)-α2, interleukin (IL)-1β, IL-6, IL-8, inducible protein (IP)-10, monocyte chemotactic protein-1, tumor necrosis factor (TNF)-α and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Anticardiolipin antibodies were evaluated using ELISA assays. Thirty-two frequency-matched plasma/serum samples from healthy donors were used as controls. Results Levels of IL-6, IP-10, sCD40L, IFN-α and TNF-α were significantly elevated in SLE patients versus controls. There was a positive but moderate correlation between SLAM-R scores at baseline and levels of IFN-α (p=0.0546). Hydroxychloroquine therapy resulted in a significant decrease in SLAM-R scores (p=0.0157), and the decrease in SLAM-R after hydroxychloroquine therapy strongly correlated with decreases in IFN-α (p=0.0087). Conclusions Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients, which strongly correlated with reductions in IFN-α levels. This indicates an important role for the inhibition of endogenous TLR activation in the action of hydroxychloroquine in SLE and provides additional evidence for the importance of type I interferons in the pathogenesis of SLE. This study underscores the use of hydroxychloroquine in the treatment of SLE. PMID:22343096

Damage in the Multiethnic Malaysian Systemic Lupus Erythematosus (SLE) Cohort: Comparison with Other Cohorts Worldwide

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Shaharir, Syahrul Sazliyana; Hussein, Heselynn; Rajalingham, Sakthiswary; Mohamed Said, Mohd Shahrir; Abdul Gafor, Abdul Halim; Mohd, Rozita; Mustafar, Ruslinda

2016-01-01

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and despite the improvement in the survival in the past few decades, the morbidity due to disease damage remains significant. The objectives of this study were to investigate the disease damagepattern and determine the associated factors of damage in the multi-ethnic Malaysian SLE patients. We consecutively 424SLE patients who attended a consistent follow-up at the National University of Malaysia Medical Centre and Putrajaya Hospital were recruited. Disease damage was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index (SDI) scores. Information on their demographics and disease characteristics were obtained from the clinical record. Univariate analysis was performed and the best model of independent predictors of disease damage was determined by multivariate logistic regression analysis. A total of 182 patients (42.9%) had disease damage (SDI ≥1). A significantly higher number of Indian patients had disease/organ damage and they predominantly developed steroid-induced diabetes mellitus (SDM). Patients with corticosteroid-induced osteoporosis (CIOP) were more likely to be Malayswhile majority of patients who developed malignancy were Chinese (p<0.05). In the univariate and multivariate analyses, disease damage was significantly associated with age, Indian ethnicity, lower mean cumulative C3 level, neuropsychiatry lupus (NPSLE), and antiphospholipid syndrome (APLS). Patients who had ever and early treatment with hydroxychloroquine(HCQ)were less likely to develop disease damage while more patients who had received oral prednisolone ≥1mg/kg daily over 2 weeks had disease damage (p<0.05). In conclusion, there were inter-ethnic differences in the damage pattern and risks among SLE patients. PMID:27846298

Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus

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Jing Li

2014-01-01

Full Text Available We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P<0.05 associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH; between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P<0.05. Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P<0.05. Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.

Demyelinating syndrome in SLE: review of different disease subtypes and report of a case series

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E. Chessa

2017-12-01

Full Text Available Demyelinating syndrome (DS is a rare manifestation of systemic lupus erythematosus (SLE (1% with high clinical heterogeneity and potentially severe prognosis. It can represent a diagnostic and therapeutic challenge for clinicians. A recent study described 5 different patterns of demyelinating disease presentation, characterised by specific clinical, laboratory and brain and spine magnetic resonance imaging abnormalities: 1 neuromyelitis optica; 2 neuromyelitis optica spectrum disorders; 3 DS prevalently involving the brain; 4 DS prevalently involving the brainstem; 5 clinically isolated syndrome. In this review we briefly discuss typical characteristics of each DS presentation in SLE and we describe 5 illustrative clinical cases, one for each subset of DS, considering both diagnostic and therapeutic options.

Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus

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Kovacs, Katalin T; Kalluri, Sudhakar Reddy; Boza-Serrano, Antonio

2016-01-01

BACKGROUND: Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. OBJECTIVE: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute...

Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes.

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Mecacci, Federico; Simeone, Serena; Cirami, Calogero Lino; Cozzolino, Mauro; Serena, Caterina; Rambaldi, Marianna Pina; Gallo, Pamela; Emmi, Lorenzo; Cammelli, Daniele; Mello, Giorgio; Matucci Cerinic, Marco

2017-11-27

Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol. Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χ 2 -test (significant values when p 1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

Detection of Catalase as a major protein target of the lipid peroxidation product 4-HNE and the lack of its genetic association as a risk factor in SLE

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Matsumoto Hiroyuki

2008-07-01

Full Text Available Abstract Background Systemic lupus erythematosus (SLE is a multifactorial disorder characterized by the presence of autoantibodies. We and others have implicated free radical mediated peroxidative damage in the pathogenesis of SLE. Since harmful free radical products are formed during this oxidative process, including 4-hydroxy 2-nonenol (4-HNE and malondialdehyde (MDA, we hypothesized that specific HNE-protein adducts would be present in SLE red blood cell (RBC membranes. Catalase is located on chromosome 11p13 where linkage analysis has revealed a marker in the same region of the genome among families with thrombocytopenia, a clinical manifestation associated with severe lupus in SLE affected pedigrees. Moreover, SLE afflicts African-Americans three times more frequently than their European-American counterparts. Hence we investigated the effects of a genetic polymorphism of catalase on risk and severity of SLE in 48 pedigrees with African American ancestry. Methods Tryptic digestion followed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS analysis was used to identify the protein modified by HNE, following Coomassie staining to visualize the bands on the acrylamide gels. Genotyping analysis for the C → T, -262 bp polymorphism in the promoter region of catalase was performed by PCR-RFLP and direct PCR-sequencing. We used a "pedigree disequilibrium test" for the family based association analysis, implemented in the PDT program to analyze the genotyping results. Results We found two proteins to be HNE-modified, migrating around 80 and 50 kD respectively. Tryptic digestion followed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS analysis of the Coomassie stained 80 kD band revealed that the target of HNE modification was catalase, a protein shown to associate with RBC membrane proteins. All the test statistics carried out on the genotyping analysis for the

The relationship between increased levels of Anti-dsDNA with clinical manifestation in patients with SLE in Haji Adam Malik General Hospital Medan

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Marpaung, B.; Patrick, J.

2018-03-01

Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease characterized by widespread inflammation and affects any organism the body. Many autoimmune diseases result in autoantibody production, but Anti-dsDNA antibodies are highly specific to SLE. Previous study found that Anti-dsDNA antibodies are associated with severe clinical manifestations of lupus. The aim of this study was to examine the relationship between anti-dsDNA level with clinical features and laboratory findings in SLE patients. This cross-sectional study was conducted in Hospital Haji Adam Malik Medan in May-October 2016.We examine anti-dsDNA, clinical features and kidney laboratory profile in all patient. Data were statistically analyzed.81 SLE patients with median level of anti-dsDNA 294 (6.1-1317). There was no significant relationship between increased level of Anti-dsDNA with clinical manifestations (p>0.05). There were significant relationships between increased level of Anti-dsDNA with renal impairment (p=0.049), urea level (p=0.016), urine protein (p=0.042) and hematology disorder (p=0.005). Arthritis is the most frequent clinical manifestation (96.3%) followed by malar rash (77.8%). Elevated anti-dsDNA level was not related with clinical manifestations but there was significant relationship with hematology disorder, urea, creatinine, and proteinuria in SLE patents.

Evaluation and treatment of acute psychosis in children with Systemic Lupus Erythematosus (SLE): consultation-liaison service experiences at a tertiary-care pediatric institution.

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Muscal, Eyal; Nadeem, Tania; Li, Xiofan; Mian, Ayesha; Harris, Toi Blakley

2010-01-01

Neurological and psychiatric manifestations of systemic lupus erythematosus (SLE) are prevalent in children with SLE. There are few data on the evaluation and management of psychotic features in children with this systemic autoimmune disorder. The authors describe contemporary Child and Adolescent Psychiatry Consultation and Liaison service management of acute psychosis in children with lupus. The authors reviewed the records (2003-2008) of all pediatric SLE inpatients who were administered a traditional or atypical antipsychotic agent. They describe clinical features, initial and discharge mental status examinations, and inpatient psychotropic medication usage. Ten pediatric SLE patients (age 10-19 years) required psychiatric management for psychosis during the review period. Paranoid delusions (70%), visual hallucinations (60%), and auditory hallucinations (60%) were the most common psychotic symptoms documented. All children were initially treated with an antipsychotic medication. Seven children were maintained on an atypical antipsychotic during their hospitalization. Two children had extrapyramidal signs, but no other adverse events were documented. All children were improved at discharge, and 40% had complete resolution of psychosis; 8 of the 10 patients were discharged on a psychotropic medication. Psychotic manifestations associated with severe disease presentations were successfully treated by child psychiatrists. Atypical antipsychotics were well-tolerated and used as an adjunct to immunosuppressive regimens in these patients. Prospective studies are necessary to improve the care of children and adolescents with SLE and severe psychiatric manifestations.

Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement

International Nuclear Information System (INIS)

Kikukawa, Kaoru; Toyama, Hiroshi; Katayama, Masao

2000-01-01

We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lode in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients. (author)

Microstructures and Microhardness Properties of CMSX-4® Additively Fabricated Through Scanning Laser Epitaxy (SLE)

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Basak, Amrita; Holenarasipura Raghu, Shashank; Das, Suman

2017-12-01

Epitaxial CMSX-4® deposition is achieved on CMSX-4® substrates through the scanning laser epitaxy (SLE) process. A thorough analysis is performed using various advanced material characterization techniques, namely high-resolution optical microscopy, scanning electron microscopy, energy-dispersive x-ray spectroscopy, x-ray diffraction, and Vickers microhardness measurements, to characterize and compare the quality of the SLE-fabricated CMSX-4® deposits to the CMSX-4® substrates. The results show that the CMSX-4® deposits have smaller primary dendritic arm spacing, finer γ/ γ' size, weaker elemental segregation, and higher microhardness compared to the investment cast CMSX-4® substrates. The results presented here demonstrate that CMSX-4® is an attractive material for laser-based AM processing and, therefore, can be used in the fabrication of gas turbine hot-section components through AM processing.

Investigations of a rabbit (Oryctolagus cuniculus model of systemic lupus erythematosus (SLE, BAFF and its receptors.

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Jiahui Yang

2009-12-01

Full Text Available B-cell activation factor belonging to the tumor necrosis factor family (BAFF is a major contributor to survival of B lymphocytes during development and maturation. A relationship between circulating BAFF levels and disease activity has been reported in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE. Clinical trials targeting BAFF or its receptors are currently in progress. In order to further characterize a rabbit (Oryctolagus cuniculus model of SLE, we investigated the expression of BAFF and its receptors in non-inbred, pedigreed rabbits derived from breeding and selection based on autoantibody responses. We immunized rabbits related to previous groups that developed autoantibodies and inflammatory responses after immunizations with peptides synthesized on multiple antigen-branched polylysine backbones. Blood and sera collected before immunization and after boosts were used for health monitoring, analyses of serum autoantibody responses by ELISA and immunofluorescence. Peripheral blood mononuclear cells (PBMC were studied by flow cytometry and were the source of mRNA for quantitative PCR analyses. We hypothesized that BAFF mRNA expression and serum BAFF levels measured indirectly through BAFF receptor binding might increase in autoantibody-producing rabbits. Immunized rabbits developed elevated levels of leucocyte populations, anti-nuclear, anti-dsDNA and other autoantibodies. BR3 mRNA levels in total PBMC decreased and BAFF levels remained low and unchanged in most immunized rabbits. By flow cytometry, percentages of BAFF positive cells decreased. Percentages of transmembrane activator and CAML interactor (TACI decreased in most rabbits from all the immunized groups. The rabbit is an important model for human autoimmune and infectious diseases, and a high quality draft rabbit genome assembly was recently completed. Human disease models developed in non-inbred pedigreed animals are better able to reflect the complexities

Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β on Clinical Manifestations in Indian SLE Patients

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Vinod Umare

2014-01-01

Full Text Available Systemic lupus erythematosus (SLE is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (P<0.001. Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL was significantly higher (P=0.0430 than those of inactive disease patients (43.85±63.36 pg/mL. Mean level of TNF-α was 44.76±68.32 pg/mL for patients with active disease while it was 25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161. Similar results were obtained for IL-1β (P=0.0002. Correlation between IL-6, TNF-α, and IL-1β serum levels and SLEDAI score was observed (r=0.20, r=0.27, and r=0.38, resp.. This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.

Complement receptor expression and activation of the complement cascade on B lymphocytes from patients with systemic lupus erythematosus (SLE)

DEFF Research Database (Denmark)

Marquart, H V; Svendsen, A; Rasmussen, J M

1995-01-01

It has previously been reported that the expression of the complement receptors, CR1 on erythrocytes and blood leucocytes and CR2 on B cells, is reduced in patients with SLE, and that the reduced expression of CR1 on erythrocytes is related to disease activity. We have earlier demonstrated...... that normal B cells are capable of activating the alternative pathway (AP) of complement in a CR2-dependent fashion. In this study we have investigated whether disturbances in this activity may be related to the altered phenotype of SLE B cells. Flow cytometry was used to measure expression of complement...

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

NARCIS (Netherlands)

Dieker, J.W.; Berden, J.H.; Bakker, M.A.; Briand, J.P.; Muller, S.; Voll, R.; Sjowall, C.; Herrmann, M.; Hilbrands, L.B.; Vlag, J. van der

2016-01-01

Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified

Association of the interferon signature metric with serological disease manifestations but not global activity scores in multiple cohorts of patients with SLE

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Kennedy, William P; Maciuca, Romeo; Wolslegel, Kristen; Tew, Wei; Abbas, Alexander R; Chaivorapol, Christina; Morimoto, Alyssa; McBride, Jacqueline M; Brunetta, Paul; Richardson, Bruce C; Davis, John C; Behrens, Timothy W; Townsend, Michael J

2015-01-01

Objectives The interferon (IFN) signature (IS) in patients with systemic lupus erythematosus (SLE) includes over 100 genes induced by type I IFN pathway activation. We developed a method to quantify the IS using three genes—the IS metric (ISM)—and characterised the clinical characteristics of patients with SLE with different ISM status from multiple clinical trials. Methods Blood microarray expression data from a training cohort of patients with SLE confirmed the presence of the IS and identified surrogate genes. We assayed these genes in a quantitative PCR (qPCR) assay, yielding an ISM from the IS. The association of ISM status with clinical disease characteristics was assessed in patients with extrarenal lupus and lupus nephritis from four clinical trials. Results Three genes, HERC5, EPSTI and CMPK2, correlated well with the IS (p>0.96), and composed the ISM qPCR assay. Using the 95th centile for healthy control data, patients with SLE from different studies were classified into two ISM subsets—ISM-Low and ISM-High—that are longitudinally stable over 36 weeks. Significant associations were identified between ISM-High status and higher titres of anti-dsDNA antibodies, presence of anti extractable nuclear antigen autoantibodies, elevated serum B cell activating factor of the tumour necrosis factor family (BAFF) levels, and hypocomplementaemia. However, measures of overall clinical disease activity were similar for ISM-High and ISM-Low groups. Conclusions The ISM is an IS biomarker that divides patients with SLE into two subpopulations—ISM-High and ISM-Low—with differing serological manifestations. The ISM does not distinguish between high and low disease activity, but may have utility in identifying patients more likely to respond to treatment(s) targeting IFN-α. Clinicaltrials.gov registration number NCT00962832. PMID:25861459

Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese.

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Yang, W; Ng, P; Zhao, M; Hirankarn, N; Lau, C S; Mok, C C; Chan, T M; Wong, R W S; Lee, K W; Mok, M Y; Wong, S N; Avihingsanon, Y; Lee, T L; Ho, M H K; Lee, P P W; Wong, W H S; Lau, Y L

2009-04-01

In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific.

High mobility group box1 (HMGB1) in relation to cutaneous inflammation in systemic lupus erythematosus (SLE)

NARCIS (Netherlands)

Abdulahad, D.A.; Westra, J.; Reefman, E.; Zuidersma, E.; Bijzet, J.; Limburg, P.C.; Kallenberg, C.G.M.; Bijl, M.

2013-01-01

Photosensitivity is characteristic of systemic lupus erythematosus (SLE). Upon ultraviolet B (UVB) exposure, patients develop inflammatory skin lesions in the vicinity of sunburn cells (SBCs). High mobility group box 1 (HMGB1) is released from apoptotic and activated cells and exerts inflammatory

3rd international software language engineering conference (SLE) : pre-proceedings, October 12-13, 2010, Eindhoven, the Netherlands

NARCIS (Netherlands)

Brand, van den M.G.J.; Malloy, B.; Staab, S.

2010-01-01

We are pleased to present the proceedings of the Third International Conference on Software Language Engineering (SLE 2010). The conference will be held in Eindhoven, the Netherlands during October 12-13, 2010 and will be co-located with The Ninth International Conference on Generative Programming

The national incidence and clinical picture of SLE in children in Australia - a report from the Australian Paediatric Surveillance Unit.

Science.gov (United States)

Mackie, F E; Kainer, G; Adib, N; Boros, C; Elliott, E J; Fahy, R; Munro, J; Murray, K; Rosenberg, A; Wainstein, B; Ziegler, J B; Singh-Grewal, D

2015-01-01

The objectives of this paper are to prospectively determine the incidence of paediatric systemic lupus erythematosus (pSLE) in Australia as well as describe the demographics, clinical presentation and one-year outcome. Newly diagnosed cases of pSLE were ascertained prospectively from October 2009 to October 2011 through the Australian Paediatric Surveillance Unit (a national monthly surveillance scheme for notification of childhood rare diseases) as well as national subspecialty groups. Questionnaires were sent to notifying physicians at presentation and at one year. The annual incidence rate was 0.32 per 10(5) children aged less than 16 years. The incidence was significantly higher in children of Asian or Australian Aboriginal and Torres Strait Islander parents. Approximately one-third of children underwent a renal biopsy at presentation and 7% required dialysis initially although only one child had end-stage kidney disease (ESKD) at one-year follow-up. The incidence of pSLE in Australia is comparable to that worldwide with a significantly higher incidence seen in children of Asian and Australian Aboriginal and Torres Strait Islander backgrounds. Renal involvement is common but progression to ESKD, at least in the short term, is rare. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Study on the brain CT scan of SLE patients

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Nagaoka, S; Narita, M; Katoh, K; Matsunaga, K; Ishigatsubo, Y [Yokohama City Univ. (Japan). Faculty of Medicine

1982-03-01

Cranial CT scanning revealed abnormality in 12 of 25 patients with SLE (48%). Ventricular sulcal enlargement was found mostly in younger patients between 16 and 36 years, an average of 25 years. Abnormality in electroencephalogram, principally paroxysmal abnormality, was found in 8 of 13 cases (62%) of normal CT findings. Non-paroxysmal slow-wave abnormality was observed in 9 of 12 abnormal CT cases. Of 13 patients with CNS symptoms, 8 had abnormal CT findings, and 5 had only mental disorder with normal CT findings. In 12 patients without neuropsychiatric involvement, 4 (33%) had abnormal CT findings. The rate of abnormal CT findings was increased in the patients receiving a high dosage of a steroid agent. Five of 6 patients who showed ventricular sulcal enlargement had been given prednisolone in a dosage of 35 mg or more per day.

Analysis of systemic lupus erythematosus (SLE) involving the central nervous system by magnetic resonance imaging (MRI)

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Suzuki, Kimihiro; Hara, Masako; Nakajima, Shinji and others

1989-04-01

Involvement of the central nervous system (CNS) commonly occurs in systemic lupus erythematosus (SLE). But definitive diagnosis remains difficult even with computed tomography (CT). In this study, we used the recently developed technique, magnetic resonance imaging (MRI) for CNS lupus and compared it with CT scans. CT was performed with a General Electric 8800 CT/T scanner. MRI was performed using a Mitsubishi Electric MMI-150 S. Ten patients with CNS lupus were divided into 3 groups. Group I included 4 cases with neurological manifestations alone. All lesions seen on CT were also detected by MRI, with greater clarity and extent. Furthermore, MRI depicted several microinfarcts in white matter without symptoms. Group II included 5 cases with psychiatric features alone. MRI detected a thalamic microinfarct in only one case while CT showed no abnormality in all cases. Group III included 1 case with both neurological and psychiatric symptoms. MRI demonstrated a small infarct of midbrain corresponding with neurological symptoms, more clearly than CT. Therefore MRI demonstrates the degree of brain involvement in SLE more accurately than CT. (author).

Analysis of systemic lupus erythematosus (SLE) involving the central nervous system by magnetic resonance imaging (MRI)

International Nuclear Information System (INIS)

Suzuki, Kimihiro; Hara, Masako; Nakajima, Shinji

1989-01-01

Involvement of the central nervous system (CNS) commonly occurs in systemic lupus erythematosus (SLE). But definitive diagnosis remains difficult even with computed tomography (CT). In this study, we used the recently developed technique, magnetic resonance imaging (MRI) for CNS lupus and compared it with CT scans. CT was performed with a General Electric 8800 CT/T scanner. MRI was performed using a Mitsubishi Electric MMI-150 S. Ten patients with CNS lupus were divided into 3 groups. Group I included 4 cases with neurological manifestations alone. All lesions seen on CT were also detected by MRI, with greater clarity and extent. Furthermore, MRI depicted several microinfarcts in white matter without symptoms. Group II included 5 cases with psychiatric features alone. MRI detected a thalamic microinfarct in only one case while CT showed no abnormality in all cases. Group III included 1 case with both neurological and psychiatric symptoms. MRI demonstrated a small infarct of midbrain corresponding with neurological symptoms, more clearly than CT. Therefore MRI demonstrates the degree of brain involvement in SLE more accurately than CT. (author)

Comparative transcriptional profiling of 3 murine models of SLE nephritis reveals both unique and shared regulatory networks.

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Ramalingam Bethunaickan

Full Text Available To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease.Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR.955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss.These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune-mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis.

Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE) : relation to lymphocyte activation and disease activity

NARCIS (Netherlands)

Bijl, M; Horst, G; Limburg, PC; Kallenberg, CGM

2001-01-01

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production, Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased Susceptibility to Fas-mediated apoptosis in

Associated factors and impact of myocarditis in patients with SLE from LUMINA, a multiethnic US cohort (LV). [corrected].

Science.gov (United States)

Apte, M; McGwin, G; Vilá, L M; Kaslow, R A; Alarcón, G S; Reveille, J D

2008-03-01

To examine the factors associated with myocarditis and its impact on disease outcomes in SLE patients. SLE patients aged > or = 16 yrs, disease duration NAture vs nurture), a multiethnic US cohort, were studied. Myocarditis was defined as per the category 3 of the pericarditis/myocarditis item of the SLAM-Revised (SLAM-R). Patients with concurrent pericardial involvement were excluded. Patients with myocarditis were compared with those without myocarditis or its sequelae in the preceding year. The association between myocarditis and baseline variables (T(0)) was first examined. The impact of myocarditis on disease activity over time (SLAM-R), damage accrual [SLICC Damage Index (SDI)] at last visit (T(L)) and mortality was evaluated. Fifty-three of the 496 patients studied had myocarditis. African American ethnicity [Odds ratio (OR) = 12.6; 95% CI 1.6, 97.8] and SLAM-R at diagnosis (OR = 1.1, 95% CI 1.0, 1.1) were significantly and independently associated with myocarditis. Myocarditis did not predict disease activity over time, but approached significance as a predictor of SDI at T(L) in multivariable analyses P = 0.051. Kaplan-Meier curves indicated that myocarditis was associated with shorter survival (log-rank = 4.87, P = 0.02), particularly in patients with > or = 5 yrs disease; however, myocarditis was not retained in the Cox proportional hazards regression model. Ethnicity and disease activity at diagnosis were associated with the occurrence of myocarditis in SLE. Myocarditis did not significantly impact on disease activity over time, but impacts some on damage accrual and survival, reflecting overall the more severe disease those patients experience.

The combination of two Sle2 lupus-susceptibility loci and Cdkn2c deficiency leads to T cell-mediated pathology in B6.Faslpr mice

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Xu, Zhiwei; Croker, Byron P.; Morel, Laurence

2013-01-01

The NZM2410 Sle2c1 lupus susceptibility locus is responsible for the expansion of the B1a cell compartment and for the induction of T-cell induced renal and skin pathology on a CD95 deficient (Faslpr)-background. We have previously shown that deficiency in cyclin-dependent kinase inhibitor p18INK4c (p18) was responsible for the B1a cell expansion but was not sufficient to account for the pathology in B6.lpr mice. This study was designed to map the additional Sle2c1 loci responsible for autoimmune pathology when co-expressed with CD95 deficiency. The production, fine-mapping and phenotypic characterization of five recombinant intervals indicated that three interacting sub-loci were responsive for inducting autoimmune pathogenesis in B6.lpr mice. One of these sub-loci corresponds most likely to p18-deficiency. Another major locus mapping to a 2 Mb region at the telomeric end of Sle2c1 is necessary to both renal and skin pathology. Finally, a third locus centromeric to p18 enhances the severity of lupus nephritis. These results provide new insights into the genetic interactions leading to SLE disease presentation, and represent a major step towards the identification of novel susceptibility genes involved in T-cell mediated organ damage. PMID:23698709

Mice, humans and haplotypes--the hunt for disease genes in SLE.

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Rigby, R J; Fernando, M M A; Vyse, T J

2006-09-01

Defining the polymorphisms that contribute to the development of complex genetic disease traits is a challenging, although increasingly tractable problem. Historically, the technical difficulties in conducting association studies across the entire human genome are such that murine models have been used to generate candidate genes for analysis in human complex diseases, such as SLE. In this article we discuss the advantages and disadvantages of this approach and specifically address some assumptions made in the transition from studying one species to another, using lupus as an example. These issues include differences in genetic structure and genetic organisation which are a reflection on the population history. Clearly there are major differences in the histories of the human population and inbred laboratory strains of mice. Both human and murine genomes do exhibit structure at the genetic level. That is to say, they comprise haplotypes which are genomic regions that carry runs of polymorphisms that are not independently inherited. Haplotypes therefore reduce the number of combinations of the polymorphisms in the DNA in that region and facilitate the identification of disease susceptibility genes in both mice and humans. There are now novel means of generating candidate genes in SLE using mutagenesis (with ENU) in mice and identifying mice that generate antinuclear autoimmunity. In addition, murine models still provide a valuable means of exploring the functional consequences of genetic variation. However, advances in technology are such that human geneticists can now screen large fractions of the human genome for disease associations using microchip technologies that provide information on upwards of 100,000 different polymorphisms. These approaches are aimed at identifying haplotypes that carry disease susceptibility mutations and rely less on the generation of candidate genes.

Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE)

DEFF Research Database (Denmark)

Li, Yan; Eskelund, Amanda; Zhou, H

2015-01-01

pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction...

Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies.

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Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

2014-01-01

SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP(®)) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis.

The Sarawak lupus cohort: clinical features and disease patterns of 633 SLE patients in a single tertiary centre from East Malaysia.

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Teh, C L; Ling, G R; Aishah, Wan Sharifah

2015-01-01

Systemic lupus erythematosus (SLE) has been well studied in West Malaysian populations but lacking in East Malaysian populations. The aim of this study was to examine the clinical features and disease patterns of patients with SLE in a multiethnic East Malaysian population in Sarawak. All SLE patients who were treated in Sarawak General Hospital were reviewed in a retrospective longitudinal study using a standard protocol from 1 January 2006 to 31 December 2013. There were a total of 633 patients in our study with the female to male ratio of 12:1. Our study patients were of multiethnic origins with predominant Chinese ethnic group. They had a mean age of 36.9 ± 13.2 years and a mean duration of illness of 7.2 ± 6.0 years. The main involvements were haematological (74.2 %), malar rash (64.0 %) and renal (58.6 %). Chinese patients were less likely to have discoid lupus, pleuritis and pericarditis, while Malay patients were more likely to have arthritis. Bidayuh patients were more likely to have oral ulcer. Secondary antiphospholipid syndrome was more common in Chinese. The majority of patients were in clinical remission with low SDI. There were 58 deaths (9.2 %) during 2006-2013 with the main causes of death being flare of disease and infection.

U-Net/SLE: A Java-Based User-Customizable Virtual Network Interface

Directory of Open Access Journals (Sweden)

Matt Welsh

1999-01-01

Full Text Available We describe U‐Net/SLE (Safe Language Extensions, a user‐level network interface architecture which enables per‐application customization of communication semantics through downloading of user extension applets, implemented as Java classfiles, to the network interface. This architecture permits applications to safely specify code to be executed within the NI on message transmission and reception. By leveraging the existing U‐Net model, applications may implement protocol code at the user level, within the NI, or using some combination of the two. Our current implementation, using the Myricom Myrinet interface and a small Java Virtual Machine subset, allows host communication overhead to be reduced and improves the overlap of communication and computation during protocol processing.

The effect of Ramadan fasting on quiescent systemic lupus erythematosus (SLE) patients' disease activity, health quality of life and lipid profile: a pilot study.

Science.gov (United States)

Goharifar, Hamid; Faezi, Seyedeh Tahereh; Paragomi, Pedram; Montazeri, Ali; Banihashemi, Arash Tehrani; Akhlaghkhah, Maryam; Abdollahi, Bahar Sadeghi; Kamazani, Zahra; Akbarian, Mahmood

2015-08-01

SLE is a common autoimmune disease with considerable morbidity. Ramadan fasting is a religious custom Muslims regularly practice. We aimed to evaluate the effect of Ramadan fasting on SLE patients' disease activity, health quality of life and lipid profile. We conducted this case control study as a pilot study in 40 quiescent SLE patients, 21 cases who decided to fast and 19 controls who decided not to have Ramadan fasting between August and November 2009 in lupus unit of Rheumatology Research Center in Tehran University of Medical Sciences, Iran. They were assessed for SLE Disease Activity Index, lipid profile and quality of life with Short-Form 36 (SF-36) Health Survey, 1 day before Ramadan, the day after and 3 months after Ramadan fasting. After 24.1 ± 5.4 (mean ± SD) days of fasting, anti-ds DNA increased for 0.34 ± 0.41 mmol/dL in cases versus 0.07 ± 0.31 in controls (P = 0.026). Likewise C3 increased more dramatically in cases (16.8 ± 17.5 vs. 2.3 ± 13.2 mg/dL, P = 0.006). Three months after fasting, anti-ds DNA was still increased 0.28 ± 0.46 mmol/dL in cases while a 0.02 ± 0.43 mmol/dL drop in controls was detected (P = 0.04). On the contrary, C3 returned to baseline. These changes were not accompanied with significant changes in disease activity and health quality of life. Ramadan fasting had no effect on lipid profile except for delayed total cholesterol decrease in cases in comparison with controls (16.4 ± 29.4 decrease vs. 4.6 ± 23.9 mg/dL decrease, P = 0.018). Ramadan fasting probably has no detrimental effect on SLE patients' disease activity and their quality of life in the quiescent phase of disease.

Expression and methylation data from SLE patient and healthy control blood samples subdivided with respect to ARID3a levels

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Julie M. Ward

2016-12-01

Full Text Available Previously published studies revealed that variation in expression of the DNA-binding protein ARID3a in B lymphocytes from patients with systemic lupus erythematosus (SLE correlated with levels of disease activity (“Disease activity in systemic lupus erythematosus correlates with expression of the transcription factor AT-rich-interactive domain 3A” (J.M. Ward, K. Rose, C. Montgomery, I. Adrianto, J.A. James, J.T. Merrill et al., 2014 [1]. The data presented here compare DNA methylation patterns from SLE peripheral blood mononuclear cells obtained from samples with high numbers of ARID3a expressing B cells (ARID3aH versus SLE samples with normal numbers of ARID3a+ B cells (ARID3aN. The methylation data is available at the gene expression omnibus (GEO repository, “Gene Expression Omnibus: NCBI gene expression and hybridization array data repository” (R. Edgar, M. Domrachev, A.E. Lash, 2002 [2]. Isolated B cells from SLE ARID3aH and ARID3aN B samples were also evaluated via qRT-PCR for Type I interferon (IFN signature and pathway gene expression levels by qRT-PCR. Similarly, healthy control B cells and B cells stimulated to express ARID3a with the TLR agonist, CpG, were also compared via qRT-PCR. Primers designed to detect 6 IFNa subtype mRNAs were tested in 4 IFNa, Epstein-Barr Virus-transformed B cell lines (“Reduced interferon-alpha production by Epstein-Barr virus transformed B-lymphoblastoid cell lines and lectin-stimulated lymphocytes in congenital dyserythropoietic anemia type I” (S.H. Wickramasinghe, R. Hasan, J. Smythe, 1997 [3]. The data in this article support the publication, “Human effector B lymphocytes express ARID3a and secrete interferon alpha” (J.M. Ward, M.L. Ratliff, M.G. Dozmorov, G. Wiley, J.M. Guthridge, P.M. Gaffney, J.A. James, C.F. Webb, 2016 [4].

A Solution Space for a System of Null-State Partial Differential Equations: Part 4

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Flores, Steven M.; Kleban, Peter

2015-01-01

This article is the last of four that completely and rigorously characterize a solution space for a homogeneous system of 2 N + 3 linear partial differential equations in 2 N variables that arises in conformal field theory (CFT) and multiple Schramm-Löwner evolution (SLE). The system comprises 2 N null-state equations and three conformal Ward identities that govern CFT correlation functions of 2 N one-leg boundary operators. In the first two articles (Flores and Kleban in Commun Math Phys, 2012; Flores and Kleban, in Commun Math Phys, 2014), we use methods of analysis and linear algebra to prove that dim , with C N the Nth Catalan number. Using these results in the third article (Flores and Kleban, in Commun Math Phys, 2013), we prove that dim and is spanned by (real-valued) solutions constructed with the Coulomb gas (contour integral) formalism of CFT. In this article, we use these results to prove some facts concerning the solution space . First, we show that each of its elements equals a sum of at most two distinct Frobenius series in powers of the difference between two adjacent points (unless is odd, in which case a logarithmic term may appear). This establishes an important element in the operator product expansion for one-leg boundary operators, assumed in CFT. We also identify particular elements of , which we call connectivity weights, and exploit their special properties to conjecture a formula for the probability that the curves of a multiple-SLE process join in a particular connectivity. This leads to new formulas for crossing probabilities of critical lattice models inside polygons with a free/fixed side-alternating boundary condition, which we derive in Flores et al. (Partition functions and crossing probabilities for critical systems inside polygons, in preparation). Finally, we propose a reason for why the exceptional speeds [certain values that appeared in the analysis of the Coulomb gas solutions in Flores and Kleban (Commun Math Phys, 2013)] and

The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus

Science.gov (United States)

Liu, Qian; Wang, Xing; Qin, Juanxiu; Cheng, Sen; Yeo, Won-Sik; He, Lei; Ma, Xiaowei; Liu, Xiaoyun; Li, Min; Bae, Taeok

2017-01-01

Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA). The increase of the protein was, at least in part, due to the reduced protease activity of the mutant, which was caused by the decreased activity of agr. On the other hand, the increase of eDNA was due to increased cell lysis caused by the higher level of Sle1. Indeed, as compared with wild type, the clpP mutant excreted an increased level of eDNA, and showed higher sensitivity to Triton-induced autolysis. The deletion of sle1 in the clpP mutant decreased the biofilm formation, the level of eDNA, and the Triton-induced autolysis to wild-type levels. Despite the increased biofilm formation capability, however, the clpP mutant showed significantly reduced virulence in a murine model of subcutaneous foreign body infection, indicating that the increased biofilm formation capability cannot compensate for the intrinsic functions of ClpP during infection. PMID:28555174

The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus

Directory of Open Access Journals (Sweden)

Qian Liu

2017-05-01

Full Text Available Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA. The increase of the protein was, at least in part, due to the reduced protease activity of the mutant, which was caused by the decreased activity of agr. On the other hand, the increase of eDNA was due to increased cell lysis caused by the higher level of Sle1. Indeed, as compared with wild type, the clpP mutant excreted an increased level of eDNA, and showed higher sensitivity to Triton-induced autolysis. The deletion of sle1 in the clpP mutant decreased the biofilm formation, the level of eDNA, and the Triton-induced autolysis to wild-type levels. Despite the increased biofilm formation capability, however, the clpP mutant showed significantly reduced virulence in a murine model of subcutaneous foreign body infection, indicating that the increased biofilm formation capability cannot compensate for the intrinsic functions of ClpP during infection.

Recent advances in percolation theory and its applications

Energy Technology Data Exchange (ETDEWEB)

Saberi, Abbas Ali, E-mail: ab.saberi@ut.ac.ir

2015-05-24

Percolation is the simplest fundamental model in statistical mechanics that exhibits phase transitions signaled by the emergence of a giant connected component. Despite its very simple rules, percolation theory has successfully been applied to describe a large variety of natural, technological and social systems. Percolation models serve as important universality classes in critical phenomena characterized by a set of critical exponents which correspond to a rich fractal and scaling structure of their geometric features. We will first outline the basic features of the ordinary model. Over the years a variety of percolation models has been introduced some of which with completely different scaling and universal properties from the original model with either continuous or discontinuous transitions depending on the control parameter, dimensionality and the type of the underlying rules and networks. We will try to take a glimpse at a number of selective variations including Achlioptas process, half-restricted process and spanning cluster-avoiding process as examples of the so-called explosive percolation. We will also introduce non-self-averaging percolation and discuss correlated percolation and bootstrap percolation with special emphasis on their recent progress. Directed percolation process will be also discussed as a prototype of systems displaying a nonequilibrium phase transition into an absorbing state. In the past decade, after the invention of stochastic Löwner evolution (SLE) by Oded Schramm, two-dimensional (2D) percolation has become a central problem in probability theory leading to the two recent Fields medals. After a short review on SLE, we will provide an overview on existence of the scaling limit and conformal invariance of the critical percolation. We will also establish a connection with the magnetic models based on the percolation properties of the Fortuin–Kasteleyn and geometric spin clusters. As an application we will discuss how percolation

Recent advances in percolation theory and its applications

Science.gov (United States)

Saberi, Abbas Ali

2015-05-01

Percolation is the simplest fundamental model in statistical mechanics that exhibits phase transitions signaled by the emergence of a giant connected component. Despite its very simple rules, percolation theory has successfully been applied to describe a large variety of natural, technological and social systems. Percolation models serve as important universality classes in critical phenomena characterized by a set of critical exponents which correspond to a rich fractal and scaling structure of their geometric features. We will first outline the basic features of the ordinary model. Over the years a variety of percolation models has been introduced some of which with completely different scaling and universal properties from the original model with either continuous or discontinuous transitions depending on the control parameter, dimensionality and the type of the underlying rules and networks. We will try to take a glimpse at a number of selective variations including Achlioptas process, half-restricted process and spanning cluster-avoiding process as examples of the so-called explosive percolation. We will also introduce non-self-averaging percolation and discuss correlated percolation and bootstrap percolation with special emphasis on their recent progress. Directed percolation process will be also discussed as a prototype of systems displaying a nonequilibrium phase transition into an absorbing state. In the past decade, after the invention of stochastic Löwner evolution (SLE) by Oded Schramm, two-dimensional (2D) percolation has become a central problem in probability theory leading to the two recent Fields medals. After a short review on SLE, we will provide an overview on existence of the scaling limit and conformal invariance of the critical percolation. We will also establish a connection with the magnetic models based on the percolation properties of the Fortuin-Kasteleyn and geometric spin clusters. As an application we will discuss how percolation

Recent advances in percolation theory and its applications

International Nuclear Information System (INIS)

Saberi, Abbas Ali

2015-01-01

Percolation is the simplest fundamental model in statistical mechanics that exhibits phase transitions signaled by the emergence of a giant connected component. Despite its very simple rules, percolation theory has successfully been applied to describe a large variety of natural, technological and social systems. Percolation models serve as important universality classes in critical phenomena characterized by a set of critical exponents which correspond to a rich fractal and scaling structure of their geometric features. We will first outline the basic features of the ordinary model. Over the years a variety of percolation models has been introduced some of which with completely different scaling and universal properties from the original model with either continuous or discontinuous transitions depending on the control parameter, dimensionality and the type of the underlying rules and networks. We will try to take a glimpse at a number of selective variations including Achlioptas process, half-restricted process and spanning cluster-avoiding process as examples of the so-called explosive percolation. We will also introduce non-self-averaging percolation and discuss correlated percolation and bootstrap percolation with special emphasis on their recent progress. Directed percolation process will be also discussed as a prototype of systems displaying a nonequilibrium phase transition into an absorbing state. In the past decade, after the invention of stochastic Löwner evolution (SLE) by Oded Schramm, two-dimensional (2D) percolation has become a central problem in probability theory leading to the two recent Fields medals. After a short review on SLE, we will provide an overview on existence of the scaling limit and conformal invariance of the critical percolation. We will also establish a connection with the magnetic models based on the percolation properties of the Fortuin–Kasteleyn and geometric spin clusters. As an application we will discuss how percolation

Association between paraoxonase-1 gene Q192R and L55M polymorphisms in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) in a population from Cairo of Egypt.

Science.gov (United States)

Ibrahim, Alshaymaa Ahmed; El-Lebedy, Dalia; Ashmawy, Ingy; Hady, Maha Abdel

2017-06-01

Paraoxonase-1 (PON1) is involved in the oxidative stress process that cause tissue damage observed in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). The aim of the present study was to investigate the association of PON1 Q192R and L55M polymorphisms with risk of SLE and associated APS among Egyptian sample. The study included 120 SLE patients (45 without APS and 75 with APS) and 120 healthy subjects. PON1 Q192R and L55M polymorphisms were genotyped by real-time PCR. No significant differences in Q192R genotypes or allele frequencies were found between patients and controls (p = 0.5 and 0.1, respectively). The frequency of the 55M allele was significantly higher in SLE patients than in controls (66.6 vs. 43.3%), while the 55L allele was more frequent in controls (56.6%) than in patients (33.3%) (p = 0.03). The LL genotype was more frequent in controls (21.6%) than in patients (10%) while M allele carrier genotypes (LM + MM) were more frequent among patients (90%) than controls (78.3%), p = 0.04. Also, the 55M allele was more frequent in APS patients (73.3%) than in patients without APS (55.6%), p = 0.004. M allele carrier genotypes (LM + MM) was significantly higher among APS patients (95.4%) than in non-APS patients (80%), p = 0.008. Our results indicated that the PON1 L55M polymorphism associated with SLE and associated APS in a population from Cairo of Egypt, while the Q192R polymorphism plays no role in disease susceptibility. A large scale study to assess PON1 polymorphisms, PON1 activity, and markers of oxidative stress interaction is needed to clarify the role of PON-1 polymorphisms in the pathogenesis of SLE and associated APS.

"We Would Still Find Things to Talk About": Assessment of Mentor Perspectives in a Systemic Lupus Erythematosus Intervention to Improve Disease Self-Management, Empowering SLE Patients.

Science.gov (United States)

Flournoy-Floyd, Minnjuan; Ortiz, Kasim; Egede, Leonard; Oates, Jim C; Faith, Trevor D; Williams, Edith M

2018-04-01

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder with significant disparate impact on African American women. The current study sought to highlight how the Peer Approaches to Lupus Self-management (PALS) intervention worked bi-directionally wherein both women with SLE leading the disease self-management program (mentors), and those participants who served as mentees, were empowered toward greater disease self-efficacy. Data was captured for this study in two formats from the seven mentors participating in the pilot study: 1) mentor logs and 2) mentor interviews with the principle investigator. This information was then analyzed for themes relating to their experience within the study. We found that empowerment was facilitated by mentors taking their mentorship responsibilities seriously and seeking several avenues for collaboratively developing success with their mentees. Mentors reported that although challenges arose, their desire for success resulted in multiple approaches to be flexible and responsive to the needs of their mentees. Additionally, reciprocity was found to be a vital element of the program. Key thematic areas supported our ability to demonstrate the usefulness of a peer mentoring program for SLE disease self-management on evoking empowerment through reciprocal relationships among mentors and mentees within our study population. Furthermore the feedback from PALS participants yielded very rich and contextual information that can be used as a thematic guide for developing and refining evidence-based interventions that seek to incorporate empowerment into disease self-management efforts for women suffering from SLE. Copyright © 2018 National Medical Association. Published by Elsevier Inc. All rights reserved.

Conformally invariant processes in the plane

International Nuclear Information System (INIS)

Lawler, G.F.

2004-01-01

These lectures will focus on recent rigorous work on continuum limits of planar lattice models from statistical physics at criticality. For an introduction, I would like to discuss the general problem of critical exponents and scaling limits for lattice models in equilibrium statistical mechanics. There are a number of models, [e.g., self-avoiding walk (polymers), percolation, loop-erased random walk (uniform spanning trees, domino tilings), Ising model, Potts model, nonintersecting simple random walks] that fall under this general framework. These lectures will consider the case d = 2. Mathematicians are now starting to understand rigorously the scaling limit of two-dimensional systems. For most of these models, the general strategy can be described as: Construct possible continuum limits for these models. Show that there are only a limited number of such limits that are conformally invariant. Prove that the lattice model approaches the continuum limit. We should think of the first step as being similar for all of these models. We will spend the next couple of lectures discussing the continuum limits. One example you should already know - the scaling limit of simple random walk is Brownian motion (which in two dimensions is conformally invariant). The important new ideas are restriction measures and stochastic Loewner evolution (SLE). The later lectures will discuss rigorous results about lattice models approaching the continuum limit - we will discuss nonintersecting random walks (which can be shown to be equivalent to problems about exceptional sets of Brownian paths), percolation on the triangular lattice, and the loop-erased random walk. As a rule, the methods used for the second step are particular to each model

SLE disease patterns in a Danish population-based lupus cohort: an 8-year prospective study

DEFF Research Database (Denmark)

Laustrup, H; Voss, A; Green, A

2009-01-01

In 1995 all systemic lupus erythematosus (SLE) patients in the county of Funen were retrieved from four separate and independent sources as part of an 8-year prospective study to determine the pattern of disease activity and damage accumulation in a community based lupus cohort of predominantly...... Scandinavian ancestry. Incident cases were subsequently identified by surveillance of these sources. Established and new cases underwent annual, structured interviews, clinical examination and blood sampling. The Systemic Lupus Erythematosus Diseases Activity Index SLEDAI and Systemic Lupus International...

Complex analysis and dynamical systems new trends and open problems

CERN Document Server

Golberg, Anatoly; Jacobzon, Fiana; Shoikhet, David; Zalcman, Lawrence

2018-01-01

This book focuses on developments in complex dynamical systems and geometric function theory over the past decade, showing strong links with other areas of mathematics and the natural sciences. Traditional methods and approaches surface in physics and in the life and engineering sciences with increasing frequency – the Schramm‐Loewner evolution, Laplacian growth, and quadratic differentials are just a few typical examples. This book provides a representative overview of these processes and collects open problems in the various areas, while at the same time showing where and how each particular topic evolves. This volume is dedicated to the memory of Alexander Vasiliev.

Pathogenic and Epiphenomenal Anti-DNA Antibodies in SLE

Directory of Open Access Journals (Sweden)

Mirjana Pavlovic

2010-01-01

Full Text Available The discoveries of natural and the development of manufactured highly efficient catalytic antibodies (abzymes opens the door to many practical applications. One of the most fascinating is the use of such antibodies in human therapy and prevention (vaccination, of cancer, AIDS, autoimmune diseases. A special entity of naturally occurring DNA hydrolytic anti-DNA antibodies is emerging within past decades linked to autoimmune and lymphoproliferative disorders, such as systemic lupus erythematosus (SLE, multiple sclerosis (MS, Sjogren Syndrome (SS, B - Chronic lymphocytic leucosis (B-CLL, and Multiple Myeloma (MM. The origin of the antibodies is unknown. The underlying mechanisms of these activities are suggested to be penetration into the living cells and translocation in the nucleus, with recognition of the specific binding sites at particular (ss or ds DNA. There are controversies in the literature whether hydrolysis is a sequence-specific event. The interplay between anti-DNA antibodies and DNA is not yet elucidated. This molecular “twist” also suggests that anti-DNA antibodies with DNA hydrolytic capacity could be the organism's immune response to a microbial attack, with microbial DNA, or specific genes within microbial DNA sequence, as a target for neutralization. The catalytic antibody-based approach can become a key tool in selective chemotherapeutic strategies.

Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE: contribution to the self-organized criticality theory.

Science.gov (United States)

Miyazaki, Yumi; Tsumiyama, Ken; Yamane, Takashi; Ito, Mitsuhiro; Shiozawa, Shunichi

2013-04-18

We have developed a systems biology concept to explain the origin of systemic autoimmunity. From our studies of systemic lupus erythematosus (SLE) we have concluded that this disease is the inevitable consequence of over-stimulating the host's immune system by repeated exposure to antigen to levels that surpass a critical threshold, which we term the system's "self-organized criticality". We observed that overstimulation of CD4 T cells in mice led to the development of autoantibody-inducing CD4 T cells (aiCD4 T) capable of generating various autoantibodies and pathological lesions identical to those observed in SLE. We show here that this is accompanied by the significant expansion of a novel population of effector T cells characterized by expression of programmed death-1 (PD-1)-positive, CD27(low), CD127(low), CCR7(low) and CD44(high)CD62L(low) markers, as well as increased production of IL-2 and IL-6. In addition, repeated immunization caused the expansion of CD8 T cells into fully-matured cytotoxic T lymphocytes (CTL) that express Ly6C(high)CD122(high) effector and memory markers. Thus, overstimulation with antigen leads to the expansion of a novel effector CD4 T cell population that expresses an unusual memory marker, PD-1, and that may contribute to the pathogenesis of SLE.

Estudo-piloto: células NK nas gestantes com LES NK cells in pregnant patients with SLE: a preliminary study

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Alessandra Cardoso Pereira

2009-08-01

SLE. OBJECTIVE: To measure the amount of circulating NK cells and their viability in pregnant SLE patients. MATERIALS AND METHODS: Blood samples from four groups of ten patients each were evaluated: 1. GLES: Pregnant SLE patients; 2. PLES: Non-pregnant SLE patients; 3. Gcontrols: Pregnant controls; 4. Controls: Healthy non-pregnant women. In all patients the amount and viability of NK cells was measured by flow cytometry, as well as the total apoptosis by annexin V and propidium iodite staining. RESULTS: Due to the great variability, median of each group was used for evaluation: CD56+ count [GLES (0.10, PLES (0.12, Gcontrols (0.15, Controls (0.08]; total apoptosis (addition of initial and late apoptosis to total number of dead cells [GLES (0.06, PLES (0.04, Gcontrols (0.11, Controls (0.11]. The results for live cells count had low variability, so the averages and standard deviations were used for comparisons: [GLES (0.91±0.06, PLES (0.95±0.03, Gcontrols (0.86±0.11, Controls (0.88+0.08]. CONCLUSION: Although not statistically significant, the total apoptosis in the SLE groups was lower than in the control groups, and the live cell count was higher. This suggests that in SLE patients, pregnant or not, the NK cells have a prolonged life cycle (or have a lower/different turnover, and that there may be a higher immune stimulus making the NK cells take longer to activate the apoptosis process.

Course of Neuropsychiatric Symptoms during Flares of Systemic Lupus Erythematosus (SLE

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Gareth Garrett

2017-01-01

Full Text Available We present the case of a seventeen-year-old girl who presents with an interesting course of neuropsychiatric symptoms during several flares of SLE. The patient was diagnosed at the age of thirteen and has had four flares in total. The latter two flares included cutaneous and neuropsychiatric symptoms. The most recent flare occurred when she was aged seventeen. She had cutaneous symptoms which coincided with an episode of hypomania. Her mental state further deteriorated following steroid treatment. She exhibited affective and psychotic symptoms. Treatment with cyclophosphamide and olanzapine was associated with an improvement in both cutaneous and neuropsychiatric symptoms. Previously aged sixteen the patient had presented with cutaneous symptoms and a moderate depressive episode which was also exacerbated by steroid treatment. The patient’s mood improved when the dose of oral steroids was reduced to a daily dose of 15–20 mg prednisolone.

A Solution Space for a System of Null-State Partial Differential Equations: Part 1

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Flores, Steven M.; Kleban, Peter

2015-01-01

This article is the first of four that completely and rigorously characterize a solution space for a homogeneous system of 2 N + 3 linear partial differential equations (PDEs) in 2 N variables that arises in conformal field theory (CFT) and multiple Schramm-Löwner evolution (SLE). In CFT, these are null-state equations and conformal Ward identities. They govern partition functions for the continuum limit of a statistical cluster or loop-gas model, such as percolation, or more generally the Potts models and O( n) models, at the statistical mechanical critical point. (SLE partition functions also satisfy these equations.) For such a lattice model in a polygon with its 2 N sides exhibiting a free/fixed side-alternating boundary condition , this partition function is proportional to the CFT correlation function where the w i are the vertices of and where is a one-leg corner operator. (Partition functions for "crossing events" in which clusters join the fixed sides of in some specified connectivity are linear combinations of such correlation functions.) When conformally mapped onto the upper half-plane, methods of CFT show that this correlation function satisfies the system of PDEs that we consider. In this first article, we use methods of analysis to prove that the dimension of this solution space is no more than C N , the Nth Catalan number. While our motivations are based in CFT, our proofs are completely rigorous. This proof is contained entirely within this article, except for the proof of Lemma 14, which constitutes the second article (Flores and Kleban, in Commun Math Phys, arXiv:1404.0035, 2014). In the third article (Flores and Kleban, in Commun Math Phys, arXiv:1303.7182, 2013), we use the results of this article to prove that the solution space of this system of PDEs has dimension C N and is spanned by solutions constructed with the CFT Coulomb gas (contour integral) formalism. In the fourth article (Flores and Kleban, in Commun Math Phys, arXiv:1405

Defects in the Zeta Chain Expression (ζ in a Group of Patients with SLE, Scleroderma and Late-onset Arthritis, Colombia 2014

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Heber Siachoque-Montañez

2014-09-01

Full Text Available Introduction: Systemic Lupus Erythematosus (SLE, Scleroderma and late-onset arthritis are autoimmune inflammatory diseases (EIA characterized by autoantibody production and presence of abnormal T cells which generate defective immune response. The abnormal expression of key signaling molecules in the defective function of T-lymphocytes plays a significant role in the pathogenesis of autoimmune disease. The T-cells exhibit numerous abnormalities TCRζ1 signaling complex, these aberrations result in altered expression of cytokines and some biochemical events involved in the expression of surface molecules. Defects in the complex may be associated TCRζ to steroids used in autoimmune disease patients due to their powerful anti-inflammatory activity and immunosuppressive properties. The synthetic corticosteroids such as examethasone inhibit the transcriptional activity of some factors such as NFKB and AP-1, which regulate the synthesis of certain cytokines and could be involved in the TCRζ synthesis. Material and Methods: A case-control study, with a 1:1 ratio of cases and controls (13:13. Cases were patients with active autoimmune disease (6 patients with SLE, 5 patients with scleroderma and 2 patients with lateonset arthritis, who have not started treatment with corticosteroids. Controls were patients with no autoimmune disease. The diagnosis was made by the criteria established by the American College of Rheumatology for patients with SLE, scleroderma and late-onset arthritis. A 10 mL sample was obtained by venipuncture whole blood. Total RNA was extracted and RT-PCR was performed using a set of primers flanking a region of 138 base pairs involving exons 2, 3 and 4 of the ζ chain. Results: The values of Z chain amplification showed significant differences in patients with autoimmune disease (0.8214 } 0.1787, med = 0.7368 compared with the control group (0.9225 } 0.1272, med = 0.9830 (p = 0.045, Mann-Withney non-parametric one tailed exact

Poly(hydroxyethyl methacrylate) based affinity membranes for in vitro removal of anti-dsDNA antibodies from SLE plasma.

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Uzun, Lokman; Yavuz, Handan; Osman, Bilgen; Celik, Hamdi; Denizli, Adil

2010-07-01

The preparation of polymeric membrane using affinity technology for application in blood filtration devices is described here. DNA attached poly(hydroxyethyl methacrylate) (PHEMA) based microporous affinity membrane was prepared for selective removal of anti-dsDNA antibodies from systemic lupus erythematosus (SLE) patient plasma in in vitro. In order to further increase blood-compatibility of affinity membrane, aminoacid based comonomer N-methacryloyl-L-alanine (MAAL) was included in the polymerization recipe. PHEMAAL membrane was produced by a photopolymerization technique and then characterized by swelling tests and scanning electron microscope (SEM) studies. Blood-compatibility tests were also performed. The water swelling ratio of PHEMAAL membrane increased significantly (133.2%) compared with PHEMA (58%). PHEMAAL membrane has large pores around in the range of 5-10 microm. All the clotting times increased when compared with PHEMA membrane. Loss of platelets and leukocytes was very low. DNA loading was 7.8 mg/g. There was a very low anti-dsDNA-antibody adsorption onto the plain PHEMAAL membrane, about 78 IU/g. The PHEMAAL-DNA membrane adsorbed anti-dsDNA-antibody in the range of 10-68 x 10(3)IU/g from SLE plasma. Anti-dsDNA-antibody concentration decreased significantly from 875 to 144 IU/ml with the time. Anti-dsDNA-antibodies could be repeatedly adsorbed and eluted without noticeable loss in the anti-dsDNA-antibody adsorption amount. (c) 2010 Elsevier B.V. All rights reserved.

Interface dermatitis in skin lesions of Kikuchi-Fujimoto's disease: a histopathological marker of evolution into systemic lupus erythematosus?

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Paradela, S; Lorenzo, J; Martínez-Gómez, W; Yebra-Pimentel, T; Valbuena, L; Fonseca, E

2008-12-01

Kikuchi's disease (KD) is a self-limiting histiocytic necrotizing lymphadenitis (HNL). Cutaneous manifestations are frequent and usually show histopathological findings similar to those observed in the involved lymph nodes. HNL with superposed histological features to KD has been described in patients with lupus erythematosus (LE), and a group of healthy patients previously reported as having HNL may evolve into LE after several months. Up to date, features to predict which HNL patients will have a self-limiting disease and which could develop LE have been not identified. In order to clarify the characteristics of skin lesions associated with KD, we report a case of HNL with evolution into systemic lupus erythematosus (SLE) and a review of previous reports of KD with cutaneous manifestations. A 17-year-old woman presented with a 4-month history of fever and generalised lymphadenopathy. A diagnosis of HNL was established based on a lymph node biopsy. One month later, she developed an erythematoedematous rash on her upper body, with histopathological findings of interface dermatitis. After 8 months, anti-nuclear antibodies (ANA) at titre of 1/320, anti-DNA-ds antibodies and marked decrease of complement levels were detected. During the following 2 years, she developed diagnostic criteria for SLE, with arthralgias, pleuritis, aseptic meningitis, haemolytic anaemia and lupus nephritis. To our knowledge, 27 cases of nodal and cutaneous KD have been reported, 9 of which later developed LE. In all these patients, the skin biopsy revealed interface dermatitis. Skin biopsy revealed a pattern of interface dermatitis in all reviewed KD cases, which evolved into LE. Even this histopathological finding was not previously considered significant; it might be a marker of evolution into LE.

Pediatric Systemic Lupus Erythematosus: Learning From Longer Follow Up to Adulthood

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Giorgio Costagliola

2018-05-01

Full Text Available Background: Pediatric systemic lupus erythematosus (pSLE is a rare condition, representing approximately 10% of SLE cases. The aim of this study was to identify variables to improve the diagnostic awareness and management of pSLE patients.Methods: This retrospective study included 25 patients diagnosed with pSLE and followed at the University of Pisa. We collected data about clinical profile at disease onset and during a long-term follow-up, including disease activity, organ damage development, and treatments received.Results: The mean patient age at disease onset was 14.6 ± 1.6 years, and the mean follow-up period was 14.17 ± 8.04 years. The most common initial manifestations were arthritis, malar rash, and cytopenias. The median time to diagnosis since the first symptoms was 6 months, and was significantly longer in patients with hematological onset (54 months. During follow-up, the number of patients with renal involvement showed a significant increase, from 36% at diagnosis to 72.2% after 10 years of disease evolution. Patients who developed chronic organ damage maintained a higher time-averaged disease activity during follow-up and received a significantly higher dose of corticosteroids.Conclusion: Patients with immune cytopenia represent a group deserving strict clinical follow-up for the risk of evolution to SLE. Intense surveillance of renal function, early treatment and steroid-sparing strategies should be strongly considered in the management of pSLE patients.

Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

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Cai Ping; Koenig, Rolf; Boor, Paul J.; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

2008-01-01

Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice

Approaches to capturing the Black and White Tegu Salvator merianae (Squamata: Teiidae

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Renata C. Vieira

2015-08-01

Full Text Available ABSTRACT The use of traps is extremely important in several types of ecological studies, and may assist in the capture of individuals in areas that are difficult to access. In the present study, we compared the effectiveness of wooden (Schramm versus "Tomahawk" traps to capture Salvator merianae (Duméril & Bibron, 1839 lizards. The study was conducted in Eldorado do Sul, Rio Grande do Sul, Brazil. Field data were collected from August 2013 to March 2015, during the reproductive period of the species. The study involved two types of baited traps: i "Tomahawk", made of galvanized steel; and ii Schramm, a wooden trap. The capture rate of the Schramm wooden traps was 1.63 individuals/day, and of the "Tomahawk" was 0.36 individuals/day. These results are important for researchers working with large lizards and may help to increase sampling efficiency for these organisms.

Influence of molecular weight of DNA on the determination of anti-DNA antibodies in systemic lupus erythematosus (SLE) sera by radioimmunoassay

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Geisert, M; Heicke, B; Metzmann, E; Zahn, R K

1975-04-01

Using a radioimmunoassay (RIA) based on the Farr technique with radioactively labeled /sup 3/H-DNA for quantitative measurements of anti-DNA antibodies in sera of patients with systemic lupus erythematosus (SLE), the influence of molecular weight of DNA (ranging from 0.1 x 10/sup 6/ to 22.0 x 10/sup 6/ daltons) on binding and precipitation in this system has been investigated. Comparing our results with mathematical models it follows that one antibody molecule is fixed on the average to a statistical DNA segment of 2 x 10/sup 6/ to 4 x 10/sup 6/ daltons. Furthermore binding capacity of the DNA was found to be independent of the molecular weight, as demonstrated in a double label experiment using /sup 14/C and /sup 3/H-labeled DNA of different size. However, the amount of radioactivity precipitated was found to depend on the molecular weight of the labeled DNA following a non-linear function. It was calculated that a minimal ratio of fixed antibody molecules per a certain size of DNA was necessary for precipitation. The mathematical treatment of the observed non-linear precipitation dependence will be discussed using various statistical models. The results indicate that the quantitative measurements of anti-DNA antibodies with the Farr technique e.g., for diagnosis and control of SLE in clinical immunology is highly dependent on the molecular weight of the labeled DNA used in the assay system and reliable results are only obtained with DNA of a sufficiently high molecular weight. (auth)

Cosmic-ray acceleration and the radio evolution of Cassiopeia A

International Nuclear Information System (INIS)

Chevalier, R.A.; Robertson, J.W.; Scott, J.S.

1976-01-01

A more detailed analysis of the Scott and Chevalier model for production of galactic cosmic rays in supernova remnants is presented. Particles are accelerated by second-order Fermi acceleration with turbulent vortices (produced by the motions of the supernova ejecta through the remnant) acting as moving scattering centers. The time-dependent equation of continuity in particle energy space is solved numerically. The results of the calculations are in substantial agreement with all time-dependent observations of the radio emission from Cas A. This mechanism implies an dependent solution yields a cosmic ray spectrum with the same slope as galactic cosmic rays. The results of our calculations and new work on γ-rays by, e.g., Stecker and by Lingenfelter and Higdon and cosmic ray composition by, e.g., Hainebach, Norman, and Schramm support our hypothesis that galactic cosmic rays are produced in supernova remnants by the mechanism proposed by Scott and Chevalier

Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

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Durcan, Laura; Clarke, William A; Magder, Laurence S.; Petri, Michelle

2015-01-01

OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

STAT4 Associates with SLE Through Two Independent Effects that Correlate with Gene Expression and Act Additively with IRF5 to Increase Risk

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Abelson, Anna-Karin; Delgado-Vega, Angélica M.; Kozyrev, Sergey V.; Sánchez, Elena; Velázquez-Cruz, Rafael; Eriksson, Niclas; Wojcik, Jerome; Reddy, Prasad Linga; Lima, Guadalupe; D’Alfonso, Sandra; Migliaresi, Sergio; Baca, Vicente; Orozco, Lorena; Witte, Torsten; Ortego-Centeno, Norberto; Abderrahim, Hadi; Pons-Estel, Bernardo A.; Gutiérrez, Carmen; Suárez, Ana; González-Escribano, Maria Francisca; Martin, Javier; Alarcón-Riquelme, Marta E.

2013-01-01

Objectives To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. Methods 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5’-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. Results In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. Conclusions These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE. PMID:19019891

Equilibrium statistical mechanics of lattice models

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Lavis, David A

2015-01-01

Most interesting and difficult problems in equilibrium statistical mechanics concern models which exhibit phase transitions. For graduate students and more experienced researchers this book provides an invaluable reference source of approximate and exact solutions for a comprehensive range of such models. Part I contains background material on classical thermodynamics and statistical mechanics, together with a classification and survey of lattice models. The geometry of phase transitions is described and scaling theory is used to introduce critical exponents and scaling laws. An introduction is given to finite-size scaling, conformal invariance and Schramm—Loewner evolution. Part II contains accounts of classical mean-field methods. The parallels between Landau expansions and catastrophe theory are discussed and Ginzburg—Landau theory is introduced. The extension of mean-field theory to higher-orders is explored using the Kikuchi—Hijmans—De Boer hierarchy of approximations. In Part III the use of alge...

Cardiac manifestation's history in the systemic lupus erythematosus

International Nuclear Information System (INIS)

Iglesias Gamarra, Antonio; Rondon, Federico; Restrepo, Jose Felix

2001-01-01

In this paper it is broadly and in depth reviewed the cardiac manifestation's history of systemic lupus erythematosus (SLE), since an historical analysis of clinical manifestations both in pre and post corticosteroids period. The way how the heart and the cardiovascular system's functions have been studied by clinical and semiological views are showed, through clinical manifestations such as myocarditis pericarditis, endocarditis, rhythm alterations, etc, and the evolution of laboratory methods used to its study as well as immunologic prognostic markers and risk factors for coronary disease in SLE

Imunidade na gestação normal e na paciente com lúpus eritematoso sistêmico (LES Immunity in the normal pregnancy and in the patient with systemic lupus erythematosus (SLE

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Alessandra Cardoso Pereira

2005-06-01

Full Text Available A gravidez é uma condição fisiológica na qual ocorrem várias mudanças imunoendócrinas com a finalidade de facilitar a imunossupressão e a tolerância aos antígenos paternos e fetais. Na gravidez humana normal existe uma relativa supressão de citocinas tipo Th1 na resposta dos linfócitos, levando a uma prevalência na resposta do tipo Th2. No LES, onde prevalece a resposta imune do tipo Th2, a gravidez pode estar relacionada com a ativação da doença. Este artigo é uma revisão dessas alterações relacionadas com a resposta imune durante a gestação normal e na da paciente com LES.Pregnancy is a physiologic condition where several immuno-endocrine changes take place with the aim of facilitating immunosuppression and tolerance towards paternal and fetal antigens. In normal human pregnancy there is a relative suppression of Th1 type cytokines in response to lymphocytes, leading to a Th2 type response. In SLE, where a Th2 type response prevails, pregnancy may exacerbate the disease. This article reviews the alterations related to the immune response during normal pregnancy and in SLE patients.

[Coexisting systemic lupus erythematosus and sickle cell disease: case report and literature review].

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Robazzi, Teresa Cristina M V; Alves, Crésio; Abreu, Laís; Lemos, Gabriela

2015-01-01

To report a case of coexisting systemic lupus erythematosus (SLE) and sickle cell disease (SCD) with a review of the literature on the topic. Report of case and research of the association between SLE and SCD in literature through scientific articles in health sciences databases, such as LILACS, MEDLINE/Pubmed and Scielo, until May 2012. Descriptors used: 1. Sickle cell anemia; 2. Sickle cell disease; 3. Systemic lupus erythematosus; 4. Hemoglobinopathies. The authors describe an association between SLE and SS hemoglobinopathy in an eight-year-old female patient displaying articular, hematologic and neuropsychiatric manifestations during clinical evolution. Forty-five cases of association between SLE and SCD are described in literature, mostly adult (62.2%), women (78%) and with the SS phenotype in 78% of the cases, and different clinical manifestations. Compared with our patient, articular, hematologic and neuropsychiatric manifestations were present in 76%, 36% and 27% of the cases, respectively. SLE and SCD are chronic diseases that have several clinical and laboratory findings in common, meaning difficult diagnosis and difficulty in finding the correct treatment. Although the association between these diseases is not common, it is described in literature, so it is imperative that physicians who treat such diseases be alert to this possibility. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Research

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abp

2015-12-14

-up at the ... Mean gestational age at presentation and delivery was 13.0 ± 6.0 weeks and 28.9 ... evolution of SLE is known to be changed by natural hormonal .... anti-hypertensive agent - 23.0%, 2 or more anti-hypertensive.

Corrigendum | Schramm | African Journal of Aquatic Science

African Journals Online (AJOL)

It is editorial policy of the African Journal of Aquatic Science to follow the revised Acacia nomenclature, based on the retypification of the genus ratified by the XVIII International Botanical Congress in Melbourne in 2011 and subsequently published in Appendix III of the International Code of Nomenclature for algae, fungi ...

Supernova neutrinos

International Nuclear Information System (INIS)

Anon.

1990-01-01

In the first part of his in-depth article on the 1987 supernova, David Schramm of the University of Chicago and the NASA/Fermilab Astrophysics Centre reviewed the background to supernovae, the composition of massive stars and the optical history of SN 1987A, and speculated on what the 1987 remnant might be. In such a Type II supernova, gravitational pressure crushes the atoms of the star's interior producing neutron matter, or even a black hole, and releasing an intense burst of neutrinos. 1987 was the first time that physicists were equipped (but not entirely ready!) to intercept these particles, and in the second part of his article, David Schramm covers the remarkable new insights from the science of supernova neutrino astronomy, born on 23 February 1987

A Solution Space for a System of Null-State Partial Differential Equations: Part 2

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Flores, Steven M.; Kleban, Peter

2015-01-01

This article is the second of four that completely and rigorously characterize a solution space for a homogeneous system of 2 N + 3 linear partial differential equations in 2 N variables that arises in conformal field theory (CFT) and multiple Schramm-Löwner evolution (SLE). The system comprises 2 N null-state equations and three conformal Ward identities which govern CFT correlation functions of 2 N one-leg boundary operators. In the first article (Flores and Kleban, Commun Math Phys, arXiv:1212.2301, 2012), we use methods of analysis and linear algebra to prove that dim , with C N the Nth Catalan number. The analysis of that article is complete except for the proof of a lemma that it invokes. The purpose of this article is to provide that proof. The lemma states that if every interval among ( x 2, x 3), ( x 3, x 4),…,( x 2 N-1, x 2 N ) is a two-leg interval of (defined in Flores and Kleban, Commun Math Phys, arXiv:1212.2301, 2012), then F vanishes. Proving this lemma by contradiction, we show that the existence of such a nonzero function implies the existence of a non-vanishing CFT two-point function involving primary operators with different conformal weights, an impossibility. This proof (which is rigorous in spite of our occasional reference to CFT) involves two different types of estimates, those that give the asymptotic behavior of F as the length of one interval vanishes, and those that give this behavior as the lengths of two intervals vanish simultaneously. We derive these estimates by using Green functions to rewrite certain null-state PDEs as integral equations, combining other null-state PDEs to obtain Schauder interior estimates, and then repeatedly integrating the integral equations with these estimates until we obtain optimal bounds. Estimates in which two interval lengths vanish simultaneously divide into two cases: two adjacent intervals and two non-adjacent intervals. The analysis of the latter case is similar to that for one vanishing

A Solution Space for a System of Null-State Partial Differential Equations: Part 3

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Flores, Steven M.; Kleban, Peter

2015-01-01

This article is the third of four that completely and rigorously characterize a solution space for a homogeneous system of 2 N + 3 linear partial differential equations (PDEs) in 2 N variables that arises in conformal field theory (CFT) and multiple Schramm-Löwner evolution (SLE κ ). The system comprises 2 N null-state equations and three conformal Ward identities that govern CFT correlation functions of 2 N one-leg boundary operators. In the first two articles (Flores and Kleban, in Commun Math Phys, arXiv:1212.2301, 2012; Commun Math Phys, arXiv:1404.0035, 2014), we use methods of analysis and linear algebra to prove that dim , with C N the Nth Catalan number. Extending these results, we prove in this article that dim and entirely consists of (real-valued) solutions constructed with the CFT Coulomb gas (contour integral) formalism. In order to prove this claim, we show that a certain set of C N such solutions is linearly independent. Because the formulas for these solutions are complicated, we prove linear independence indirectly. We use the linear injective map of Lemma 15 in Flores and Kleban (Commun Math Phys, arXiv:1212.2301, 2012) to send each solution of the mentioned set to a vector in , whose components we find as inner products of elements in a Temperley-Lieb algebra. We gather these vectors together as columns of a symmetric matrix, with the form of a meander matrix. If the determinant of this matrix does not vanish, then the set of C N Coulomb gas solutions is linearly independent. And if this determinant does vanish, then we construct an alternative set of C N Coulomb gas solutions and follow a similar procedure to show that this set is linearly independent. The latter situation is closely related to CFT minimal models. We emphasize that, although the system of PDEs arises in CFT in away that is typically non-rigorous, our treatment of this system here and in Flores and Kleban (Commun Math Phys, arXiv:1212.2301, 2012; Commun Math Phys, arXiv:1404

[Depressive disorder in Mexican pediatric patients with systemic lupus erythematosus (SLE)].

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Carbajal-Alonso, Hilda Lilian; García-Moreno, Norberta Prisilia; Rodríguez-Arreola, Brenda; Barrera de León, Juan Carlos

2016-01-01

To identify the prevalence of depression in Mexican pediatric patients with systemic lupus erythematosus. Analytical transversal study including patients aged 7-16 years with a diagnosis of systemic lupus erythematosus seen at the Pediatric Rheumatology Consultation Service. The disease was classified by means of the MEX-SLEDAI questionnaire. Descriptive statistics with central tendency and dispersion and comparative measurements with chi-squared and Mann-Whitney U tests. Logistic regression and association with odds ratios. SPSS v.21.0 statistical software package. We evaluated 45 patients who presented depression, n=9 (20%), including eight females (89%) and one male (11%), median age 13 years (range, 7-16) in children with depression vs. 13 years (range, 9-14) p=0.941, depression more frequent in schoolchildren. Habitual residence, disease evolution time, and duration of the immunosuppressor did not show a significant difference between both groups. Divorced parents p=0.037. Neuropsychiatric manifestations of lupus presented in 2.2% of all patients and in 100% of patients with depression. Disease activity index (MEX-SLEDAI) did not demonstrate a relationship with the presence of depression. Prevalences in pediatric populations are less that that reported in adults, association with disease activity, evolution time, and immunosuppressor use and duration not found.

Trib1 Is Overexpressed in Systemic Lupus Erythematosus, While It Regulates Immunoglobulin Production in Murine B Cells

Directory of Open Access Journals (Sweden)

Léa Simoni

2018-03-01

Full Text Available Systemic lupus erythematosus (SLE is a severe and heterogeneous autoimmune disease with a complex genetic etiology, characterized by the production of various pathogenic autoantibodies, which participate in end-organ damages. The majority of human SLE occurs in adults as a polygenic disease, and clinical flares interspersed with silent phases of various lengths characterize the usual evolution of the disease in time. Trying to understand the mechanism of the different phenotypic traits of the disease, and considering the central role of B cells in SLE, we previously performed a detailed wide analysis of gene expression variation in B cells from quiescent SLE patients. This analysis pointed out an overexpression of TRIB1. TRIB1 is a pseudokinase that has been implicated in the development of leukemia and also metabolic disorders. It is hypothesized that Trib1 plays an adapter or scaffold function in signaling pathways, notably in MAPK pathways. Therefore, we planned to understand the functional significance of TRIB1 overexpression in B cells in SLE. We produced a new knock-in model with B-cell-specific overexpression of Trib1. We showed that overexpression of Trib1 specifically in B cells does not impact B cell development nor induce any development of SLE symptoms in the mice. By contrast, Trib1 has a negative regulatory function on the production of immunoglobulins, notably IgG1, but also on the production of autoantibodies in an induced model. We observed a decrease of Erk activation in BCR-stimulated Trib1 overexpressing B cells. Finally, we searched for Trib1 partners in B cells by proteomic analysis in order to explore the regulatory function of Trib1 in B cells. Interestingly, we find an interaction between Trib1 and CD72, a negative regulator of B cells whose deficiency in mice leads to the development of autoimmunity. In conclusion, the overexpression of Trib1 could be one of the molecular pathways implicated in the negative regulation

Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.

Science.gov (United States)

Cohen, H; Doré, C J; Clawson, S; Hunt, B J; Isenberg, D; Khamashta, M; Muirhead, N

2015-09-01

The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5. © The Author(s) 2015.

Renal expression of polyomavirus large T antigen is associated with nephritis in human systemic lupus erythematosus

DEFF Research Database (Denmark)

Fenton, Kristin Andreassen; Mjelle, Janne Erikke; Jacobsen, Søren

2008-01-01

) that these complexes bound induced anti-nucleosome antibodies and finally (iv) that they associated with glomerular membranes as immune complexes. This process may be relevant for human lupus nephritis, since productive polyomavirus infection is associated with this organ manifestation. Here, we compare nephritis...... to the evolution of lupus nephritis in human SLE....

The local limit of the uniform spanning tree on dense graphs

Czech Academy of Sciences Publication Activity Database

Hladký, Jan; Nachmias, A.; Tran, Tuan

First Online: 10 January (2018) ISSN 0022-4715 R&D Projects: GA ČR GJ16-07822Y Keywords : uniform spanning tree * graph limits * Benjamini-Schramm convergence * graphon * branching process Subject RIV: BA - General Mathematics Impact factor: 1.349, year: 2016

From the Gut of an Insect to the Global Climate: Denitrification and Nitrous Oxide Production inside Lake Chironomidae

DEFF Research Database (Denmark)

Stief, Peter; Nielsen, Lars Peter; Revsbech, Niels Peter

2006-01-01

FROM THE GUT OF AN INSECT TO THE GLOBAL CLIMATE: DENITRIFICATION AND NITROUS OXIDE PRODUCTION INSIDE LAKE CHIRONOMIDAE P. Stief, L.P. Nielsen, N.P. Revsbech, A. Schramm Department of Biological Sciences, Microbiology, University of Aarhus, Denmark Denitrifying bacteria in lake sediments drive...

Erosion behaviour of hydro turbine steels

Indian Academy of Sciences (India)

WINTEC

creases grain size hardening (Ikegami and Nemoto 1996). Nitrogen solubility ... 116. Table 1. Chemical composition of 13/4 martensitic and 21–4–N nitronic steel (wt %). Steel. C. Si Mn. Cr. Ni. N. S ..... In Fe–Cr–Ni alloys, Schramm and Reed ...

Fokker-Planck equation of the reduced Wigner function associated to an Ohmic quantum Langevin dynamics

Science.gov (United States)

Colmenares, Pedro J.

2018-05-01

This article has to do with the derivation and solution of the Fokker-Planck equation associated to the momentum-integrated Wigner function of a particle subjected to a harmonic external field in contact with an ohmic thermal bath of quantum harmonic oscillators. The strategy employed is a simplified version of the phenomenological approach of Schramm, Jung, and Grabert of interpreting the operators as c numbers to derive the quantum master equation arising from a twofold transformation of the Wigner function of the entire phase space. The statistical properties of the random noise comes from the integral functional theory of Grabert, Schramm, and Ingold. By means of a single Wigner transformation, a simpler equation than that mentioned before is found. The Wigner function reproduces the known results of the classical limit. This allowed us to rewrite the underdamped classical Langevin equation as a first-order stochastic differential equation with time-dependent drift and diffusion terms.

Ethics and the Press: Readings in Mass Media Morality.

Science.gov (United States)

Merrill, John C., Ed.; Barney, Ralph D., Ed.

This collection of 35 articles addresses the topic of the ethical considerations and implications involved in reporting the news. Included in this book are such articles as: "Ethics and Journalism" by John Merrill, "Quality in Mass Communications" by Wilbur Schramm, "The American Press: Some Truths About Truths" by…

Keila vabrikuala ideevõistluse võitsid noored Leedu arhitektid / Piret Peensoo

Index Scriptorium Estoniae

Peensoo, Piret

2007-01-01

Keila endise riidevabriku kinnistu planeerimise võistluse võitsid Leedu arhitektid Andrius Uogintas, Margarita Podagelyte ja Matas Cirtautas ("Active edge"), teise koha sai PiKaSch Architecture Studio Zoltan Schrammeli juhtimisel Ungarist ("Keila 14") ja kolmanda koha Hannes Koppel ja Sander Aas ("Kegel") arhitektuuribüroost Asum Arhitektid

Relations between the galactic evolution and the stellar evolution

International Nuclear Information System (INIS)

Audouze, J.

1984-01-01

After a quick definition of the galactic evolution and a summary of the basic ingredients (namely the abundances of the chemical elements observed in different astrophysical sites), the parameters directly related to the stellar evolution which govern the galactic evolution are outlined. They are the rates of star formation, the initial mass functions and the various nucleosynthetic yields. The 'classical' models of chemical evolution of galaxies are then briefly recalled. Finally, attention is drawn to three recent contributions concerning both the galactic evolution and the stellar evolution. They are (i) some prediction of the rate of star formation for low mass stars made from the planetary nebula abundance distribution (ii) the chemical evolution of C, O and Fe and (iii) the chemical evolution of the galactic interstellar medium. (Auth.)

A percolation process on the square lattice where large finite clusters are frozen

NARCIS (Netherlands)

van den Berg, J.; de Lima, B.N.B.; Nolin, P.

2012-01-01

In (Aldous, Math. Proc. Cambridge Philos. Soc. 128 (2000), 465-477), Aldous constructed a growth process for the binary tree where clusters freeze as soon as they become infinite. It was pointed out by Benjamini and Schramm that such a process does not exist for the square lattice. This motivated us

Microthrombotic renal involvement in an SLE patient with concomitant catastrophic antiphospholipid syndrome: the beneficial effect of rituximab treatment.

Science.gov (United States)

Diószegi, Á; Tarr, T; Nagy-Vincze, M; Nánásy-Vass, M; Veisz, R; Bidiga, L; Dezső, B; Balla, J; Szodoray, P; Szekanecz, Z; Soltész, P

2018-01-01

Antiphospholipid syndrome is characterized by multiple arterial and/or venous thrombotic events, recurrent fetal losses in the presence of antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome is a life-threatening, rare subset of antiphospholipid syndrome when the thrombotic events affect at least three organs, and clinical manifestations develop simultaneously or within a week. Diagnostically, small vessel occlusions can be detected by histopathology in the presence of aPL. Our case report describes an 18-year-old man who has been treated for antiphospholipid syndrome associated with systemic lupus erythematosus (SLE) since 2011. The clinical findings were dominated by recurrent deep vein thrombosis, and severe proteinuria caused by lupus nephritis, accompanied by mild serological and laboratory findings. The patient was hospitalized in March 2014 because of severe thrombocytopenia and infective diarrhoea. At this time the renal functions deteriorated rapidly. Simultaneously, left upper extremity paresis was observed; computed tomography showed ischaemic lesions in the territory of the middle cerebral artery. Abdominal discomfort and pain occurred. On computed tomography scan ischaemic lesions were seen in the spleen, the right kidney and the coeliac trunk. Laboratory and serological findings verified the presence of aPL and anti-DNA antibodies, anaemia and thrombocytopenia. Based on the above-mentioned clinical and laboratory findings, the diagnosis of catastrophic antiphospholipid syndrome was established. Anticoagulation, corticosteroids and plasma exchange treatment, as well as haemodiafiltration were initiated. Although the thrombotic cascade decelerated following these interventions, we could not see an improvement in the renal function. Rituximab treatment was started, leading to a significant improvement in renal function. After 5 weeks of treatment the patient was discharged from hospital.

46-Year Trends in Systemic Lupus Erythematosus Mortality in the United States, 1968 to 2013: A Nationwide Population-Based Study.

Science.gov (United States)

Yen, Eric Y; Shaheen, Magda; Woo, Jennifer M P; Mercer, Neil; Li, Ning; McCurdy, Deborah K; Karlamangla, Arun; Singh, Ram R

2017-12-05

No large population-based studies have been done on systemic lupus erythematosus (SLE) mortality trends in the United States. To identify secular trends and population characteristics associated with SLE mortality. Population-based study using a national mortality database and census data. United States. All U.S. residents, 1968 through 2013. Joinpoint trend analysis of annual age-standardized mortality rates (ASMRs) for SLE and non-SLE causes by sex, race/ethnicity, and geographic region; multiple logistic regression analysis to determine independent associations of demographic variables and period with SLE mortality. There were 50 249 SLE deaths and 100 851 288 non-SLE deaths from 1968 through 2013. Over this period, the SLE ASMR decreased less than the non-SLE ASMR, with a 34.6% cumulative increase in the ratio of the former to the latter. The non-SLE ASMR decreased every year starting in 1968, whereas the SLE ASMR decreased between 1968 and 1975, increased between 1975 and 1999, and decreased thereafter. Similar patterns were seen in both sexes, among black persons, and in the South. However, statistically significant increases in the SLE ASMR did not occur among white persons over the 46-year period. Females, black persons, and residents of the South had higher SLE ASMRs and larger cumulative increases in the ratio of the SLE to the non-SLE ASMR (31.4%, 62.5%, and 58.6%, respectively) than males, other racial/ethnic groups, and residents of other regions, respectively. Multiple logistic regression showed independent associations of sex, race, and region with SLE mortality risk and revealed significant racial/ethnic differences in associations of SLE mortality with sex and region. Underreporting of SLE on death certificates may have resulted in underestimates of SLE ASMRs. Accuracy of coding on death certificates is difficult to ascertain. Rates of SLE mortality have decreased since 1968 but remain high relative to non-SLE mortality, and significant sex

[The association of fibromyalgia and systemic lupus erythematosus change the presentation and severity of both diseases?].

Science.gov (United States)

de Araújo, Ana Luiza P Kasemodel; Paliares, Isabella Cristina; de Araújo, Maria Izabel P Kasemodel; Novo, Neil Ferreira; Cadaval, Ricardo Augusto M; Martinez, José Eduardo

2015-01-01

The association of fibromyalgia (FM) and systemic lupus erythematosus (SLE) have been investigated, with conflicting results regarding the impact of a condition on the other. To determine the frequency of FM in a sample of patients with SLE treated at the Hospital Complex of Sorocaba (CHS) and the impact of FM in SLE activity and quality of life, as well as of SLE in FM. Descriptive and correlational study. Patients who met the American College of Rheumatology (ACR) criteria for SLE and/or FM were included. The total sample was divided into three groups: FM/SLE (patients with association of SLE and FM), SLE (SLE patients only) and FM (FM patients only). The following variables were used: Fibromyalgia Impact Questionnaire (FIQ), activity index of SLE (SLEDAI), Indices of Diagnostic Criteria for Fibromyalgia 2010 (SSI end GPI) and SF-36. The prevalence of patients with FM among SLE patients was 12%. FIQ showed no difference between groups, indicating that SLE did not affect the impact caused by FM alone. The presence of FM in SLE patients did not influence the clinical activity of this disease. A strong impact of FM on the quality of life in patients with SLE was observed; the opposite was not observed. The prevalence of FM observed in SLE patients is 12%. The presence of FM adversely affects the quality of life of patients with SLE. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

En bog om Michael Strunge

DEFF Research Database (Denmark)

Mai, Anne-Marie

Antologi med bidrag om Michael Strunges forfatterskab. Bidrag af Anne-Marie Mai, Jørgen Aabenhus, Marianne Stidsen, Moritz Schramm, Tue Andersen Nexø, Lars Bukdahl, Jon Helt Haarder, Rune Kühl er optaget efter fagfællesbedømmelse. Antologien er redigeret af Anne-Marie Mai og Jørgen Aabenhus....

ATLAS Thesis Awards 2015

CERN Multimedia

Biondi, Silvia

2016-01-01

Winners of the ATLAS Thesis Award were presented with certificates and glass cubes during a ceremony on Thursday 25 February. The winners also presented their work in front of members of the ATLAS Collaboration. Winners: Javier Montejo Berlingen, Barcelona (Spain), Ruth Pöttgen, Mainz (Germany), Nils Ruthmann, Freiburg (Germany), and Steven Schramm, Toronto (Canada).

Subclinical impairment of ovarian reserve in systemic lupus erythematosus patients with normal menstruation not using alkylating therapy.

Science.gov (United States)

Ma, Wenhong; Zhan, Zhongping; Liang, Xiaoyan; Chen, Jianhui; Huang, Xingfang; Liao, Caiyun

2013-12-01

Disease activity is a major factor in menstrual disorders in systemic lupus erythematosus (SLE) patients not receiving alkylating therapy. However, the ovarian reserve of SLE women with normal menstruation is still unclear. Twenty-three SLE patients naïve to cytotoxic agents (SLE group) and nineteen SLE patients receiving current or previous cyclophosphamide (CTX) therapy (without other cytotoxic agents; SLE-CTX group) were enrolled. Twenty-one age-matched healthy women served as controls. All patients and controls had a regular menstrual cycle. Basal hormone levels, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), and antral follicle count (AFC) were analyzed in the two study groups and compared with the control group. No significant differences were found between the SLE, SLE-CTX, and control groups in age, body mass index (BMI), and basal FSH and LH levels. The E2 (P=0.023) levels were high and the AMH (P=0.000) values and AFC (P=0.001) were significantly lower in the SLE and SLE-CTX groups compared to control. However, these values were similar between the SLE and SLE-CTX groups. SLE patients not receiving alkylating therapy who had normal menstruation and short illness duration still had an impaired ovarian reserve.

Healthcare Utilization and Costs of Systemic Lupus Erythematosus in Medicaid

Directory of Open Access Journals (Sweden)

Hong J. Kan

2013-01-01

Full Text Available Objective. Healthcare utilization and costs associated with systemic lupus erythematosus (SLE in a US Medicaid population were examined. Methods. Patients ≥ 18 years old with SLE diagnosis (ICD-9-CM 710.0x were extracted from a large Medicaid database 2002–2009. Index date was date of the first SLE diagnosis. Patients with and without SLE were matched. All patients had a variable length of followup with a minimum of 12 months. Annualized healthcare utilization and costs associated with SLE and costs of SLE flares were assessed during the followup period. Multivariate regressions were conducted to estimate incremental healthcare utilization and costs associated with SLE. Results. A total of 14,777 SLE patients met the study criteria, and 14,262 were matched to non-SLE patients. SLE patients had significantly higher healthcare utilization per year than their matched controls. The estimated incremental annual cost associated with SLE was $10,984, with the highest increase in inpatient costs (P<0.001. Cost per flare was $11,716 for severe flares, $562 for moderate flares, and $129 for mild flares. Annual total costs for patients with severe flares were $49,754. Conclusions. SLE patients had significantly higher healthcare resource utilization and costs than non-SLE patients. Patients with severe flares had the highest costs.

Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.

Directory of Open Access Journals (Sweden)

Sharon A Chung

2011-03-01

Full Text Available Systemic lupus erythematosus (SLE is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811 and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906 SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20 compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04, with p(heterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti-dsDNA + SLE and were not associated with anti-dsDNA - SLE. In conclusion, we identified differential genetic associations with SLE based on anti-dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti-dsDNA - SLE.

MONTE CARLO SIMULATIONS OF GLOBULAR CLUSTER EVOLUTION. V. BINARY STELLAR EVOLUTION

International Nuclear Information System (INIS)

Chatterjee, Sourav; Umbreit, Stefan; Rasio, Frederic A.; Fregeau, John M.

2010-01-01

We study the dynamical evolution of globular clusters containing primordial binaries, including full single and binary stellar evolution using our Monte Carlo cluster evolution code updated with an adaptation of the single and binary stellar evolution codes SSE and BSE from Hurley et al. We describe the modifications that we have made to the code. We present several test calculations and comparisons with existing studies to illustrate the validity of the code. We show that our code finds very good agreement with direct N-body simulations including primordial binaries and stellar evolution. We find significant differences in the evolution of the global properties of the simulated clusters using stellar evolution compared with simulations without any stellar evolution. In particular, we find that the mass loss from the stellar evolution acts as a significant energy production channel simply by reducing the total gravitational binding energy and can significantly prolong the initial core contraction phase before reaching the binary-burning quasi-steady state of the cluster evolution. We simulate a large grid of models varying the initial cluster mass, binary fraction, and concentration parameter, and we compare properties of the simulated clusters with those of the observed Galactic globular clusters (GGCs). We find that simply including stellar evolution in our simulations and assuming the typical initial cluster half-mass radius is approximately a few pc independent of mass, our simulated cluster properties agree well with the observed GGC properties such as the core radius and the ratio of the core radius to the half-mass radius. We explore in some detail qualitatively different clusters in different phases of their evolution and construct synthetic Hertzsprung-Russell diagrams for these clusters.

Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti–dsDNA Autoantibody Production

Science.gov (United States)

Chung, Sharon A.; Taylor, Kimberly E.; Graham, Robert R.; Nititham, Joanne; Lee, Annette T.; Ortmann, Ward A.; Jacob, Chaim O.; Alarcón-Riquelme, Marta E.; Tsao, Betty P.; Harley, John B.; Gaffney, Patrick M.; Moser, Kathy L.; Petri, Michelle; Demirci, F. Yesim; Kamboh, M. Ilyas; Manzi, Susan; Gregersen, Peter K.; Langefeld, Carl D.; Behrens, Timothy W.; Criswell, Lindsey A.

2011-01-01

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti–dsDNA autoantibody production, a SLE–related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti–dsDNA autoantibody positive (anti–dsDNA +, n = 811) and anti–dsDNA autoantibody negative (anti–dsDNA –, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti–dsDNA + SLE. Far fewer and weaker associations were observed for anti–dsDNA – SLE. For example, rs7574865 in STAT4 had an OR for anti–dsDNA + SLE of 1.77 (95% CI 1.57–1.99, p = 2.0E-20) compared to an OR for anti–dsDNA – SLE of 1.26 (95% CI 1.12–1.41, p = 2.4E-04), with pheterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti–dsDNA + SLE and were not associated with anti–dsDNA – SLE. In conclusion, we identified differential genetic associations with SLE based on anti–dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti–dsDNA – SLE. PMID

Effective Strategies for Teaching Evolution: The Primary Evolution Project

Science.gov (United States)

Hatcher, Chris

2015-01-01

When Chris Hatcher joined the Primary Evolution Project team at the University of Reading, his goal was to find effective strategies to teach evolution in a way that keeps children engaged and enthused. Hatcher has collaborated with colleagues at the University's Institute of Education to break the evolution unit down into distinct topics and…

Development of Myasthenia Gravis in Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Nano Kigawa

2014-02-01

Full Text Available Objectives: To perform a literature review and estimate MG incidence in an SLE cohort.  Materials and methods: We searched MEDLINE and PubMed for case reports of SLE and MG. We also calculated MG incidence within our clinical SLE cohort (females only. Results: Eleven articles met our criteria, providing 13 SLE patients who developed MG. The majority were female (84.6%, with the average ages of 25.6 and 33.5 years at diagnoses of SLE and MG, respectively. In 380 SLE female patients followed for 2,850 person-years, one MG case occurred. Conclusion: MG in SLE is a rare event.

Pain and systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

M. Di Franco

2014-06-01

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease characterized by heterogeneous clinical manifestations involving virtually the entire body. The pain in SLE can have different causes. The SLE classification criteria include mainly the musculoskeletal manifestations of pain, which are commonly reported as initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic widespread pain, which is typical of fibromyalgia (FM, is frequently associated with SLE. The aim of this review is to describe widespread pain and fatigue in SLE, and the association of SLE and FM. Although secondary FM is not correlated with the disease activity, it may interfere with the daily activities of SLE patients. Therefore it is necessary to identify its symptoms and treat them promptly to improve the quality of life of patients. In conclusion, it is essential to identify the origin of pain in SLE in order to avoid dangerous over-treatment in patients with co-existing widespread pain and FM.

The involvement of HLA-DRBI, DQAI, DQBI and complement C4A Loci in diagnosing systemic lupus erythematosus among Tunisians

International Nuclear Information System (INIS)

Ayed, Khaled; Gorgi, Youser; Ayed-Jendoubi, Saloua; Bardi, Rafiqa

2004-01-01

Genetic susceptibility to systemetic lupus erythematosus (SLE) varies among populations. Few data exist on associations of HLA class II and class III allels of major histocompatibility complex (MHC) and susceptibility to SLE in Tunisians. We compared HLA-DRBI, DQAI, DQBI and C4 allotypes in 62 Tunisians SLE patients and 100 matched controls. We also assessed the association of specific allels with distinct autoantibody profiles in SLE patients. HLA-DRBI *0301, -DRBI*1501 and C4AQO allels were increased in the SLE patients, while the frequencies of HLA-DRBI*04 and DQBI*03 were decreased. HLA-DQA1*0102 and DQAI*0501 were significantly increased in the SLE patients. HLA-DQBI*0201 and and DQBI*0602 were more frequent in the SLE patients. C4A*QO and C4B*QO were increased in the frequency in the SLE patients compared to the controls, but only C4A null was significantly increased. 11 of 17 SLE patients with the C4 null allele were HLA-DRBI*0301 positive. 3 of the 16 SLE patients with HLA-DRBI*1501 were associated with the HLA-DQBI*0501 rather than DQBI*0602, as has been reported in European SLE patients. The MHC class II allels (DRBI, DQA1, DQB1)and C$ null assosiations noted in other ethnic groups are also found in Tunisians, suggesting shared suspectibility factors across ethnic lines in predisposition to SLE. In contrast to other ethnic groups, MHC class II allels are not associated with the presence of specific autoantibodies in Tunisians SLE patients. (author)

Annual incidence and standardized incidence ratio of cerebrovascular accidents in patients with systemic lupus erythematosus.

Science.gov (United States)

Mok, C C; Ho, L Y; To, C H

2009-01-01

To study the annual incidence and standardized incidence ratio (SIR) of cerebrovascular accident (CVA) in patients with systemic lupus erythematosus (SLE). The annual incidence of CVA from 1999 to 2007 in a longitudinal cohort of SLE patients was calculated each year and compared with that of the regional population within the same study period. Age-specific SIRs and outcome of CVA in SLE patients were also studied. In 2007, there were 490 SLE patients in our cohort. The mean annual incidence of CVA between 1999 and 2007 was 6.45/1000 patients and no obvious trend over time was observed. Of the 20 CVAs in patients with SLE, 18 (90%) were ischaemic stroke whereas two (10%) were haemorrhagic stroke. The mean SIR of all types of CVA in SLE patients was 2.02 [95% confidence interval (CI) 1.30-3.81; p = 0.002]. The SIR of ischaemic stroke decreased with age and the stroke incidence was no longer significantly higher than that of the population in patients aged >or= 60 years. Haemorrhagic stroke occurred mainly in younger SLE patients. The duration of hospitalization and the mortality rate for CVA was non-significantly higher in SLE than in non-SLE patients. The incidence of CVA in SLE remained constant over the 8 years between 1999 and 2007. Younger SLE patients are at substantially increased risk of CVA compared to age-matched population. The duration of hospitalization and the mortality rate for CVA are similar in SLE and non-SLE patients.

The great supernova of 1987

International Nuclear Information System (INIS)

Anon.

1990-01-01

Despite their apparently very different objectives, astrophysics - the study of the largest structures in the Universe - and particle physics - the study of the smallest - have always had common ground. On 23 February 1987 a supernova explosion provided additional impetus to reinforce these links. In this article, David Schramm of the University of Chicago and the NASA/Fermilab Astrophysics Center, explains why

Effects of obesity on health-related quality of life in juvenile-onset systemic lupus erythematosus.

Science.gov (United States)

Mina, R; Klein-Gitelman, M S; Nelson, S; Eberhard, B A; Higgins, G; Singer, N G; Onel, K; Tucker, L; O'Neil, K M; Punaro, M; Levy, D M; Haines, K; Ying, J; Brunner, H I

2015-02-01

This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE). Obesity was defined as a body mass index (BMI) ≥ 95 th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed to evaluate the relationship between obesity and HRQOL measures. Among the 202 jSLE patients, 25% (n = 51) were obese. Obesity had a significant negative impact on HRQOL in jSLE, even after adjusting for differences in current corticosteroid use, disease activity, disease damage, gender and race between groups. Obese jSLE patients had lower physical functioning compared to non-obese jSLE patients, and to non-obese and obese healthy controls. Compared to their non-obese counterparts, obese jSLE patients also had worse school functioning, more pain, worse social functioning and emotional functioning. Parents of obese jSLE patients worry more. The CHQ scores for obese jSLE patients were also worse compared to non-obese jSLE patients in several other domains. Our study demonstrates the detrimental effects of obesity on patient-reported outcomes in jSLE. This supports the importance of weight management for the therapeutic plan of jSLE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Reduced response to Epstein–Barr virus antigens by T-cells in systemic lupus erythematosus patients

Science.gov (United States)

Draborg, Anette Holck; Jacobsen, Søren; Westergaard, Marie; Mortensen, Shila; Larsen, Janni Lisander; Houen, Gunnar; Duus, Karen

2014-01-01

Objective Epstein–Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients. Methods T cells were analyzed by flow cytometry and antibodies were analyzed by enzyme-linked immunosorbent assay. Results SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV. Furthermore, an inverse correlation was revealed between the number of lytic antigen EBV-specific T-cells and disease activity of the SLE patients, with high-activity SLE patients having fewer T-cells than low-activity SLE patients. Conclusions These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation. A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed. PMID:25396062

Towards developing high-fidelity simulated learning environment training modules in audiology.

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Dzulkarnain, A A; Rahmat, S; Mohd Puzi, N A F; Badzis, M

2017-02-01

This discussion paper reviews and synthesises the literature on simulated learning environment (SLE) from allied health sciences, medical and nursing in general and audiology specifically. The focus of the paper is on discussing the use of high-fidelity (HF) SLE and describing the challenges for developing a HF SLE for clinical audiology training. Through the review of the literature, this paper discusses seven questions, (i) What is SLE? (ii) What are the types of SLEs? (iii) How is SLE classified? (iv) What is HF SLE? (v) What types of SLEs are available in audiology and their level of fidelity? (vi) What are the components needed for developing HF SLE? (vii) What are the possible types of HF SLEs that are suitable for audiology training? Publications were identified by structured searches from three major databases PubMed, Web of Knowledge and PsychInfo and from the reference lists of relevant articles. The authors discussed and mapped the levels of fidelity of SLE audiology training modules from the literature and the learning domains involved in the clinical audiology courses. The discussion paper has highlighted that most of the existing SLE audiology training modules consist of either low- or medium-fidelity types of simulators. Those components needed to achieve a HF SLE for audiology training are also highlighted. Overall, this review recommends that the combined approach of different levels and types of SLE could be used to obtain a HF SLE training module in audiology training.

Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients

DEFF Research Database (Denmark)

Garred, P; Voss, A; Madsen, H O

2001-01-01

This study describes the importance of mannose-binding lectin (MBL) variant alleles for systemic lupus erythematosus (SLE) and accompanying infections in a population-based cohort. MBL alleles were determined in 99 SLE patients recruited from a representative Danish region. Patients were classified...... according to the 1982 revised ACR criteria as definite SLE (D-SLE) (n = 77) fulfilling > or =4 criteria and incomplete SLE (I-SLE) (n = 22) with 0.99, respectively). A meta-analysis of eight previously published studies suggested that the presence of MBL variant alleles confer a 1.6 times overall increased...... risk for D-SLE (P disease activity (SLEDAI-index) in a 2-year follow-up period (P = 0.02) and had an increased risk of acquiring complicating infections in general (P = 0.03) and respiratory infections in particular (P = 0.0006). Only in SLE patients...

Breast cancer in systemic lupus

DEFF Research Database (Denmark)

Bernatsky, S.; Ramsey-Goldman, R.; Petri, M.

2017-01-01

Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi......-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results...... There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug...

Chemical evolution coefficients for the study of galactic evolution

International Nuclear Information System (INIS)

Mallik, D.C.V.

1980-01-01

A new evaluation of chemical evolution coefficients has been made using recent stellar evolution and nucleosynthesis data. The role of the low and intermediate mass stars in galactic nuclosynthesis has been emphasized. A significant amount of 4 He, 12 C and neutron-rich species is found to be contributed by these stars. Comparison with observed abundances suggests a primary origin of 14 N. The simple model of galactic evolution with the new coefficients has been used to derive the ratio of helium to heavy element enrichment in the Galaxy. The new stellar evolution data do not explain the large value of this ratio that has been determined observationally. (orig.)

Chemical evolution coefficients for the study of galactic evolution

Energy Technology Data Exchange (ETDEWEB)

Mallik, D C.V. [Indian Inst. of Astrophysics, Bangalore

1980-05-01

A new evaluation of chemical evolution coefficients has been made using recent stellar evolution and nucleosynthesis data. The role of the low and intermediate mass stars in galactic nucleosynthesis has been emphasized. A significant amount of /sup 4/He, /sup 12/C and neutron-rich species is found to be contributed by these stars. Comparison with observed abundances suggests a primary origin of /sup 14/N. The simple model of galactic evolution with the new coefficients has been used to derive the ratio of helium to heavy element enrichment in the Galaxy. The new stellar evolution data do not explain the large value of this ratio that has been determined observationally.

Factors Associated With Subjective Life Expectancy: Comparison With Actuarial Life Expectancy

Directory of Open Access Journals (Sweden)

Jaekyoung Bae

2017-07-01

Full Text Available Objectives Subjective life expectancy (SLE has been found to show a significant association with mortality. In this study, we aimed to investigate the major factors affecting SLE. We also examined whether any differences existed between SLE and actuarial life expectancy (LE in Korea. Methods A cross-sectional survey of 1000 individuals in Korea aged 20-59 was conducted. Participants were asked about SLE via a self-reported questionnaire. LE from the National Health Insurance database in Korea was used to evaluate differences between SLE and actuarial LE. Age-adjusted least-squares means, correlations, and regression analyses were used to test the relationship of SLE with four categories of predictors: demographic factors, socioeconomic factors, health behaviors, and psychosocial factors. Results Among the 1000 participants, women (mean SLE, 83.43 years; 95% confidence interval, 82.41 to 84.46 years; 48% of the total sample had an expected LE 1.59 years longer than that of men. The socioeconomic factors of household income and housing arrangements were related to SLE. Among the health behaviors, smoking status, alcohol status, and physical activity were associated with SLE. Among the psychosocial factors, stress, self-rated health, and social connectedness were related to SLE. SLE had a positive correlation with actuarial estimates (r=0.61, p<0.001. Gender, household income, history of smoking, and distress were related to the presence of a gap between SLE and actuarial LE. Conclusions Demographic factors, socioeconomic factors, health behaviors, and psychosocial factors showed significant associations with SLE, in the expected directions. Further studies are needed to determine the reasons for these results.

Om religion og evolution

DEFF Research Database (Denmark)

Geertz, Armin W.

2011-01-01

for kulturens kausale virkning på den menneskelige kognition og ikke mindst den hominine evolution. Ud fra, hvad vi ved om den menneskelige evolution, ses det, at den hominine evolution har en dybde, som sjældent medtænkes i teorier og hypoteser om den menneskelige evolution. Den menneskelige evolution er...

Teaching genetics prior to teaching evolution improves evolution understanding but not acceptance

Science.gov (United States)

Mead, Rebecca; Hejmadi, Momna

2017-01-01

What is the best way to teach evolution? As microevolution may be configured as a branch of genetics, it being a short conceptual leap from understanding the concepts of mutation and alleles (i.e., genetics) to allele frequency change (i.e., evolution), we hypothesised that learning genetics prior to evolution might improve student understanding of evolution. In the UK, genetics and evolution are typically taught to 14- to 16-y-old secondary school students as separate topics with few links, in no particular order and sometimes with a large time span between. Here, then, we report the results of a large trial into teaching order of evolution and genetics. We modified extant questionnaires to ascertain students’ understanding of evolution and genetics along with acceptance of evolution. Students were assessed prior to teaching, immediately post teaching and again after several months. Teachers were not instructed what to teach, just to teach in a given order. Regardless of order, teaching increased understanding and acceptance, with robust signs of longer-term retention. Importantly, teaching genetics before teaching evolution has a significant (p Teaching genetics first additionally had positive effects on genetics understanding, by increasing knowledge. These results suggest a simple, minimally disruptive, zero-cost intervention to improve evolution understanding: teach genetics first. This same alteration does not, however, result in a significantly increased acceptance of evolution, which reflects a weak correlation between knowledge and acceptance of evolution. Qualitative focus group data highlights the role of authority figures in determination of acceptance. PMID:28542179

Teaching genetics prior to teaching evolution improves evolution understanding but not acceptance.

Science.gov (United States)

Mead, Rebecca; Hejmadi, Momna; Hurst, Laurence D

2017-05-01

What is the best way to teach evolution? As microevolution may be configured as a branch of genetics, it being a short conceptual leap from understanding the concepts of mutation and alleles (i.e., genetics) to allele frequency change (i.e., evolution), we hypothesised that learning genetics prior to evolution might improve student understanding of evolution. In the UK, genetics and evolution are typically taught to 14- to 16-y-old secondary school students as separate topics with few links, in no particular order and sometimes with a large time span between. Here, then, we report the results of a large trial into teaching order of evolution and genetics. We modified extant questionnaires to ascertain students' understanding of evolution and genetics along with acceptance of evolution. Students were assessed prior to teaching, immediately post teaching and again after several months. Teachers were not instructed what to teach, just to teach in a given order. Regardless of order, teaching increased understanding and acceptance, with robust signs of longer-term retention. Importantly, teaching genetics before teaching evolution has a significant (p genetics was taught first. Teaching genetics first additionally had positive effects on genetics understanding, by increasing knowledge. These results suggest a simple, minimally disruptive, zero-cost intervention to improve evolution understanding: teach genetics first. This same alteration does not, however, result in a significantly increased acceptance of evolution, which reflects a weak correlation between knowledge and acceptance of evolution. Qualitative focus group data highlights the role of authority figures in determination of acceptance.

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

Science.gov (United States)

İlgen, U; Yayla, M E; Ateş, A; Okatan, İ E; Yurteri, E U; Torgutalp, M; Keleşoğlu, A B D; Turgay, T M; Kınıklı, G

2018-04-01

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

The management of pediatric systemic lupus erythematosus.

Science.gov (United States)

Ardoin, Stacy P; Schanberg, Laura E

2005-12-01

Most children and adolescents with systemic lupus erythematosus (SLE) now survive into adulthood, leading the pediatric rheumatology community to focus on preventing long-term complications of SLE, including atherosclerosis, obesity, and osteoporosis, and their treatment. Unfortunately, because of the paucity of data in pediatric SLE, little is known about epidemiology, long-term outcome, and optimal treatment. Most research focuses on adults with SLE, but pediatric SLE differs significantly from adult SLE in many aspects, including disease expression, approaches to pharmacologic intervention, management of treatment toxicity, and psychosocial issues. Children and adolescents with SLE require specialized, multidisciplinary care. Treatment can be optimized by early recognition of disease flares and complications, minimizing medication toxicity, educating families about prevention, promoting school performance, addressing concerns about reproductive health, and negotiating the transition to adult-centered medical care. Developmentally appropriate concerns about pain, appearance, and peers often affect treatment adherence and must be addressed by the health-care team. Research in pediatric SLE is desperately needed and provides a unique opportunity to understand how developmental immunology and the hormonal changes associated with puberty affect the pathophysiology of SLE.

The Real Culprit in Systemic Lupus Erythematosus: Abnormal Epigenetic Regulation

Science.gov (United States)

Wu, Haijing; Zhao, Ming; Chang, Christopher; Lu, Qianjin

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are attributed to the development of SLE. The latest research findings point to the association between abnormal epigenetic regulation and SLE, which has attracted considerable interest worldwide. It is the purpose of this review to present and discuss the relationship between aberrant epigenetic regulation and SLE, including DNA methylation, histone modifications and microRNAs in patients with SLE, the possible mechanisms of immune dysfunction caused by epigenetic changes, and to better understand the roles of aberrant epigenetic regulation in the initiation and development of SLE and to provide an insight into the related therapeutic options in SLE. PMID:25988383

Supplementing rooster sperm with Cholesterol-Loaded-Cyclodextrin improves fertility after cryopreservation.

Science.gov (United States)

Chuaychu-Noo, Napapach; Thananurak, Pachara; Chankitisakul, Vibantita; Vongpralub, Thevin

2017-02-01

Little is known about the effects of Cholesterol-Loaded Cyclodextrin (CLC) on post-thaw semen quality in chicken. The aim of the present study is to investigate the efficacy of CLC levels (0, 1, 2 and 3 mg/mL Schramm diluent) on post-thawed semen quality and fertility in two breeds of chicken Pradu Hang Dum (native chicken) and Rhode Island Red. Semen samples of each breed were pooled, divided into 4 aliquots and diluted with Schramm diluents, cooled to 5 °C when DMF was added (6% of final volume). Semen straws were subjected to cryopreservation using the liquid nitrogen vapor method. Post-thawed sperm motility, viability, acrosome integrity, mitochondrial function, and the Malondialdehyde (MDA) level were determined. The fertility of frozen semen was tested by inseminating laying hens. Post-thaw motility between Pradu Hang Dum and Rhode Island Red was no different; but Rhode Island Red had a higher semen viability and live cell intact acrosomes than Pradu Hang Dum (P rooster semen. There was no interaction among breeds and CLC on post-thaw semen quality and fertility. Copyright © 2017 Elsevier Inc. All rights reserved.

Voice disorder in systemic lupus erythematosus.

Directory of Open Access Journals (Sweden)

Milena S F C de Macedo

Full Text Available Systemic lupus erythematosus (SLE is a chronic disease characterized by progressive tissue damage. In recent decades, novel treatments have greatly extended the life span of SLE patients. This creates a high demand for identifying the overarching symptoms associated with SLE and developing therapies that improve their life quality under chronic care. We hypothesized that SLE patients would present dysphonic symptoms. Given that voice disorders can reduce life quality, identifying a potential SLE-related dysphonia could be relevant for the appraisal and management of this disease. We measured objective vocal parameters and perceived vocal quality with the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain scale in SLE patients and compared them to matched healthy controls. SLE patients also filled a questionnaire reporting perceived vocal deficits. SLE patients had significantly lower vocal intensity and harmonics to noise ratio, as well as increased jitter and shimmer. All subjective parameters of the GRBAS scale were significantly abnormal in SLE patients. Additionally, the vast majority of SLE patients (29/36 reported at least one perceived vocal deficit, with the most prevalent deficits being vocal fatigue (19/36 and hoarseness (17/36. Self-reported voice deficits were highly correlated with altered GRBAS scores. Additionally, tissue damage scores in different organ systems correlated with dysphonic symptoms, suggesting that some features of SLE-related dysphonia are due to tissue damage. Our results show that a large fraction of SLE patients suffers from perceivable dysphonia and may benefit from voice therapy in order to improve quality of life.

[A case of anti-LKM 1 positive autoimmune hepatitis accompanied by systemic lupus erythematosus].

Science.gov (United States)

Choi, Dae Han; Kim, Hae Kyung; Park, Tae Il; John, Byung Min; Kang, Sung Hwan; Lee, Yoon Serk; Kim, Tae Hyun; Lee, Uh Joo; Lee, Tae Seung; Yoon, Gwi Ok

2008-03-01

Overlap of autoimmune hepatitis and systemic lupus erythematosus (SLE) is a comparatively rare condition. Although both autoimmune hepatitis and SLE can share common autoimmune features such as polyarthralgia, hypergammaglobulinemia and positive ANA, it has been considered as two different entities. We report a case of anti-LKM1 positive autoimmune hepatitis who developed SLE two years later. The presence of interface hepatitis with lymphoplasma cell infiltrates and rosette formation points to the autoimmune hepatitis rather than SLE hepatitis. Autoimmune hepatitis is infrequently accompanied by SLE, therefore, it could be recommended to investigate for SLE in patients with autoimmune hepatitis.

High Health Care Utilization Preceding Diagnosis of Systemic Lupus Erythematosus in Youth.

Science.gov (United States)

Chang, Joyce C; Mandell, David S; Knight, Andrea M

2017-12-01

Childhood-onset systemic lupus erythematosus (SLE) is associated with high risk for organ damage, which may be mitigated by early diagnosis and treatment. We characterized health care utilization for youth in the year preceding SLE diagnosis compared to controls. Using Clinformatics ™ DataMart (OptumInsight, Eden Prairie, MN) de-identified administrative data from 2000 to 2013, we identified 682 youth ages 10-24 years with new-onset SLE (≥3 International Classification of Diseases, Ninth Revision (ICD-9) codes for SLE 710.0, each >30 days apart), and 1,364 age and sex-matched healthy controls. We compared the incidence of ambulatory, emergency, and inpatient visits 12 months before SLE diagnosis, and frequency of primary diagnoses. We examined subject characteristics associated with utilization preceding SLE diagnosis. Youth with SLE had significantly more visits in the year preceding diagnosis than controls across ambulatory (incidence rate ratio (IRR) 2.48, p<0.001), emergency (IRR 3.42, p<0.001) and inpatient settings (IRR 3.02, p<0.001). The most frequent acute care diagnoses and median days to SLE diagnosis were: venous thromboembolism (313, interquartile range (IQR) 18-356), thrombocytopenia (278, IQR 39-354), chest pain (73, IQR 29.5-168), fever (52, IQR 17-166), and acute kidney failure (14, IQR 5-168). Having a psychiatric diagnosis prior to SLE diagnosis was strongly associated with increased utilization across all settings. Youth with SLE have high health care utilization throughout the year preceding SLE diagnosis. Examining variable diagnostic trajectories of youth presenting for acute care preceding SLE diagnosis, and increased attention to psychiatric morbidity may help improve care for youth with new-onset SLE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A new paradigma on the plant evolution: from a natural evolution to an artificial evolution?

Science.gov (United States)

Bennici, Andrea

2005-01-01

After evidencing the great importance of plants for animals and humans in consequence of the photosynthesis, several considerations on plant evolution are made. One of the peculiar characteristics of the plant is the sessile property, due especially to the cell wall. This factor, principally, strengthened by the photosynthetic process, determined the particular developmental pattern of the plant, which is characterized by the continuous formation of new organs. The plant immobility, although negative for its survival, has been, in great part, overcome by the acquisition of the capacity of adaptation (plasticity) to the environmental stresses and changes, and the establishment of more adapted genotypes. This capacity to react to the external signals induced Trewavas to speak of "plant intelligence". The plant movement incapacity and the evolution of the sexual reproduction system were strongly correlated. In this context, the evolution of the flower in the Angiosperms has been particularly important to allow the male gamete to fertilize the immobile female gamete. Moreover, the formation of fruit and seed greatly improved the dispersal and conservation of the progeny in the environment. With the flower, mechanisms to favour the outcrossing among different individuals appeared, which are essential to increase the genetic variability and, then, the plant evolution itself. Although the Angiosperms seem highly evolved, the plant evolution is not surely finished, because many reported morpho-physiological processes may be still considered susceptible of further improvement. In the last years the relationships among humans, plants and environment are becoming closer and closer. This is due to the use of the DNA recombinant techniques with the aim to modify artificially plant characters. Therefore, the risk of a plant evolution strongly directed towards practical or commercial objectives, or "an artificial evolution", may be hypothesized.

Molecular characterization of circulating plasma cells in patients with active systemic lupus erythematosus.

Directory of Open Access Journals (Sweden)

Patricia L Lugar

Full Text Available Systemic lupus erythematosus (SLE is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC. The molecular characteristics and nature of circulating PC and B cells in SLE have not been completely characterized. Microarray analysis of gene expression was used to characterize circulating PC in subjects with active SLE. Flow cytometry was used to sort PC and comparator B cell populations from active SLE blood, normal blood and normal tonsil. The gene expression profiles of the sorted B cell populations were then compared. SLE PC exhibited a similar gene expression signature as tonsil PC. The differences in gene expression between SLE PC and normal tonsil PC and tonsil plasmablasts (PB suggest a mature Ig secreting cell phenotype in the former population. Despite this, SLE PC differed in expression of about half the genes from previously published gene expression profiles of normal bone marrow PC, indicating that these cells had not achieved a fully mature status. Abnormal expression of several genes, including CXCR4 and S1P(1, suggests a mechanism for the persistence of SLE PC in the circulation. All SLE B cell populations revealed an interferon (IFN gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells. These data indicate that SLE PC are a unique population of Ig secreting cells with a gene expression profile indicative of a mature, but not fully differentiated phenotype.

An evidence-based approach to pre-pregnancy counselling for patients with systemic lupus erythematosus.

Science.gov (United States)

Teng, Y K Onno; Bredewold, Edwin O W; Rabelink, Ton J; Huizinga, Tom W J; Eikenboom, H C Jeroen; Limper, Maarten; Fritsch-Stork, Ruth D E; Bloemenkamp, Kitty W M; Sueters, Marieke

2017-11-20

Patients with SLE are often young females of childbearing age and a pregnancy wish in this patient group is common. However, SLE patients are at high risk for adverse pregnancy outcomes that require adequate guidance. It is widely acknowledged that pre-pregnancy counselling is the pivotal first step in the management of SLE patients with a wish to become pregnant. Next, management of these patients is usually multidisciplinary and often requires specific expertise from the different physicians involved. Very recently a EULAR recommendation was published emphasizing the need for adequate preconception counselling and risk stratification. Therefore the present review specifically addresses the issue of pre-pregnancy counselling for SLE patients with an evidence-based approach. The review summarizes data retrieved from recently published, high-quality cohort studies that have contributed to a better understanding and estimation of pregnancy-related risks for SLE patients. The present review categorizes risks from a patient-oriented point of view, that is, the influence of pregnancy on SLE, of SLE on pregnancy, of SLE on the foetus/neonate and of SLE-related medication. Lastly, pre-pregnancy counselling of SLE patients with additional secondary APS is reviewed. Collectively these data can guide clinicians to formulate appropriate preventive strategies and patient-tailored monitoring plans during pre-pregnancy counselling of SLE patients. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Inlet Geomorphology Evolution

Science.gov (United States)

2015-04-01

APR 2015 2. REPORT TYPE 3. DATES COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Inlet Geomorphology Evolution 5a. CONTRACT NUMBER 5b...Std Z39-18 Coastal Inlets Research Program Inlet Geomorphology Evolution The Inlet Geomorphology Evolution work unit of the CIRP evaluates

[The motive force of evolution based on the principle of organismal adjustment evolution.].

Science.gov (United States)

Cao, Jia-Shu

2010-08-01

From the analysis of the existing problems of the prevalent theories of evolution, this paper discussed the motive force of evolution based on the knowledge of the principle of organismal adjustment evolution to get a new understanding of the evolution mechanism. In the guide of Schrodinger's theory - "life feeds on negative entropy", the author proposed that "negative entropy flow" actually includes material flow, energy flow and information flow, and the "negative entropy flow" is the motive force for living and development. By modifying my own theory of principle of organismal adjustment evolution (not adaptation evolution), a new theory of "regulation system of organismal adjustment evolution involved in DNA, RNA and protein interacting with environment" is proposed. According to the view that phylogenetic development is the "integral" of individual development, the difference of negative entropy flow between organisms and environment is considered to be a motive force for evolution, which is a new understanding of the mechanism of evolution. Based on such understanding, evolution is regarded as "a changing process that one subsystem passes all or part of its genetic information to the next generation in a larger system, and during the adaptation process produces some new elements, stops some old ones, and thereby lasts in the larger system". Some other controversial questions related to evolution are also discussed.

Metabolic syndrome in patients with systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

T Y Popkova

2008-01-01

Full Text Available Objective. To characterize metabolic syndrome (M S in pts wit h systemic lupus erythematosus (SLE and determine contribution of immune inflammation to the development of MS. Material and methods. 156 females with SLE (mean age 35 years, mean disease duration 99 months were included. Control group consisted of 69 people of comparable age without rheumatic diseases. MS was diagnosed according to ATP III criteria, \\fascular atherosclerotic damage was assessed by carotid sonographic evaluation. Serum cholesterol (CS, triglycerides (TG and high-density lipoprotein (HDLP CS concentration was assessed with colorimetric and photometric methods, hs CRP level — with nephelometric immunoassay. Results. MS was revealed in 29 from 154 (19% pts with SLE and in 5 from 69 (7% controls (p=0,02. MS components (hypertension, TG elevation and a lipoprotein decrease in SLE were significantly more frequent than in control group. TG, HDLP CS and CRP levels in SLE were higher than in control. Thickness of carotid intima-media complex did not differ in SLE and control. Frequency of atherosclerotic plaques (15% and coronary heart disease (14% in SLE was higher than in control (4% and 2% respectively, p=0,01. Pts with SLE and MS were older, had higher disease activity and maximal glucocorticoid dose during disease period (p<0,05. CRP concentration in SLE with MS was significantly higher. Subclinical signs of atherosclerosis in SLE with MS were more frequent than in SLE without MS (p<0,05. Frequency of clinical signs of atherosclerosis did not differ in these groups. Conclusion. Autoimmune inflammation in SLE plays an important role in the development of MS.

Validation of Systemic Lupus Erythematosus Diagnosis as the Primary Cause of Renal Failure in the US Renal Data System.

Science.gov (United States)

Broder, Anna; Mowrey, Wenzhu B; Izmirly, Peter; Costenbader, Karen H

2017-04-01

Using American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria for systemic lupus erythematosus (SLE) classification as gold standards, we determined sensitivity, specificity, positive and negative predictive values (PPV and NPV) of having SLE denoted as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS). ESRD patients were identified by International Classification of Diseases, Ninth Revision codes in electronic medical records of 1 large tertiary care center, Montefiore Hospital, from 2006 to 2012. Clinical data were extracted and reviewed to establish SLE diagnosis. Data were linked by social security number, name, and date of birth to the USRDS, where primary causes of ESRD were ascertained. Of 7,396 ESRD patients at Montefiore, 97 met ACR/SLICC SLE criteria, and 86 had SLE by record only. Among the 97 SLE patients, the attributed causes of ESRD in the USRDS were 77 SLE and 12 with other causes (unspecified glomerulonephritis, hypertension, scleroderma), and 8 missing. Sensitivity, specificity, PPV, and NPV for SLE in the USRDS were 79%, 99.9%, 93%, and 99.7%, respectively. Of the 60 patients with biopsy-proven lupus nephritis, 44 (73%) had SLE as primary ESRD cause in the USRDS. Attribution of the primary ESRD causes among SLE patients with ACR/SLICC criteria differed by race, ethnicity, and transplant status. The diagnosis of SLE as the primary cause of ESRD in the USRDS has good sensitivity, and excellent specificity, PPV, and NPV. Nationwide access to medical records and biopsy reports may significantly improve sensitivity of SLE diagnosis. © 2016, American College of Rheumatology.

Human papilloma virus and lupus: the virus, the vaccine and the disease.

Science.gov (United States)

Segal, Yahel; Calabrò, Michele; Kanduc, Darja; Shoenfeld, Yehuda

2017-07-01

Systemic lupus erythematosus (SLE) is a well known, widespread autoimmune disease, involving multiple organ systems, with a multifaceted, widely unmapped etiopathogenesis. Recently, a new aspect of morbidity has been described among SLE patients: infection with human papilloma virus (HPV). We set out to review data regarding the intricate relationship between the two and attempt to determine whether HPV may pose as a contributing factor to the development of SLE. We relate to epidemiological, molecular and clinical data. We have found evidence in all these fields suggesting HPV to be involved in the pathogenesis of SLE: increased prevalence of HPV infection among SLE patients; vast molecular homology between viral peptides and human proteins associated with SLE; several reports of SLE development post-HPV vaccination. Our findings suggest a possible involvement of HPV infection in the induction of SLE, via a mechanism of immune cross-reaction due to molecular homology. We review clinical, epidemiological and molecular data suggesting involvement of HPV infection in the pathogenesis of SLE. We suggest that these findings may justify the development of new HPV vaccines containing viral peptides that bear no homology to the human proteome, in order to avoid possible adverse immune cross-reactivity.

Thrombotic thrombocytopenic purpura and deep vein thrombosis as the presenting manifestations of systemic lupus erythematosus: A case report and review of literature

Directory of Open Access Journals (Sweden)

Mohammad AH Mashhadi

2011-01-01

Full Text Available Systemic lupus erythematosus (SLE, is sometimes complicated by the rare fatal syndrome, Thrombotic thrombocyto-penic purpura (TTP, but the occurrence of TTP as the initial manifestation of SLE is very rare. Since they have similar-ities in some features, the differentiation of TTP from SLE may be missed. SLE patients are also more prone to throm-botic events. Here we report a case with TTP and deep vein thrombosis as the presenting symptoms of SLE.

Estrogen in cardiovascular disease during systemic lupus erythematosus.

Science.gov (United States)

Gilbert, Emily L; Ryan, Michael J

2014-12-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against cardiovascular risk factors in

Estrogen in Cardiovascular Disease during Systemic Lupus Erythematosus

Science.gov (United States)

Gilbert, Emily L.; Ryan, Michael J.

2015-01-01

Purpose Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. Methods PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. Findings The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against

Stellar evolution

CERN Document Server

Meadows, A J

2013-01-01

Stellar Evolution, Second Edition covers the significant advances in the understanding of birth, life, and death of stars.This book is divided into nine chapters and begins with a description of the characteristics of stars according to their brightness, distance, size, mass, age, and chemical composition. The next chapters deal with the families, structure, and birth of stars. These topics are followed by discussions of the chemical composition and the evolution of main-sequence stars. A chapter focuses on the unique features of the sun as a star, including its evolution, magnetic fields, act

Aggregation behavior of sodium lauryl ether sulfate with a positively bicharged organic salt and effects of the mixture on fluorescent properties of conjugated polyelectrolytes.

Science.gov (United States)

Tang, Yongqiang; Liu, Zhang; Zhu, Linyi; Han, Yuchun; Wang, Yilin

2015-02-24

The aggregation behavior of anionic single-chain surfactant sodium lauryl ether sulfate containing three ether groups (SLE3S) with positively bicharged organic salt 1,2-bis(2-benzylammoniumethoxy)ethane dichloride (BEO) has been investigated in aqueous solution, and the effects of the BEO/SLE3S aggregate transitions on the fluorescent properties of anionic conjugated polyelectrolyte MPS-PPV with a larger molecular weight and cationic conjugated oligoelectrolyte DAB have been evaluated. Without BEO, SLE3S does not affect the fluorescent properties of MPS-PPV and only affects the fluorescent properties of DAB at a higher SLE3S concentration. With the addition of BEO, SLE3S and BEO form gemini-like surfactant (SLE3S)2-BEO. When the BEO/SLE3S molar ratio is fixed at 0.25, with increasing the BEO/SLE3S concentration, the BEO/SLE3S mixture forms large, loosely arranged aggregates and then transforms to closely packed spherical aggregates and finally to long thread-like micelles. The photoluminescence (PL) intensity of MPS-PPV varies with the morphologies of the BEO/SLE3S aggregates, while the PL intensity of DAB is almost independent of the aggregate morphologies. The results demonstrate that gemini-like surfactants formed through intermolecular interactions can effectively adjust the fluorescent properties of conjugated polyelectrolytes.

Systemic lupus erythematosus and risk of preterm birth: a systematic review and meta-analysis of observational studies.

Science.gov (United States)

Wei, S; Lai, K; Yang, Z; Zeng, K

2017-05-01

We performed a meta-analysis to identify the association between systemic lupus erythematosus (SLE) and preterm birth. In this study, we studied the effects of SLE, SLE disease activity, a history of nephritis and active nephritis on preterm birth. Searches were conducted before 20 May 2016 of PubMed, Embase, Medline and Cochrane Library of literature and article reference lists. Eleven observational case-control studies and thirteen cohort studies met the inclusion criteria. The pooled relative risk (RR) for the risk of preterm birth in SLE patients versus controls was 2.05 (95% confidence interval (CI): 1.72-3.32); for active SLE patients versus inactive was 2.98 (95% CI: 2.32-3.83); for SLE patients with a history of lupus nephritis versus those without nephritis it was 1.62 (95% CI: 1.35-1.95); and for SLE patients with active nephritis versus those with quiescent nephritis it was 1.78 (95% CI: 1.17-2.70). In summary, this study identified a significant association in the above results. This association was more significant in active SLE patients versus inactive. With respect to SLE itself, active inflammation (such as disease activity) may be more hazardous for the management of the pregnancy. This suggests that it is essential to control disease activity in order to achieve a better outcome of SLE pregnancy.

Association of STAT4 rs7574865 with susceptibility to systemic lupus erythematosus in Iranian population.

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Mirkazemi, Sedigheh; Akbarian, Mahmoud; Jamshidi, Ahmad Reza; Mansouri, Reza; Ghoroghi, Shima; Salimi, Yahya; Tahmasebi, Zahra; Mahmoudi, Mahdi

2013-12-01

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with complex genetic inheritance that affecting different organs and systems. STAT4 has been newly identified as a susceptible gene in the development of SLE. According to recent studies, STAT4 has been associated with SLE in various populations. We investigated whether STAT4 single nucleotide polymorphisms (SNPs) were associated with susceptibility and clinical features of SLE in Iranian patients. The study group comprised 280 patients with SLE and 281 sex-, age-, and ethnicity-matched healthy controls of Iranian ancestry. Two SNPs (rs7574865 and rs7601754) were genotyped using the TaqMan MGB Allelic Discrimination method. Our results showed a significant association between rs7574865 T allele (odds ratio (OR) = 1.50, 95 % CI = 1.18-1.92, P = 0.002) and susceptibility to SLE. The rs7574865TT genotype (P = 0.02, OR = 1.94, 95 % CI = 1.74-3.19) and GT genotype (P = 0.008, OR = 1.71, 95 % CI = 1.19-2.45) showed a significant association with the risk of SLE in the Iranian population. We concluded that STAT4 rs7574865 is associated with SLE susceptibility in the Iranian population and this SNP might be a factor in the pathogenesis of SLE. However, further studies are required to investigate the mechanism by which polymorphisms in this gene lead to SLE.

Breast Cancer in Systemic Lupus Erythematosus

DEFF Research Database (Denmark)

Tessier Cloutier, B; Clarke, A E; Ramsey-Goldman, R

2013-01-01

Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.......Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries....

Altered lipoproteins in patients with systemic lupus erythematosus are associated with augmented oxidative stress: a potential role in atherosclerosis.

Science.gov (United States)

Park, Jin Kyun; Kim, Jae-Yong; Moon, Jin Young; Ahn, Eun Young; Lee, Eun Young; Lee, Eun Bong; Cho, Kyung-Hyun; Song, Yeong Wook

2016-12-30

To examine the structural and oxidative properties of lipoproteins from patients with systemic lupus erythematosus (SLE). The lipid profiles of 35 SLE patients and 15 healthy controls (HCs) were compared. Oxidation status, susceptibility to oxidation, and structural integrity of low-density lipoprotein (LDL) were determined by measuring malondialdehyde (MDA), de novo formation of conjugated dienes in the presence of CuSO 4 , and mobility on gel electrophoresis, respectively. In vitro foam cell formation and the oxidative potential in zebrafish embryos were examined. LDL levels in SLE patients and HCs were similar (p = 0.277). LDL from SLE patients was more fragmented than that from HCs. In addition, LDL from SLE patients was more oxidized than LDL from HCs (p Lipoproteins from SLE patients exhibited greater oxidative potential, which might contribute to accelerated atherosclerosis in SLE.

Epstein-Barr virus-associated infectious mononucleosis and risk of systemic lupus erythematosus.

Science.gov (United States)

Ulff-Møller, Constance J; Nielsen, Nete M; Rostgaard, Klaus; Hjalgrim, Henrik; Frisch, Morten

2010-09-01

Elevated levels of serological markers of EBV infection in patients with SLE and observations that infectious mononucleosis (IM) may precede some cases of SLE suggest a possible role of EBV in the aetiology of SLE. We evaluated the relationship between EBV-associated IM and subsequent risk of SLE in a population-based cohort study. We followed cohorts of Danes tested serologically for IM using the Paul-Bunnell (PB) heterophile antibody test between 1939 and 1989, and patients hospitalized with IM between 1977 and 2007 for subsequent first hospitalizations with SLE in the period 1977-2008. Standardized incidence ratios (SIRs) with 95% CI served as measures of relative risk. Risk of SLE was not increased either in individuals with a positive PB test (SIR = 1.1; 95% CI 0.8, 1.6; n = 27) or in individuals hospitalized with IM (SIR = 1.3; 95% CI 0.7, 2.2; n = 12). However, SLE risk in PB-negative individuals was significantly increased (SIR = 2.6; 95% CI 2.1, 3.2; n = 82), a risk that was particularly high 1-4 years after the PB test (SIR = 6.6; 95% CI 3.3, 13.2) and remained significantly elevated for >25 years. EBV-associated IM does not seem to be a risk factor for SLE. The temporal pattern of increased SLE risk in individuals with a negative PB test suggests that some patients who go on to develop SLE may present with unspecific symptoms, for which they may be tested for IM, long in advance of their SLE diagnosis.

Adaptability and evolution.

Science.gov (United States)

Bateson, Patrick

2017-10-06

The capacity of organisms to respond in their own lifetimes to new challenges in their environments probably appeared early in biological evolution. At present few studies have shown how such adaptability could influence the inherited characteristics of an organism's descendants. In part, this has been because organisms have been treated as passive in evolution. Nevertheless, their effects on biological evolution are likely to have been important and, when they occurred, accelerated the pace of evolution. Ways in which this might have happened have been suggested many times since the 1870s. I review these proposals and discuss their relevance to modern thought.

Selective involvement of the amygdala in systemic lupus erythematosus.

Directory of Open Access Journals (Sweden)

Bart J Emmer

2006-12-01

Full Text Available BACKGROUND: Antibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE. The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE. METHODS AND FINDINGS: We analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE, 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI. In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 x 10(-6 mm2/s; p = 0.006 and 949 x 10(-6 mm2/s; p = 0.019, respectively was lower than in healthy control participants (1152 x 10(-6 mm2/s. Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 x 10(-6 mm2/s was lower (p = 0.029 than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 x 10(-6 mm2/s and also lower (p = 0.001 than in healthy control participants. CONCLUSIONS: This is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies.

Evolution: from cosmogenesis to biogenesis

International Nuclear Information System (INIS)

Lukacs, B.; Berczi, Sz.; Molnar, I.; Paal, G.

1990-11-01

The volume contains the material of an interdisciplinary evolution symposium. The purpose was to shed some light on possible connections between steps of evolution of matter on different levels of organisation. The topics involved are as follow: cosmogenesis; galactic and stellar evolution; formation and evolution of the solar system; global atmospheric and tectonic changes of Earth; viral evolution; phylogeny and evolution of terrestrial life; evolution of neural system; hominization. The material also includes some discussions of the underlying phenomena and laws of nature. (author)

Has Human Evolution Stopped?

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Alan R. Templeton

2010-07-01

Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

Prevalence and genetic diversity of torque teno virus in patients with systemic lupus erythematosus in a reference service in Mato Grosso do Sul.

Science.gov (United States)

Costa, Márcio Reis da; Costa, Izaias Pereira da; Devalle, Sylvie; Castro, Ana Rita Coimbra Motta de; Freitas, Solange Zacalusni

2012-01-01

Recent studies on the torque teno virus (TTV), genus Anellovirus, have allowed formulating the hypothesis that TTV may trigger autoimmune rheumatic diseases or have some pathogenic role in them. To determine the frequency of TTV infection in patients with systemic lupus erythematosus (SLE), the genetic diversity of TTV, the correlation between TTV infection and SLE clinical manifestations, and SLE clinical course and serological profile. Serum samples were obtained from 46 SLE patients treated at the University-Affiliated Hospital of Campo Grande (NHU/FAMED/UFMS), Brazil. For controls, serum samples were obtained from 46 healthy volunteer blood donors. Viral DNA was extracted from samples using the QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany) and amplified using nested PCR. Positivity for TTV was found in 17 (37%) of SLE patients and in only seven (15.2%) of the controls (z test, P = 0.03). There was no correlation between TTV infection, SLE clinical manifestations, SLE clinical course, and the serological profile of the patients evaluated. Further studies on the presence of TTV in SLE patients are required.

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

DEFF Research Database (Denmark)

Draborg, Anette H; Lydolph, Magnus; Westergaard, Marie

2015-01-01

, FLCs' association with Epstein-Barr virus (EBV) antibodies was examined. METHODS: Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations......OBJECTIVE: In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore...... of serum FLCs due to decreased clearance. RESULTS: Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (pdisease activity (SLE disease activity...

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies.

Directory of Open Access Journals (Sweden)

Anette H Draborg

Full Text Available In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs in systemic lupus erythematosus (SLE patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs' association with Epstein-Barr virus (EBV antibodies was examined.Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance.Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001 also after adjusting for Ig levels (p<0.0001. The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI score of the SLE patients (r = 0.399, p = 0.007. Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009, and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation whereas EBV-directed antibodies reflect the extent of previous infection/reactivations.SLE patients have elevated concentrations of serum FLCs that correlate with global disease

Occurrence of systemic lupus erythematosus in a Danish community

DEFF Research Database (Denmark)

Laustrup, H; Voss, A; Green, A

2009-01-01

Objectives: To determine the prevalence and annual incidence of definite systemic lupus erythematosus (D-SLE) and incomplete SLE (I-SLE) in a community-based lupus cohort of predominantly Nordic ancestry in an 8-year prospective study from 1995 to 2003, and also to calculate the annual transition......-years at risk [95% confidence interval (CI) 1.44-7.55]. Conclusions: Denmark is a low-incidence lupus area but lupus prevalence is increasing slowly. I-SLE is a disease variant that may eventually convert into D-SLE....

Quasars and galactic evolution

CERN Document Server

Woltjer, L

1978-01-01

The evolution of quasars is discussed. It is noted that substantial clustering may be present at faint magnitudes. The relationship between quasar evolution and galactic evolution is considered. (4 refs).

Infecção pelo vírus Epstein-Barr em pacientes com lúpus eritematoso sistêmico Epstein-Barr virus infection in patients with systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

Samuel Kosminsky

2006-10-01

of which 34 (85% belonged to the inactive SLE group and 20 (95.2% to the active group. For 5 (12.5% inactive SLE patients, the avidity index reached values ranging from 20 to 40; while for only 2 (3.3% patients this index was lower than 20. Adopting 20, 30 or 40 as a cutoff point of the avidity index for diagnosis of reactivation of the EBV infection, the author classified as having reactivated infection, for active and inactive SLE groups, respectively: 1 (4.8% x 1 (2.5% patient; 1 (4.8% x 4 (10% patients and 1 (4.8% x 5 (12.5% patients. CONCLUSION: Association between EBV activity and SLE was not demonstrated. This appears to indicate that persistence of infected B lymphocytes may be due to failure in the apopotosis mechanism or to the action of T cytotoxic lymphocytes, permitting evolution of SLE.

Pregnancy in women with systemic lupus erythematosus.

Science.gov (United States)

Kiss, Emese; Bhattoa, Harjit P; Bettembuk, Peter; Balogh, Adam; Szegedi, Gyula

2002-03-10

Systemic lupus erythematosus (SLE) is an autoimmune disorder which may be affected by hormonal changes, such as those of pregnancy. Women with SLE have increased adverse pregnancy outcomes. A retrospective analysis of the gynecologic and immunologic case history of 140 women with SLE and the outcome of 263 pregnancies in 99 women with SLE. In patients diagnosed with SLE, the proportion of pregnancies ending with live birth at term decreased to one-third compared with three quarters in those without a diagnosis of SLE and the incidence of pre-term deliveries and spontaneous abortions increased by 6.8 and 4.7 times, respectively. When SLE was associated with secondary antiphospholipid (APL) syndrome, and lupus anticoagulant (LA) or beta2-glycoprotein antibodies were present, a further increase in the incidence of pregnancy loss was observed. Pregnancy did not cause a flare-up of SLE in all cases, the disease remained stable in about 30% of the patients. Lupus was mild in the majority of the women who carried out their pregnancy to term. We also observed mothers with active SLE who successfully carried out pregnancies to term. These findings accord with previous literature and should inform rheumatologists, obstetricians and neonatologists who guide patients in their reproductive decisions.

Protein-losing enteropathy in systemic lupus erythematosus: 12 years experience from a Chinese academic center.

Science.gov (United States)

Chen, Zhen; Li, Meng-Tao; Xu, Dong; Yang, Hong; Li, Jing; Zhao, Jiu-Liang; Zhang, Heng-Hui; Han, Shao-Mei; Xu, Tao; Zeng, Xiao-Feng

2014-01-01

Protein-losing enteropathy (PLE) is a complication in some systemic lupus erythematosus (SLE) patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease. A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group) and 88 patients with active SLE (control group) admitted to our care from January 2000-January 2012. Risk factors for SLE-related PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents. The PLE group had lower mean serum albumin and 24-hour urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti-SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (PLE. SLE-related PLE should be considered when an SLE patient presents with generalized edema, anti-SSA antibody seropositivity, hypercholesterolemia, severe hypoalbuminemia, and low 24-hour urine protein levels. Aggressive treatment for lupus might improve prognosis.

Thin-section chest CT findings in systemic lupus erythematosus with antiphospholipid syndrome: A comparison with systemic lupus erythematosus without antiphospholipid syndrome

International Nuclear Information System (INIS)

Oki, Hodaka; Aoki, Takatoshi; Saito, Kazuyoshi; Yamashita, Yoshiko; Hanamiya, Mai; Hayashida, Yoshiko; Tanaka, Yoshiya; Korogi, Yukunori

2012-01-01

Purpose: To assess thin-section chest CT findings in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), in comparison with SLE without APS. Materials and methods: We retrospectively reviewed the medical records and thin-section CT findings of 17 consecutive patients with an established diagnosis of SLE with APS, comparing with 37 consecutive SLE patients without APS, between 2004 and 2008, and patients who had other autoimmune disease, such as Sjögren syndrome, were excluded. No significant differences were seen between the two groups in age, gender, smoking habits, or history of steroid pulse and biological therapy. CT images of 2 mm thickness obtained with a 16- or 64-detector row CT were retrospectively evaluated by two radiologists in consensus on ultra high-resolution gray-scale monitors. Results: The frequency of thin-section CT abnormalities was higher in SLE with APS group (82%) than in SLE without APS group (43%). Ground-glass opacity (59%), architectural distortion (47%), reticulation (41%), enlarged peripheral pulmonary artery (29%), and mosaic attenuation (29%) were significantly more common in the SLE with APS group than in the SLE without APS group (Fisher's exact test, p < 0.01). Conclusion: SLE patients with APS have increased prevalence of thin-section chest CT abnormalities than those without APS.

[Role of anti c-mpl antibody in systemic lupus erythematosus with thrombocytopenia].

Science.gov (United States)

Yang, Tuo; Huang, Ci Bo; Lai, Bei; Zhao, Li Ke; Chen, Ying Juan; Zhao, Yue Tao; Zhang, Chun Mei; Zeng, Xiao Feng

2012-04-18

To determine whether anti-thrompoietin receptor (TPO-R, c-mpl) antibody contributes to thrombocytopenia in systemic lupus erytematosus (SLE) and explore the pathogenic role of this antibody. Sera from 24 SLE patients with thrombocytopenia, 27 SLE patients having normal platelet counts with a history of thrombocytopenia, 18 SLE patients with neither thrombocytopenia nor post thrombocytopenia and 18 healthy controls were collected. Anti c-mpl antibodies were detected by an indirected ELISA assay. The serum TPO levels were measured by an ELISA assay. Clinical findings, autoantibody profiles, and SLEDAI were evaluated. Serum anti c-mpl antibodies were detected in 18.8% of the SLE patientis. The frequency of this antibody in SLE with thrombocytopenia, SLE with a history of thrombocytopenia and SLE without thrombocytopenia were of no difference (P=0.600). In the patients with anti c-mpl antibodies, their platelet counts were decreased(P=0.025) and serum TPO levels elevated(P=0.038) than those in the patients without, while there were no differences between the two groups in C3, C4, ESR, CRP level, the frequency of ANA, dsDNA, ANCA and SLEDAI. Anti c-mpl antibody contributes to SLE-associated thrombocytopenia by functionally blocking an interaction between thrombopoietin and c-mpl, which might inhibit TPO-dependent megakaryocyte proliferation and differentiation.

Splenectomy increases the subsequent risk of systemic lupus erythematosus.

Science.gov (United States)

Hsu, Chao-Yu; Chen, Hsuan-Ju; Hsu, Chung Y; Kao, Chia-Hung

2016-02-01

Splenectomy may be necessary to treat systemic lupus erythematosus (SLE) patients with thrombocytopenia; however, whether performing a splenectomy on patients without SLE increases the subsequent risk of SLE remains unknown. Therefore, this study was conducted to determine the association between splenectomy and SLE. We conducted a cohort study by using data from the Taiwan National Health Institute Research Database to identify 10,298 patients with received a splenectomy between 2000 and 2006 and 41,192 participants without received a splenectomy who were selected by frequency matched based on sex, age, and the index year. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of developing SLE associated with splenectomy compared with patients who did not receive a splenectomy. During the study period, the overall incidence density rate of SLE was higher in the splenectomy cohort than in the non-splenectomy cohort (adjusted HR 10.55; 95 % CI 50.55-20.05). The incidence density rates of SLE in women and men who received a splenectomy were higher than those of patients who did not receive a splenectomy. Non-traumatic splenectomy increases the subsequent risk of SLE. The risk of SLE should be considered before performing a splenectomy, particularly in women and younger patients.

Schumpeter's Evolution

DEFF Research Database (Denmark)

Andersen, Esben Sloth

reworking of his basic theory of economic evolution in Development from 1934, and this reworking was continued in Cycles from 1939. Here Schumpeter also tried to handle the statistical and historical evidence on the waveform evolution of the capitalist economy. Capitalism from 1942 modified the model...

Darwinian evolution

NARCIS (Netherlands)

Jagers op Akkerhuis, Gerard A.J.M.; Spijkerboer, Hendrik Pieter; Koelewijn, Hans Peter

2016-01-01

Darwinian evolution is a central tenet in biology. Conventionally, the defi nition of Darwinian evolution is linked to a population-based process that can be measured by focusing on changes in DNA/allele frequencies. However, in some publications it has been suggested that selection represents a

Cepheid evolution

International Nuclear Information System (INIS)

Becker, S.A.

1984-05-01

A review of the phases of stellar evolution relevant to Cepheid variables of both Types I and II is presented. Type I Cepheids arise as a result of normal post-main sequence evolutionary behavior of many stars in the intermediate to massive range of stellar masses. In contrast, Type II Cepheids generally originate from low-mass stars of low metalicity which are undergoing post core helium-burning evolution. Despite great progress in the past two decades, uncertainties still remain in such areas as how to best model convective overshoot, semiconvection, stellar atmospheres, rotation, and binary evolution as well as uncertainties in important physical parameters such as the nuclear reaction rates, opacity, and mass loss rates. The potential effect of these uncertainties on stellar evolution models is discussed. Finally, comparisons between theoretical predictions and observations of Cepheid variables are presented for a number of cases. The results of these comparisons show both areas of agreement and disagreement with the latter result providing incentive for further research

Whole-genome transcription and DNA methylation analysis of peripheral blood mononuclear cells identified aberrant gene regulation pathways in systemic lupus erythematosus.

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Zhu, Honglin; Mi, Wentao; Luo, Hui; Chen, Tao; Liu, Shengxi; Raman, Indu; Zuo, Xiaoxia; Li, Quan-Zhen

2016-07-13

Recent achievement in genetics and epigenetics has led to the exploration of the pathogenesis of systemic lupus erythematosus (SLE). Identification of differentially expressed genes and their regulatory mechanism(s) at whole-genome level will provide a comprehensive understanding of the development of SLE and its devastating complications, lupus nephritis (LN). We performed whole-genome transcription and DNA methylation analysis in PBMC of 30 SLE patients, including 15 with LN (SLE LN(+)) and 15 without LN (SLE LN(-)), and 25 normal controls (NC) using HumanHT-12 Beadchips and Illumina Human Methy450 chips. The serum proinflammatory cytokines were quantified using Bio-plex Human Cytokine 27-plex assay. Differentially expressed genes and differentially methylated CpG were analyzed with GenomeStudio, R, and SAM software. The association between DNA methylation and gene expression were tested. Gene interaction pathways of the differentially expressed genes were analyzed by IPA software. We identified 552 upregulated genes and 550 downregulated genes in PBMC of SLE. Integration of DNA methylation and gene expression profiling showed that 334 upregulated genes were hypomethylated, and 479 downregulated genes were hypermethylated. Pathway analysis on the differential genes in SLE revealed significant enrichment in interferon (IFN) signaling and toll-like receptor (TLR) signaling pathways. Nine IFN- and seven TLR-related genes were identified and displayed step-wise increase in SLE LN(-) and SLE LN(+). Hypomethylated CpG sites were detected on these genes. The gene expressions for MX1, GPR84, and E2F2 were increased in SLE LN(+) as compared to SLE LN(-) patients. The serum levels of inflammatory cytokines, including IL17A, IP-10, bFGF, TNF-α, IL-6, IL-15, GM-CSF, IL-1RA, IL-5, and IL-12p70, were significantly elevated in SLE compared with NC. The levels of IL-15 and IL1RA correlated with their mRNA expression. The upregulation of IL-15 may be regulated by hypomethylated

The Evolution of Musicality: What Can Be Learned from Language Evolution Research?

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Ravignani, Andrea; Thompson, Bill; Filippi, Piera

2018-01-01

Language and music share many commonalities, both as natural phenomena and as subjects of intellectual inquiry. Rather than exhaustively reviewing these connections, we focus on potential cross-pollination of methodological inquiries and attitudes. We highlight areas in which scholarship on the evolution of language may inform the evolution of music. We focus on the value of coupled empirical and formal methodologies, and on the futility of mysterianism , the declining view that the nature, origins and evolution of language cannot be addressed empirically. We identify key areas in which the evolution of language as a discipline has flourished historically, and suggest ways in which these advances can be integrated into the study of the evolution of music.

The Evolution of Musicality: What Can Be Learned from Language Evolution Research?

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Andrea Ravignani

2018-02-01

Full Text Available Language and music share many commonalities, both as natural phenomena and as subjects of intellectual inquiry. Rather than exhaustively reviewing these connections, we focus on potential cross-pollination of methodological inquiries and attitudes. We highlight areas in which scholarship on the evolution of language may inform the evolution of music. We focus on the value of coupled empirical and formal methodologies, and on the futility of mysterianism, the declining view that the nature, origins and evolution of language cannot be addressed empirically. We identify key areas in which the evolution of language as a discipline has flourished historically, and suggest ways in which these advances can be integrated into the study of the evolution of music.

Squared ligament of the elbow: anatomy and contribution to forearm stability.

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Otayek, Salma; Tayeb, Abd-el-Kader Ait; Assabah, Bouchra; Viard, Brice; Dayan, Romain; Lazure, Thierry; Soubeyrand, Marc

2016-03-01

The present study describes the macroscopic and microscopic features of the squared ligament of the elbow (SLE). In addition, the SLE biomechanical behavior and contribution to the forearm stability were also examined. Ten forearms from freshly frozen cadavers were used for this work. Each forearm was mounted in an experimental frame for quantification of longitudinal and transverse stability. Macroscopic features and biomechanical behavior were analyzed on dynamic videos obtained during forearm rotation. Then, the SLE was harvested from the 10 forearms for microscopic analysis on histological slices stained with hematoxylin-eosin-saffron. Two main SLE configurations were identified. One in which the SLE had three distinct bundles (anterior, middle, posterior) and another in which it was homogeneous. The anterior part of the SLE had a mean length of 11.2 mm (±2.4 mm) and a mean width of 1.2 mm (±0.2 mm) while the posterior part had a mean length of 9.9 mm (±2.2 mm) and a mean width of 1 mm (±0.2 mm). Microscopic examination showed that the SLE is composed of a thin layer of arranged collagen fibers. During forearm rotation, the SLE progressively tightens upon pronation and supination by wrapping around the radial neck. Tightening of the SLE during forearm rotation provides transverse and longitudinal stability to the forearm, mainly in maximal pronation and supination. The SLE is a true ligament and provides forearm stability when it is stretched in pronation and supination.

[NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS].

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Stryjer, Rafael; Shriki Tal, Liron; Gizunterman, Alex; Amital, Daniela; Amital, Howard; Kotler, Moshe

2017-12-01

This review deals with the neuropsychiatric disorders resulting from systemic lupus erythematosus (SLE). SLE is a chronic autoimmune disease that impacts all systems in the human body, including the central nervous system. Neuropsychiatric symptoms in SLE are a common complication of the disease. This complication has significant implications for the severity of the illness. In most cases no thorough psychiatric assessment is performed during initial evaluation of the disease and no protocol or clear guidelines for treating the psychiatric symptoms in SLE are available. Early diagnosis of the psychiatric symptoms in SLE is critical since absence of treatment may result in severe psychiatric complications. Clinical pharmacological studies are needed in order to develop guidelines for treating psychiatric symptoms in SLE.

An intriguing association of Turner syndrome with severe nephrotic syndrome: searching for a diagnosis.

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Minzala, G; Ismail, G

2016-10-01

Systemic lupus erythematosus (SLE) is a chronic disease caused by an aberrant autoimmune response, with a large spectrum of clinical manifestations. It strikingly affects women. Recent papers reveal that the men with Klinefelter syndrome (47, XXY) have a higher incidence of lupus than the men in the general population, similar with that of genotypic females. On the other hand, there is a great lack of information regarding the association of SLE with Turner syndrome, but it seems to be a lower risk for females with Turner to develop SLE. We present a rare association of a Turner syndrome with SLE, with negative immunology for SLE and with diagnosis made on renal biopsy. These data suggest that the presence of two X chromosomes may predispose to SLE, the ligand (CD40 ligand) for one of the genes that contributes to the pathogenesis of SLE being located on the X chromosome. © The Author(s) 2016.

The pathway of estradiol-induced apoptosis in patients with systemic lupus erythematosus.

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Rastin, Maryam; Hatef, Mohammad Reza; Tabasi, Nafisseh; Mahmoudi, Mahmoud

2012-03-01

Systemic lupus erythematosus (SLE) is a disease with unknown etiology. The pathologic role of sex hormones and apoptosis in SLE has often been discussed. We studied the effects of estradiol in the pathway of induced apoptosis in Iranian SLE patients. T lymphocytes from 35 SLE patients and 20 age-matched controls were isolated and cultured in the presence of 10(-8) M 17-β estradiol. The expression levels of Fas, Fas ligand (FasL), Bcl-2, caspase-8, and caspase-9 mRNAs were determined semiquantitatively in comparison to the expression level of beta actin RNA. Estradiol exposure did not have any significant effects on the expression levels of Fas, Bcl-2, and caspase-9 in SLE patients and controls. However, the expression levels of FasL and caspase-8 were significantly increased in SLE patients, but not in controls. This suggests the probable involvement of extrinsic apoptosis pathway in estradiol-induced apoptosis in SLE.

An update on diet and nutritional factors in systemic lupus erythematosus management.

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Aparicio-Soto, Marina; Sánchez-Hidalgo, Marina; Alarcón-de-la-Lastra, Catalina

2017-06-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease characterised by multiple organ involvement and a large number of complications. SLE management remains complicated owing to the biological heterogeneity between patients and the lack of safe and specific targeted therapies. There is evidence that dietary factors can contribute to the geoepidemiology of autoimmune diseases such as SLE. Thus, diet therapy could be a promising approach in SLE owing to both its potential prophylactic effects, without the side effects of classical pharmacology, and its contribution to reducing co-morbidities and improving quality of life in patients with SLE. However, the question arises as to whether nutrients could ameliorate or exacerbate SLE and how they could modulate inflammation and immune function at a molecular level. The present review summarises preclinical and clinical experiences to provide the reader with an update of the positive and negative aspects of macro- and micronutrients and other nutritional factors, including dietary phenols, on SLE, focusing on the mechanisms of action involved.

Cutaneous Manifestations of Systemic Lupus Erythematosus

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Uva, Luís; Miguel, Diana; Pinheiro, Catarina; Freitas, João Pedro; Marques Gomes, Manuel; Filipe, Paulo

2012-01-01

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. The skin is one of the target organs most variably affected by the disease. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. Cutaneous lesions account for four of these 11 revised criteria of SLE. Skin lesions in patients with lupus may be specific or nonspecific. This paper covers the SLE-specific cutaneous changes: malar rash, discoid rash, photosensitivity, and oral mucosal lesions as well as SLE nonspecific skin manifestations, their pathophysiology, and management. A deeper thorough understanding of the cutaneous manifestations of SLE is essential for diagnosis, prognosis, and efficient management. Thus, dermatologists should cooperate with other specialties to provide optimal care of SLE patient. PMID:22888407

Episodic memory impairment in systemic lupus erythematosus: involvement of thalamic structures.

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Zimmermann, Nicolle; Corrêa, Diogo Goulart; Netto, Tania Maria; Kubo, Tadeu; Pereira, Denis Batista; Fonseca, Rochele Paz; Gasparetto, Emerson Leandro

2015-02-01

Episodic memory deficits in systemic lupus erythematosus (SLE) have been frequently reported in the literature; however, little is known about the neural correlates of these deficits. We investigated differences in the volumes of different brain structures of SLE patients with and without episodic memory impairments diagnosed by the Rey Auditory Verbal Learning Test (RAVLT). Groups were paired based on age, education, sex, Mini Mental State Examination score, accumulation of disease burden (SLICC), and focused attention dimension score. Patients underwent magnetic resonance imaging (MRI). Cortical volumetric reconstruction and segmentation of the MR images were performed with the FreeSurfer software program. SLE patients with episodic memory deficits presented shorter time of diagnosis than SLE patients without episodic memory deficits. ANOVA revealed that SLE patients with episodic memory deficits had a larger third ventricle volume than SLE patients without episodic memory deficits and controls. Additionally, covariance analysis indicated group effects on the bilateral thalamus and on the third ventricle. Our findings indicate that episodic memory may be impaired in SLE patients with normal hippocampal volume. In addition, the thalamus may undergo volumetric changes associated with episodic memory loss in SLE.

Comparison of plasma/serum levels of procalcitonin between infection and febrile disease flare in patients with systemic lupus erythematosus: a meta-analysis.

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Liu, Li-Na; Wang, Peng; Guan, Shi-Yang; Li, Xiao-Mei; Li, Bao-Zhu; Leng, Rui-Xue; Pan, Hai-Feng

2017-12-01

Currently published data regarding the potential role of procalcitonin (PCT) for the discrimination between systemic lupus erythematosus (SLE) flare and infection are contradictory. To derive a more precise evaluation, a meta-analysis was performed. Published literatures from PubMed, Embase, and the Cochrane Library were obtained. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2 . Eight studies including 205 SLE flare patients and 198 SLE patients with infection were finally incorporated in the meta-analysis after examining title, type, abstracts, and full text. No significant differences in plasma/serum PCT levels were found between SLE patients with flare and SLE patients with infection when all studies were pooled into the meta-analysis (pooled SMD = - 0.45, 95% CI = - 0.96 to 0.06). However, subgroup analysis showed that Asian SLE patients with infection had higher plasma/serum PCT levels when compared with SLE patients with flare (p infection. However, plasma/serum PCT levels are significantly higher in Asian SLE patients with infection.

Systemic lupus erythematosus and splenic abscess

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Guarnizo Z, Pilar; Ramirez R, Francisco Alejandro; Ramirez G, Luis Alberto

2006-01-01

Systemic lupus erythematosus is an autoimmune disease in which there is an increase risk of infections by common germ as by opportunistic germs. This fact is explained by the alterations in the humoral and cellular immunity, and phagocytic mononuclear system due to the disease and the immunosuppressive therapy use for its treatment. Multiple infectious processes have been describes in patients with SLE and within them, the splenic abscess, although in few cases. Usually its presence is associated with an underlying disease such as sepsis or peritonitis, with multiple outcomes. Due to its low frequency as well as the unusual presentation, we reported a case of a solitary splenic abscess documented by ultrasound in a teenager with SLE and immunosuppressive treatment, without any underlying infection, who presents with fever, abdominal pain, leucocytosis and elevation of acute phase reactants. He received antibiotic therapy with clindamycin and ceftriaxone and percutaneous drainage of the abscess guided by ultrasound and sent to culture in which grew non-typificable anaerobe germs, with a favorable evolution after 5 year of follow up

Predisposition to Cervical Atypia in Systemic Lupus Erythematosus: A Clinical and Cytopathological Study

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Hend Hilal Al-Sherbeni

2015-01-01

Full Text Available Introduction. Systemic lupus erythematosus (SLE is a complex disease with variable presentations, course, and prognosis. The female genital tract may be a potential target organ in SLE since cervical inflammation may be associated with disease activity. An increase in cervical dysplasia, a precursor of cervical cancer, has been reported in females with SLE. Aim of the Work. This work aimed to study the prevalence of abnormal cervicovaginal smears in patients with systemic lupus erythematosus (SLE and to correlate abnormal smear findings with exposure to infection with human papilloma virus (HPV in SLE patients. Patients and Methods. Thirty-two patients with SLE, fulfilling the 1997 revised criteria for the classification of SLE, were included in this study. They were subjected to full history taking, clinical examination, laboratory investigations, and cervicovaginal smearing. Twenty healthy subjects not known to suffer from any rheumatological disease were used as controls, and they were subjected to cervicovaginal smearing. Results. Four out of 32 SLE patients showed abnormal Pap smears (12.5% compared to none showing any cervical changes in the control group (0%. Among these 4 patients, 3 were having ASCU and one was having LSIL (HPV. Conclusion. Cervicovaginal smearing is an easy, economic, safe, repeatable, and noninvasive technique for screening and early detection of cervical neoplastic lesions in SLE.

Expression patterns of signaling lymphocytic activation molecule family members in peripheral blood mononuclear cell subsets in patients with systemic lupus erythematosus.

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Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Kyttaris, Vasileios C; Tsokos, George C

2017-01-01

Genome-wide linkage analysis studies (GWAS) studies in systemic lupus erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory receptors expressed predominantly on hematopoietic cells. Activation of cells of the adaptive immune system is aberrant in SLE and dysregulated expression of certain SLAMF molecules has been reported. We examined the expression of SLAMF1-7 on peripheral blood T cells, B cells, monocytes, and their respective differentiated subsets, in patients with SLE and healthy controls in a systematic manner. SLAMF1 levels were increased on both T cell and B cells and their differentiated subpopulations in patients with SLE. SLAMF2 was increased on SLE CD4+ and CD8+ T cells. The frequency of SLAMF4+ and SLAMF7+ central memory and effector memory CD8+ T cells was reduced in SLE patients. Naïve CD4+ and CD8+ SLE T cells showed a slight increase in SLAMF3 levels. No differences were seen in the expression of SLAMF5 and SLAMF6 among SLE patients and healthy controls. Overall, the expression of various SLAMF receptors is dysregulated in SLE and may contribute to the immunopathogenesis of the disease.

The African Lupus Genetics Network (ALUGEN) registry: standardized, prospective follow-up studies in African patients with systemic lupus erythematosus.

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Hodkinson, B; Mapiye, D; Jayne, D; Kalla, A; Tiffin, N; Okpechi, I

2016-03-01

The prevalence and severity of systemic lupus erythematosus (SLE) differs between ethnic groups and geographical regions. Although initially reported as rare, there is growing evidence that SLE is prevalent and runs a severe course in Africa. There is a paucity of prospective studies on African SLE patients. The African Lupus Genetics Network (ALUGEN) is a multicentred framework seeking to prospectively assess outcomes in SLE patients in Africa. Outcomes measured will be death, hospital admission, disease activity flares, and SLE-related damage. We will explore predictors for these outcomes including clinical, serological, socio-demographic, therapeutic and genetic factors. Further, we will investigate comorbidities and health-related quality of life amongst these patients. Data of patients recently (≤ 5 yrs) diagnosed with SLE will be collected at baseline and annual follow-up visits, and captured electronically. The ALUGEN project will facilitate standardized data capture for SLE cases in Africa, allowing participating centres to develop their own SLE registries, and enabling collaboration to enrich our understanding of inter-ethnic and regional variations in disease expression. Comprehensive, high-quality multi-ethnic data on African SLE patients will expand knowledge of the disease and inform clinical practice, in addition to augmenting research capacity and networking links and providing a platform for future biomarker and interventional studies. © The Author(s) 2015.

Inverse Association of Parkinson Disease With Systemic Lupus Erythematosus: A Nationwide Population-based Study.

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Liu, Feng-Cheng; Huang, Wen-Yen; Lin, Te-Yu; Shen, Chih-Hao; Chou, Yu-Ching; Lin, Cheng-Li; Lin, Kuen-Tze; Kao, Chia-Hung

2015-11-01

The effects of the inflammatory mediators involved in systemic lupus erythematous (SLE) on subsequent Parkinson disease have been reported, but no relevant studies have focused on the association between the 2 diseases. This nationwide population-based study evaluated the risk of Parkinson disease in patients with SLE.We identified 12,817 patients in the Taiwan National Health Insurance database diagnosed with SLE between 2000 and 2010 and compared the incidence rate of Parkinson disease among these patients with that among 51,268 randomly selected age and sex-matched non-SLE patients. A Cox multivariable proportional-hazards model was used to evaluate the risk factors of Parkinson disease in the SLE cohort.We observed an inverse association between a diagnosis of SLE and the risk of subsequent Parkinson disease, with the crude hazard ratio (HR) being 0.60 (95% confidence interval 0.45-0.79) and adjusted HR being 0.68 (95% confidence interval 0.51-0.90). The cumulative incidence of Parkinson disease was 0.83% lower in the SLE cohort than in the non-SLE cohort. The adjusted HR of Parkinson disease decreased as the follow-up duration increased and was decreased among older lupus patients with comorbidity.We determined that patients with SLE had a decreased risk of subsequent Parkinson disease. Further research is required to elucidate the underlying mechanism.

Protein-losing enteropathy in systemic lupus erythematosus: 12 years experience from a Chinese academic center.

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Zhen Chen

Full Text Available Protein-losing enteropathy (PLE is a complication in some systemic lupus erythematosus (SLE patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease.A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group and 88 patients with active SLE (control group admitted to our care from January 2000-January 2012. Risk factors for SLE-related PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents.The PLE group had lower mean serum albumin and 24-hour urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti-SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (<22 g/l and 24-hour urine protein (<0.8 g/24 h had high specificity, positive predictive value, negative predictive value, and positive likelihood ratio, a low negative likelihood ratio and no significant reduction in sensitivity. High dosage of glucocorticosteroid combined with cyclophosphomide were mostly prescribed for SLE-related PLE.SLE-related PLE should be considered when an SLE patient presents with generalized edema, anti-SSA antibody seropositivity, hypercholesterolemia, severe hypoalbuminemia, and low 24-hour urine protein levels. Aggressive treatment for lupus might improve prognosis.

Subjective life expectancy and actual mortality: results of a 10-year panel study among older workers.

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van Solinge, Hanna; Henkens, Kène

2018-06-01

This research examined the judgemental process underlying subjective life expectancy (SLE) and the predictive value of SLE on actual mortality in older adults in the Netherlands. We integrated theoretical insights from life satisfaction research with existing models of SLE. Our model differentiates between bottom-up (objective data of any type) and top-down factors (psychological variables). The study used data from the first wave of the Netherlands Interdisciplinary Demographic Institute Work and Retirement Panel. This is a prospective cohort study among Dutch older workers. The analytical sample included 2278 individuals, assessed at age 50-64 in 2001, with vital statistics tracked through 2011. We used a linear regression model to estimate the impact of bottom-up and top-down factors on SLE. Cox proportional hazard regression was used to determine the impact of SLE on the timing of mortality, crude and adjusted for actuarial correlates of general life expectancy, family history, health and trait-like dispositions. Results reveal that psychological variables play a role in the formation of SLE. Further, the results indicate that SLE predicts actual mortality, crude and adjusted for socio-demographic, biomedical and psychological confounders. Education has an additional effect on mortality. Those with higher educational attainment were less likely to die within the follow-up period. This SES gradient in mortality was not captured in SLE. The findings indicate that SLE is an independent predictor of mortality in a pre-retirement cohort in the Netherlands. SLE does not fully capture educational differences in mortality. Particularly, higher-educated individuals underestimate their life expectancy.

Galactic evolution

International Nuclear Information System (INIS)

Pagel, B.

1979-01-01

Ideas are considered concerning the evolution of galaxies which are closely related to those of stellar evolution and the origin of elements. Using information obtained from stellar spectra, astronomers are now able to consider an underlying process to explain the distribution of various elements in the stars, gas and dust clouds of the galaxies. (U.K.)

Carotid intima-media thickness and arterial stiffness in pediatric systemic lupus erythematosus.

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Su-Angka, N; Khositseth, A; Vilaiyuk, S; Tangnararatchakit, K; Prangwatanagul, W

2017-08-01

Objectives The carotid intima-media thickness (CIMT) and carotid arterial stiffness index (CASI) act as the surrogate markers of atherosclerosis. We aim to assess CIMT and CASI in pediatric systemic lupus erythematosus (SLE). Methods Patients ≤ 20 years old fulfilling diagnostic criteria for SLE were enrolled. Patients with active smoking, coronary heart disease, cerebrovascular disease, arterial thrombosis, family history of hypercholesterolemia, chronic liver disease, or other chronic severe diseases were excluded. The patients were categorized into four groups: active SLE, age- and sex-matched control (control A), inactive SLE, and age- and sex-matched control (control I), according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). All subjects underwent ultrasound of carotid arteries to evaluate CIMT and CASI. Results One hundred and two SLE patients (26 active and 76 inactive) and one hundred and three healthy controls (26 control A and 77 control I) were enrolled. The median CIMT in all groups were not significantly different (0.43, 0.41-0.44; 0.43, 0.41-0.44; 0.42, 0.41-0.43; and 0.42, 0.41-0.43 mm, respectively).The CASI in active SLE (13.5, 11.4-17.3) was significantly higher than in control A (8.2, 7.2-9.2) ( p < 0.0001), whereas CASI in inactive SLE (12.7, 10.9-15.7) was significantly higher than in control I (8.9, 7.6-9.8). However, the CASI in active and inactive SLE was not significantly different. Conclusions The higher CASI in active and inactive pediatric SLE, implying functional change of carotid arteries, may be early evidence of increased atherosclerosis in pediatric SLE. This functional dysfunction has been found both in inactive and active SLE.

A Comparitive Study of Anticardiolipin Antibodies among Systemic Lupus Erythematosus Patients from Western and Eastern India.

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Doley, D; Kakati, S; Saikia, L; Rajadhyaksha, A; Nadkar, Milind; Khadilkar, P; Patwardhan, M; Pradhan, V

2017-03-01

Anti-phospholipid antibodies (APA) like anticardiolipin antibodies (ACA) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. Prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA in SLE patients from Eastern and Western India and to correlate them with disease activity. Seventy SLE patients from Assam Medical College, Dibrugarh, Assam and 85 SLE patients from Rheumatology Department, KEM Hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease. Demographic data showed significant variations in the clinical manifestations of SLE between two regions. Renal manifestations were higher (42.9%) among SLE patients from Eastern region as compared with 37.6% patients from Western region. These patients were categorized as Lupus Nephritis (LN) and patients that did not show any renal manifestations were categories as non-LN. ACA to IgG and IgM subclasses were tested by ELISA. IgGACA positivity was 20%, 12.9% and IgM-ACA positivity was 18.6%, 12.9% where asIgG + IgM ACA positivity as found in 12.9%, 3.5% patients respectively among SLE patients from Eastern and Western India. ACA positivity was higher among LN patients from Eastern India whereas the same was higher among non-LN patients from Western India. Hence detection of ACA alongwith associated clinical manifestations were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA antibodies without thrombotic event is needed to detect their possible thrombotic event in future along with their clinical presentation from these two different geographic regions from India.

Brain unidentified bright objects ("UBO") in systemic lupus erythematosus: sometimes they come back. A study of microembolism by cMRI and Transcranial Doppler ultrasound.

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Bortoluzzi, A; Padovan, M; Azzini, C; De Vito, A; Trotta, F; Govoni, M

2016-02-01

The objectives of this report are to assess the occurrence of microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (SLE) neuropsychiatric involvement, and to verify the correlation between MES, clinical characteristics, especially the patent foramen ovale (PFO), and the presence of punctuate T2-hyperintense white matter lesions (WMHLs) detected by conventional magnetic resonance imaging (cMRI). A TCD registration to detect MES from the middle cerebral artery was carried out in SLE and NPSLE patients after exclusion of aortic and/or carotid atheromatous disease. In all patients conventional brain magnetic resonance imaging (cMRI) and transesophageal echocardiography were performed. Patients were stratified in two groups, with and without WMHLs, and compared. Twenty-three SLE patients (16 NPSLE and seven SLE) were enrolled in the study. Overall MES were detected in 12 patients (52.1%), WHMLs were detectable in 15 patients (13 NPSLE and two SLE) while eight patients had normal cMRI (three NPSLE and five SLE). Matching TCD ultrasound and neuroimaging data, MES were detected in 10 (nine NPSLE and one SLE) out of 15 patients with WHMLs and in only two out of eight patients (two NPSLE and six SLE) with normal cMRI, both with NP involvement. A PFO was confirmed in all cases of MES detection. MES are frequent findings in SLE patients, especially in those with focal WMHLs detected by cMRI and correlating with PFO. These findings should be taken into account and suggest caution in the interpretation of cMRI pictures along with a careful evaluation of MES in patients with cMRI abnormalities that should be included in the workup of SLE patients. © The Author(s) 2015.

Evolution of complex dynamics

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Wilds, Roy; Kauffman, Stuart A.; Glass, Leon

2008-09-01

We study the evolution of complex dynamics in a model of a genetic regulatory network. The fitness is associated with the topological entropy in a class of piecewise linear equations, and the mutations are associated with changes in the logical structure of the network. We compare hill climbing evolution, in which only mutations that increase the fitness are allowed, with neutral evolution, in which mutations that leave the fitness unchanged are allowed. The simple structure of the fitness landscape enables us to estimate analytically the rates of hill climbing and neutral evolution. In this model, allowing neutral mutations accelerates the rate of evolutionary advancement for low mutation frequencies. These results are applicable to evolution in natural and technological systems.

Variation in STAT4 is associated with systemic lupus erythematosus in Chinese Northern Han population.

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Su, Yin; Zhao, Yi; Liu, Xu; Guo, Jian-Ping; Jiang, Quan; Liu, Xiang-Yuan; Zhang, Feng-Chun; Zheng, Yi; Li, Xiao-Xia; Song, Hui; Huang, Ci-Bo; Huang, Yan-Hong; Wang, Tian; Pan, Si-Si; Li, Chun; Liu, Xia; Zhu, Lei; Zhang, Chun-Fang; Li, Zhan-Guo

2010-11-01

Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. In order to examine whether the allele distribution of the single nucleotide polymorphism (SNP) in gene STAT4 rs7574865 in patients with SLE is different from those of healthy controls in Chinese Northern Han population, we investigated whether the variants of STAT4 rs7574865 were associated with any specific clinical features of SLE. We genotyped SNPs in STAT4 rs7574865 in 252 patients with SLE and 497 healthy controls. All subjects were from the Northern part of Chinese Han population. The genotypes in rs7574865 were determined by polymerase chain reaction (PCR) and consequence direct sequencing of PCR products in the DNA samples. There was a significant difference in distribution of the SNPs in rs7574865 between the SLE patients and healthy controls. Compared with healthy controls, there was a significant correlation between TT genotypes in rs7574865 and the risk of SLE when GG genotype was used as a reference genotype after adjusting for gender and age. The frequency of T allele in the SLE patients was strongly significantly higher than that of healthy controls. Furthermore, there was a significant difference in the distribution of SNP in rs7574865 between male and female SLE patients, when compared with healthy controls. The frequency of T allele in rs7574865 in male patients was significantly higher than that of male healthy controls or female patients. There was no significant correlation between the frequencies of T allele in STAT4 rs7574865 and the clinical features of SLE. The SNP rs7574865 in STAT4 is strongly associated with risk of SLE in the Chinese Northern Han population. The TT genotype and T allele in STAT4 rs7574869 are susceptibility factors for SLE, especially for male SLE patients.

Coexistence of systemic lupus erythematosus and multiple sclerosis. A case report and literature review.

Science.gov (United States)

Jácome Sánchez, Elisa Carolina; García Castillo, María Ariana; González, Victor Paredes; Guillén López, Fernando; Correa Díaz, Edgar Patricio

2018-01-01

Multiple sclerosis (MS) and systemic lupus erythematous (SLE) are autoimmune diseases, the coexistence of which is uncommon in patients. Owing to the rarity of this condition, the distinction between MS and SLE is a diagnostic challenge for neurologists. We present a case report in which MS and SLE were present in the same patient. There are few case reports in the world on the association between MS and SLE. The following case report is the first of its kind in which both MS and SLE are present in a patient from a country with low prevalence of MS such as Ecuador.

Sialyl Lewis x expression in canine malignant mammary tumours: correlation with clinicopathological features and E-Cadherin expression

International Nuclear Information System (INIS)

Pinho, Salomé S; Matos, Augusto JF; Lopes, Célia; Marcos, Nuno T; Carvalheira, Júlio; Reis, Celso A; Gärtner, Fátima

2007-01-01

Sialyl Lewis x (sLe x ) antigen is a carbohydrate antigen that is considered not only a marker for cancer but also implicated functionally in the malignant behaviour of cancer cells. Overexpression of sLe x is associated with enhanced progression and metastases of many types of cancer including those of the mammary gland. Canine mammary tumours can invade and give rise to metastases via either lymphatic or blood vessels. E-Cadherin is specifically involved in epithelial cell-to-cell adhesion. In cancer, E-Cadherin underexpression is one of the alterations that characterizes the invasive phenotype and is considered an invasion/tumour suppressor gene. Partial or complete loss of E-Cadherin expression correlates with poor prognosis in canine malignant mammary cancer. The aim of this study was to analyse the sLe x expression in canine malignant mammary tumours and to evaluate if the presence of sLe x correlates with the expression of E-Cadherin and with clinicopathological features. Fifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLe x (IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLe x tumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLe x and E-Cadherin. sLe x expression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLe x expression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLe x was reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship. In the present study we demonstrate the importance of sLe x in the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLe x as a prognostic tumour

Bio-cellulose Production by Beijerinckia fluminensis WAUPM53 and Gluconacetobacter xylinus 0416 in Sago By-product Medium.

Science.gov (United States)

Voon, W W Y; Muhialdin, B J; Yusof, N L; Rukayadi, Y; Meor Hussin, A S

2018-06-19

Bio-cellulose is the microbial extracellular cellulose that is produced by growing several microorganisms on agriculture by-products, and it is used in several food applications. This study aims to utilize sago by-product, coconut water, and the standard medium Hestrin-Schramm as the carbon sources in the culture medium for bio-cellulose production. The bacteria Beijerinkia fluminensis WAUPM53 and Gluconacetobacter xylinus 0416 were selected based on their bio-cellulose production activity. The structure was determined by Fourier transform infrared spectroscopy and scanning electron microscopy, while the toxicity safety was evaluated by brine shrimp lethality test. The results of Fourier transform infrared spectroscopy showed that the bio-cellulose produced by B. fluminensis cultivated in sago by-products was of high quality. The bio-cellulose production by B. fluminensis in the sago by-product medium was slightly higher than that in the coconut water medium and was comparable with the production in the Hestrin-Schramm medium. Brine shrimp lethality test confirmed that the bio-cellulose produced by B. fluminensis in the sago by-product medium has no toxicity, which is safe for applications in the food industry. This is the first study to determine the high potential of sago by-product to be used as a new carbon source for the bio-cellulose production.

Constrained evolution in numerical relativity

Science.gov (United States)

Anderson, Matthew William

The strongest potential source of gravitational radiation for current and future detectors is the merger of binary black holes. Full numerical simulation of such mergers can provide realistic signal predictions and enhance the probability of detection. Numerical simulation of the Einstein equations, however, is fraught with difficulty. Stability even in static test cases of single black holes has proven elusive. Common to unstable simulations is the growth of constraint violations. This work examines the effect of controlling the growth of constraint violations by solving the constraints periodically during a simulation, an approach called constrained evolution. The effects of constrained evolution are contrasted with the results of unconstrained evolution, evolution where the constraints are not solved during the course of a simulation. Two different formulations of the Einstein equations are examined: the standard ADM formulation and the generalized Frittelli-Reula formulation. In most cases constrained evolution vastly improves the stability of a simulation at minimal computational cost when compared with unconstrained evolution. However, in the more demanding test cases examined, constrained evolution fails to produce simulations with long-term stability in spite of producing improvements in simulation lifetime when compared with unconstrained evolution. Constrained evolution is also examined in conjunction with a wide variety of promising numerical techniques, including mesh refinement and overlapping Cartesian and spherical computational grids. Constrained evolution in boosted black hole spacetimes is investigated using overlapping grids. Constrained evolution proves to be central to the host of innovations required in carrying out such intensive simulations.

Micro-droplet based directed evolution outperforms conventional laboratory evolution

DEFF Research Database (Denmark)

Sjostrom, Staffan L.; Huang, Mingtao; Nielsen, Jens

2014-01-01

We present droplet adaptive laboratory evolution (DrALE), a directed evolution method used to improve industrial enzyme producing microorganisms for e.g. feedstock digestion. DrALE is based linking a desired phenotype to growth rate allowing only desired cells to proliferate. Single cells are con...... a whole-genome mutated library of yeast cells for α-amylase activity....

Pleuro-pulmonary abnormalities in patients with systemic lupus erythematosus assessment with high resolution computed tomography, chest radiography and pulmonary function tests

Energy Technology Data Exchange (ETDEWEB)

Sant, S.M.; Doran, M.; Fenelon, H.M.; Breatnach, E.S. [University of Michigan (United States)

1998-04-01

The objective has to assess the nature of pleuro-pulmonary abnormalities, with particular reference to interstitial lung disease (ILD), in patients with systemic lupus erythematosus (SLE) In conclusion, HRCT is more sensitive than PFTs or CXR in the evaluation of pleuro-pulmonary disease in SLE. We report an unusually high prevalence of HRCT appearances suggestive of ILD in patients with SLE. subclinical lung disease is common in patients with SLE. (author)

Appearance of Systemic Lupus Erythematosus in Patients with Myasthenia Gravis following Thymectomy: Two Case Reports

OpenAIRE

Park, Mi-Jeong; Kim, Yun-A; Lee, Shin-Seok; Kim, Byeong-Chae; Kim, Myeong-Kyu; Cho, Ki-Hyun

2004-01-01

We report two cases of systemic lupus erythematosus (SLE) in myasthenia gravis (MG) patients who had undergone thymectomy. SLE developed in the patients 3 months or 13 yr after thymectomy, and polyarthritis was the main clinical manifestation of SLE. Both patients fulfilled at least four of the revised criteria for the classification of SLE. In this report, we describe two postthymectomy lupus patients and perform a comparative review of previous cases.

Pleuro-pulmonary abnormalities in patients with systemic lupus erythematosus assessment with high resolution computed tomography, chest radiography and pulmonary function tests

International Nuclear Information System (INIS)

Sant, S.M.; Doran, M.; Fenelon, H.M.; Breatnach, E.S.

1998-01-01

The objective has to assess the nature of pleuro-pulmonary abnormalities, with particular reference to interstitial lung disease (ILD), in patients with systemic lupus erythematosus (SLE) In conclusion, HRCT is more sensitive than PFTs or CXR in the evaluation of pleuro-pulmonary disease in SLE. We report an unusually high prevalence of HRCT appearances suggestive of ILD in patients with SLE. subclinical lung disease is common in patients with SLE. (author)

Research

African Journals Online (AJOL)

cqq1a

2010-08-29

Aug 29, 2010 ... by SLE Disease Activity Index (SLEDAI), and quality of life was measured by ... support to SLE patients beside rapid meticulous control of disease activity. ..... Table 2: Clinical and laboratory findings in studied SLE population.

Experimental evolution and the dynamics of adaptation and genome evolution in microbial populations.

Science.gov (United States)

Lenski, Richard E

2017-10-01

Evolution is an on-going process, and it can be studied experimentally in organisms with rapid generations. My team has maintained 12 populations of Escherichia coli in a simple laboratory environment for >25 years and 60 000 generations. We have quantified the dynamics of adaptation by natural selection, seen some of the populations diverge into stably coexisting ecotypes, described changes in the bacteria's mutation rate, observed the new ability to exploit a previously untapped carbon source, characterized the dynamics of genome evolution and used parallel evolution to identify the genetic targets of selection. I discuss what the future might hold for this particular experiment, briefly highlight some other microbial evolution experiments and suggest how the fields of experimental evolution and microbial ecology might intersect going forward.

Enhanced Airport Surface Detection Equipment Applications,

Science.gov (United States)

1985-04-17

of runway capacity for the single mixed runway case . The ASDE display, however, provides independent position and timing information on runway...restored to within approximately 5 percent of the good visibility capacity for the single mixed runway case . The lack of identity informa- tion on the ASDE...D.C. 20591 ENGINEERING AND ECONOMICS RESEARCH, INC. Technical Support Staff Henry R. Schramm Mignonette E. Stephen A-2 I m i . . . -i , ’ ,.i

Neues aus dem Forschungsfeld Deutsch als Zweitsprache. Sammelrezension

Directory of Open Access Journals (Sweden)

Claus Altmayer

2015-03-01

Full Text Available Neues aus dem Forschungsfeld Deutsch als Zweitsprache. Sammelrezension (Teil 2 von Bernt Ahrenholz (Hrsg. (2009, Empirische Befunde zu DaZ-Erwerb und Sprachförderung. Beiträge aus dem 3. ‚Workshop Kinder mit Migrationshintergrund‘; Karen Schramm & Christoph Schröder (Hrsg. (2009, Empirische Zugänge zu Spracherwerb und Sprachförderung in Deutsch als Zweitsprache; Stefan Jeuk (2010, Deutsch als Zweitsprache in der Schule. Grundlagen - Diagnose – Förderung

Prevalence of systemic lupus erythematosus among patients of hypothyroidism in a tertiary care center

Directory of Open Access Journals (Sweden)

Rudrajit Paul

2012-01-01

Full Text Available Context: Hypothyroidism is a common public health problem in India. With iodine sufficiency, autoimmune thyroiditis is becoming the most important etiology of hypothyroidism. Often, thyroiditis is associated with other systemic autoimmune diseases. Aims: We undertook thisobservational study to find the prevalence of systemic lupus erythematosus (SLE amongst the hypothyroid patients at our Institution. Settings and Design: This is probably the first study of its kind from India. Materials and Methods: 185 patients with diagnosed hypothyroidism were included and screening for SLE was done by standard epidemiological criteria. Majority of the patients (63.8% were young adults (20-40 years. Statistical Analysis Used: Two by two contingency tables were analyzed by Chi-square test or Fisher′s exact test as needed. Logistic regression model was used considering the presence of SLE as a dependent variable. Results: Eleven (5.94% patients were found to have SLE. However, anti nuclear factor was positive in 145 cases (78.4%. Of the patients with SLE, 8 (72.7% were found to be anti TPO positive, but the titers of ANF and anti TPO did not correlate. Presence of discoid rash, haematological criteria and presence of antibodies like anti-dsDNA were significantly correlated with the presence of SLE in hypothyroid patients. Presence of ANF was also correlated with the grade of goiter (r=0.62; P<0.05. Also four patients with SLE had a positive family history (OR=9.37. Logistic regression model showed anti-TPO has OR=1.54 (P=0.02 for the development of SLE. Conclusions: Prevalence of SLE in hypothyroid patients is high compared to the general population, especially, as thyroiditis is very common in SLE.

Expressions of interferon-inducible genes IFIT1 and IFIT4 mRNA in PBMCs of patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Liu Chunyan; Chen Xingguo; Wang Zizheng

2009-01-01

To investigate the expression levels of interferon-inducible genes (IFIT1, IFIT4) in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), and the relations between these genes expression levels and disease activity, the expression levels of IFIT1 and IFIT4 mRNA in the 95 patients with SLE and 48 normal controls were detected by Sybr green dye based real-time quantitative PCR method, and these genes expression levels were compared with anti-double strand DNA antibody. The associations between the expression levels of IFIT1, IFIT4 mRNA, anti-double strand DNA antibody and SLEDAI scores in patients with SLE were analyzed. The results showed that the expression levels of IFIT1, IFIT4 mRNA in the SLE patients were significantly higher than those of the normal controls (P<0.01). The expression levels of IFIT1, IFIT4 mRNA in the active SLE patients were higher than those of the inactive SLE patients (P<0.05). The real time expression levels of IFIT1 and IFIT4 mRNA showed positive correlations with each other (P<0.05) in patients with SLE. There was positively correlation between the expression levels of IFIT1, IFIT4 mRNA and the anti-double strand DNA antibody (P<0.05). The expression levels of IFIT1, IFIT4 mRNA in patients with SLE were significantly higher than those of the normal controls, and positively associated with SLEDAI scores, so they were helpful in evaluating SLE disease activity and severity. To inhibit the expressions of IFIT1, IFIT4 mRNA may provide a novel target for SLE treatment. (authors)

Periodontal disease in Chinese patients with systemic lupus erythematosus.

Science.gov (United States)

Zhang, Qiuxiang; Zhang, Xiaoli; Feng, Guijaun; Fu, Ting; Yin, Rulan; Zhang, Lijuan; Feng, Xingmei; Li, Liren; Gu, Zhifeng

2017-08-01

Disease of systemic lupus erythematosus (SLE) and periodontal disease (PD) shares the common multiple characteristics. The aims of the present study were to evaluate the prevalence and severity of periodontal disease in Chinese SLE patients and to determine the association between SLE features and periodontal parameters. A cross-sectional study of 108 SLE patients together with 108 age- and sex-matched healthy controls was made. Periodontal status was conducted by two dentists independently. Sociodemographic characteristics, lifestyle factors, medication use, and clinical parameters were also assessed. The periodontal status was significantly worse in SLE patients compared to controls. In univariate logistic regression, SLE had a significant 2.78-fold [95% confidence interval (CI) 1.60-4.82] increase in odds of periodontitis compared to healthy controls. Adjusted for potential risk factors, patients with SLE had 13.98-fold (95% CI 5.10-38.33) increased odds against controls. In multiple linear regression model, the independent variable negatively and significantly associated with gingival index was education (P = 0.005); conversely, disease activity (P periodontitis of SLE in multivariate logistic regression (OR 1.348; 95% CI: 1.183-1.536, P < 0.001). Chinese SLE patients were likely to suffer from higher odds of PD. These findings confirmed the importance of early interventions in combination with medical therapy. It is necessary for a close collaboration between dentists and clinicians when treating those patients.

Gastrointestinal system involvement in systemic lupus erythematosus.

Science.gov (United States)

Li, Z; Xu, D; Wang, Z; Wang, Y; Zhang, S; Li, M; Zeng, X

2017-10-01

Systemic lupus erythematosus (SLE) is a multisystem disorder which can affect the gastrointestinal (GI) system. Although GI symptoms can manifest in 50% of patients with SLE, these have barely been reviewed due to difficulty in identifying different causes. This study aims to clarify clinical characteristics, diagnosis and treatment of the four major SLE-related GI system complications: protein-losing enteropathy (PLE), intestinal pseudo-obstruction (IPO), hepatic involvement and pancreatitis. It is a systematic review using MEDLINE and EMBASE databases and the major search terms were SLE, PLE, IPO, hepatitis and pancreatitis. A total of 125 articles were chosen for our study. SLE-related PLE was characterized by edema and hypoalbuminemia, with Technetium 99m labeled human albumin scintigraphy ( 99m Tc HAS) and alpha-1-antitrypsin fecal clearance test commonly used as diagnostic test. The most common site of protein leakage was the small intestine and the least common site was the stomach. More than half of SLE-related IPO patients had ureterohydronephrosis, and sometimes they manifested as interstitial cystitis and hepatobiliary dilatation. Lupus hepatitis and SLE accompanied by autoimmune hepatitis (SLE-AIH overlap) shared similar clinical manifestations but had different autoantibodies and histopathological features, and positive anti-ribosome P antibody highly indicated the diagnosis of lupus hepatitis. Lupus pancreatitis was usually accompanied by high SLE activity with a relatively high mortality rate. Early diagnosis and timely intervention were crucial, and administration of corticosteroids and immunosuppressants was effective for most of the patients.

Differences in disease features between childhood-onset and adult-onset systemic lupus erythematosus patients presenting with acute abdominal pain.

Science.gov (United States)

Tu, Yu-Ling; Yeh, Kuo-Wei; Chen, Li-Chen; Yao, Tsung-Chieh; Ou, Liang-Shiou; Lee, Wen-I; Huang, Jing-Long

2011-04-01

Abdominal pain in systemic lupus erythematosus (SLE) patients has rarely been analyzed in pediatric populations. We planned to investigate the potential differences between childhood-onset and adult-onset SLE patients who were hospitalized because of acute abdominal pain. A retrospective study including 23 childhood-onset SLE patients with 38 admissions and 88 adult-onset SLE patients with 108 admissions from 1999 to 2008 were conducted in our hospital. All of them had the chief complaint of diffuse abdominal pain. The etiologies of acute abdominal pain in adult-onset SLE patients were more diverse than childhood-onset SLE patients. The most common cause of acute abdominal pain in SLE patients was lupus mesenteric vasculitis (LMV) (18.5%), followed by acute gastroenteritis (14.4%), pancreatitis (10.3%), appendicitis (7.5%), and cholecystitis (6.2%). Compared with adults, children were admitted more often due to LMV (31.6% versus 13.9%; P = 0.016), had more frequently recurrent episodes (39.1% versus 14.8%; P = 0.009), and were more often treated with immunosuppressive agents (31.6% versus 7.4%; P abdominal pain should be considered in SLE patients. LMV is the most common cause of acute abdomen in childhood-onset SLE patients with low mortality and morbidity provided by prompt diagnosis and timely administration of high-dose intravenous corticosteroids after excluding real surgical abdomen. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Systemic lupus erythematosus and thyroid disease - Experience in a single medical center in Taiwan.

Science.gov (United States)

Liu, Yu-Chuan; Lin, Wen-Ya; Tsai, Ming-Chin; Fu, Lin-Shien

2017-06-28

To investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan. This is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia. Compared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement. Copyright © 2017. Published by Elsevier B.V.

Retracted Association of STAT4 gene polymorphism with systemic lupus erythematosus / lupus nephritis risk.

Science.gov (United States)

Zhou, Tian-Biao; Jiang, Zong-Pei; Qin, Yuan-Han; Zhou, Jia-Fan

2014-04-16

The association of STAT4 gene polymorphism with systemic lupus erythematosus (SLE) / lupus nephritis (LN) results from the published studies is still conflicting. This meta-analysis was performed to evaluate the relationship between STAT4 rs7574865, rs16833431, rs11889341, rs8179673, rs10168266, rs7582694, rs3821236, rs7601754 gene polymorphism and SLE / LN, and to explore whether STAT4 gene polymorphism could become a predictive marker for SLE / LN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2013, and eligible investigations were synthesized using meta-analysis method. 24 investigations were identified for the analysis of association between STAT4 gene polymorphism and SLE, consisting of 31190 patients with SLE and 43940 controls. In STAT4 rs7574865, there was a marked association between T allele or TT genotype and SLE susceptibility (T: OR=1.53, 95% CI: 1.30-1.79, Prs7574865 gene polymorphism was not associated with the LN risk. Our results indicate that T allele or TT homozygous is a significant risk genetic molecular marker to predict the SLE susceptibility and GG genotype is a valuable marker to against the SLE risk, but the association was not found for LN. However, more investigations are required to further clarify the association of the T allele or TT homozygous with SLE / LN susceptibility. This article is protected by copyright. All rights reserved.

Advances in our understanding of immunization and vaccines for patients with systemic lupus erythematosus.

Science.gov (United States)

Bragazzi, Nicola Luigi; Watad, Abdulla; Sharif, Kassem; Adawi, Mohammad; Aljadeff, Gali; Amital, Howard; Shoenfeld, Yehuda

2017-10-01

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. In SLE, immune system dysfunction is postulated to result by virtue of the disease itself as well as by the impact of treatment modalities employed. A myriad of immune dysregulations occur including complement system dysfunction among others. Infectious agents are known to complicate the disease course in close to 25-45% of SLE patients. Areas covered: In this review a discussion of the immunogenicity and safety of viral and bacterial vaccinations in SLE was performed. The search included ISI Web of Science (WoS), Scopus, MEDLINE/PubMed, Google-Scholar, DOAJ, EbscoHOST, Scirus, Science Direct, Cochrane Library and ProQuest. Proper string made up of a key-words including 'SLE', 'vaccination', 'safety' and 'efficacy' was used. Expert commentary: Vaccination of SLE patients is proven to be immunogenic. Concerns regarding vaccine safety are postulated, yet no direct relationship between vaccination and disease exacerbation were established. While live virus vaccines are generally contraindicated in immunosuppressive states, generally live attenuated vaccinations are recommended in SLE patients on a case-to-case basis. In SLE patients, clinical parameters such as vaccination during disease exacerbations have not been intensively studied and therefore while apparently safe, vaccination is generally recommended while disease is quiescent.

An evaluation of vitamin D status in individuals with systemic lupus erythematosus.

Science.gov (United States)

Breslin, Leanne C; Magee, Pamela J; Wallace, Julie M W; McSorley, Emeir M

2011-11-01

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease where genetic susceptibility coupled with largely undefined environmental factors is reported to underlie the aetiology of the disease. One such factor is low vitamin D status. The primary source of vitamin D is endogenous synthesis following exposure of the skin to UVB light. Photosensitivity, sunlight avoidance and the use of sun protection factor in combination with medications prescribed to treat the symptoms of the disease, puts SLE patients at increased risk of vitamin D deficiency. Decreased conversion of 25-hydroxyvitamin D to the metabolically active form, 1,25-dihydroxyvitamin D3, is possible, due to renal impairment common in SLE putting additional stress on vitamin D metabolism. The majority of studies have identified low 25-hydroxyvitamin D in SLE patients, albeit using varying cut-offs (importance of optimal vitamin D status in SLE, critically evaluates research carried out to date that has investigated vitamin D in SLE, and highlights the need for a well-designed observational study that controls for diet, medication use, dietary supplements, UV exposure and seasonality, that uses sensitive methods for measuring vitamin D status and disease activity in SLE to conclusively establish the role of vitamin D in SLE.

Exploring the social and interpersonal experiences of South Asian women with a diagnosis of Systemic Lupus Erythematosus.

Science.gov (United States)

Rutter, S J; Kiemle, G

2015-01-01

Systemic Lupus Erythematosus (SLE) negatively impacts life quality, disproportionately affecting women and UK ethnic minorities. The study aimed to explore how UK South Asian women with SLE make sense of their social and interpersonal experiences, within the context of their ethnicity and perceived cultural influences. A qualitative design was employed to collect data from a homogenous sample of six South Asian women with SLE. Semi-structured interviews elicited participants' experiences of living with SLE and data were analysed using Interpretative Phenomenological Analysis. Master themes were (1) 'SLE: Complexities and Ironies', (2) 'The Power of SLE', (3) 'A Sense of Personal Responsibility and Accountability', (4) 'Essential Relationships: Qualities and Consequences' and (5) 'Struggling in Public View'. Findings revealed that illness, function and emotion were experienced as interrelated, and psychosocial issues were a powerful feature in SLE illness processes. Body image concerns, difficulties maintaining roles and the perceived views of others, triggered embarrassment and withdrawal, negatively influencing social function and relationships. Interestingly, explicit references to ethnicity and culture were minimal, suggesting that for these women, the key features of experience tended to reflect those of other SLE groups. These findings call for an integrated, biopsychosocial and multidisciplinary approach to health care provision in this area.

Rationale and design of the screening of pulmonary hypertension in systemic lupus erythematosus (SOPHIE) study.

Science.gov (United States)

Huang, Duo; Cheng, Yang-Yang; Chan, Pak-Hei; Hai, Jojo; Yiu, Kai-Hang; Tse, Hung-Fat; Wong, Ka-Lam; Fan, Katherine; Li, Ying Wah; Ng, Woon-Leung; Yim, Cheuk-Wan; Wong, Cheuk-Hon John; Tam, Lai-Shan; Wong, Priscilla C H; Wong, Chi-Yuen; Ho, Chup-Hei; Leung, Alexander M H; Mok, Chi-Chiu; Lam, Ho; Lau, Chak-Sing; Cheung, Tommy; Ho, Carmen; Law, Sharon W Y; Chan, Esther W; Yin, Li-Xue; Yue, Wen-Sheng; Mok, Toi Meng; Evora, Mario Alberto; Siu, Chung-Wah

2018-01-01

Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study. Standard right heart catheterisation will be provided to patients with intermediate or high echocardiographic probability of pulmonary hypertension. Those with low echocardiographic probability will rescreen within 1 year. The primary measure will be the diagnosis and types of pulmonary hypertension and prevalence of pulmonary hypertension in SLE patients. The secondary measures will be the predictors and prediction models for pulmonary hypertension in SLE patients. The estimated sample size is approximately 895 participants. The results of the SOPHIE study will be an important contribution to the literature of SLE-related pulmonary hypertension and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for screening of pulmonary hypertension in SLE patients.

The substantial burden of systemic lupus erythematosus on the productivity and careers of patients: a European patient-driven online survey.

Science.gov (United States)

Gordon, Caroline; Isenberg, David; Lerstrøm, Kirsten; Norton, Yvonne; Nikaï, Enkeleida; Pushparajah, Daphnee S; Schneider, Matthias

2013-12-01

The objective of this study was to explore the burden of SLE and its effect on patients' lives. The Lupus European Online (LEO) survey included patient-designed questions on demographics, SLE diagnosis, and the impact of SLE on careers. Three SLE-specific patient-reported outcome (PRO) questionnaires were also completed: the Lupus Quality of Life (LupusQoL), the Fatigue Severity Scale (FSS), and the Work Productivity and Activity Impairment (WPAI)-Lupus v2.0. The survey was available online in five languages from May through August 2010. All self-identified SLE participants were eligible to respond. Survey results were analysed using descriptive statistics. Multivariate linear regression explored factors contributing to impaired productivity. Of the 2070 European SLE patients completing the survey, 93.1% were women, 86.7% were aged Productivity was impaired across all WPAI domains, both at work and in general activities. Fatigue, an inability to plan and reduced physical health were significantly associated with impaired productivity. Patients whose careers were affected by SLE had worse health-related quality of life, more fatigue and worse productivity than patients whose careers were not affected. LEO survey respondents reported that SLE negatively affects their daily lives, productivity and career choices.

PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility

Directory of Open Access Journals (Sweden)

Pradhan V

2010-01-01

Full Text Available Systemic lupus erythematosus (SLE is a prototype autoimmune disease. SLE is a result of one or more immune mechanisms, like autoantibody production, complement activation, multiple inflammation and immune complex deposition leading to organ tissue damage. SLE affected patients are susceptible to common and opportunistic infections. There are several reports suggesting that Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Genetic factors and environmental factors also play an important role in the overall susceptibility to SLE pathophysiology. Recently, protein tyrosine phosphatase, non-receptor type 22 (PTPN22 gene, has been found to be associated with several autoimmune diseases like SLE, Grave′s disease and Hashimoto thyroiditis. The missense R620W polymorphism, rs 2476601, in PTPN22 gene at the nucleotide 1858 in codon 620 (620Arg > Trp has been associated with autoimmune diseases. The PTPN22 locus is also found to be responsible for development of pulmonary tuberculosis in certain populations. The PTPN22 1858C/T gene locus will be ideal to look for SLE susceptibility to tuberculosis in the Indian population. In this review, we focus on human PTPN22 gene structure and function as well as the association of PTPN22 gene polymorphisms with SLE susceptibility

Influence of psychological stress on headache in patients with systemic lupus erythematosus.

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Vargas-Hitos, José Antonio; Sabio, José Mario; Martínez-Egea, Isabel; Jiménez-Jáimez, Enrique; Rodríguez-Guzmán, Manuel; Navarrete-Navarrete, Nuria; López-Lozano, Esther; Romero-Alegría, Ángela; de la Calle, Cristina; Jáimez-Gámiz, Laura; Baños-Piñero, Pilar; Nebrera-Navarro, Fernando; Fidalgo, Alba; Caminal, Luis; de Ramón Garrido, Enrique; Ortego-Centeno, Norberto; Expósito, Manuela; Zamora-Pasadas, Mónica; Jiménez-Alonso, Juan

2014-03-01

To compare the prevalence and disability of headache in patients with systemic lupus erythematosus (SLE) with the general population and to assess the role of chronic psychological stress (CPS) in headache development. One hundred seventy patients with SLE and 102 control subjects matched for age, sex, and level of education were included in this multicenter, cross-sectional study. CPS, headache-related disability, and chronic analgesic intake (CAI) were evaluated in all participants. No statistical differences in the prevalence of headache between both groups were observed but headache disability was significantly higher in patients with SLE. In addition, a higher average score in the Cohen Perceived Stress Scale (CPSS) and a higher prevalence of patients with CAI were observed in patients with SLE. In multivariate analysis, CPSS score was positively (OR 1.09; 95% CI: 1.03-1.14; p = 0.001) and CAI negatively (OR 0.43; 95% CI: 0.19-0.99; p = 0.049) associated with headache in patients with SLE. Despite the prevalence of headache in patients with SLE and the general population being similar, headache-related disability may be higher in patients with SLE. Moreover, CPS might play a role in the pathogenesis of SLE headache, whereas CAI might have a protective effect against it.

Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

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Yang, J; Li, Q; Yang, X; Li, M

2016-04-01

Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

Depression Risk in Young Adults With Juvenile- and Adult-Onset Lupus: Twelve Years of Followup.

Science.gov (United States)

Knight, Andrea M; Trupin, Laura; Katz, Patricia; Yelin, Edward; Lawson, Erica F

2018-03-01

To compare major depression risk among young adults with juvenile-onset and adult-onset systemic lupus erythematosus (SLE), and to determine demographic and health-related predictors of depression. Young adults with SLE ages 18-45 years (n = 546) in the Lupus Outcomes Study completed annual telephone surveys from 2002-2015, including assessment of depression using the Center for Epidemiologic Studies Depression Scale (CES-D), and self-report measures of sociodemographics and health characteristics. Juvenile-onset SLE was defined as age adult-onset SLE. Older age, lower educational attainment, and physical function, higher disease activity, and a history of smoking were associated with an increased depression risk. Juvenile-onset SLE patients had a higher risk of major depression across all educational groups. Young adults with SLE, particularly those with juvenile-onset disease, are at high risk for major depression, which is associated with increased disease activity, poorer physical functioning, and lower educational attainment. Early depression intervention in young adults with SLE has the potential to improve both medical and psychosocial outcomes. © 2017, American College of Rheumatology.

Identification of substituent groups and related genes involved in salecan biosynthesis in Agrobacterium sp. ZX09.

Science.gov (United States)

Xu, Linxiang; Cheng, Rui; Li, Jing; Wang, Yang; Zhu, Bin; Ma, Shihong; Zhang, Weiming; Dong, Wei; Wang, Shiming; Zhang, Jianfa

2017-01-01

Salecan, a soluble β-1,3-D-glucan produced by a salt-tolerant strain Agrobacterium sp. ZX09, has been the subject of considerable interest in recent years because of its multiple bioactivities and unusual rheological properties in solution. In this study, both succinyl and pyruvyl substituent groups on salecan were identified by an enzymatic hydrolysis following nuclear magnetic resonance (NMR), HPLC, and MS analysis. The putative succinyltransferase gene (sleA) and pyruvyltransferase gene (sleV) were determined and cloned. Disruption of the sleA gene resulted in the absence of succinyl substituent groups on salecan. This defect could be complemented by expressing the sleA cloned in a plasmid. Thus, the sleA and sleV genes located in a 19.6-kb gene cluster may be involved in salecan biosynthesis. Despite the lack of succinyl substituents, the molecular mass of salecan generated by the sleA mutant did not substantially differ from that generated by the wild-type strain. Loss of succinyl substituents on salecan changed its rheological characteristics, especially a decrease in intrinsic viscosity.

Genetic Risk Factors of Systemic Lupus Erythematosus in the Malaysian Population: A Minireview

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Hwa Chia Chai

2012-01-01

Full Text Available SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes include MHC genes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring in MHC genes and genes coding for TNF-α, IL-1β, IL-1RN, and IL-6.

Clinical characteristics and outcomes of the meningitides in systemic lupus erythematosus.

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Baizabal-Carvallo, José Fidel; Delgadillo-Márquez, German; Estañol, Bruno; García-Ramos, Guillermo

2009-01-01

The meningitides are rare but well-identified complications in patients with systemic lupus erythematosus (SLE). To determine the clinical characteristics, risk factors, prevalence and outcomes of the meningitides (septic and aseptic) in patients with SLE. From January 1988 to December 2006, we identified patients with SLE and septic or aseptic meningitis. We identified 25 episodes of meningitis in 23 patients with SLE, from a total of 1,411 SLE patients (1.63%); in 15 out of 25 episodes, a microorganism was identified. Mycobacterium tuberculosis, Listeria monocytogenes and Criptococcus neoformans represented the main microorganisms. In 10 episodes, aseptic meningitis was diagnosed. Lymphopenia, steroid use, chronic damage and systemic activity of SLE were frequent in both kinds of meningitis. Although the clinical presentation did not differ significantly, patients with septic meningitis had more residual neurological deficits (p = 0.04). Meningitis was observed in about 1.6% of the patients with SLE; in 40% of the cases, no microorganism could be isolated. A residual neurological deficit was more common in patients with septic meningitis. Copyright (c) 2008 S. Karger AG, Basel.

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

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Barraclough, M; Elliott, R; McKie, S; Parker, B; Bruce, I N

2015-10-01

Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE. © The Author(s) 2015.

Outcome of total hip arthroplasty for avascular necrosis of the femoral head in systemic lupus erythematosus.

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Woo, Min Su; Kang, Joon Soon; Moon, Kyoung Ho

2014-12-01

This study evaluated the result of total hip arthroplasty (THA) for avascular necrosis of the femur head (AVNFH) in systemic lupus erythematosus (SLE) patients. Nineteen THAs were performed on 13 patients with SLE. The results of these patients were compared with the results of the control group (19 patients) who had THR due to AVNFH with none-SLE conditions. The Harris hip score increased from a preoperative average of 65.3 points to 94.9 at the most recent follow-up. In the control group, the mean HHS was 67.2 preoperatively and 96.1 postoperatively at the last follow-up. No significant difference was found between SLE patients and non-SLE patients who underwent hip arthroplasty. In conclusion, THA is an acceptable treatment for achieving functional improvement in patients who had SLE and AVNFH. Copyright © 2014 Elsevier Inc. All rights reserved.

Central nervous system systemic lupus erythematosus in children

International Nuclear Information System (INIS)

Osborn, A.G.; Boyer, R.S.

1989-01-01

Ischemic neurologic events and neuropsychiatric disorders occur in approximately 70% of patients with systematic lupus erythematosus (SLE). The CT and MR findings in adults with central nervous system (CNS) SLE have been described, but to the authors' knowledge no pediatric series has been reported. The MR and CT findings in four children with CNS SLE are compared with those reported in adults. Large infarcts are less frequent in children than in adults with CNS SLE, while multiple small infarctions and white matter lesions are more common. These findings in children who have no obvious source of emboli, intracardiac shunt, or history of trauma should raise the suspicion of SLE

Contemporary evolution strategies

CERN Document Server

Bäck, Thomas; Krause, Peter

2013-01-01

Evolution strategies have more than 50 years of history in the field of evolutionary computation. Since the early 1990s, many algorithmic variations of evolution strategies have been developed, characterized by the fact that they use the so-called derandomization concept for strategy parameter adaptation. Most importantly, the covariance matrix adaptation strategy (CMA-ES) and its successors are the key representatives of this group of contemporary evolution strategies. This book provides an overview of the key algorithm developments between 1990 and 2012, including brief descriptions of the a

Speed of quantum evolution of entangled two qubits states: Local vs. global evolution

International Nuclear Information System (INIS)

Curilef, S; Zander, C; Plastino, A R

2008-01-01

There is a lower bound for the 'speed' of quantum evolution as measured by the time needed to reach an orthogonal state. We show that, for two-qubits systems, states saturating the quantum speed limit tend to exhibit a small amount of local evolution, as measured by the fidelity between the initial and final single qubit states after the time τ required by the composite system to reach an orthogonal state. Consequently, a trade-off between the speed of global evolution and the amount of local evolution seems to be at work.

T-helper 1 Immune Response in Systemic Lupus Erythematosus ...

African Journals Online (AJOL)

) and osteopontin (OPN) in SLE patients and their correlation with the disease activity. Methods: The study included 24 patients with SLE and 20 age- and sex- matched control subjects. The disease activity was evaluated with the SLE disease ...

On the question of increasing the frequency of caesarean section and effects on maternal and neonatal outcomes (Part 1

Directory of Open Access Journals (Sweden)

Iu. Davydova

2016-06-01

Full Text Available Purpose: Systemic lupus erythematosus (SLE is an autoimmune disease that primarily affects young women. Pregnancy in women with SLE is regarded as a high risk of obstetric and perinatal complications, as well as at high risk of maternal and perinatal morbidity and mortality. The aim — to analyze the features of pregnancy and childbirth in women with systemic lupus erythematosus and antiphospholipid syndrome. Materials and methods. The prospective study included 96 pregnant women with systemic lupus erythematosus (SLE and APF, among them only 62 SLE (group 1 and 34 with SLE and APS (group 2. Review during the analysis of pregnancy, childbirth postpartum period in these groups of pregnant women. A control group comprised 36 somatically healthy pregnant women with physiological pregnancy. Results. SLE and APS women are a group at high risk for the development of obstetric complications that caused of abnormal placentation (hypertensive complications, premature birth. The frequency was significantly higher in the SLE group. Substantiated and implemented a system of improved perinatal care for pregnant women this groups include a unified approach to the diagnosis of SLE and SLE activity assessment. Use a personalized approach based on the data on the age debut SLE, duration at the time of the onset of the pregnancy, treatment, SLEDAI score at the time of the taking under observation, SLEDAI score in the first and second half of pregnancy. In the group of pregnant women with SLE and APS risks of thromboembolic disorders is very high and require adequate thromboprophylaxis. However, it is necessary when using LMWHs in these patients to carry out careful monitoring of the platelet count, as in autoimmune processes, which include SLE and APS, and inadequate monitoring of SLE activity likely thrombocytopenia. It should be noted the high incidence of complications of pregnancy and labor in a previous pregnancy in multiparous both groups. In patients 1

The association between metabolic syndrome and its components with systemic lupus erythematosus: a comprehensive systematic review and meta-analysis of observational studies.

Science.gov (United States)

Hallajzadeh, J; Khoramdad, M; Izadi, N; Karamzad, N; Almasi-Hashiani, A; Ayubi, E; Qorbani, M; Pakzad, R; Sullman, M J M; Safiri, S

2018-01-01

Objectives Based upon inflammatory-related factors in chronic systemic lupus erythematosus (SLE), as well as the long-term prescription of corticosteroids, metabolic syndrome (MetS) prevalence is expected to be higher in SLE patients than among those without SLE. The aim of this study was to systematically analyze: (1) the worldwide prevalence of MetS in patients with SLE using different criteria, (2) the risk of MetS in patients with SLE compared with those without SLE, and (3) the risk of MetS component in patients with SLE compared with healthy controls. Methods We searched international databases, such as: Web of Science, Medline, PubMed, Scopus, Embase, CABI, CINAHL, DOAJ and Google Scholar. The articles which reported the prevalence of MetS in SLE patients, between 2006 and 2017, were included in the study if they had a: clear study design, study time and location, sound sampling approach and appropriate statistical analyses. Studies without sufficient data to determine the prevalence of MetS were excluded. Also, studies in patients suffering from other clinical diseases were not included. Results The meta-analyses of the prevalence (40 studies ( n = 6085)) and risk (20 studies ( n = 2348)) of MetS in SLE patients were conducted separately. The pooled prevalence of MetS among SLE patients was found to be 26% (95% confidence interval (CI): 22-30%), but varied from 18% (95% CI: 11-25%) to 34% (95% CI: 25-42%), depending upon the diagnostic criteria used. The overall pooled odds ratio (OR) of MetS in SLE patients, compared with healthy controls, was (OR = 2.50; 95% CI: 1.86-3.35), but this ranged from (OR = 1.23; 95% CI: 0.61-2.49) to (OR = 10.71; 95% CI: 1.33-86.48), depending upon the criteria used. Also, the risk of high fasting blood sugar (FBS; OR = 1.59; 95% CI: 1.05-2.40), low high-density lipoprotein cholesterol (HDL-C; OR = 1.43; 95% CI: 1.02-2.01), high blood pressure (BP; OR = 2.76; 95% CI: 2.19-3.47), high

Circulating prolactin level in systemic lupus erythematosus and its correlation with disease activity: a meta-analysis.

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Song, G G; Lee, Y H

2017-10-01

Objective This study aimed to evaluate the relationship between circulating prolactin level and systemic lupus erythematosus (SLE), and to establish a correlation between plasma/serum prolactin levels and SLE activity. Methods We performed a meta-analysis comparing the plasma/serum prolactin levels in patients with SLE to controls, and examined correlation coefficients between circulating prolactin level and SLE disease activity. Results Twenty-five studies with a total of 1056 SLE patients and 426 controls were included. Prolactin levels were significantly higher overall in the SLE group than in the control group (standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 × 10 -5 ). Stratification by ethnicity showed significantly elevated prolactin levels in the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95% CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD = 1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European population. Subgroup analysis by sample size showed significantly higher prolactin levels in the SLE group by small ( n  30). Meta-analysis of correlation coefficients showed a significantly positive correlation between circulating prolactin level and SLE activity (correlation coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 × 10 -9 ). Circulating prolactin levels were positively associated with SLE activity in European, Asian, and mixed populations (SMD = 0.532, 95% CI = 0.443-0.609  p < 1.0 × 10 -8 ; SMD = 0.427, 95% CI = 0.240-0.583, p = 2.4 × 10 -5 ; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 × 10 -5 , respectively). Conclusions Our meta-analysis demonstrated that circulating prolactin levels are higher in patients with SLE, and that a significantly positive correlation exists between prolactin levels and SLE activity.

Analysis of gender differences in genetic risk: association of TNFAIP3 polymorphism with male childhood-onset systemic lupus erythematosus in the Japanese population.

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Keisuke Kadota

Full Text Available Systemic lupus erythematosus (SLE is a systemic multisystem autoimmune disorder influenced by genetic background and environmental factors. Our aim here was to replicate findings of associations between 7 of the implicated single nucleotide polymorphisms (SNPs in IRF5, BLK, STAT4, TNFAIP3, SPP1, TNIP1 and ETS1 genes with susceptibility to childhood-onset SLE in the Japanese population. In particular, we focused on gender differences in allelic frequencies.The 7 SNPs were genotyped using TaqMan assays in 75 patients with childhood-onset SLE and in 190 healthy controls. The relationship between the cumulative number of risk alleles and SLE manifestations was explored in childhood-onset SLE. Logistic regression was used to test the effect of each polymorphism on susceptibility to SLE, and Wilcoxon rank sum testing was used for comparison of total risk alleles. Data on rs7574865 in the STAT4 gene and rs9138 in SPP1 were replicated for associations with SLE when comparing cases and controls (corrected P values ranging from 0.0043 to 0.027. The rs2230926 allele of TNFAIP3 was associated with susceptibility to SLE in males, but after Bonferroni correction there were no significant associations with any of the other four SNPs in IRF5, BLK, TNIP1 and ETS1 genes. The cumulative number of risk alleles was significantly increased in childhood-onset SLE relative to healthy controls (P = 0.0000041. Male SLE patients had a slightly but significantly higher frequency of the TNFAIP3 (rs2230926G risk allele than female patients (odds ratio [OR] = 4.05, 95% confidence interval [95%CI] = 1.46-11.2 P<0.05.Associations of polymorphisms in STAT4 and SPP1 with childhood-onset SLE were confirmed in a Japanese population. Although these are preliminary results for a limited number of cases, TNFAIP3 rs2230926G may be an important predictor of disease onset in males. We also replicated findings that the cumulative number of risk alleles was significantly

Statistical and physical evolution of QSO's

International Nuclear Information System (INIS)

Caditz, D.; Petrosian, V.

1989-09-01

The relationship between the physical evolution of discrete extragalactic sources, the statistical evolution of the observed population of sources, and the cosmological model is discussed. Three simple forms of statistical evolution: pure luminosity evolution (PLE), pure density evolution (PDE), and generalized luminosity evolution (GLE), are considered in detail together with what these forms imply about the physical evolution of individual sources. Two methods are used to analyze the statistical evolution of the observed distribution of QSO's (quasars) from combined flux limited samples. It is shown that both PLE and PDE are inconsistent with the data over the redshift range 0 less than z less than 2.2, and that a more complicated form of evolution such as GLE is required, independent of the cosmological model. This result is important for physical models of AGN, and in particular, for the accretion disk model which recent results show may be inconsistent with PLE

Infections Increase Risk of Arterial and Venous Thromboses in Danish Patients with Systemic Lupus Erythematosus

DEFF Research Database (Denmark)

Baronaite Hansen, Renata; Jacobsen, Søren

2014-01-01

OBJECTIVE: Infections and thromboses are known complications of systemic lupus erythematosus (SLE). We investigated if infectious episodes in patients with SLE were followed by an increased risk of thrombotic events. METHODS: A cohort of 571 patients with prevalent or incident SLE was followed...

Subjective life expectancy and actual mortality: results of a 10‑year panel study among older workers

NARCIS (Netherlands)

van Solinge, H.; Henkens, K.

2017-01-01

This research examined the judgemental process underlying subjective life expectancy (SLE) and the predictive value of SLE on actual mortality in older adults in the Netherlands. We integrated theoretical insights from life satisfaction research with existing models of SLE. Our model differentiates

Family history of systemic lupus erythematosus and risk of autoimmune disease: Nationwide Cohort Study in Denmark 1977-2013.

Science.gov (United States)

Ulff-Møller, Constance Jensina; Simonsen, Jacob; Kyvik, Kirsten Ohm; Jacobsen, Søren; Frisch, Morten

2017-06-01

To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients. A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link and followed for SLE and other ADs between 1977 and 2013 through linkage to the National Patient Register. Twin zygosity was established through the Danish Twin Registry. Hazard ratios (HRs) with 95% CIs were calculated using Cox proportional hazards regression analyses. During 117.5 million person-years of follow-up, 3612 persons were hospitalized with SLE. HRs of SLE were high among first-degree (HR = 10.3; 95% CI: 8.25, 12.9; n = 80) and second- or third-degree relatives of SLE patients (HR = 3.60; 95% CI: 2.20, 5.90; n = 16). HRs for any AD were elevated in first-degree (HR = 1.51; 95% CI: 1.41, 1.62; n = 785) and second- or third-degree relatives of SLE patients (HR = 1.28; 95% CI: 1.18, 1.39; n = 582). Among individuals with SLE-affected first-degree relatives, the risk was significantly increased for RA (HR = 1.64; 95% CI: 1.35, 1.99; n = 103), IBD (HR = 1.21; 95% CI: 1.02, 1.43; n = 130) and type 1 diabetes mellitus (HR = 1.23; 95% CI: 1.01, 1.48; n = 106). Risk of other ADs was significantly increased both among SLE-affected first-degree (HR = 2.08; 95% CI: 1.88, 2.31; n = 371) and second- or third-degree relatives (HR = 1.38; 95% CI: 1.23, 1.54; n = 313). Family history of SLE is associated with a clearly elevated risk of SLE and, to a much lesser degree, of RA and other ADs. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Nocturnal Hypertension and Attenuated Nocturnal Blood Pressure Dipping is Common in Pediatric Lupus

Science.gov (United States)

Campbell, J. Fallon; Swartz, Sarah J.; Wenderfer, Scott E.

2015-01-01

Hypertension is an important manifestation of systemic lupus erythematosus (SLE) but reports of prevalence vary between 20-70% in published reports of adult and pediatric patients. For both children and adults with SLE, the clinical diagnosis and management of hypertension has traditionally been based on guidelines developed for the general population. In clinical trials, the criteria used for defining participants with hypertension are mostly undefined. As a first step towards formally assessing the blood pressure (BP) patterns of children diagnosed with SLE, 24-hr ambulatory BP monitoring data was analyzed on clinic patients who presented with prehypertension or stage I hypertension. In this pediatric SLE cohort (n=10), 20% met daytime criteria for a diagnosis of hypertension. Patterns of BP elevation varied widely with white coat, masked, isolated systolic, and diastolic nocturnal hypertension all identified. Nocturnal hypertension was detected in 60% and attenuated nocturnal BP dipping in 90% of both hypertensive and normotensive SLE patients. In SLE patients, the median nighttime systolic and diastolic loads were 25% and 15.5% compared with median daily loads of 12.5% and 11.5%. Daytime and nighttime systolic and diastolic BP load and nocturnal dipping was compared to a control population consisting of 85 non-SLE patients under 21 years old with prehypertension or stage 1 hypertension presenting to hypertension clinic. Median systolic BP dipped 5.3 mmHg in SLE patients compared to 11.9 mmHg in non-lupus ( p-value = 0.001). Median diastolic BP dipped 12.9 mmHg versus 18.5 mmHg in non-lupus ( p-value = 0.003). Patterns of BP dysregulation in pediatric SLE merit further exploration. Children with or without SLE displaying prehypertensive or stage 1 casual BP measurements had similar rates of hypertension by ambulatory BP monitoring. However, regardless of BP diagnosis, and independent of kidney involvement, there was an increased proportion with attenuated

Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

Science.gov (United States)

Taylor, Kimberly E.; Remmers, Elaine F.; Lee, Annette T.; Ortmann, Ward A.; Plenge, Robert M.; Tian, Chao; Chung, Sharon A.; Nititham, Joanne; Hom, Geoffrey; Kao, Amy H.; Demirci, F. Yesim; Kamboh, M. Ilyas; Petri, Michelle; Manzi, Susan; Kastner, Daniel L.; Seldin, Michael F.; Gregersen, Peter K.; Behrens, Timothy W.; Criswell, Lindsey A.

2008-01-01

Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2 = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10−16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10−19), nephritis (MAF = 34.3%, OR = 1.80, p<10−11), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10−13). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10−4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease. PMID

Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus.

Directory of Open Access Journals (Sweden)

Kimberly E Taylor

2008-05-01

Full Text Available Systemic lupus erythematosus (SLE is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398 and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r(2 = 0.94 to 0.99 were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10(-16. This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19, nephritis (MAF = 34.3%, OR = 1.80, p<10(-11, and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13. An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10(-4 in the homogeneous subset of subjects. In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease.

Anti-C1q antibodies in systemic lupus erythematosus

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Orbai, A-M; Truedsson, L; Sturfelt, G

2015-01-01

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

Do subjective cognitive complaints correlate with cognitive impairment in systemic lupus erythematosus? A Danish outpatient study

DEFF Research Database (Denmark)

Vogel, A; Bhattacharya, S; Larsen, J L

2011-01-01

This study examined the prevalence of cognitive impairment and its association with depressive symptoms and self-reported cognitive complaints in Danish outpatients with systemic lupus erythematosus (SLE). Fifty-seven consecutive female SLE-outpatients were examined with a comprehensive neuropsyc......This study examined the prevalence of cognitive impairment and its association with depressive symptoms and self-reported cognitive complaints in Danish outpatients with systemic lupus erythematosus (SLE). Fifty-seven consecutive female SLE-outpatients were examined with a comprehensive...

CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status.

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Zhong, Wei; Jiang, Zhenyu; Wu, Jiang; Jiang, Yanfang; Zhao, Ling

2018-01-01

Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA + SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6 + Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity. We recruited 25 anti-DNA + and 25 anti-DNA - treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6 + Th cells and their additional subsets were analyzed in each patient by flow cytometry. Anti-DNA + SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6 + Th cell subsets showed that anti-DNA + SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6 - Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6 + Th subsets and clinical indicators, specifically in anti-DNA + SLE patients. Our data indicated that CCR6 + Th cells and their subsets were elevated and correlated with disease activity in anti-DNA + SLE patients. We speculated that CCR6 + Th cells may contribute to distinct disease severity in anti-DNA + SLE patients.

The association between systemic lupus erythematosus and valvular heart disease: an extensive data analysis.

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Watad, Abdulla; Tiosano, Shmuel; Grysman, Noam; Comaneshter, Doron; Cohen, Arnon D; Shoenfeld, Yehuda; Amital, Howard

2017-05-01

Association between antiphospholipid syndrome in systemic lupus erythematosus (SLE) and valvular heart disease (VHD) is well reported, but relatively few studies have been carried out to establish the linkage between VHD and SLE itself. We aimed to investigate link between VHD and SLE and to evaluate the association of diverse factors with VHD among these patients in a large-scale population-based study. We used the databases of the largest state-mandated health service organization in Israel. All SLE patients were included (n = 5018) as well as their age and sex-matched controls (n = 25 090), creating a cross-sectional population-based study. Medical records of all subjects were analysed for documented VHD and the presence of antiphospholipid antibodies (aPLs). A logistic regression model was carried out to evaluate the diverse factors including SLE and aPLs as independent risk factors for VHD. Valvular heart disease were found to be more frequent among SLE group when compared to controls (aortic stenosis, 1·08% vs. 0·35% respectively, P < 0·001; aortic insufficiency, 1·32% vs. 0·29% respectively, P < 0·001; mitral stenosis, 0·74% vs. 0·21% respectively, P < 0·001; mitral insufficiency, 1·91% vs. 0·39% respectively, P < 0·001). Male sex, hypertension, aPLs and SLE were found to be significant independent risk factors for VHD. All VHD are more prevalent among SLE patients when compared to controls. SLE and aPLs are independent risk factor for VHD (OR of 2·46 and 1·7, respectively). Physicians must be aware of such significant association, and routine echocardiography should be considered in SLE patients regardless of their aPL status. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Serious Infections among Adult Medicaid Beneficiaries with Systemic Lupus Erythematosus and Lupus Nephritis

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Feldman, Candace H.; Hiraki, Linda T.; Winkelmayer, Wolfgang C.; Marty, Francisco M.; Franklin, Jessica M.; Kim, Seoyoung C.; Costenbader, Karen H.

2015-01-01

Objective While serious infections are significant causes of morbidity and mortality in systemic lupus erythematosus (SLE), the epidemiology in a nationwide cohort of SLE and lupus nephritis (LN) patients has not been examined. Methods Using the Medicaid Analytic eXtract (MAX) database, 2000-2006, we identified patients 18-64 years with SLE and a subset with LN. We ascertained hospitalized serious infections using validated algorithms, and 30-day mortality rates. We used Poisson regression to calculate infection incidence rates (IR), and multivariable Cox proportional hazards models to calculate hazard ratios (HR) for first infection, adjusted for sociodemographics, medication use, and a SLE-specific risk adjustment index. Results We identified 33,565 patients with SLE and 7,113 with LN. There were 9,078 serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN patients. The infection IR per 100 person-years was 10.8 in SLE and 23.9 in LN. In adjusted models, in SLE, we observed increased risks of infection among males compared to females (HR 1.33, 95% CI 1.20-1.47), in Blacks compared to Whites (HR 1.14, 95% CI 1.06-1.21), and glucocorticoid users (HR 1.51, 95% CI 1.43-1.61) and immunosuppressive users (HR 1.11, 95% CI 1.03-1.20) compared with non-users. Hydroxychloroquine users had a reduced risk of infection compared to non-users (HR 0.73, 95% CI 0.68-0.77). The 30-day mortality rate per 1,000 person-years among those hospitalized with infections was 21.4 in SLE and 38.7 in LN. Conclusion In this diverse, nationwide cohort of SLE patients, we observed a substantial burden of serious infections with many subsequent deaths. PMID:25772621

Neuroimmune interactions in Sjögren's syndrome: relationship of exocrine gland dysfunction with autoantibodies to muscarinic acetylcholine receptor-3 and mental health status parameters.

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Deák, Magdolna; Szvetnik, Attila; Balog, Attila; Sohár, Nicolette; Varga, Renáta; Pokorny, Gyula; Tóth, Gábor; Kiss, Mária; Kovács, László

2013-01-01

Antimuscarinic acetylcholine receptor-3 (m3AChR) autoantibodies have been described in primary Sjögren's syndrome (pSS). The aim of this study was to compare various methods for their detection and to assess the contributions of anti-m3AChR and other immunological and psychosocial factors to the pathomechanism of secondary SS (sSS). Sixty-five rheumatoid arthritis (RA) patients, 103 systemic lupus erythematosus (SLE) patients, 76 pSS patients and 50 controls were compared. Three immunodominant epitopes of m3AChR were synthesized and used in ELISA. Two extracellular epitopes were also prepared in fusion with glutathione-S-transferase and one in conjugation with bovine serum albumin. Mental health status was assessed with the 36-item Short-Form Health Survey and Functional Assessment of Chronic Illness Therapy fatigue scale. Correlations were evaluated between glandular function and anti-m3AChR positivities and specificities, features of SLE and RA, and mental health parameters. Fourteen RA and 27 SLE patients had sSS. The autoantibody levels to all epitopes of m3AChR were significantly higher in pSS and SLE patients than in the controls. The fusion protein forms discriminated RA from pSS and SLE; furthermore, the YNIP fusion protein also distinguished pSS from SLE. The prevalence and the mean levels of all autoantibodies did not differ statistically between sicca and non-sicca SLE or RA patients. Glandular dysfunction correlated with higher age in SLE and RA and an impaired health-related quality of life in SLE. The second and third extracellular loops of m3AChR are antigenic in pSS. Immunoassays with antigens as fusion peptides demonstrate the best performance. Sicca SLE patients have worse mental health status. Anti-m3AChR antibodies represent a peculiar example of neuroimmune interactions. Copyright © 2012 S. Karger AG, Basel.

Cigarette smoking, STAT4 and TNFRSF1B polymorphisms, and systemic lupus erythematosus in a Japanese population.

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Kiyohara, Chikako; Washio, Masakazu; Horiuchi, Takahiko; Tada, Yoshifumi; Asami, Toyoko; Ide, Saburo; Atsumi, Tatsuya; Kobashi, Gen; Takahashi, Hiroki

2009-10-01

Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. Similarly, tumor necrosis factor receptor superfamily, member 1B (TNFRSF1B) has been reported to be associated with SLE risk in Japanese populations. Along with environmental factors such as smoking, both polymorphisms may modulate an individual's susceptibility to SLE. We investigated these relationships in a case-control study to evaluate risk factors for SLE among Japanese women. We investigated the relationship of the STAT4 rs7574865 and TNFRSF1B rs1061622 polymorphisms to SLE risk with special reference to their combination and interaction with cigarette smoking among 152 SLE cases and 427 controls. The TT genotype of STAT4 rs7574865 was significantly associated with increased risk of SLE (OR 2.21, 95% CI 1.10-4.68). Subjects with at least one G allele of TNFRSF1B rs1061622 had an increased risk of SLE (OR 1.56, 95% CI 0.99-2.47). The attributable proportion due to the interaction between the TNFRSF1B rs1061622 genotypes and smoking was estimated to be 0.49 (95% CI 0.07-0.92), indicating that 49% of the excess risk for SLE in smokers with at least one G allele was due to an additive interaction. A lack of significant associations of STAT4 with smoking was observed. No significant gene-gene interactions were found among polymorphisms of STAT4 and TNFRSF1B. Our findings suggest that the association between cigarette smoking and SLE could be differentiated by the TNFRSF1B rs1061622 T allele among female Japanese subjects. This preliminary exploratory result should be confirmed in a larger study.

Simulation can contribute a part of cardiorespiratory physiotherapy clinical education: two randomized trials.

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Blackstock, Felicity C; Watson, Kathryn M; Morris, Norman R; Jones, Anne; Wright, Anthony; McMeeken, Joan M; Rivett, Darren A; O'Connor, Vivienne; Peterson, Raymond F; Haines, Terry P; Watson, Geoffrey; Jull, Gwendolen Anne

2013-02-01

Simulated learning environments (SLEs) are used worldwide in health professional education, including physiotherapy, to train certain attributes and skills. To date, no randomized controlled trial (RCT) has evaluated whether education in SLEs can partly replace time in the clinical environment for physiotherapy cardiorespiratory practice. Two independent single-blind multi-institutional RCTs were conducted in parallel using a noninferiority design. Participants were volunteer physiotherapy students (RCT 1, n = 176; RCT 2, n = 173) entering acute care cardiorespiratory physiotherapy clinical placements. Two SLE models were investigated as follows: RCT 1, 1 week in SLE before 3 weeks of clinical immersion; RCT 2, 2 weeks of interspersed SLE/clinical immersion (equivalent to 1 SLE week) within the 4-week clinical placement. Students in each RCT were stratified on academic grade and randomly allocated to an SLE plus clinical immersion or clinical immersion control group. The primary outcome was competency to practice measured in 2 clinical examinations using the Assessment of Physiotherapy Practice. Secondary outcomes were student perception of experience and clinical educator and patient rating of student performance. There were no significant differences in student competency between the SLE and control groups in either RCT, although students in the interspersed group (RCT 2) achieved a higher score in 5 of 7 Assessment of Physiotherapy Practice standards (all P Students rated the SLE experience positively. Clinical educators and patients reported comparability between groups. An SLE can replace clinical time in cardiorespiratory physiotherapy practice. Part education in the SLE satisfied clinical competency requirements, and all stakeholders were satisfied.

Lung clearance of {sup 99m} Tc- DTPA in systemic lupus erythematous

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Dalcin, P.T.R; Barreto, S.S.M.; Xavier, R.M.; Brenol, J.C.T. [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Hospital de Clinicas. Dept. de Medicina Interna; Cunha, R.D.; Marroni, B.J. [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Hospital de Clinicas. Servico de Medicina Nuclear]. E-mail: rxavier@hcpa.ufrgs.br

2002-06-01

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99 mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99 mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnoea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99 m Tc-DTPA is increased in SLE patients with active disease. (author)

Lung clearance of 99m Tc- DTPA in systemic lupus erythematous

International Nuclear Information System (INIS)

Dalcin, P.T.R; Barreto, S.S.M.; Xavier, R.M.; Brenol, J.C.T.; Cunha, R.D.; Marroni, B.J.

2002-01-01

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99 mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99 mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnoea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99 m Tc-DTPA is increased in SLE patients with active disease. (author)

The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus.

Science.gov (United States)

Lewis, Myles J; Jawad, Ali S

2017-04-01

In this in-depth review, we examine the worldwide epidemiology of SLE and summarize current knowledge on the influence of race/ethnicity on clinical manifestations, disease activity, damage accumulation and outcome in SLE. Susceptibility to SLE has a strong genetic component, and trans-ancestral genetic studies have revealed a substantial commonality of shared genetic risk variants across different genetic ancestries that predispose to the development of SLE. The highest increased risk of developing SLE is observed in black individuals (incidence 5- to 9-fold increased, prevalence 2- to 3-fold increased), with an increased risk also observed in South Asians, East Asians and other non-white groups, compared with white individuals. Black, East Asian, South Asian and Hispanic individuals with SLE tend to develop more severe disease with a greater number of manifestations and accumulate damage from lupus more rapidly. Increased genetic risk burden in these populations, associated with increased autoantibody reactivity in non-white individuals with SLE, may explain the more severe lupus phenotype. Even after taking into account socio-economic factors, race/ethnicity remains a key determinant of poor outcome, such as end-stage renal failure and mortality, in SLE. Community measures to expedite diagnosis through increased awareness in at-risk racial/ethnic populations and ethnically personalized treatment algorithms may help in future to improve long-term outcomes in SLE. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hypoparathyroidism in a patient with systemic lupus erythematosus coexisted with ankylosing spondylitis: a case report and review of literature.

Science.gov (United States)

Jiang, Lindi; Dai, Xiaomin; Liu, Jun; Ma, Lili; Yu, Fei

2010-12-01

Hypoparathyroidism is rare in patients with systemic lupus erythematosus (SLE). Here we describe a case of SLE coexisted with hypoparathyroidism and ankylosing spondylitis with definite diagnosis, and also give a review of past five cases of SLE with hypoparathyroidism. We find that hypoparathyroidism is easily ignored by subtle manifestations despite of its significant complications. More attention should be paid to clues to hypocalcemia, symptoms of central nervous system and prolonged QT interval on electrocardiogram. The three diseases may be coexistent of genetically determined markers. The cause of hypoparathyroidism in SLE patient is not clear. It may be independent of SLE. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Lack of Association between an Interleukin-I Receptor Antagonist Gene Polymorphism and Systemic Lupus Erythematosus

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Victor A. Danis

1994-01-01

Full Text Available Non-MHC linked genes may contribute to genetic predisposition to the development of systemic lupus erythematosus. The possibility that cytokine genes may be involved was raised by the observation of increased frequency in expression of an uncommon allele of an interleukin-I receptor antagonist gene polymorphism and SLE in a recent U.K. study. We have not been able to show any significant differences in expression of this allele in SLE patients as a whole or in any patient subgroups. Our results actually show a slight decrease in the expression of this allele in SLE patients compared with healthy controls and in SLE patients with malar rash compared with SLE patients without malar rash.

Anmeldelse af Evolution, Literature and Film

DEFF Research Database (Denmark)

Grodal, Torben Kragh

2011-01-01

Diskussion af basisproblemer i evolutionær fiktionsteori med udgangspunkt i en anmeldelse af Evolution, Literature and Film......Diskussion af basisproblemer i evolutionær fiktionsteori med udgangspunkt i en anmeldelse af Evolution, Literature and Film...

Depression in systemic lupus erythematosus, dependent on or independent of severity of disease

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van Exel, E.; Jacobs, J.; Korswagen, L.A.; Voskuyl, A.E.; Stek, M.L.; Dekker, J.; Bultink, I.E.M.

2013-01-01

Objectives: To estimate the prevalence of depression in subjects with systemic lupus erythematosus (SLE) in relation to the general population and to unravel the relation between depression and SLE disease characteristics. Methods: One hundred and two subjects with SLE (mean age 44.4 years) were

MRI pattern of arthritis in systemic lupus erythematosus: a comparative study with rheumatoid arthritis and healthy subjects

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Tani, Chiara; Possemato, Niccolo; Delle Sedie, Andrea; Bombardieri, Stefano; Mosca, Marta [University of Pisa, Rheumatology Unit, Department of Clinical and Experimental Medicine, Pisa (Italy); D' aniello, Dario; Caramella, Davide [Radiology Unit, University of Pisa, Pisa (Italy)

2014-10-24

In this study we aimed to describe the magnetic resonance imaging (MRI) pattern of the distribution of bone marrow edema (BME) and joint erosion in hands and wrists of patients with systemic lupus erythematosus (SLE) with arthritis in comparison with rheumatoid arthritis (RA) and healthy subjects (H). SLE patients with arthritis (n = 50), patients with RA (n = 22), and H (n = 48) were enrolled. Every patient underwent a non-dominant hand (2nd-5th metacarpophalangeal joints) and wrist MRI without contrast injection with a low-field extremity dedicated 0.2-Tesla instrument. BME was observed in two SLE patients in the hand (4 %) and in 15 in the wrist (13 %) versus three (30 %), and 14 (63 %) RA patients. No BME was found in H. Erosions were observed in the hand in 24 SLE patients (48 %), 15 RA patients (68 %), and 9 H (18 %); in the wrist, in 41 (82 %) SLE, all RA and 47 (97 %) H. The cumulative erosive burden in SLE was significantly higher than in H (c = 0.002) but similar to RA patients. Joint involvement of the wrist in SLE is similar to RA and is not as rare as expected, as shown by the comparison with healthy subjects. On the contrary, the involvement of the hand in SLE is significantly lower compared to RA. (orig.)

MRI pattern of arthritis in systemic lupus erythematosus: a comparative study with rheumatoid arthritis and healthy subjects

International Nuclear Information System (INIS)

Tani, Chiara; Possemato, Niccolo; Delle Sedie, Andrea; Bombardieri, Stefano; Mosca, Marta; D'aniello, Dario; Caramella, Davide

2015-01-01

In this study we aimed to describe the magnetic resonance imaging (MRI) pattern of the distribution of bone marrow edema (BME) and joint erosion in hands and wrists of patients with systemic lupus erythematosus (SLE) with arthritis in comparison with rheumatoid arthritis (RA) and healthy subjects (H). SLE patients with arthritis (n = 50), patients with RA (n = 22), and H (n = 48) were enrolled. Every patient underwent a non-dominant hand (2nd-5th metacarpophalangeal joints) and wrist MRI without contrast injection with a low-field extremity dedicated 0.2-Tesla instrument. BME was observed in two SLE patients in the hand (4 %) and in 15 in the wrist (13 %) versus three (30 %), and 14 (63 %) RA patients. No BME was found in H. Erosions were observed in the hand in 24 SLE patients (48 %), 15 RA patients (68 %), and 9 H (18 %); in the wrist, in 41 (82 %) SLE, all RA and 47 (97 %) H. The cumulative erosive burden in SLE was significantly higher than in H (c = 0.002) but similar to RA patients. Joint involvement of the wrist in SLE is similar to RA and is not as rare as expected, as shown by the comparison with healthy subjects. On the contrary, the involvement of the hand in SLE is significantly lower compared to RA. (orig.)

Serum 25-OH vitamin D level in treatment-naïve systemic lupus erythematosus patients: Relation to disease activity, IL-23 and IL-17.

Science.gov (United States)

Shahin, D; El-Farahaty, R M; Houssen, M E; Machaly, S A; Sallam, M; ElSaid, T O; Neseem, N O

2017-08-01

Objectives The aim of this study was to assess the vitamin D status in treatment-naïve SLE patients and its association with clinical and laboratory markers of disease activity, including serum levels of IL-17 and IL-23. Methods Fifty-seven treatment-naïve SLE patients along with 42 matched controls were included. SLEDAI score was used to estimate disease activity. Serum levels of 25(OH) D, IL-17 and IL-23 were measured. Results The median level of 25(OH) D in SLE patients (40.8; 4-70 ng/ml) was significantly lower than in the controls (47; 25-93 ng/ml) ( P = 0.001). A total of 38.6% of SLE cases had 25 (OH) D levels < 30 ng/ml (hypovitaminosis D) vs. 4.8% of the controls ( P < 0.0001). Apart from thrombocytopenia, vitamin D was not associated with clinical signs of SLE. There were negative correlations between serum 25(OH) D and serum levels of IL-17, IL-23 and ANA (rho = -0.5, -0.8, -0.5, P ≤ 0.05) in SLE patients. Conclusion Hypovitaminosis D is prevalent in treatment naïve SLE patients. It contributes to ANA antibody production and is associated with high serum levels of IL-23 and IL-17; thus they may trigger the inflammatory process in SLE.

Prevalence, severity, and clinical features of acute and chronic pancreatitis in patients with systemic lupus erythematosus.

Science.gov (United States)

Wang, Qiang; Shen, Min; Leng, Xiaomei; Zeng, Xiaofeng; Zhang, Fengchun; Qian, Jiaming

2016-10-01

Pancreatitis is a rare, life-threatening complication of systemic lupus erythematosus (SLE). This study aimed to describe the clinical features of acute pancreatitis (AP) and chronic pancreatitis (CP) in patients with SLE. Data of patients who fulfilled the revised criteria of the American Rheumatism Association for diagnosis of SLE were retrospectively analyzed. SLE activity was graded according to the SLE Disease Activity Index. Logistic regression analysis was conducted to find out independent associations. Survival rates were estimated by using Kaplan-Meier plots. This study included 5665 SLE patients admitted between January 1983 and January 2014, of whom 52 patients were diagnosed with pancreatitis. Pancreatitis prevalence in SLE patients was 0.92 % (52/5665). AP (0.8 %, 46/5665) was more prevalent than CP (0.1 %, 6/5665), presented mostly during active SLE, and affected more organs. Hypertriglyceridemia occurred in 76.9 % of AP patients and in none of the CP patients. AP patients were divided into severe (n = 10) or mild (n = 20) cases. The average triglyceride level in severe AP cases was higher than that in mild AP cases (P = 0.006), and the mortality rate of lupus-associated AP was 32.6 % (15/46). Concomitant infections and thrombocytopenia were independently associated with poor prognosis (P risk factors for poor prognosis.

HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response

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Mudan Lu

2015-01-01

Full Text Available Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE; however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure. Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues. Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-α and IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response. Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.

Evolution across the Curriculum: Microbiology

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Alita R. Burmeister

2016-05-01

Full Text Available An integrated understanding of microbiology and evolutionary biology is essential for students pursuing careers in microbiology and healthcare fields. In this Perspective, we discuss the usefulness of evolutionary concepts and an overall evolutionary framework for students enrolled in microbiology courses. Further, we propose a set of learning goals for students studying microbial evolution concepts. We then describe some barriers to microbial evolution teaching and learning and encourage the continued incorporation of evidence-based teaching practices into microbiology courses at all levels. Next, we review the current status of microbial evolution assessment tools and describe some education resources available for teaching microbial evolution. Successful microbial evolution education will require that evolution be taught across the undergraduate biology curriculum, with a continued focus on applications and applied careers, while aligning with national biology education reform initiatives.

Evolution across the Curriculum: Microbiology

Science.gov (United States)

Burmeister, Alita R.; Smith, James J.

2016-01-01

An integrated understanding of microbiology and evolutionary biology is essential for students pursuing careers in microbiology and healthcare fields. In this Perspective, we discuss the usefulness of evolutionary concepts and an overall evolutionary framework for students enrolled in microbiology courses. Further, we propose a set of learning goals for students studying microbial evolution concepts. We then describe some barriers to microbial evolution teaching and learning and encourage the continued incorporation of evidence-based teaching practices into microbiology courses at all levels. Next, we review the current status of microbial evolution assessment tools and describe some education resources available for teaching microbial evolution. Successful microbial evolution education will require that evolution be taught across the undergraduate biology curriculum, with a continued focus on applications and applied careers, while aligning with national biology education reform initiatives. Journal of Microbiology & Biology Education PMID:27158306

Chemical evolution of galaxies

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Matteucci, Francesca

2012-01-01

The term “chemical evolution of galaxies” refers to the evolution of abundances of chemical species in galaxies, which is due to nuclear processes occurring in stars and to gas flows into and out of galaxies. This book deals with the chemical evolution of galaxies of all morphological types (ellipticals, spirals and irregulars) and stresses the importance of the star formation histories in determining the properties of stellar populations in different galaxies. The topic is approached in a didactical and logical manner via galaxy evolution models which are compared with observational results obtained in the last two decades: The reader is given an introduction to the concept of chemical abundances and learns about the main stellar populations in our Galaxy as well as about the classification of galaxy types and their main observables. In the core of the book, the construction and solution of chemical evolution models are discussed in detail, followed by descriptions and interpretations of observations of ...

Stellar structure and evolution

International Nuclear Information System (INIS)

Kippernhahn, R.; Weigert, A.

1990-01-01

This book introduces the theory of the internal structure of stars and their evolution in time. It presents the basic physics of stellar interiors, methods for solving the underlying equations, and the most important results necessary for understanding the wide variety of stellar types and phenomena. The evolution of stars is discussed from their birth through normal evolution to possibly spectacular final stages. Chapters on stellar oscillations and rotation are included

How compelling are the data for Epstein-Barr virus being a trigger for systemic lupus and other autoimmune diseases?

Science.gov (United States)

Draborg, Anette; Izarzugaza, Jose M G; Houen, Gunnar

2016-07-01

Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immunodeficiencies and environmental factors including infections. An association with Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental studies on EBV, and present our integrated theory of SLE development. SLE patients have dysfunctional control of EBV infection resulting in frequent reactivations and disease progression. These comprise impaired functions of EBV-specific T-cells with an inverse correlation to disease activity and elevated serum levels of antibodies against lytic cycle EBV antigens. The presence of EBV proteins in renal tissue from SLE patients with nephritis suggests direct involvement of EBV in SLE development. As expected for patients with immunodeficiencies, studies reveal that SLE patients show dysfunctional responses to other viruses as well. An association with EBV infection has also been demonstrated for other autoimmune diseases, including Sjögren's syndrome, rheumatoid arthritis, and multiple sclerosis. Collectively, the interplay between an impaired immune system and the cumulative effects of EBV and other viruses results in frequent reactivation of EBV and enhanced cell death, causing development of SLE and concomitant autoreactivities.

Systemic lupus erythematosus activity and beta two microglobulin levels

Directory of Open Access Journals (Sweden)

Thelma Larocca Skare

Full Text Available CONTEXT AND OBJECTIVE: Systemic lupus erythematosus (SLE is an autoimmune disease with a cyclical clinical course. Evaluation of the clinical activity of this disease is important for choosing the correct treatment. The objective of this study was to analyze the value of beta-2 microglobulin (β2M serum levels in determining SLE clinical activity.DESIGN AND SETTING: Cross-sectional analytical study conducted at the rheumatology outpatient clinic of a private university hospital.METHODS: 129 SLE patients were studied regarding disease activity using SLEDAI (SLE Disease Activity Index and cumulative damage using SLICC ACR (SLE International Collaborating Clinics/American College of Rheumatology Damage Index for SLE. At the same time, the β2M serum level, ESR (erythrocyte sedimentation rate, anti-dsDNA (anti-double-stranded DNA and C3 and C4 complement fractions were determined.RESULTS: β2M levels correlated positively with SLEDAI (P = 0.02 and ESR (P = 0.0009 and negatively with C3 (P = 0.007. Patients who were positive for anti-dsDNA had higher β2M serum levels (P = 0.009.CONCLUSION: β2M levels are elevated in SLE patients with active disease.

The correlations of psychological status, quality of life, self-esteem, social support and body image disturbance in Chinese patients with Systemic Lupus Erythematosus.

Science.gov (United States)

Zhao, Qian; Chen, Haoyang; Yan, Hongyan; He, Yan; Zhu, Li; Fu, WenTing; Shen, Biyu

2018-01-31

This study aimed (i) to complement existing research by focusing on body image disturbance issues in Chinese Systemic Lupus Erythematosus (SLE) patients; (ii) to investigate how Chinese patients make sense of disease diagnosis and perceived cultural influences within the context of their SLE. A total of 118 SLE patients underwent standardized laboratory examinations and completed several questionnaires. Independent sample t-test, Mann-Whitney U-test, Chi-square test, and multivariate analysis using backward stepwise logistic regression model were used to analyze these data. We found 18.3% SLE patients had BID, which were significantly higher than the control group (.8%). SLE patients are more concerned about their physical changes caused by disease. There were significant correlations among personal health insurance, complication of diabetes, appearance of new rash, depression, anxiety, self-esteem and BID in patients with SLE. Meanwhile, logistic regression analysis revealed that appearance of new rash and high anxiety were significantly associated with BID in SLE patients. In conclusion, it is beneficial to pay attention to the physical and mental health of patients with rheumatic disease from the perspective of body image, to understand their needs and to provide effective and effective service for them.

Kluver–Bucy syndrome in one case with systemic lupus erythematosus

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Hsiu-Fen Lin

2011-04-01

Full Text Available Kluver–Bucy syndrome (KBS is a collection of neuropsychiatric symptoms, including visual agnosia (prosopagnosia, hypermetamorphosis, placidity, hypersexuality, and hyperorality. Although neuropsychiatric manifestation is prevalent in cases with systemic lupus erythematosus (SLE, only one literature reported a case with SLE that had KBS previously. In this article, a 37-year-old woman with SLE who developed KBS and other neuropsychiatric symptoms is presented. Brain imaging proved the relevant structural lesion. The possible explanation of pathogenesis of KBS in SLE is discussed.

Autoantibody to MDM2: A Potential Serological Marker of Systemic Lupus Erythematosus

OpenAIRE

Liu, Yuan; Dai, Liping; Liu, Weihong; Shi, Guixiu; Zhang, Jianying

2015-01-01

Introduction. Systemic lupus erythematosus (SLE) is one of the systemic autoimmune diseases characterized by the polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is well known as the negative regulator of p53. MDM2 has been reported to be overexpressed in SLE animal model and to promote SLE. Since abnormally expressed proteins can induce autoimmune response, anti-MDM2 autoantibody was examined in SLE patients. Methods. Anti-MDM2 antibody in sera from...

Chemical evolution and life

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Malaterre Christophe

2015-01-01

Full Text Available In research on the origins of life, the concept of “chemical evolution” aims at explaining the transition from non-living matter to living matter. There is however strong disagreement when it comes to defining this concept more precisely, and in particular with reference to a chemical form of Darwinian evolution: for some, chemical evolution is nothing but Darwinian evolution applied to chemical systems before life appeared; yet, for others, it is the type of evolution that happened before natural selection took place, the latter being the birthmark of living systems. In this contribution, I review the arguments defended by each side and show how both views presuppose a dichotomous definition of “life”.

Dual phase evolution

CERN Document Server

Green, David G; Abbass, Hussein A

2014-01-01

This book explains how dual phase evolution operates in all these settings and provides a detailed treatment of the subject. The authors discuss the theoretical foundations for the theory, how it relates to other phase transition phenomena and its advantages in evolutionary computation and complex adaptive systems. The book provides methods and techniques to use this concept for problem solving. Dual phase evolution concerns systems that evolve via repeated phase shifts in the connectivity of their elements. It occurs in vast range of settings, including natural systems (species evolution, landscape ecology, geomorphology), socio-economic systems (social networks) and in artificial systems (annealing, evolutionary computing).

Integrated Theoretical, Computational, and Experimental Studies for Transition Estimation and Control

Science.gov (United States)

2014-06-03

characteristics of Pitot noise. Int. Symp. on Shock Waves, 29th, Madison 82. Hornung HG, Schramm JM, Hannemann K. 2011. Sonic line and stand-off...a hypervelocity boundary layer on a 5-degree half-angle cone in air/CO2 mixtures. AIAA Pap. No. 2013-0523 93. Karl S, Hannemann K, Hornung HG...Hypersonic Stability and Transition, Sedona 232. Hornung HG, Karl S, Hannemann K. 2011. Sonic line and stand-off distance on reentry capsule shapes

Increased serum ß2-microglobulin is associated with clinical and immunological markers of disease activity in systemic lupus erythematosus patients

DEFF Research Database (Denmark)

Hermansen, M-L F; Hummelshøj, L; Lundsgaard, Dorte

2012-01-01

The objective of this study was to explore the relationship between serum levels of ß2-microglobulin (ß2MG), which some studies suggest reflect disease activity in systemic lupus erythematosus (SLE), and various clinical and immunological markers of disease activity in SLE. Twenty-six SLE patients...

Incidence of systemic lupus erythematosus and lupus nephritis in Denmark

DEFF Research Database (Denmark)

Hermansen, Marie-Louise From; Lindhardsen, Jesper; Torp-Pedersen, Christian

2016-01-01

Objective. To determine the incidence of systemic lupus erythematosus (SLE) and SLE with concomitant or subsequent lupus nephritis (LN) in Denmark during 1995.2011, using data from the Danish National Patient Registry (NPR).  Methods. To assess the incidence of SLE, we identified all persons aged...

Seasonal distribution of active systemic lupus erythematosus and its correlation with meteorological factors

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Zhang Hua-Li

2011-01-01

Full Text Available OBJECTIVE: To explore the characteristics of seasonal distribution of active systemic lupus erythematosus (SLE and the influences of meteorological factors including temperature and humidity on active systemic lupus erythematosus. METHODS: The characteristics of seasonal distribution of active SLE and its correlation with meteorological factors were retrospectively analyzed in 640 patients living in the city of Zhanjiang, China and had active SLE between January 1997 and December 2006. RESULTS: In winter, when there are weaker ultraviolet (UV rays, the ratio of patients with active SLE to total inpatients was 3.89 %o, which is significantly higher than in other seasons with stronger UV rays, including 2.17 %o in spring, 1.87 0 in summer and 2.12 0 in autumn. The number of patients with active SLE had significant negative correlation with mean temperature and was not significantly related to mean humidity. CONCLUSION: Active SLE has the characteristics of seasonal distribution and is associated with temperature. The mechanism remains to be further studied.

Different types of headache in patients with systemic lupus erythematosus.

Science.gov (United States)

Badry, Reda; Gamal, Rania M

2015-05-01

Headache in patients with systemic lupus erythematosus (SLE) is considered a common neurological finding, although the relationship is unclear. In this study, we aimed to evaluate frequency and characteristics of different types of headache in patients with SLE. 40 SLE patients were chosen from those referred to the out patient clinic using the American College of Rheumatology (ACR) criteria for the diagnosis of SLE. Headache classification was done regarding the ICD-II criteria in the patients. Headache severity was assessed by visual analog scale (VAS), and subjects with VAS ≥4 were included in the study. 30 patients out of 40 SLE patients (75%) have different headache types: tension type in 37.5% (n = 15) and migraine in 30% (n = 12), cluster 2.5% (n = 1), and intracranial hypertension 5% (n = 2) of all patients. Headache is frequent in SLE especially tension and migraine types, but overall, it is not associated with disease activity.

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis.

Science.gov (United States)

Mota, Pedro; Reddy, Venkat; Isenberg, David

2017-07-01

Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

Asymptomatic cerebrovascular lesions detected by magnetic resonance imaging in patients with systemic lupus erythematosus lacking a history of neuropsychiatric events

Energy Technology Data Exchange (ETDEWEB)

Nomura, Kumiko; Yamano, Shigeru; Ikeda, Yukiko [Nara Medical Univ., Kashihara (Japan)] (and others)

1999-10-01

To clarify the extent of asymptomatic cerebrovascular involvement in systemic lupus erythematosus (SLE). Cerebral magnetic resonance imaging (MRI) findings and ultrasonography findings of 100 patients with SLE lacking present or past clinical neurologic deficits were compared with 66 age-matched volunteers to determine the combined intima-media thickness (IMT) of the common carotid artery, and tests for anti-cardiolipin antibodies (aCL). Thirty-eight patients, but only 2 controls, showed imaging abnormalities. Among 23 SLE patients with cerebrovascular lesions by MRI who underwent single-photon emission computed tomography (SPECT), 14 showed hypoperfusion of the lesion. The IMT value and prevalence of aCL did not differ between the 55 SLE patients tested and controls. SLE disease activity index (SLEDAI) as assessed by a quantitative clinical index was significantly greater in patients with brain lesions than in those without. The prevalence of asymptomatic brain lesions in SLE patients is high, and shows a relationship to disease activity. (author)

The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

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Isaac T. W. Harley

2010-01-01

Full Text Available Systemic lupus erythematosus (SLE is a systemic autoimmune disease characterized by increased type I interferons (IFNs and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility. We studied IFNK single nucleotide polymorphisms (SNPs in 3982 SLE cases and 4275 controls, composed of European (EA, African-American (AA, and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio=1.93, P=2.5×10−4, but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes. The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.

Analysis of the Science and Technology Preservice Teachers' Opinions on Teaching Evolution and Theory of Evolution

Science.gov (United States)

Töman, Ufuk; Karatas, Faik Özgür; Çimer, Sabiha Odabasi

2014-01-01

In this study, we investigate of science and technology teachers' opinions about the theory of evolution and the evolution teaching. The aim of this study, we investigate of science and technology teachers' opinions about the theory of evolution and the evolution teaching. This study is a descriptive study. Open-ended questions were used to…

Inlet Geomorphology Evolution Work Unit

Science.gov (United States)

2015-10-30

Coastal Inlets Research Program Inlet Geomorphology Evolution Work Unit The Inlet Geomorphology Evolution work unit of the CIRP develops methods...morphologic response. Presently, the primary tool of the Inlet Geomorphology Evolution work unit is the Sediment Mobility Tool (SMT), which allows the user

Toward Documentation of Program Evolution

DEFF Research Database (Denmark)

Vestdam, Thomas; Nørmark, Kurt

2005-01-01

The documentation of a program often falls behind the evolution of the program source files. When this happens it may be attractive to shift the documentation mode from updating the documentation to documenting the evolution of the program. This paper describes tools that support the documentatio....... It is concluded that our approach can help revitalize older documentation, and that discovery of the fine grained program evolution steps help the programmer in documenting the evolution of the program....

Student Visual Communication of Evolution

Science.gov (United States)

Oliveira, Alandeom W.; Cook, Kristin

2017-06-01

Despite growing recognition of the importance of visual representations to science education, previous research has given attention mostly to verbal modalities of evolution instruction. Visual aspects of classroom learning of evolution are yet to be systematically examined by science educators. The present study attends to this issue by exploring the types of evolutionary imagery deployed by secondary students. Our visual design analysis revealed that students resorted to two larger categories of images when visually communicating evolution: spatial metaphors (images that provided a spatio-temporal account of human evolution as a metaphorical "walk" across time and space) and symbolic representations ("icons of evolution" such as personal portraits of Charles Darwin that simply evoked evolutionary theory rather than metaphorically conveying its conceptual contents). It is argued that students need opportunities to collaboratively critique evolutionary imagery and to extend their visual perception of evolution beyond dominant images.

modelling of directed evolution: Implications for experimental design and stepwise evolution

OpenAIRE

Wedge , David C.; Rowe , William; Kell , Douglas B.; Knowles , Joshua

2009-01-01

In silico modelling of directed evolution: Implications for experimental design and stepwise evolution correspondence: Corresponding author. Tel.: +441613065145. (Wedge, David C.) (Wedge, David C.) Manchester Interdisciplinary Biocentre, University of Manchester - 131 Princess Street--> , Manchester--> , M1 7ND--> - UNITED KINGDOM (Wedge, David C.) UNITED KINGDOM (Wedge, David C.) Man...

Multicolour Observations, Inhomogeneity & Evolution

OpenAIRE

Hellaby, Charles

2000-01-01

We propose a method of testing source evolution theories that is independent of the effects of inhomogeneity, and thus complementary to other studies of evolution. It is suitable for large scale sky surveys, and the new generation of large telescopes. In an earlier paper it was shown that basic cosmological observations - luminosity versus redshift, area distance versus redshift and number counts versus redshift - cannot separate the effects of cosmic inhomogeneity, cosmic evolution and sourc...

Student Teachers' Approaches to Teaching Biological Evolution

Science.gov (United States)

Borgerding, Lisa A.; Klein, Vanessa A.; Ghosh, Rajlakshmi; Eibel, Albert

2015-06-01

Evolution is fundamental to biology and scientific literacy, but teaching high school evolution is often difficult. Evolution teachers face several challenges including limited content knowledge, personal conflicts with evolution, expectations of resistance, concerns about students' conflicts with religion, and curricular constraints. Evolution teaching can be particularly challenging for student teachers who are just beginning to gain pedagogical knowledge and pedagogical content knowledge related to evolution teaching and who seek approval from university supervisors and cooperating teachers. Science teacher educators need to know how to best support student teachers as they broach the sometimes daunting task of teaching evolution within student teaching placements. This multiple case study report documents how three student teachers approached evolution instruction and what influenced their approaches. Data sources included student teacher interviews, field note observations for 4-5 days of evolution instruction, and evolution instructional artifacts. Data were analyzed using grounded theory approaches to develop individual cases and a cross-case analysis. Seven influences (state exams and standards, cooperating teacher, ideas about teaching and learning, concerns about evolution controversy, personal commitment to evolution, knowledge and preparation for teaching evolution, and own evolution learning experiences) were identified and compared across cases. Implications for science teacher preparation and future research are provided.

The theory of evolution

Directory of Open Access Journals (Sweden)

Oleg Bazaluk

2015-06-01

Full Text Available The book The Theory of Evolution: from the Space Vacuum to Neural Ensembles and Moving Forward, an edition of 100 copies, was published in Russian language, in December 2014 in Kiev. Its Russian version is here: http://en.bazaluk.com/journals.html. Introduction, Chapter 10 and Conclusion published in English for the first time. Since 2004 author have been researching in the field of theory of Evolution, Big History. The book was written on the base of analysis of more than 2000 primary sources of this research topic. The volume is 90,000 words (with Reference. The book is for a wide range of professionals, from students to professors and researchers working in the fields of: philosophical anthropology, philosophy, Big History, cosmology, biology, neuroscience and etc. In the book, the author defines the evolution as continuous and nonlinear complication of the structure of matter, the types of interaction and environments; analyzes existing in modern science and philosophy approaches to the research of the process of evolution, degree of development of the factors and causes of evolution. Unifying interdisciplinary researches of evolution in cosmology, biology, neuroscience and philosophy, the author presents his vision of the model of «Evolving Matter», which allows us to consider not only the laws of transition of space vacuum in neural ensembles but also to see our Universe as a complication, heterogeneous organization. Interdisciplinary amount of information on the theory of evolution is systematized and a new method of world perception is proposed in the book.

Evolution of Constructivism

Science.gov (United States)

Liu, Chu Chih; Chen, I Ju

2010-01-01

The contrast between social constructivism and cognitive constructivism are depicted in different ways in many studies. The purpose of this paper is to summarize the evolution of constructivism and put a focus on social constructivism from the perception of Vygotsky. This study provides a general idea of the evolution of constructivism for people…

Evolution and transitions in complexity

NARCIS (Netherlands)

Jagers op Akkerhuis, Gerard A.J.M.

2016-01-01

This book discusses several recent theoretic advancements in interdisciplinary and transdisciplinary integration in the field of evolution. While exploring novel views, the text maintains a close link with one of the most broadly held views on evolution, namely that of "Darwinian evolution." This

THE PSEUDO-EVOLUTION OF HALO MASS

International Nuclear Information System (INIS)

Diemer, Benedikt; Kravtsov, Andrey V.; More, Surhud

2013-01-01

A dark matter halo is commonly defined as a spherical overdensity of matter with respect to a reference density, such as the critical density or the mean matter density of the universe. Such definitions can lead to a spurious pseudo-evolution of halo mass simply due to redshift evolution of the reference density, even if its physical density profile remains constant over time. We estimate the amount of such pseudo-evolution of mass between z = 1 and 0 for halos identified in a large N-body simulation, and show that it accounts for almost the entire mass evolution of the majority of halos with M 200ρ-bar ≲ 10 12 h -1 M ☉ and can be a significant fraction of the apparent mass growth even for cluster-sized halos. We estimate the magnitude of the pseudo-evolution assuming that halo density profiles remain static in physical coordinates, and show that this simple model predicts the pseudo-evolution of halos identified in numerical simulations to good accuracy, albeit with significant scatter. We discuss the impact of pseudo-evolution on the evolution of the halo mass function and show that the non-evolution of the low-mass end of the halo mass function is the result of a fortuitous cancellation between pseudo-evolution and the absorption of small halos into larger hosts. We also show that the evolution of the low-mass end of the concentration-mass relation observed in simulations is almost entirely due to the pseudo-evolution of mass. Finally, we discuss the implications of our results for the interpretation of the evolution of various scaling relations between the observable properties of galaxies and galaxy clusters and their halo masses.

SOBRE EL CONTROL EN SISTEMAS DINÁMICOS DE DIMENSIÓN INFINITA EN ESPACIOS DE HILBERT Y DE FRECHÉT

Directory of Open Access Journals (Sweden)

Nancy López-Reyes

2017-07-01

Full Text Available Se revisa el Control sobre sistemas dinámicos lineales de dimensión infnita que evolucionan en espacios con propiedades geométrico-algebraicas diferentes. En un caso, sobre espacios de Hilbert, los cuales poseen una rica estructura geométrico-algebraica, muy útil para el tratamiento del control, desde el punto de vista del enfoque dominio-frecuencia y del enfoque espacio-estado. En el otro caso, sobre espacios de Frechét, en particular sobre H(D, cuyas propiedades geométricas implican un tratamiento diferente del Control. Ambos casos se ilustran con sendos ejemplos de aplicaciones interesantes, uno relacionado con Sistemas Integrables y el otro con la conocida Ecuaci on de Loewner.

Concordance of autoimmune disease in a nationwide Danish systemic lupus erythematosus twin cohort

DEFF Research Database (Denmark)

Ulff-Møller, Constance Jensina; Svendsen, Anders Jørgen; Viemose, Louise Nørgaard

2018-01-01

OBJECTIVE: To determine the concordance of systemic lupus erythematosus (SLE) and co-aggregating autoimmune diseases among Danish twins. METHODS: SLE-affected twins were ascertained by record linkage between the National Patient Register (NPR) and the Danish Twin Registry (DTR). Registered SLE....... Another four co-twins had other autoimmune disease, corresponding to a probandwise concordance of any autoimmune disease of 50.0% in MZ (95% CI: 21.5-78.5) and 23.1% in DZ twins (95% CI: 8.18-50.3). CONCLUSION: Population-based Danish data suggest that SLE twin concordance is lower than previously...... reported, but still point to the importance of both genetic and environmental factors, and indicate a substantial co-aggregation of other autoimmune diseases in SLE twins....

A critical review of clinical trials in systemic lupus erythematosus

Science.gov (United States)

Mahieu, Mary A.; Strand, Vibeke; Simon, Lee S.; Lipsky, Peter E.; Ramsey-Goldman, Rosalind

2016-01-01

One challenge in caring for patients with systemic lupus erythematosus (SLE) is a paucity of approved therapeutics for treatment of the diverse disease manifestations. In the last 60 years, only one drug, belimumab, has been approved for SLE treatment. Critical evaluation of investigator initiated and pharma-sponsored randomized controlled trials (RCTs) highlights barriers to successful drug development in SLE, including disease heterogeneity, inadequate trial size or duration, insufficient dose finding before initiation of large trials, handling of background medications, and choice of primary endpoint. Herein we examine lessons learned from landmark SLE RCTs and subsequent advances in trial design, as well as discuss efforts to address limitations in current SLE outcome measures that will improve detection of true therapeutic responses in future RCTs. PMID:27497257

Pentraxin-3 levels are associated with vasculitis and disease activity in childhood-onset systemic lupus erythematosus.

Science.gov (United States)

Sahin, S; Adrovic, A; Barut, K; Durmus, S; Gelisgen, R; Uzun, H; Kasapcopur, O

2017-09-01

Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune disease characterized by inflammatory organ damage by means of vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory processes, predominantly from endothelial cells. In adult studies, PTX3 has shown to be an indicator of active vasculitis both in large-vessel and small-vessel vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated with disease activity, and with some of the clinical manifestations and laboratory parameters. We aimed to ascertain if PTX3 might be a significant mediator in cSLE and if it might indicate active vasculitis during the course of the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and 41 healthy subjects. We have investigated its relation with disease activity, damage, clinical features, laboratory parameters and medications. Results Serum levels of PTX3 were found to be increased in cSLE compared to healthy controls (mean ± SD; 10.6 ± 8.2 ng/mL vs 2.7 ± 1.3 ng/mL, p Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected. Conclusions Patients with cSLE have increased levels of serum PTX3 compared to healthy controls. Thus, serum PTX-3 level might be a significant mediator in cSLE. Apart from these, the results support that PTX3 reflects active cutaneous vasculitis in cSLE and correlates with disease activity.

Distribution of Human Leukocyte Antigen alleles in Systemic Lupus Erythematosus patients with Angiotensin Converting Enzyme Insertion/Deletion Polymorphism

Directory of Open Access Journals (Sweden)

Nageen Hussain

2013-02-01

Full Text Available Systemic Lupus Erythematosus is one of the classic examples of autoimmune diseases among human beings and is a rare disease in Pakistani population. Clinically it is a quite diverse and complicated autoimmune disease in a sense that it involves multiple organs of the body and mimics with other diseases as well. This study focused on the distribution of HLA alleles in SLE patients with ACE I/D Polymorphism. A total of 122 individuals were enrolled in this study, 61 were the SLE patients who fulfilled revised ACR criteria and 61 were the healthy controls. Mean age of SLE patients at diagnosis was 30.35 ± 1.687 years (12-68 years. ACE gene I/D polymorphism was performed by nested PCR and DNA based HLA typing technique was used. ACE gene I/D polymorphism of Intron16 was studied and found to be involved in the activity of SLE. There is high frequency of HLA-A*01, HLA-B*40, HLA-DRB1*01 alleles in SLE patients with ACE DD genotype. The distribution of HLA-A, -B, -DRB1 alleles was analyzed in SLE patients with various disease phenotypes. HLA-A*01 and HLA-B*40 was the most common allele found in SLE patients with the involvement of skin. HLA-A*01, -A*03, HLA-B*13 and -B*46 were common in SLE patients with arthritis while HLA-A*26 and -A*69 were commonly found in Lupus nephritis cases. SLE patients involving both skin and kidney had an allele HLA-DRB1*01 common in them.

Increased risk of thyroid diseases in patients with systemic lupus erythematosus: A nationwide population-based Study in Korea.

Directory of Open Access Journals (Sweden)

Jae-Seung Yun

Full Text Available We investigated the association between autoimmune thyroid disease and systemic lupus erythematosus (SLE using nationwide insurance claims data for the entire Korean population. Claims data for the period 2009-2013 were retrieved from the National Health Insurance System database. SLE and thyroid disease were identified using the International Classification of Diseases codes and medication information. Logistic regression analyses were used to evaluate the association between SLE and thyroid disease. The study used records from 17,495 patients with SLE and 52,485 age- and sex-matched control subjects. A greater prevalence of Graves' disease (0.94% vs. 0.46%, P < 0.001, Hashimoto's thyroiditis (2.68% vs. 0.80%, P < 0.001, and thyroid cancer (1.81% vs. 1.30%, P < 0.001 was observed in SLE patients than in control subjects. Multivariate regression analyses demonstrated that SLE was significantly associated with an increased risk of both autoimmune thyroid disease and thyroid cancer (Graves' disease: odds ratio [OR] 2.07, 95% confidence interval [CI] 1.70-2.53; Hashimoto's thyroiditis: OR 3.42, 95% CI 3.00-3.91; thyroid cancer: OR 1.40, 95% CI 1.22-1.60. Age- and sex- stratified analyses revealed that the risk of autoimmune thyroid disease in SLE patients was increased for all age groups and the female group. An association between thyroid cancer and SLE was identified only in the 20- to 59-year-old age group and in the female group. Using a large population-based study, we demonstrated that patients with SLE are at a greater risk of developing thyroid disease than matched control individuals.

Association between polymorphisms of the IKZF3 gene and systemic lupus erythematosus in a Chinese Han population.

Directory of Open Access Journals (Sweden)

Xinze Cai

Full Text Available OBJECTIVE: It has been reported that IKAROS family of zinc finger 3 (IKZF3-deficient mice spontaneously develop human systemic lupus erythematosus (SLE-like phenotypes and produce anti-dsDNA Ab leading to immune complex-mediated glomerulonephritis. Polymorphism of the IKZF3 gene corresponds with the susceptibility to several immune-related diseases. Our intention was to establish an association between polymorphisms in the IKZF3 gene and SLE in the Chinese Han population. METHODS: The study involved obtaining blood samples for DNA extraction and genotyping the 4 selected single-nucleotide polymorphisms (SNPs in IKZF3, including rs12150079, rs9909593, rs907091, and rs2872507, by performing PCR restriction fragment length polymorphism analysis (PCR-RFLP. A group of 366 SLE patients were compared to 455 healthy controls. RESULTS: A significant decrease in frequencies of the rs907091 CC genotype and C allele appeared in the SLE patients unlike that observed in the controls (p = 0.001 and 0.015, respectively. The frequencies of the rs12150079 genotype and allele were different between the SLE patients and the control individuals, although the significance was only marginal (p = 0.046 and 0.049, respectively. In addition, a significantly low frequency of the GGCG haplotype was observed in the SLE patients, suggesting that it may provide protection against SLE (p = 0.011. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate an important association between polymorphisms in IKZF3 and SLE in the Chinese Han population. A strong association between rs907091 in the IKZF3 gene and SLE was identified.

A hot spot for systemic lupus erythematosus, but not for psoriatic arthritis, identified by spatial analysis suggests an interaction between ethnicity and place of residence.

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Al-Maini, Mustafa; Jeyalingam, Thurarshen; Brown, Patrick; Lee, Jennifer J Y; Li, Lennon; Su, Jiandong; Gladman, Dafna D; Fortin, Paul R

2013-06-01

To describe the spatial distribution of incident cases of systemic lupus erythematosus (SLE) using geographic information systems (GIS). Spatial analyses were carried out on 890 SLE patients and 541 psoriatic arthritis (PsA) patients (controls). Age- and sex-adjusted rates for SLE/PsA for each census tract were calculated using denominator population values from the Canadian census. Spatial variations in relative risk were estimated by modeling risk as the product of a time effect, an age effect, and a spatially autocorrelated risk surface to identify hot spots. Patients within the detected hot spot were compared to those outside the hot spot to identify explanatory factors. SLE patients were predominantly female (87.75%) and the incidence rate was highest among those 15-19 years of age (2.4 cases/100,000 person-years). In an SLE hot spot containing 59 patients, 100% of the patients were female and 49.1% (n = 29) were Caucasian, while outside of the hot spot, 86.9% (n = 722) of the patients were female and 68.4% (n = 568) were Caucasian. The proportion of cases of Chinese ethnicity was significantly greater within the hot spot. An interaction was found between Chinese ethnicity and residence within the hot spot, with the risk of SLE to the Chinese population found to be twice the risk to the non-Chinese population. GIS was used to map SLE cases and a hot spot was identified after adjustment for age and sex. Ethnicity by itself did not confer an increased risk of SLE, but the interaction of ethnicity with location of residence significantly increased the risk of SLE. Copyright © 2013 by the American College of Rheumatology.

Increased risk of adverse pregnancy outcomes for hospitalisation of women with lupus during pregnancy: a nationwide population-based study.

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Chen, C-Y; Chen, Y-H; Lin, H-C; Chen, S-F; Lin, H-C

2010-01-01

Using a nationwide population-based dataset to examine the risk of adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with and without SLE hospitalisation during pregnancy. We identified 1,010 pregnant women who had SLE during 2001 2003 as the study cohort and 5,050 randomly selected pregnant women (five for every woman with SLE) as a comparison cohort. Conditional logistic regression analyses were performed to explore the relationship between women with and without SLE and the risk of low birth weight (LBW), preterm birth, and babies small for gestational age (SGA), after adjusting for the characteristics of the infant, mother, and father. We found that there were significant differences in the risk of LBW (14.9% vs. 7.2%), preterm birth (14.4% vs. 8.5%), and SGA (28.5% vs. 17.5%) for women with SLE compared to women without. In addition, the adjusted odds of LBW, preterm birth, and SGA babies for women who had SLE during pregnancy were 6.15 (95% CI=4.15-9.13), 4.19 (95% CI=2.77-6.36), and 4.25 (95% CI=2.95-6.11) times, respectively, compared to women without any chronic illness. The adjusted odds of LBW, preterm birth, and SGA babies for women who had SLE but were not hospitalized during pregnancy were 1.80 (95% CI=1.43-2.26), 1.62 (95% CI=1.30-2.03), and 1.63 (95% CI=1.38-1.94) times, respectively, compared to unaffected mothers. We conclude that SLE can impact the pregnancy outcomes, especially if hospitalisation occurs during the pregnancy.

Gene-gene interactions of IRF5, STAT4, IKZF1 and ETS1 in systemic lupus erythematosus.

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Dang, J; Shan, S; Li, J; Zhao, H; Xin, Q; Liu, Y; Bian, X; Liu, Q

2014-06-01

Interferon (IFN) activation signaling and T helper 17 (Th17)-cell/B-cell regulation play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Several studies have provided convincing evidence that polymorphisms in IRF5, STAT4, IKZF1 and ETS1 from these pathways may be involved in SLE by affecting gene expression or epistasis. We analyzed the genetic interaction in known SLE susceptibility loci from the four genes in northern Han Chinese. A total of 946 northern Han Chinese participated in this study (370 unrelated SLE patients and 576 healthy controls). Subjects underwent genotyping for the single-nucleotide polymorphisms (SNPs) rs2004640 in IRF5, rs7574865 in STAT4, rs4917014 in IKZF1 and rs1128334 in ETS1 by use of a TaqMan SNP genotyping assay and direct sequencing. Gene-gene interaction analysis involved direct counting, multifactor dimensionality reduction (MDR) and linear regression analysis. SLE patients and controls differed in allele frequencies of rs7574865, rs1128334 (P < 0.001) and rs4917014 (P < 0.01). Direct counting revealed that the frequency of risk homozygote combinations was higher for SLE patients than controls (P < 0.01). Furthermore, 2-, 3- and 4-way gene-gene epistasis in SLE was confirmed by parametric methods and MDR analysis. Gene expression analysis partially supported the findings. Our study confirmed the association of the IFN pathway or Th17/B-cells and the pathogenesis of SLE, and gene-gene interaction in this pathway may increase the risk of SLE. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Plant domestication slows pest evolution.

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Turcotte, Martin M; Lochab, Amaneet K; Turley, Nash E; Johnson, Marc T J

2015-09-01

Agricultural practices such as breeding resistant varieties and pesticide use can cause rapid evolution of pest species, but it remains unknown how plant domestication itself impacts pest contemporary evolution. Using experimental evolution on a comparative phylogenetic scale, we compared the evolutionary dynamics of a globally important economic pest - the green peach aphid (Myzus persicae) - growing on 34 plant taxa, represented by 17 crop species and their wild relatives. Domestication slowed aphid evolution by 13.5%, maintained 10.4% greater aphid genotypic diversity and 5.6% higher genotypic richness. The direction of evolution (i.e. which genotypes increased in frequency) differed among independent domestication events but was correlated with specific plant traits. Individual-based simulation models suggested that domestication affects aphid evolution directly by reducing the strength of selection and indirectly by increasing aphid density and thus weakening genetic drift. Our results suggest that phenotypic changes during domestication can alter pest evolutionary dynamics. © 2015 John Wiley & Sons Ltd/CNRS.

Oxygen evolution reaction catalysis

Energy Technology Data Exchange (ETDEWEB)

Haber, Joel A.; Jin, Jian; Xiang, Chengxiang; Gregoire, John M.; Jones, Ryan J.; Guevarra, Dan W.; Shinde, Aniketa A.

2016-09-06

An Oxygen Evolution Reaction (OER) catalyst includes a metal oxide that includes oxygen, cerium, and one or more second metals. In some instances, the cerium is 10 to 80 molar % of the metals in the metal oxide and/or the catalyst includes two or more second metals. The OER catalyst can be included in or on an electrode. The electrode can be arranged in an oxygen evolution system such that the Oxygen Evolution Reaction occurs at the electrode.

Patient-reported outcome measures for systemic lupus erythematosus clinical trials: a review of content validity, face validity and psychometric performance.

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Holloway, Laura; Humphrey, Louise; Heron, Louise; Pilling, Claire; Kitchen, Helen; Højbjerre, Lise; Strandberg-Larsen, Martin; Hansen, Brian Bekker

2014-07-22

Despite overall progress in treatment of autoimmune diseases, patients with systemic lupus erythematosus (SLE) experience many inflammatory symptoms representing an unmet medical need. This study aimed to create a conceptual model of the humanistic and economic burden of SLE, and review the patient-reported outcomes (PROs) used to measure such concepts in SLE clinical trials. A conceptual model for SLE was developed from structured review of published articles from 2007 to August 2013 identified from literature databases (MEDLINE, EMBASE, PsycINFO, EconLit) plus other sources (PROLabels, FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptoms/impacts were identified from the literature. They were reviewed in the context of available guidance and assessed for face and content validity and psychometric properties to determine appropriateness for use in SLE trials. The conceptual model identified fatigue, pain, cognition, daily activities, emotional well-being, physical/social functioning and work productivity as key SLE concepts. Of the 68 articles reviewed, 38 reported PRO data. From these and the other sources, 15 PROs were selected for review, including SLE-specific health-related quality of life (HRQoL) measures (n = 5), work productivity (n = 1), and generic measures of fatigue (n = 3), pain (n = 2), depression (n = 2) and HRQoL (n = 2). The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue), Brief Pain Inventory (BPI-SF) and LupusQoL demonstrated the strongest face validity, conceptual coverage and psychometric properties measuring key concepts in the conceptual model. All PROs reviewed, except for three Lupus-specific measures, lacked qualitative SLE patient involvement during development. The Hospital Anxiety and Depression Scale (HADS), Short Form [36 item] Health Survey version 2 (SF-36v2), EuroQoL 5-dimensions (EQ-5D-3L and EQ-5D-5L) and Work Productivity and Activity Impairment Questionnaire: Lupus (WPAI

Time trend and risk factors of avascular bone necrosis in patients with systemic lupus erythematosus.

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Tse, Sau Mei; Mok, Chi Chiu

2017-06-01

Objectives The objective of this paper is to study the time trend and risk factors of avascular bone necrosis (AVN) in patients with systemic lupus erythematosus (SLE). Methods Between 1999 and 2014, patients who fulfilled the ACR criteria for SLE and developed symptomatic AVN were identified from our cohort database and compared with those without AVN, matched for age, sex and SLE duration. The standardized incidence ratios (SIRs) of AVN in different SLE age groups were calculated from data derived from our hospital registry and population census. Risk factors for AVN were studied by logistic regression, adjusted by a propensity score for ever use of high-dose glucocorticoids (GCs). Results Fifty-five SLE patients with AVN and 220 SLE patients without AVN were studied. There were 104 AVN sites involved, with the hips being most commonly affected (82%). The point prevalence of AVN in our SLE cohort was 7.4%. The SIRs of AVN in our SLE patients were 131 (86.6-199; p < 0.001) and 56.0 (34.3-91.4; p < 0.001), respectively, in the periods 1995-2004 and 2005-2014. In both decades, the age-stratified SIR was highest in the youngest age group (<19 years). AVN patients were more likely to be treated with GCs and had received a significantly higher cumulative dose of prednisolone since SLE diagnosis (16.5 vs 10.7 grams; p = 0.001). The SLE damage score (excluding AVN) was also significantly higher in AVN than non-AVN patients (2.5 vs 0.4; p < 0.001). Logistic regression revealed that preceding septic arthritis of the involved joint (odds ratio (OR) 17.7 (1.5-205); p = 0.02), cushingoid body habitus (OR 2.4 (1.1-5.2); p = 0.04), LDL cholesterol level (OR 1.4 (1.0-1.9); p = 0.04), maximum daily dose of prednisolone (OR 6.4 (1.2-33.3); p = 0.03) and cumulative dose of prednisolone received in the first six months of the first lupus flare (OR 1.3 (1.0-1.8); p = 0.046) were independently associated with AVN. Conclusions AVN is prevalent in SLE

Prevalence, incidence, and associated factors of avascular necrosis in Korean patients with systemic lupus erythematosus: a nationwide epidemiologic study.

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Joo, Young Bin; Sung, Yoon-Kyoung; Shim, Jee-Seon; Kim, Jae-Hoon; Lee, Eui-Kyung; Lee, Hye-Soon; Bae, Sang-Cheol

2015-05-01

Avascular necrosis (AVN) is one of the most frequent types of organ damage in systemic lupus erythematosus (SLE). However, little is currently known about the epidemiology of AVN in SLE patients. The aim of this study was to estimate the prevalence and incidence of AVN in Korean patients with SLE based on National Health Insurance (NHI) claims data and to determine the risk factors for AVN among SLE patients. This study was conducted using the 2006-2010 data of 25,358 SLE patients from the NHI program. AVN cases were defined as those with at least one diagnosis of AVN. The prevalence was calculated by dividing the number of AVN cases by the number of SLE cases in the same year. The annual incidence was calculated by dividing the number of incident AVN cases by the number of SLE-prevalent cases not previously diagnosed with AVN. Patients who developed AVN in 2008-2010 were compared with SLE patients who did not develop AVN to identify any risk factors. The prevalence of AVN among SLE patients (2006-2010) was 31.5-34.2 per 1,000 persons and was similar in all the years studied. The incidence per 1,000 persons of AVN among SLE patients was 8.6 [95 % confidence interval (95 % CI) 6.9-10.3] in 2008, 9.8 (95 % CI 8.0-11.6) in 2009, and 8.4 (95 % CI 6.8-10.0) in 2010. Regression analysis indicated that taking an oral corticosteroid [odds ratio (OR) 2.12, 95 % CI 1.39-3.23] or an intravenous corticosteroid (OR 1.5, 95 % CI 1.2-1.89) was significantly associated with AVN. In addition, AVN was associated with use of immunosuppressive agents (OR 2.12, 95 % CI 1.66-2.72), hydroxychloroquine (OR 1.4, 95 % CI 1.09-1.81), and lipid-lowering agents (OR 1.78, 95 % CI 1.24-2.57) among the prescribed medications, and with hypertension (OR 1.39, 95 % CI 1.08-1.79) among the comorbidities. The prevalence and incidence of AVN among SLE patients, which were 31.5-34.2 and 8.4-9.8 per 1,000 persons, respectively, may be representative of the entire population of symptomatic AVN patients

Patient-reported outcome measures for systemic lupus erythematosus clinical trials: a review of content validity, face validity and psychometric performance

Science.gov (United States)

2014-01-01

Background Despite overall progress in treatment of autoimmune diseases, patients with systemic lupus erythematosus (SLE) experience many inflammatory symptoms representing an unmet medical need. This study aimed to create a conceptual model of the humanistic and economic burden of SLE, and review the patient-reported outcomes (PROs) used to measure such concepts in SLE clinical trials. Methods A conceptual model for SLE was developed from structured review of published articles from 2007 to August 2013 identified from literature databases (MEDLINE, EMBASE, PsycINFO, EconLit) plus other sources (PROLabels, FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptoms/impacts were identified from the literature. They were reviewed in the context of available guidance and assessed for face and content validity and psychometric properties to determine appropriateness for use in SLE trials. Results The conceptual model identified fatigue, pain, cognition, daily activities, emotional well-being, physical/social functioning and work productivity as key SLE concepts. Of the 68 articles reviewed, 38 reported PRO data. From these and the other sources, 15 PROs were selected for review, including SLE-specific health-related quality of life (HRQoL) measures (n = 5), work productivity (n = 1), and generic measures of fatigue (n = 3), pain (n = 2), depression (n = 2) and HRQoL (n = 2). The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue), Brief Pain Inventory (BPI-SF) and LupusQoL demonstrated the strongest face validity, conceptual coverage and psychometric properties measuring key concepts in the conceptual model. All PROs reviewed, except for three Lupus-specific measures, lacked qualitative SLE patient involvement during development. The Hospital Anxiety and Depression Scale (HADS), Short Form [36 item] Health Survey version 2 (SF-36v2), EuroQoL 5-dimensions (EQ-5D-3L and EQ-5D-5L) and Work Productivity and

Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

Science.gov (United States)

Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S

2009-01-01

To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Methodological Aspects of Subjective Life Expectancy: Effects of Culture-Specific Reporting Heterogeneity Among Older Adults in the United States.

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Lee, Sunghee; Smith, Jacqui

2016-05-01

Subjective life expectancy (SLE) has been suggested as a predictor of mortality and mortality-related behaviors. Although critical for culturally diverse societies, these findings do not consider cross-cultural methodological comparability. Culture-specific reporting heterogeneity is a well-known phenomenon introducing biases, and research on this issue with SLE is not established. Using data from the Health and Retirement Study, we examined reporting heterogeneity in SLE focusing on item nonresponse, focal points, and reports over time for five ethnic-cultural groups: non-Hispanic Whites, non-Hispanic Blacks, non-Hispanic other races, English-interviewed Hispanics, and Spanish-interviewed Hispanics. On item nonresponse, Spanish-interviewed Hispanics said, "I don't know," to SLE significantly more than any other groups. Nearly half of the respondents chose 0, 50, or 100, making them focal points. However, the focal points differed: 50 for Whites, 100 for Blacks, and 0 for Spanish-interviewed Hispanics. The relationship of SLE measured at two time points was higher for Whites than minorities. Moreover, those who said "I don't know" to SLE showed higher subsequent mortality than those who gave an answer. SLE was not a significant mortality predictor for Hispanics. Overall, SLE is not free from culture-specific reporting heterogeneity. This warrants further research about its culture-relevant measurement mechanisms. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

American Muslim Undergraduates' Views on Evolution

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Fouad, Khadija Engelbrecht

2016-01-01

A qualitative investigation into American Muslim undergraduates' views on evolution revealed three main positions on evolution: theistic evolution, a belief in special creation of all species, and a belief in special creation of humans with evolution for all non-human species. One can conceive of the manner in which respondents chose their…

Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients.

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Calvo-Alén, J; Alarcón, G S; Campbell, R; Fernández, M; Reveille, J D; Cooper, G S

2005-09-01

To determine to what extent the diagnosis of systemic lupus erythematosus (SLE) in deceased lupus patients is under-reported in death certificates, and the patient characteristics associated with such an occurrence. The death certificates of 76 of the 81 deceased SLE patients from two US lupus cohorts (LUMINA for Lupus in Minorities: Nature vs Nurture and CLU for Carolina Lupus Study), including 570 and 265 patients, respectively, were obtained from the Offices of Vital Statistics of the states where the patients died (Alabama, Georgia, North Carolina, South Carolina, Tennessee and Texas). Both cohorts included patients with SLE as per the American College of Rheumatology criteria, aged > or =16 yr, and disease duration at enrolment of < or =5 yr. The median duration of follow-up in each cohort at the time of these analyses ranged from 38.1 to 53.0 months. Standard univariable analyses were performed comparing patients with SLE recorded anywhere in the death certificate and those without it. A multivariable logistic regression model was performed to identify the variables independently associated with not recording SLE in death certificates. In 30 (40%) death certificates, SLE was not recorded anywhere in the death certificate. In univariable analyses, older age was associated with lack of recording of SLE in death certificates [mean age (standard deviation) 50.9 (15.6) years and 39.1 (18.6) yr among those for whom SLE was omitted and included on the death certificates, respectively, P = 0.005]. Patients without health insurance, those dying of a cardiovascular event and those of Caucasian ethnicity were also more likely to be in the non-recorded group. In the multivariable analysis, variables independently associated with not recording SLE as cause of death were older age [odds ratio = (95% confidence interval) 1.043 (1.005-1.083 per yr increase); P = 0.023] and lack of health insurance [4.649 (1.152-18.768); P = 0.031]. A high proportion of SLE diagnoses are not

Dicty_cDB: VHJ195 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available -B/AFN547Q.Seq.d/ 1342 0.0 SLE172 (SLE172Q) /CSM/SL/SLE1-C/SLE172Q.Seq.d/ 1102 0.0 SLD492 (SLD492Q) /CSM/SL/SLD4-D/SLD492...8502 ) Dictyostelium discoideum cDNA clone:dda28m11, 5' ... 839 0.0 2 ( AU052538 ) Dictyostelium discoideum slug cDNA, clone SLD492...2597 ) Dictyostelium discoideum slug cDNA, clone SLD569. 113 2e-20 1 ( AU061182 ) Dictyostelium discoideum slug cDNA, clone SLD492

Systemic lupus erythematosus: Clinical and experimental aspects

International Nuclear Information System (INIS)

Smolen, J.S.

1987-01-01

This text covers questions related to the history, etiology, pathogenesis, clinical aspects and therapy of systematic lupus erythematosus (SLE). Both animal models and human SLE are considered. With regard to basic science, concise information on cellular immunology, autoantibodies, viral aspects and molecular biology in SLE is provided. Clinical topics then deal with medical, dermatologic, neurologic, radiologic, pathologic, and therapeutic aspects. The book not only presents the most recent information on clinical and experimental insights, but also looks at future aspects related to the diagnosis and therapy of SLE

Expanding the Understanding of Evolution

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Musante, Susan

2011-01-01

Originally designed for K-12 teachers, the Understanding Evolution (UE) Web site ("www.understandingevolution.org") is a one-stop shop for all of a teacher's evolution education needs, with lesson plans, teaching tips, lists of common evolution misconceptions, and much more. However, during the past five years, the UE project team learned that…

Animal evolution

DEFF Research Database (Denmark)

Nielsen, Claus

This book provides a comprehensive analysis of evolution in the animal kingdom. It reviews the classical, morphological information from structure and embryology, as well as the new data gained from studies using immune stainings of nerves and muscles and blastomere markings, which makes it possi......This book provides a comprehensive analysis of evolution in the animal kingdom. It reviews the classical, morphological information from structure and embryology, as well as the new data gained from studies using immune stainings of nerves and muscles and blastomere markings, which makes...

Hypothalamic-mediated model for systemic lupus erythematosis: relation to hemispheric chemical dominance.

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Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-11-01

The isoprenoid pathway including endogenous digoxin was assessed in systemic lupus erythematosis (SLE). All the patients with SLE were right-handed/left hemispheric dominant by the dichotic listening test. This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with SLE and in those with right hemispheric dominance. In this group of patients (i) the tryptophan catabolites were increased and the tyrosine catabolites reduced, (ii) the dolichol and glycoconjugate levels were elevated, (iii) lysosomal stability was reduced, (iv) ubiquinone levels were low and free radical levels increased, and (v) the membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with left hemispheric dominance the reverse patterns were obtained. The biochemical patterns obtained in SLE is similar to those obtained in left-handed/right hemispheric chemically dominant individuals. But all the patients with SLE were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. SLE occurs in right hemispheric chemically dominant individuals, and is a reflection of altered brain function. The role of the isoprenoid pathway in the pathogenesis of SLE and its relation to hemispheric dominance is discussed.

Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

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Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C

2016-06-15

T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. Copyright © 2016 by The American Association of Immunologists, Inc.

Functional relevance for associations between genetic variants and systemic lupus erythematosus.

Directory of Open Access Journals (Sweden)

Fei-Yan Deng

Full Text Available Systemic lupus erythematosus (SLE is a serious prototype autoimmune disease characterized by chronic inflammation, auto-antibody production and multi-organ damage. Recent association studies have identified a long list of loci that were associated with SLE with relatively high statistical power. However, most of them only established the statistical associations of genetic markers and SLE at the DNA level without supporting evidence of functional relevance. Here, using publically available datasets, we performed integrative analyses (gene relationship across implicated loci analysis, differential gene expression analysis and functional annotation clustering analysis and combined with expression quantitative trait loci (eQTLs results to dissect functional mechanisms underlying the associations for SLE. We found that 14 SNPs, which were significantly associated with SLE in previous studies, have cis-regulation effects on four eQTL genes (HLA-DQA1, HLA-DQB1, HLA-DQB2, and IRF5 that were also differentially expressed in SLE-related cell groups. The functional evidence, taken together, suggested the functional mechanisms underlying the associations of 14 SNPs and SLE. The study may serve as an example of mining publically available datasets and results in validation of significant disease-association results. Utilization of public data resources for integrative analyses may provide novel insights into the molecular genetic mechanisms underlying human diseases.

Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder.

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Saito, Tomoyuki; Tamura, Maasa; Chiba, Yuhei; Katsuse, Omi; Suda, Akira; Kamada, Ayuko; Ikura, Takahiro; Abe, Kie; Ogawa, Matsuyoshi; Minegishi, Kaoru; Yoshimi, Ryusuke; Kirino, Yohei; Ihata, Atsushi; Hirayasu, Yoshio

2017-08-15

Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences of serum procalcitonin levels between bacterial infection and flare in systemic lupus erythematosus patients

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Patrick, J.; Marpaung, B.; Ginting, Y.

2018-03-01

Differentiate bacterial infections from flare in SLE patients is difficult to do because clinical symptoms of infection is similar to flare. SLE patients with infection require antibiotic therapy with decreased doses of immunosuppressant while in flare diseases require increased immunosuppressant. Procalcitonin (PCT), a biological marker, increased in serum patients with bacterial infections and expected to be a solution of problem. The aim of this study was to examine the function of PCT serum as marker to differentiate bacterial infection and flare in SLE patients. This cross-sectional study was conducted in Adam Malik Hospital from January-July 2017. We examined 80 patients SLE flare (MEX-SLEDAI>5), screen PCT and culture according to focal infection. Data were statistically analyzed. 80 SLE patients divided into 2 groups: bacterial infection group (31 patients) and non-infection/flare group (49 patients). Median PCT levels of bacterial infection group was 1.66 (0.04-8.45)ng/ml while flare group was 0.12 (0.02-0.81)ng/ml. There was significant difference of serum Procalcitonin level between bacterial infection and flare group in SLE patients (p=0.001). Procalcitonin serum levels can be used as a biomarker to differentiate bacterial infections and flare in SLE patients.

Insight into Gene Polymorphisms Involved in Toll-Like Receptor/Interferon Signalling Pathways for Systemic Lupus Erythematosus in South East Asia

Directory of Open Access Journals (Sweden)

Hwa Chia Chai

2014-01-01

Full Text Available Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms within TNFAIP3, STAT4, and IRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles of STAT4 rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P=0.028, odds ratio (OR=1.42; P=0.035, OR=1.80, respectively. Polymorphisms in TNFAIP3 and IRF5 did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was significantly associated with the Malaysian SLE as a whole (P=0.014; OR=1.435. The meta-analysis of STAT4 rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 and P value of <0.001.

Cortical Thickness and Episodic Memory Impairment in Systemic Lupus Erythematosus.

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Bizzo, Bernardo Canedo; Sanchez, Tiago Arruda; Tukamoto, Gustavo; Zimmermann, Nicolle; Netto, Tania Maria; Gasparetto, Emerson Leandro

2017-01-01

The purpose of this study was to investigate differences in brain cortical thickness of systemic lupus erythematosus (SLE) patients with and without episodic memory impairment and healthy controls. We studied 51 patients divided in 2 groups (SLE with episodic memory deficit, n = 17; SLE without episodic memory deficit, n = 34) by the Rey Auditory Verbal Learning Test and 34 healthy controls. Groups were paired based on sex, age, education, Mini-Mental State Examination score, and accumulation of disease burden. Cortical thickness from magnetic resonance imaging scans was determined using the FreeSurfer software package. SLE patients with episodic memory deficits presented reduced cortical thickness in the left supramarginal cortex and superior temporal gyrus when compared to the control group and in the right superior frontal, caudal, and rostral middle frontal and precentral gyri when compared to the SLE group without episodic memory impairment considering time since diagnosis of SLE as covaried. There were no significant differences in the cortical thickness between the SLE without episodic memory and control groups. Different memory-related cortical regions thinning were found in the episodic memory deficit group when individually compared to the groups of patients without memory impairment and healthy controls. Copyright © 2016 by the American Society of Neuroimaging.

Classification of Multiple Seizure-Like States in Three Different Rodent Models of Epileptogenesis.

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Guirgis, Mirna; Serletis, Demitre; Zhang, Jane; Florez, Carlos; Dian, Joshua A; Carlen, Peter L; Bardakjian, Berj L

2014-01-01

Epilepsy is a dynamical disease and its effects are evident in over fifty million people worldwide. This study focused on objective classification of the multiple states involved in the brain's epileptiform activity. Four datasets from three different rodent hippocampal preparations were explored, wherein seizure-like-events (SLE) were induced by the perfusion of a low - Mg(2+) /high-K(+) solution or 4-Aminopyridine. Local field potentials were recorded from CA3 pyramidal neurons and interneurons and modeled as Markov processes. Specifically, hidden Markov models (HMM) were used to determine the nature of the states present. Properties of the Hilbert transform were used to construct the feature spaces for HMM training. By sequentially applying the HMM training algorithm, multiple states were identified both in episodes of SLE and nonSLE activity. Specifically, preSLE and postSLE states were differentiated and multiple inner SLE states were identified. This was accomplished using features extracted from the lower frequencies (1-4 Hz, 4-8 Hz) alongside those of both the low- (40-100 Hz) and high-gamma (100-200 Hz) of the recorded electrical activity. The learning paradigm of this HMM-based system eliminates the inherent bias associated with other learning algorithms that depend on predetermined state segmentation and renders it an appropriate candidate for SLE classification.

IgA nephropathy in systemic lupus erythematosus patients: case report and literature review

Directory of Open Access Journals (Sweden)

Leonardo Sales da Silva

2016-06-01

Full Text Available Abstract Systemic erythematosus lupus (SLE is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non‐lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN, the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1,280, nuclear fine speckled pattern, and anticardiolipin IgM and 280 U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non‐SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in the short and long term.

[Preparation and applications of a supported liquid-liquid extraction column with a composite diatomite material].

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Bao, Jianmin; Ma, Zhishuang; Sun, Ying; Wang, Yongzun; Li, Youxin

2012-08-01

A rapid and special supported liquid-liquid extraction (SLE) column was developed with a composite diatomite material. The SLE column was evaluated by high performance liquid chromatography (HPLC) with acidic, neutral and alkaline compounds dissolved in water. Furthermore, some real complex samples were also analyzed by HPLC with the SLE method. The recoveries of benzoic acid (acidic), p-nitroaniline (alkaline) and 4-hydroxy-benzoic methyl ester (neutral) treated by the SLE column were 90.6%, 98.1% and 97.7%. However, the recoveries of the three compounds treated by traditional liquid-liquid extraction (LLE) method were 71.9%, 81.9% and 83.9%. The results showed that the SLE technique had higher recoveries than the traditional LLE method. The spiked recoveries of the complex samples, such as benzoic acid in Sprite and dexamethasone acetate, chlorphenamine maleate, indomethacin in bovine serum, were between 80% and 110% and the relative standard deviations (RSDs) were less than 15%. For biological specimen, the results could be accepted. Meantime, many disadvantages associated with traditional LLE method, such as emulsion formation, didn't occur using SLE column. The SLE column technique is a good sample preparation method with many advantages, such as rapid, simple, robust, easily automated, high recovery and high-throughput, which would be widely used in the future.

Insight into Gene Polymorphisms Involved in Toll-Like Receptor/Interferon Signalling Pathways for Systemic Lupus Erythematosus in South East Asia

Science.gov (United States)

Chua, Kek Heng; Lim, Soo Kun; Phipps, Maude Elvira

2014-01-01

Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms within TNFAIP3, STAT4, and IRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles of STAT4 rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P = 0.028, odds ratio (OR) = 1.42; P = 0.035, OR = 1.80, respectively). Polymorphisms in TNFAIP3 and IRF5 did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was significantly associated with the Malaysian SLE as a whole (P = 0.014; OR = 1.435). The meta-analysis of STAT4 rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 and P value of <0.001. PMID:24741605

Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus.

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Luo, Xin M; Edwards, Michael R; Mu, Qinghui; Yu, Yang; Vieson, Miranda D; Reilly, Christopher M; Ahmed, S Ansar; Bankole, Adegbenga A

2018-02-15

Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae ) and was less diverse, with increased representation of Gram-negative bacteria. The Firmicutes / Bacteroidetes ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. IMPORTANCE SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a

Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

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Catoggio, L J; Soriano, E R; Imamura, P M; Wojdyla, D; Jacobelli, S; Massardo, L; Chacón Díaz, R; Guibert-Toledano, M; Alvarellos, A; Saurit, V; Manni, J A; Pascual-Ramos, V; Silva de Sauza, A W; Bonfa, E; Tavares Brenol, J C; Ramirez, L A; Barile-Fabris, L A; De La Torre, I Garcia; Alarcón, G S; Pons-Estel, B A

2015-07-01

To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (lupus, adjusting for other variables. Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p  0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements. © The Author(s) 2014.

Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US Medicaid beneficiary population.

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Hiraki, Linda T; Feldman, Candace H; Liu, Jun; Alarcón, Graciela S; Fischer, Michael A; Winkelmayer, Wolfgang C; Costenbader, Karen H

2012-08-01

To investigate the nationwide prevalence, incidence, and sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among children in the US Medicaid beneficiary population. Children ages 3 years to Classification of Diseases, Ninth Revision [ICD-9] code of 710.0 for SLE, each >30 days apart) were identified from the US Medicaid Analytic eXtract database from 2000 to 2004. This database contains all inpatient and outpatient Medicaid claims for 47 US states and the District of Columbia. Lupus nephritis was identified from ≥2 ICD-9 billing codes for glomerulonephritis, proteinuria, or renal failure, each recorded >30 days apart. The prevalence and incidence of SLE and lupus nephritis were calculated among Medicaid-enrolled children overall and within sociodemographic groups. Of the 30,420,597 Medicaid-enrolled children during these years, 2,959 were identified as having SLE. The prevalence of SLE was 9.73 (95% confidence interval [95% CI] 9.38-10.08) per 100,000 Medicaid-enrolled children. Among the children with SLE, 84% were female, 40% were African American, 25% were Hispanic, 21% were White, and 42% resided in the South region of the US. Moreover, of the children with SLE, 1,106 (37%) had lupus nephritis, representing a prevalence of 3.64 (95% CI 3.43-3.86) per 100,000 children. The average annual incidence of SLE was 2.22 cases (95% CI 2.05-2.40) and that of lupus nephritis was 0.72 cases (95% CI 0.63-0.83) per 100,000 Medicaid enrollees per year. The prevalence and incidence rates of SLE and lupus nephritis increased with age, were higher in girls than in boys, and were higher in all non-White racial/ethnic groups. In the current study, the prevalence and incidence rates of SLE among Medicaid-enrolled children in the US are high compared to studies in other populations. In addition, these data represent the first population-based estimates of the prevalence and incidence of lupus nephritis in the US to date. Copyright © 2012 by the American

Serum IP-10 is useful for identifying renal and overall disease activity in pediatric systemic lupus erythematosus.

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Zhang, Chen-Xing; Cai, Li; Shao, Kang; Wu, Jing; Zhou, Wei; Cao, Lan-Fang; Chen, Tong-Xin

2018-05-01

Traditional serological biomarkers often fail to assess systemic lupus erythematosus (SLE) disease activity and discriminate lupus nephritis (LN). The aim of this study was to identify novel markers for evaluating renal and overall disease activity in Chinese patients with pediatric systemic lupus erythematosus (pSLE). The study included 46 patients with pSLE (35 girls, 11 boys; average age 13.3 ± 2.6 years) and 31 matched healthy controls (22 girls, 9 boys; average age 12.3 ± 2.4 years). The SLE Disease Activity Index (SLEDAI) and renal SLEDAI were used to assess disease activity. Nine different soluble mediators in plasma, including tumor necrosis factor alpha (TNF-α), platelet-derived growth factor-BB (PDGF-BB), interferon (IFN) gamma inducible protein 10 (IP-10), interleukin (IL)-1β, IFN-γ, IL-17A, IL-2, Fas and Fas ligand, were measured by Luminex assay and compared between patients with active and inactive pSLE as well as between patients with pSLE with active and inactive renal disease. Receiver operating characteristic curve analysis was used to measure the discrimination accuracy. Of the 46 patients with pSLE, 30 (65.2%) had LN. These patients had significantly elevated levels of serum TNF-α, PDGF-BB, IP-10 and Fas. The serum levels of IP-10 were also significantly higher in patients with active pSLE. We found that IP-10 was also more sensitive and specific than conventional laboratory parameters, including anti-double-stranded DNA and complement components C3 and C4, for distinguishing active lupus from quiescent lupus. The serum level of IP-10 was also significantly increased in children with pSLE with active renal disease relative to those with inactive renal disease. There was also a positive correlation between serum IP-10 levels and renal SLEDAI scores as well as with 24 h urine protein. Serum IP-10 is useful for identifying renal and overall disease activity in children with pSLE.

Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region

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Kawasaki, Aya; Ito, Ikue; Hikami, Koki; Ohashi, Jun; Hayashi, Taichi; Goto, Daisuke; Matsumoto, Isao; Ito, Satoshi; Tsutsumi, Akito; Koga, Minori; Arinami, Tadao; Graham, Robert R; Hom, Geoffrey; Takasaki, Yoshinari; Hashimoto, Hiroshi; Behrens, Timothy W; Sumida, Takayuki; Tsuchiya, Naoyuki

2008-01-01

Introduction Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. Methods In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. Results In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P rs7574865) (P = 1.5 × 10-6). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in Americans of European descent (19.5%). Conclusions The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic susceptibility to SLE was not detected. The contribution of STAT4 for the genetic background of SLE may be greater in the

Software architecture evolution

DEFF Research Database (Denmark)

Barais, Olivier; Le Meur, Anne-Francoise; Duchien, Laurence

2008-01-01

Software architectures must frequently evolve to cope with changing requirements, and this evolution often implies integrating new concerns. Unfortunately, when the new concerns are crosscutting, existing architecture description languages provide little or no support for this kind of evolution....... The software architect must modify multiple elements of the architecture manually, which risks introducing inconsistencies. This chapter provides an overview, comparison and detailed treatment of the various state-of-the-art approaches to describing and evolving software architectures. Furthermore, we discuss...... one particular framework named Tran SAT, which addresses the above problems of software architecture evolution. Tran SAT provides a new element in the software architecture descriptions language, called an architectural aspect, for describing new concerns and their integration into an existing...

Binary evolution and observational constraints

International Nuclear Information System (INIS)

Loore, C. de

1984-01-01

The evolution of close binaries is discussed in connection with problems concerning mass and angular momentum losses. Theoretical and observational evidence for outflow of matter, leaving the system during evolution is given: statistics on total masses and mass ratios, effects of the accretion of the mass gaining component, the presence of streams, disks, rings, circumstellar envelopes, period changes, abundance changes in the atmosphere. The effects of outflowing matter on the evolution is outlined, and estimates of the fraction of matter expelled by the loser, and leaving the system, are given. The various time scales involved with evolution and observation are compared. Examples of non conservative evolution are discussed. Problems related to contact phases, on mass and energy losses, in connection with entropy changes are briefly analysed. For advanced stages the disruption probabilities for supernova explosions are examined. A global picture is given for the evolution of massive close binaries, from ZAMS, through WR phases, X-ray phases, leading to runaway pulsars or to a binary pulsar and later to a millisecond pulsar. (Auth.)

Epidemiology of systemic lupus erythematosus: an update.

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Stojan, George; Petri, Michelle

2018-03-01

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease with a significant disease burden across the world among different ethnic, racial, and age groups. The pathophysiological understanding of SLE is constantly evolving and with it, the need for a better definition of the disease itself, for understanding the risk among the different affected populations, and for identifying the factors responsible for the damage accrual through the years. More accurate estimates of incidence and prevalence of SLE among different ethnicities and minority groups not only in the USA, but also in Europe, Middle East, and Asia have provided new insights into the disease burden around the world. Despite advances in treatment, mortality among SLE patients remains high with significant ethnic and geographic variations. Sex, race, and ethnicity significantly affect SLE incidence, prevalence, and mortality.

Understanding Collateral Evolution in Linux Device Drivers

DEFF Research Database (Denmark)

Padioleau, Yoann; Lawall, Julia Laetitia; Muller, Gilles

2006-01-01

no tools to help in this process, collateral evolution is thus time consuming and error prone.In this paper, we present a qualitative and quantitative assessment of collateral evolution in Linux device driver code. We provide a taxonomy of evolutions and collateral evolutions, and use an automated patch......-analysis tool that we have developed to measure the number of evolutions and collateral evolutions that affect device drivers between Linux versions 2.2 and 2.6. In particular, we find that from one version of Linux to the next, collateral evolutions can account for up to 35% of the lines modified in such code....

Evolution, epigenetics and cooperation.

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Bateson, Patrick

2014-04-01

Explanations for biological evolution in terms of changes in gene frequencies refer to outcomes rather than process. Integrating epigenetic studies with older evolutionary theories has drawn attention to the ways in which evolution occurs. Adaptation at the level of the gene is givingway to adaptation at the level of the organism and higher-order assemblages of organisms. These ideas impact on the theories of how cooperation might have evolved. Two of the theories, i.e. that cooperating individuals are genetically related or that they cooperate for self-interested reasons, have been accepted for a long time. The idea that adaptation takes place at the level of groups is much more controversial. However, bringing together studies of development with those of evolution is taking away much of the heat in the debate about the evolution of group behaviour.

Multidimensional single cell based STAT phosphorylation profiling identifies a novel biosignature for evaluation of systemic lupus erythematosus activity.

Directory of Open Access Journals (Sweden)

Xinfang Huang

Full Text Available INTRODUCTION: Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE, a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE. METHODS: Phospho-specific flow cytometry was used to measure the basal STAT signaling activation in three immune cell types of peripheral-blood mononuclear cells from 20 lupus patients, 9 rheumatoid arthritis (RA patients and 13 healthy donors (HDs. A panel of 27 cytokines, including inflammatory cytokines, was measured with Bio-Plex™ Human Cytokine Assays. Serum Prolactin levels were measured with an immunoradiometric assay. STAT signaling responses to inflammatory cytokines (interferon α [IFNα], IFNγ, interleukin 2 [IL2], IL6, and IL10 were also monitored. RESULTS: We observed the basal activation of STAT3 in SLE T cells and monocytes, and the basal activation of STAT5 in SLE T cells and B cells. The SLE samples clustered into two main groups, which were associated with the SLE Disease Activity Index 2000, their erythrocyte sedimentation rate, and their hydroxychloroquine use. The phosphorylation of STAT5 in B cells was associated with cytokines IL2, granulocyte colony-stimulating factor (G-CSF, and IFNγ, whereas serum prolactin affected STAT5 activation in T cells. The responses of STAT1, STAT3, and STAT5 to IFNα were greatly reduced in SLE T cells, B cells, and monocytes, except for the STAT1 response to IFNα in monocytes. The response of STAT3 to IL6 was reduced in SLE T cells. CONCLUSIONS: The basal activation of STATs signaling and reduced response to cytokines may be helpful us to identify the activity and severity of SLE.

Population Pharmacokinetics of Hydroxychloroquine in Japanese Patients With Cutaneous or Systemic Lupus Erythematosus.

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Morita, Shigemichi; Takahashi, Toshiya; Yoshida, Yasushi; Yokota, Naohisa

2016-04-01

Hydroxychloroquine (HCQ) is an effective treatment for patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) and has been used for these patients in more than 70 nations. However, in Japan, HCQ has not been approved for CLE or SLE. To establish an appropriate therapeutic regimen and to clarify the pharmacokinetics (PK) of HCQ in Japanese patients with CLE with or without SLE (CLE/SLE), a population pharmacokinetic (PopPK) analysis was performed. In a clinical study of Japanese patients with a diagnosis of CLE irrespective of the presence of SLE, blood and plasma drug concentration-time data receiving multiple oral doses of HCQ sulfate (200-400 mg daily) were analyzed using nonlinear mixed-effects model software. The blood and plasma concentrations of HCQ were analyzed using a high-performance liquid chromatography tandem mass spectrometry method. Model evaluation and validation were performed using goodness-of-fit (GOF) plots, visual predictive check, and a bootstrap. The PopPKs of HCQ in the blood and plasma of 90 Japanese patients with CLE/SLE were well described by a 1-compartment model with first-order absorption and absorption lag time. Body weight was a significant (P < 0.001) covariate of oral clearance of HCQ. The final model was assessed using GOF plots, a bootstrap, and visual predictive check, and this model was appropriate. Simulations based on the final model suggested that the recommended daily doses of HCQ sulfate (200-400 mg) based on the ideal body weight in Japanese patients with CLE/SLE were in the similar concentration ranges. The PopPK models derived from both blood and plasma HCQ concentrations of Japanese patients with CLE/SLE were developed and validated. Based on this study, the dosage regimens of HCQ sulfate for Japanese patients with CLE/SLE should be calculated using the individual ideal body weight.

Pathogenic inflammation and its therapeutic targeting in systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

Timothy Andrew Gottschalk

2015-10-01

Full Text Available Systemic Lupus Erythematosus (SLE, lupus is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues including skin, kidneys and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B and T lymphocyte activation, and, with the single exception of an agent known as Belimumab which targets the B cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immuno-suppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and

[Treatment of systemic lupus erythematosus: myths, certainties and doubts].

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Ruiz-Irastorza, Guillermo; Danza, Alvaro; Khamashta, Munther

2013-12-21

Systemic lupus erythematosus (SLE) is a complex disease with different clinical forms of presentation, including a wide range of severity and organic involvement. Such circumstance, along with the fact of the uncommon nature of the disease and the absence of clinically representative response criteria, make it difficult to design controlled clinical trials in SLE patients. As a result, observational studies have a special relevance, being a source of valuable information of SLE prognosis and outcome as well as of the efficacy and adverse effects of the different therapies. Herein we update some of the main treatments used in SLE. Steroids may have more risks than benefits if used at high doses. New mechanisms of action have been described, supporting the use of lower doses, possibly with the same efficacy and less adverse effects. Intravenous pulses of cyclophosphamide still have a role in the treatment of proliferative lupus nephritis and other serious SLE manifestations. Mycophenolate mofetil has shown its efficacy both as induction and maintenance therapy of selected cases of lupus nephritis. Biological therapies have emerged as new promising options. Although clinical trials have not confirmed a clear superiority of rituximab in SLE, observational studies have shown good response rates in severe SLE manifestations or refractory forms. Belimumab has recently been added to the therapeutic armamentarium of SLE; although its place in clinical practice is not well-defined, it may be recommended in active patients with no response or good tolerance to standard therapies. Hydroxichloroquine improves survival, decreases the risk of thrombosis and flares and is safe in pregnancy, and should be considered the baseline therapy in most SLE patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Risk of Childhood Rheumatic and Non-Rheumatic Autoimmune Diseases in Children Born to Women with Systemic Lupus Erythematosus.

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Couture, Julie; Bernatsky, Sasha; Scott, Susan; Pineau, Christian A; Vinet, Evelyne

2018-05-23

Several autoimmune diseases have familial aggregation and possibly, common genetic predispositions. In a large population-based study, we evaluated if children born to mothers with SLE have an increased risk of rheumatic and non-rheumatic autoimmune diseases, versus children born to mothers without SLE. Using the "Offspring of SLE mothers Registry (OSLER)", we identified children born live to SLE mothers and their matched controls, and ascertained autoimmune diseases based on ≥1 hospitalization or ≥2 physician visits with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetrical complications, calendar birth year, and sex of child. 509 women with SLE had 719 children, while 5824 matched controls had 8493 children. Mean follow-up was 9.1 (SD 5.8) years. Children born to mothers with SLE had similar frequency of rheumatic autoimmune diagnoses (0.14%, 95% CI 0.01, 0.90) versus controls (0.19%, 95% CI 0.11, 0.32). There was a trend towards more non-rheumatic autoimmune diseases in SLE offspring (1.11%, 95% CI 0.52, 2.27) versus controls (0.48%, 95% CI 0.35, 0.66). In multivariate analyses, we did not see a clear increase in rheumatic autoimmune disease (OR 0.71, 95% CI 0.11-4.82) but children born to mothers with SLE had a substantially increased risk of non-rheumatic autoimmune disease versus controls (OR 2.30, 95% CI 1.06-5.03). Although the vast majority of offspring have no autoimmune disease, children born to women with SLE may have an increased risk of non-rheumatic autoimmune diseases, versus controls. Additional studies assessing offspring through to adulthood would be additionally enlightening. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Haematological manifestations of lupus

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Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

2015-01-01

Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus

Science.gov (United States)

Zhao, Ming; Zhou, Yin; Zhu, Bochen; Wan, Mengjie; Jiang, Tingting; Tan, Qiqun; Liu, Yan; Jiang, Juqing; Luo, Shuaihantian; Tan, Yixin; Wu, Haijing; Renauer, Paul; Gutiérrez, Maria del Mar Ayala; Palma, Maria Jesús Castillo; Castro, Rafaela Ortega; Fernández-Roldán, Concepción; Raya, Enrique; Faria, Raquel; Carvalho, Claudia; Alarcón-Riquelme, Marta E; Xiang, Zhongyuan; Chen, Jinwei; Li, Fen; Ling, Guanghui; Zhao, Hongjun; Liao, Xiangping; Lin, Youkun; Sawalha, Amr H; Lu, Qianjin

2016-01-01

Objective Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. Methods IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren’s syndrome (pSS) were used for validation. Results Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. Conclusions The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE. PMID:26787370

The Impact of Systemic Lupus Erythematosus on the Clinical Phenotype of Antiphospholipid Antibody Positive Patients: Results from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository.

Science.gov (United States)

Unlu, Ozan; Erkan, Doruk; Barbhaiya, Medha; Andrade, Danieli; Nascimento, Iana; Rosa, Renata; Banzato, Alessandra; Pengo, Vittorio; Ugarte, Amaia; Gerosa, Maria; Ji, Lanlan; Efthymiou, Maria; Branch, D Ware; de Jesus, Guilherme Raires; Tincani, Angela; Belmont, H Michael; Fortin, Paul R; Petri, Michelle; Rodriguez, Esther; Pons-Estel, Guillermo J; Knight, Jason S; Atsumi, Tatsuya; Willis, Rohan; Zuily, Stephane; Tektonidou, Maria G

2018-04-18

Although systemic lupus erythematosus (SLE) is the most common autoimmune disease associated with antiphospholipid antibodies (aPL), limited data exist on the impact of SLE on the clinical phenotype of aPL-positive patients. The primary objective was to compare the clinical, laboratory, and treatment characteristics of aPL-positive patients with or without SLE. A secure web-based data capture system stores patient demographics, and aPL-related clinical and laboratory characteristics. Inclusion criteria include aPL positivity according to the Updated Sapporo Classification Criteria. Patients fulfilling the SLE Classification Criteria and those with no other autoimmune diseases were included in the analysis. 672 aPL-positive patients were recruited from 24 international centers; 426 were without other autoimmune diseases and 197 with SLE. The aPL with SLE group had higher rates of thrombocytopenia, hemolytic anemia, low complements, and IgA anti-β 2 glycoprotein-I antibodies (aβ₂GPI), whereas the aPL only group had higher rates of cognitive dysfunction and IgG aβ₂GPI. The frequency of arterial and venous thromboses (including recurrent) as well as the pregnancy morbidity were similar between the groups. The prevalence of cardiovascular disease risk factors at the registry entry did not differ between the two groups, except current smoking, which was more frequent in aPL with SLE group. Although the frequencies of thrombosis and pregnancy morbidity are similar between aPL-positive patients with or without SLE, the diagnosis of SLE in persistently aPL-positive patients is associated with an increased frequency of thrombocytopenia, hemolytic anemia, low complements, and IgA aβ₂GPI positivity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

E-selectin: sialyl Lewis, a dependent adhesion of colon cancer cells, is inhibited differently by antibodies against E-selectin ligands.

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Srinivas, U; Påhlsson, P; Lundblad, A

1996-09-01

Recent studies have demonstrated that selectins, a new family of cell-adhesion molecules with similar domain structures, mediate the adhesion of peripheral blood cells to interleukin-1 (IL-1)-activated endothelium. In the present study the authors evaluated the role of E-selectin-Sialyl Lewis x (SLe(x))/ Sialyl Lewis a (SLe(a)) interaction in mediating in vitro adhesion of two colon cancer cell lines, HT-29 and COLO 201, to human umbilical cord endothelial cells (HUVEC). Colon cancer cell lines had a strong expression of blood group-related carbohydrate epitopes as evaluated by fluorescence-activated cell sorter (FACS) analysis. It was established that adhesion of HT-29 and COLO 201 cells to IL-1 stimulated HUVEC was calcium dependent and could be inhibited by a monoclonal antibody directed against E-selectin. Prior incubation of cells with two different antibodies directed against SLe(x) and antibodies directed against related Lewis epitopes, Le(x) and Le(a), had no significant effect on adhesion. Three antibodies directed against SLe(a) differed in their capacity to inhibit the adhesion of HT-29 and COLO 201 cells to HUVEC. Only one antibody directed against the SLe(a) structure was effective in inhibiting adhesion of both COLO 201 and HT-29 cells. The difference could not be attributed to titre, the type or number of glycoproteins, or to a difference in the amount of SLe(a) present on individual proteins, suggesting that presence and right presentation of SLe(a) epitope might be important for adhesion of colon cancer cells. Finally, in the in vitro system used, adhesion of HT-29 and COLO 201 cells to activated HUVEC is mediated predominantly by E-selectin/SLe(a) interaction. SLe(x) and related epitopes, Le(x) and Le(a), seem to have limited relevance for colon cancer cell recognition of E-selectin.

Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

Science.gov (United States)

Gottschalk, Timothy A.; Tsantikos, Evelyn; Hibbs, Margaret L.

2015-01-01

Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immunosuppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B-cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here, we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and review the known

Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

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Gulati, Gaurav; Jones, Jordan T; Lee, Gregory; Altaye, Mekibib; Beebe, Dean W; Meyers-Eaton, Jamie; Wiley, Kasha; Brunner, Hermine I; DiFrancesco, Mark W

2017-02-01

To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to

Clinical consequences of hospital variation in use of oral anticoagulant therapy after first-time admission for atrial fibrillation

DEFF Research Database (Denmark)

Hansen, M L; Gadsbøll, N; Rasmussen, S

2009-01-01

Abstract. Hansen ML, Gadsbøll N, Rasmussen S, Gislason GH, Folke F, Andersen SS, Schramm TK, Sørensen R, Fosbøl EL, Abildstrøm SZ, Madsen M, Poulsen HE, Køber L, Torp-Pedersen C (Gentofte University Hospital, Hellerup; Sygehus Nord, Køge; National Institute of Public Health; Rigshospitalet-Copenh...... thromboembolic events were observed amongst patients from low OAC use hospitals. Our study emphasizes the need for a continued vigilance on implementation of international AF management guidelines....

Approaches to capturing the Black and White Tegu Salvator merianae (Squamata: Teiidae)

OpenAIRE

Vieira,Renata C.; Oliveira,Arthur S. de; Fagundes,Nelson J.R.; Verrastro,Laura

2015-01-01

ABSTRACT The use of traps is extremely important in several types of ecological studies, and may assist in the capture of individuals in areas that are difficult to access. In the present study, we compared the effectiveness of wooden (Schramm) versus "Tomahawk" traps to capture Salvator merianae (Duméril & Bibron, 1839) lizards. The study was conducted in Eldorado do Sul, Rio Grande do Sul, Brazil. Field data were collected from August 2013 to March 2015, during the reproductive period of th...

Impact of Childbearing Decisions on Family Size of Korean Women with Systemic Lupus Erythematosus.

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Kim, In Je; Kim, Hyoun-Ah; Suh, Chang-Hee; Park, Yong-Wook; Lee, Hye-Soon; Bang, So-Young; Bae, Sang-Cheol; Kang, Young Mo; Lee, Won Kyung; Park, Hyesook; Lee, Jisoo

2016-05-01

Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years and has a significant impact on childbearing. We investigated the influence of personal decision on family size among Korean women with SLE and factors that affect the decisions. A case-control study comparing childbearing history and decisions of 112 SLE patients and 135 controls was performed. Women with SLE participating in the Network for Lupus Clinical Research in South Korea and matching controls between ages of 18-45, who are/were married or living with a partner were included. Data regarding socio-demographics, reproductive history, and childbearing decisions were collected through a survey using a standardized questionnaire and medical record review. More women with SLE reported at least one pregnancy (85.7% vs. 71.9%, P = 0.009) or at least one live birth (85.7% vs. 71.9%, P = 0.003) compared with controls. Mean number of pregnancies was significantly higher (2.4 ± 1.6 vs. 1.4 ± 1.3, P family size and childbearing decisions among Korean women with SLE.

Correlation between Antistress and Hepatoprotective Effects of Schisandra Lignans Was Related with Its Antioxidative Actions in Liver Cells

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Hao-Jie Pu

2012-01-01

Full Text Available The present study was conducted to investigate the relationship between the anti-stress and hepato-protective effects of Schisandra Lignans Extract (SLE on stress-induced liver damage. Seven weeks old male mice were fixed in a restraint tube for 18 h to induce liver damage. SLE was orally administered to animals for 5 days at dosages of 100 and 200 mg/kg/day before exposed to restraint stress. Oral administration of SLE significantly reduced restraint-induced liver damage in experimental animal. SLE was further found to significantly alleviate the provocation of corticosterone in stressed mice. SLE also significantly decreased oxidative damage and increased anti-oxidative capability of liver cells by preventing the over production and accumulation of free radicals. In conclusion, the protective effects of SLE on stress-induced liver damage were confirmed, and the correlation between hepatoprotective and anti-stress effects of schisandra lignans was possible related to its alleviation on the malignant effects of stressors for bio-homeostasis, such as balance of oxidation and reduction in cells.

The involvement of galectin-3 in skin injury in systemic lupus erythematosus patients.

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Shi, Z; Meng, Z; Han, Y; Cao, C; Tan, G; Wang, L

2018-04-01

Objective Our previous research suggested that anti-galectin-3 antibody was highly associated with the development of lupus skin lesions in systemic lupus erythematosus (SLE). In this study we aimed to investigate the involvement of galectin-3 in SLE skin damage. Methods The study consisted of 49 patients with SLE, 16 with dermatomyositis and 11 with systemic scleroderma and 20 healthy controls. Galectin-3 was examined by ELISA and immunohistochemical staining in serum and skin, respectively. Results Serum galectin-3 was significantly higher in patients with SLE than in those with dermatomyositis ( P  0.05). As for subtypes of skin lesions in SLE, galectin-3 expression was lower in chronic cutaneous lupus erythematosus than in acute cutaneous lupus erythematosus ( P = 0.0439). Conclusion Serum galectin-3 is unlikely to play a role in the pathogenesis of lupus skin damage, but can be a potential biomarker for the measurement of SLE disease activity. Galectin-3 is greatly reduced in patients with lupus lesions compared with healthy controls, which may contribute to the recruitment of inflammatory cells in the skin.

Association of TNFAIP3 Polymorphism with Susceptibility to Systemic Lupus Erythematosus in a Japanese Population

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Aya Kawasaki

2010-01-01

Full Text Available Recent genome-wide association studies demonstrated association of single nucleotide polymorphisms (SNPs in the TNFAIP3 region at 6q23 with systemic lupus erythematosus (SLE in European-American populations. In this study, we investigated whether SNPs in the TNFAIP3 region are associated with SLE also in a Japanese population. A case-control association study was performed on the SNPs rs13192841, rs2230926, and rs6922466 in 318 Japanese SLE patients and 444 healthy controls. Association of rs2230926 G allele with SLE was replicated in Japanese (allelic association P=.033, odds ratio [OR] 1.47, recessive model P=.023, OR 8.52. The association was preferentially observed in the SLE patients with nephritis. When the TNFAIP3 mRNA levels of the HapMap samples were examined using GENEVAR database, the presence of TNFAIP3 rs2230926 G allele was associated with lower mRNA expression of TNFAIP3 (P=.013. These results indicated that TNFAIP3 is a susceptibility gene to SLE both in the Caucasian and Asian populations.

Spectral evolution of galaxies: current views

International Nuclear Information System (INIS)

Bruzual, A.G.

1985-01-01

A summary of current views on the interpretation of the various evolutionary tests aimed at detecting spectral evolution in galaxies is presented. It is concluded that the evolution taking place in known galaxy samples is a slow process (perhaps consistent with no evolution at all), and that the early phases of rapid spectral evolution in early-type galaxies have not yet been detected. (author)

An evaluation of quality of life in ambulatory patients with systemic ...

African Journals Online (AJOL)

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that affects all organs of the body. It is becoming increasingly clear that SLE is not as rare in Kenya as was previously thought. Due to its chronicity SLE has been known to affect the quality of life of those affected by it. There is minimal data ...

Research Progress on Systemic Lupus Erythematosus Complicated with Infection

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Zhang Weisan

2015-06-01

Full Text Available In recent years, in treatment standardization of systemic lupus erythematosus (SLE, infections and serious complications became the leading cause of death related to this disease, exceeding those of renal involvement and lupus encephalopathy. SLE coinfection is mainly related to defects in humoral immunity and cellular immunity, SLE disease activity, and doses of hormone and immune inhibitors.

Increased susceptibility to in vitro ultraviolet B radiation in fibroblasts and lymphocytes cultured from systemic lupus erythematosus patients

International Nuclear Information System (INIS)

Golan, T.D.; Foltyn, V.; Roueff, A.

1991-01-01

Sunlight is known to induce exacerbations of systemic lupus erythematosus (SLE) but its mechanism remains unclear. We have previously reported that ultraviolet A (UVA) exposure induces an increase in total DNA synthesis (DS) in vitro but a decrease in unscheduled DNA repair synthesis (UDRS) of splenocytes of murine SLE strains. In order to investigate whether similar observations are characteristic of human SLE, peripheral blood lymphocytes (PBL) and dermal fibroblast (DF) cultures of 20 patients and 15 matched controls were exposed in vitro to UVA or UVB at different doses. Thirteen (65%) SLE DF cultures exposed to UVB light (12-24 J/m2) showed an increase in DS compared to paired unirradiated cultures. In contrast, UVB-irradiated DF from normal individuals had no significant increase in DS following UVB irradiation. When SLE DF were exposed to higher doses of UVB (48-96 J/m2), 90% of cultures showed a decrease in DS compared to only 20% in the control group. All of the SLE DF cultures showed a decrease of their unscheduled DNA repair capacity following UVB (24-48 J/m2) irradiation whereas no UDRS was apparent in 74% of controls under the same conditions. Similar findings regarding UDRS were observed in SLE PBL cultures and were also confirmed by autoradiography. UVA exposure (0-3840 J/m2) had no effect on DS nor on UDRS in DF or PBL cultured from SLE and controls. The relevance of these in vitro findings to the in vivo pathogenesis of the disease is discussed

Abnormal findings of magnetic resonance imaging (MRI) in patients with systemic lupus erythematosus involving the brain

Energy Technology Data Exchange (ETDEWEB)

Ishikawa, Akira; Okada, Jun; Kondo, Hirobumi (Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine); Kashiwazaki, Sadao

1992-06-01

To elucidate the clinical significance of MRI on central nervous system systemic lupus erythematosus (CNS-SLE), MRI and CT scans were performed in 35 patients with SLE, of 18 patients who had CNS manifestations at the time of MRI examinations. The investigations were also carried out in 17 patients without CNS-SLE. The rate of detection of abnormal findings on MRI in patients with CNS-SLE was 77.2% (14/18), which was high, as compared with the rate of those on CT scans (50%: 9/18). Especially, all of 4 patients with seizure and 3 patients with encephalopathy showed abnormal MRI findings, although respectively 50% and 33.3% of them had abnormal CT scan findings. MRI findings were classified into 4 groups below: (1) Large focal are as increased signal intensity at T2 weighted image. These were observed in 2 of 4 patients with seizure and 1 of 3 patients with encephalopathy, which were completely resolved after treatment. (2) Patchy subcortical foci of increased signal intensity at T2 weighted image. These were observed in 11 of 18 CNS-SLE and 7 of 17 without CNS-SLE, which were not detected by CT scan. (3) All of six patients with cerebral infarctions showed high signal intensity areas at T2 weighted image and low signal intensity areas at T1 weighted image. (4) Normal findings were observed in 4 of 18 CNS-SLE (22.2%). We concluded that MRI is useful for the evaluation of CNS-SLE and provides more information than CT scan. (author).

Systemic Lupus Erythematosus: Definitions, Contexts, Conflicts, Enigmas

Science.gov (United States)

Rekvig, Ole Petter

2018-01-01

Systemic lupus erythematosus (SLE) is an inadequately defined syndrome. Etiology and pathogenesis remain largely unknown. SLE is on the other hand a seminal syndrome that has challenged immunologists, biologists, genetics, and clinicians to solve its nature. The syndrome is characterized by multiple, etiologically unlinked manifestations. Unexpectedly, they seem to occur in different stochastically linked clusters, although single gene defects may promote a smaller spectrum of symptoms/criteria typical for SLE. There is no known inner coherence of parameters (criteria) making up the disease. These parameters are, nevertheless, implemented in The American College of Rheumatology (ACR) and The Systemic Lupus Collaborating Clinics (SLICC) criteria to classify SLE. Still, SLE is an abstraction since the ACR or SLICC criteria allow us to define hundreds of different clinical SLE phenotypes. This is a major point of the present discussion and uses “The anti-dsDNA antibody” as an example related to the problematic search for biomarkers for SLE. The following discussion will show how problematic this is: the disease is defined through non-coherent classification criteria, its complexity is recognized and accepted, its pathogenesis is plural and poorly understood. Therapy is focused on dominant symptoms or organ manifestations, and not on the syndrome itself. From basic scientific evidences, we can add substantial amount of data that are not sufficiently considered in clinical medicine, which may change the paradigms linked to what “The Anti-DNA antibody” is—and is not—in context of the imperfectly defined syndrome SLE. PMID:29545801

Joint ultrasound baseline abnormalities predict a specific long-term clinical outcome in systemic lupus erythematosus patients.

Science.gov (United States)

Corzo, P; Salman-Monte, T C; Torrente-Segarra, V; Polino, L; Mojal, S; Carbonell-Abelló, J

2017-06-01

Objective To describe long-term clinical and serological outcome in all systemic lupus erythematosus (SLE) domains in SLE patients with hand arthralgia (HA) and joint ultrasound (JUS) inflammatory abnormalities, and to compare them with asymptomatic SLE patients with normal JUS. Methods SLE patients with HA who presented JUS inflammatory abnormalities ('cases') and SLE patients without HA who did not exhibit JUS abnormalities at baseline ('controls') were included. All SLE clinical and serological domain involvement data were collected. End follow-up clinical activity and damage scores (systemic lupus erythematosus disease activity index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR)) were recorded. JUS inflammatory abnormalities were defined based on the Proceedings of the Seventh International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials (OMERACT-7) definitions. Statistical analyses were carried out to compare 'cases' and 'controls'. Results A total of 35 patients were recruited. The 'cases', n = 18/35, had a higher incidence of musculoskeletal involvement (arthralgia and/or arthritis) through the follow-up period (38.9% vs 0%, p = 0.008) and received more hydroxychloroquine (61.1% vs 25.0%, p = 0.034) and methotrexate (27.8% vs 0%, p = 0.046) compared to 'controls', n = 17/35. Other comparisons did not reveal any statistical differences. Conclusions We found SLE patients with arthralgia who presented JUS inflammatory abnormalities received more hydroxychloroquine and methotrexate, mainly due to persistent musculoskeletal involvement over time. JUS appears to be a useful technique for predicting worse musculoskeletal outcome in SLE patients.

Abnormal findings of magnetic resonance imaging (MRI) in patients with systemic lupus erythematosus involving the brain

International Nuclear Information System (INIS)

Ishikawa, Akira; Okada, Jun; Kondo, Hirobumi; Kashiwazaki, Sadao.

1992-01-01

To elucidate the clinical significance of MRI on central nervous system systemic lupus erythematosus (CNS-SLE), MRI and CT scans were performed in 35 patients with SLE, of 18 patients who had CNS manifestations at the time of MRI examinations. The investigations were also carried out in 17 patients without CNS-SLE. The rate of detection of abnormal findings on MRI in patients with CNS-SLE was 77.2% (14/18), which was high, as compared with the rate of those on CT scans (50%: 9/18). Especially, all of 4 patients with seizure and 3 patients with encephalopathy showed abnormal MRI findings, although respectively 50% and 33.3% of them had abnormal CT scan findings. MRI findings were classified into 4 groups below: 1) Large focal are as increased signal intensity at T2 weighted image. These were observed in 2 of 4 patients with seizure and 1 of 3 patients with encephalopathy, which were completely resolved after treatment. 2) Patchy subcortical foci of increased signal intensity at T2 weighted image. These were observed in 11 of 18 CNS-SLE and 7 of 17 without CNS-SLE, which were not detected by CT scan. 3) All of six patients with cerebral infarctions showed high signal intensity areas at T2 weighted image and low signal intensity areas at T1 weighted image. 4) Normal findings were observed in 4 of 18 CNS-SLE (22.2%). We concluded that MRI is useful for the evaluation of CNS-SLE and provides more information than CT scan. (author)

Using simulation pedagogy to teach clinical education skills: A randomized trial.

Science.gov (United States)

Holdsworth, Clare; Skinner, Elizabeth H; Delany, Clare M

2016-05-01

Supervision of students is a key role of senior physiotherapy clinicians in teaching hospitals. The objective of this study was to test the effect of simulated learning environments (SLE) on educators' self-efficacy in student supervision skills. A pilot prospective randomized controlled trial with concealed allocation was conducted. Clinical educators were randomized to intervention (SLE) or control groups. SLE participants completed two 3-hour workshops, which included simulated clinical teaching scenarios, and facilitated debrief. Standard Education (StEd) participants completed two online learning modules. Change in educator clinical supervision self-efficacy (SE) and student perceptions of supervisor skill were calculated. Between-group comparisons of SE change scores were analyzed with independent t-tests to account for potential baseline differences in education experience. Eighteen educators (n = 18) were recruited (SLE [n = 10], StEd [n = 8]). Significant improvements in SE change scores were seen in SLE participants compared to control participants in three domains of self-efficacy: (1) talking to students about supervision and learning styles (p = 0.01); (2) adapting teaching styles for students' individual needs (p = 0.02); and (3) identifying strategies for future practice while supervising students (p = 0.02). This is the first study investigating SLE for teaching skills of clinical education. SLE improved educators' self-efficacy in three domains of clinical education. Sample size limited the interpretation of student ratings of educator supervision skills. Future studies using SLE would benefit from future large multicenter trials evaluating its effect on educators' teaching skills, student learning outcomes, and subsequent effects on patient care and health outcomes.

Do clinical manifestations of Systemic Lupus Erythematosus in Pakistan correlate with rest of Asia?

Science.gov (United States)

Rabbani, Malik Anas; Siddiqui, Bilal Karim; Tahir, Muhammad Hammad; Ahmad, Bushra; Shamim, A; Majid, Shahid; Ali, Syed Sohail; Shah, Syed Mansoor Ahmed; Ahmad, Aasim

2006-05-01

Systemic Lupus Erythematosus (SLE) is known to be different among people with different racial, geographical and socio-economic back grounds. Asia has diverse ethnic groups broadly, Orientals in the East and Southeast Asia, Indians in South Asia and Arabs in the Middle East. These regions differ significantly from the Caucasians with reference to SLE. The purpose of this study was, therefore, to delineate the clinical pattern and disease course in Pakistani patients with SLE and compare it with Asian data. Patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association admitted at the Aga Khan University Hospital between 1986 and 2001 were studied by means of a retrospective review of their records. The results were compared with various studies in different regions of Asia. Demographically, it was seen that SLE is a disease predominantly of females in their third decade, which is generally consistent with Asian data. There was less cutaneous manifestations, arthritis, serositis, haematological and renal involvement compared to various regions in Asia. The neurological manifestations of SLE, however, place Pakistani patients in the middle of a spectrum between South Asians and other Asian races. This study has shown that the clinical characteristics of SLE patients in our country may be different to those of other Asian races. Although our population is similar to South Asians, but clinical manifestations of our SLE patients are considerably different, suggesting some unknown etiology. Further studies are required to confirm the above results and to find statistically sounder associations.

Physical Complexity and Cognitive Evolution

Science.gov (United States)

Jedlicka, Peter

Our intuition tells us that there is a general trend in the evolution of nature, a trend towards greater complexity. However, there are several definitions of complexity and hence it is difficult to argue for or against the validity of this intuition. Christoph Adami has recently introduced a novel measure called physical complexity that assigns low complexity to both ordered and random systems and high complexity to those in between. Physical complexity measures the amount of information that an organism stores in its genome about the environment in which it evolves. The theory of physical complexity predicts that evolution increases the amount of `knowledge' an organism accumulates about its niche. It might be fruitful to generalize Adami's concept of complexity to the entire evolution (including the evolution of man). Physical complexity fits nicely into the philosophical framework of cognitive biology which considers biological evolution as a progressing process of accumulation of knowledge (as a gradual increase of epistemic complexity). According to this paradigm, evolution is a cognitive `ratchet' that pushes the organisms unidirectionally towards higher complexity. Dynamic environment continually creates problems to be solved. To survive in the environment means to solve the problem, and the solution is an embodied knowledge. Cognitive biology (as well as the theory of physical complexity) uses the concepts of information and entropy and views the evolution from both the information-theoretical and thermodynamical perspective. Concerning humans as conscious beings, it seems necessary to postulate an emergence of a new kind of knowledge - a self-aware and self-referential knowledge. Appearence of selfreflection in evolution indicates that the human brain reached a new qualitative level in the epistemic complexity.

A comparison of biological and cultural evolution.

Science.gov (United States)

Portin, Petter

2015-03-01

This review begins with a definition of biological evolution and a description of its general principles. This is followed by a presentation of the biological basis of culture, specifically the concept of social selection. Further, conditions for cultural evolution are proposed, including a suggestion for language being the cultural replicator corresponding to the concept of the gene in biological evolution. Principles of cultural evolution are put forward and compared to the principles of biological evolution. Special emphasis is laid on the principle of selection in cultural evolution, including presentation of the concept of cultural fitness. The importance of language as a necessary condition for cultural evolution is stressed. Subsequently, prime differences between biological and cultural evolution are presented, followed by a discussion on interaction of our genome and our culture. The review aims at contributing to the present discussion concerning the modern development of the general theory of evolution, for example by giving a tentative formulation of the necessary and sufficient conditions for cultural evolution, and proposing that human creativity and mind reading or theory of mind are motors specific for it. The paper ends with the notion of the still ongoing coevolution of genes and culture.

Primary Adrenal Insufficiency (Addison's Disease) Associated with Systemic Lupus Erythematosus: A Rare Occurrence.

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Godswill, Okwuonu Chimezie; Odigie, Ojeh-Oziegbe

2014-10-01

Coexistence of Addison's disease and systemic lupus erythematosus (SLE) is a rare occurrence with only few reported cases in the literature. We describe a 29-year-old woman who presented to us with clinical features of acute Addisonian crisis and SLE. Laboratory investigations were confirmatory of Addison's disease in a background of SLE. The patient made remarkable improvement on administration of steroids as replacement therapy for adrenal insufficiency and treatment of SLE. Clinicians need to have a high-index of suspicion of this possible coexistence in order to avoid the associated deleterious hemodynamic and metabolic consequences.

Systemic lupus erythematosus : abdominal radiologic findings

Energy Technology Data Exchange (ETDEWEB)

Oh, Jae Cheon; Cho, On Koo; Lee, Yong Joo; Bae, Jae Ik; Kim, Yong Soo; Rhim, Hyun Chul; Ko, Byung Hee [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)

1999-06-01

Systemic lupus erythematosus(SLE) is a systemic disease of unknown etiology. Its main pathology is vasculitis and serositis, due to deposition of the immune complex or antibodies. Most findings are nonspecific ; abdominal manifestations include enteritis, hepatomegaly, pancreatic enlargement, serositis, lymphadenopathy, splenomegaly, nephritis, interstitial cystitis, and thrombophlebitis. We described radiologic findings of various organ involvement of SLE; digestive system, serosa, reticuloendothelial system, urinary system, and venous system. Diagnosis of SLE was done according to the criteria of American Rheumatism Association. Understanding of the variable imaging findings in SLE may be helpful for the early detection of abdominal involvement and complications.

The selective value of computed tomography of the brain in Cerebritis due to systemic lupus erythematosus

International Nuclear Information System (INIS)

Gaylis, N.B.; Altman, R.D.; Ostrov, S.; Quencer, R.

1982-01-01

Systemic lupus erythematosus (SLE) and steroid effects on the brain were measured by computed tomography (CT). Of 14 patients with SLE cerebritis, 10 (71%) had marked cortical atrophy and 4 (29%) minimal atrophy. None were normal by CT. Controls included 22 patients with SLE without cerebritis receiving cortiocosteroids; this group had normal CT scans in 16 (73%) and minimal cortical atrophy in the remaining 6 (27%). Follow-up CT on 5 patients with cerebritis was unchanged. CT of the brain is a minimally invasive technique for documenting SLE cerebritis. CT may also help differentiate cerebritis from the neuropsychiatric side effects of corticosteroids

A simple model for binary star evolution

International Nuclear Information System (INIS)

Whyte, C.A.; Eggleton, P.P.

1985-01-01

A simple model for calculating the evolution of binary stars is presented. Detailed stellar evolution calculations of stars undergoing mass and energy transfer at various rates are reported and used to identify the dominant physical processes which determine the type of evolution. These detailed calculations are used to calibrate the simple model and a comparison of calculations using the detailed stellar evolution equations and the simple model is made. Results of the evolution of a few binary systems are reported and compared with previously published calculations using normal stellar evolution programs. (author)

Landscape Evolution Modelling-LAPSUS

Energy Technology Data Exchange (ETDEWEB)

Baartman, J. E. M.; Temme, A. J. A. M.; Schoorl, J. M.; Claessens, L.; Viveen, W.; Gorp, W. van; Veldkamp, A.

2009-07-01

Landscape evolution modelling can make the consequences of landscape evolution hypotheses explicit and theoretically allows for their falsification and improvement. ideally, landscape evolution models (LEMs) combine the results of all relevant landscape forming processes into an ever-adapting digital landscape (e.g. DEM). These processes may act on different spatial and temporal scales. LAPSUS is such a LEM. Processes that have in different studies been included in LAPSUS are water erosion and deposition, landslide activity, creep, solidification, weathering, tectonics and tillage. Process descriptions are as simple and generic as possible, ensuring wide applicability. (Author) 25 refs.

Landscape Evolution Modelling-LAPSUS

International Nuclear Information System (INIS)

Baartman, J. E. M.; Temme, A. J. A. M.; Schoorl, J. M.; Claessens, L.; Viveen, W.; Gorp, W. van; Veldkamp, A.

2009-01-01

Landscape evolution modelling can make the consequences of landscape evolution hypotheses explicit and theoretically allows for their falsification and improvement. ideally, landscape evolution models (LEMs) combine the results of all relevant landscape forming processes into an ever-adapting digital landscape (e.g. DEM). These processes may act on different spatial and temporal scales. LAPSUS is such a LEM. Processes that have in different studies been included in LAPSUS are water erosion and deposition, landslide activity, creep, solidification, weathering, tectonics and tillage. Process descriptions are as simple and generic as possible, ensuring wide applicability. (Author) 25 refs.

Weathering and landscape evolution

Science.gov (United States)

Turkington, Alice V.; Phillips, Jonathan D.; Campbell, Sean W.

2005-04-01

In recognition of the fundamental control exerted by weathering on landscape evolution and topographic development, the 35th Binghamton Geomorphology Symposium was convened under the theme of Weathering and Landscape Evolution. The papers and posters presented at the conference imparted the state-of-the-art in weathering geomorphology, tackled the issue of scale linkage in geomorphic studies and offered a vehicle for interdisciplinary communication on research into weathering and landscape evolution. The papers included in this special issue are encapsulated here under the general themes of weathering mantles, weathering and relative dating, weathering and denudation, weathering processes and controls and the 'big picture'.

Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

Science.gov (United States)

Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia

2014-01-01

Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease. PMID:25147296

Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

Steve P. Crampton

2014-09-01

Full Text Available Systemic lupus erythematosus (SLE represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease.

Evolution algebras generated by Gibbs measures

International Nuclear Information System (INIS)

Rozikov, Utkir A.; Tian, Jianjun Paul

2009-03-01

In this article we study algebraic structures of function spaces defined by graphs and state spaces equipped with Gibbs measures by associating evolution algebras. We give a constructive description of associating evolution algebras to the function spaces (cell spaces) defined by graphs and state spaces and Gibbs measure μ. For finite graphs we find some evolution subalgebras and other useful properties of the algebras. We obtain a structure theorem for evolution algebras when graphs are finite and connected. We prove that for a fixed finite graph, the function spaces have a unique algebraic structure since all evolution algebras are isomorphic to each other for whichever Gibbs measures are assigned. When graphs are infinite graphs then our construction allows a natural introduction of thermodynamics in studying of several systems of biology, physics and mathematics by theory of evolution algebras. (author)

Universal pacemaker of genome evolution.

Science.gov (United States)

Snir, Sagi; Wolf, Yuri I; Koonin, Eugene V

2012-01-01

A fundamental observation of comparative genomics is that the distribution of evolution rates across the complete sets of orthologous genes in pairs of related genomes remains virtually unchanged throughout the evolution of life, from bacteria to mammals. The most straightforward explanation for the conservation of this distribution appears to be that the relative evolution rates of all genes remain nearly constant, or in other words, that evolutionary rates of different genes are strongly correlated within each evolving genome. This correlation could be explained by a model that we denoted Universal PaceMaker (UPM) of genome evolution. The UPM model posits that the rate of evolution changes synchronously across genome-wide sets of genes in all evolving lineages. Alternatively, however, the correlation between the evolutionary rates of genes could be a simple consequence of molecular clock (MC). We sought to differentiate between the MC and UPM models by fitting thousands of phylogenetic trees for bacterial and archaeal genes to supertrees that reflect the dominant trend of vertical descent in the evolution of archaea and bacteria and that were constrained according to the two models. The goodness of fit for the UPM model was better than the fit for the MC model, with overwhelming statistical significance, although similarly to the MC, the UPM is strongly overdispersed. Thus, the results of this analysis reveal a universal, genome-wide pacemaker of evolution that could have been in operation throughout the history of life.

Student Teachers' Approaches to Teaching Biological Evolution

Science.gov (United States)

Borgerding, Lisa A.; Klein, Vanessa A.; Ghosh, Rajlakshmi; Eibel, Albert

2015-01-01

Evolution is fundamental to biology and scientific literacy, but teaching high school evolution is often difficult. Evolution teachers face several challenges including limited content knowledge, personal conflicts with evolution, expectations of resistance, concerns about students' conflicts with religion, and curricular constraints. Evolution…

Association Between Stressful Life Events and Depression; Intersection of Race and Gender.

Science.gov (United States)

Assari, Shervin; Lankarani, Maryam Moghani

2016-06-01

Although stressful life events (SLEs) and depression are associated, we do not know if the intersection of race and gender modifies the magnitude of this link. Using a nationally representative sample of adults in the USA, we tested if the association between SLE and major depressive episode (MDE) depends on the intersection of race and gender. Data came from the National Survey of American Life (NSAL), 2003, a cross-sectional survey that enrolled 5899 adults including 5008 Blacks (African-Americans or Caribbean Blacks), and 891 Non-Hispanic Whites. Logistic regression was used for data analysis. Stressful life events (past 30 days) was the independent variable, 12-month MDE was the dependent variable, and age, educational level, marital status, employment, and region of country were controls. In the pooled sample, SLE was associated with MDE above and beyond all covariates, without the SLE × race interaction term being significant. Among men, the SLE × race interaction was significant, suggesting a stronger association between SLE and MDE among White men compared to Black men. Such interaction between SLE × race could not be found among women. The association between SLE and depression may be stronger for White men than Black men; however, this link does not differ between White and Black women. More research is needed to better understand the mechanism behind race by gender variation in the stress-depression link.

A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese.

Directory of Open Access Journals (Sweden)

Yukinori Okada

2012-01-01

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8% compared to the genome-wide SNPs (6.9%. In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1 gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10(-9, odds ratio = 1.21. The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05. As AFF1 transcripts were prominently expressed in CD4(+ and CD19(+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset.

Expression of BAFF and BR3 in patients with systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

J.H. Duan

2016-03-01

Full Text Available The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE. Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3 on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01. The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01. BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01. The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01. The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus.

Science.gov (United States)

Yuan, Hui; Feng, Jin-Bao; Pan, Hai-Feng; Qiu, Li-Xin; Li, Lian-Hong; Zhang, Ning; Ye, Dong-Qing

2010-06-01

STAT4 has been newly identified as a susceptibility gene for systemic lupus erythematosus (SLE) in recent reports. To more precisely estimate the association between STAT4 polymorphism and SLE risk, a meta-analysis was performed. Studies on the association of STAT4 rs7574865 or rs7601754 with SLE were fully considered and carefully selected using three electronic databases (PubMed, Embase, and Web of Science). A total of 17 comparisons from 8 relevant studies involving 7,381 patients and 11,431 controls were included to analyze the association between STAT4 rs7574865 and SLE risk. The pooled OR for the minor T allele of STAT4 rs7574865 was 1.65 (95% CI 1.56-1.75, P rs7574865 with SLE susceptibility was similar in populations of European or Asian origin, although significant differences in the minor T allele frequencies were observed in the two population controls. As for rs7601754, there were five comparisons from four relevant studies involving 2,498 patients and 4,825 controls in this meta-analysis. The pooled OR for the minor C allele of STAT4 rs7601754 was 0.67 (95% CI 0.59-0.75, P rs7574865 polymorphism as a susceptibility factor for SLE in populations of European and Asian origin. Our results also suggest that STAT4 rs7601754 polymorphism might be associated with SLE risk.

Boussinesq evolution equations

DEFF Research Database (Denmark)

Bredmose, Henrik; Schaffer, H.; Madsen, Per A.

2004-01-01

This paper deals with the possibility of using methods and ideas from time domain Boussinesq formulations in the corresponding frequency domain formulations. We term such frequency domain models "evolution equations". First, we demonstrate that the numerical efficiency of the deterministic...... Boussinesq evolution equations of Madsen and Sorensen [Madsen, P.A., Sorensen, O.R., 1993. Bound waves and triad interactions in shallow water. Ocean Eng. 20 359-388] can be improved by using Fast Fourier Transforms to evaluate the nonlinear terms. For a practical example of irregular waves propagating over...... a submerged bar, it is demonstrated that evolution equations utilising FFT can be solved around 100 times faster than the corresponding time domain model. Use of FFT provides an efficient bridge between the frequency domain and the time domain. We utilise this by adapting the surface roller model for wave...

Helicity evolution at small x

International Nuclear Information System (INIS)

Kovchegov, Yuri V.; Pitonyak, Daniel; Sievert, Matthew D.

2016-01-01

We construct small-x evolution equations which can be used to calculate quark and anti-quark helicity TMDs and PDFs, along with the g 1 structure function. These evolution equations resum powers of α s ln 2  (1/x) in the polarization-dependent evolution along with the powers of α s ln (1/x) in the unpolarized evolution which includes saturation effects. The equations are written in an operator form in terms of polarization-dependent Wilson line-like operators. While the equations do not close in general, they become closed and self-contained systems of non-linear equations in the large-N c and large-N c   N f limits. As a cross-check, in the ladder approximation, our equations map onto the same ladder limit of the infrared evolution equations for the g 1 structure function derived previously by Bartels, Ermolaev and Ryskin http://dx.doi.org/10.1007/s002880050285.

Formal Definitions of Unbounded Evolution and Innovation Reveal Universal Mechanisms for Open-Ended Evolution in Dynamical Systems.

Science.gov (United States)

Adams, Alyssa; Zenil, Hector; Davies, Paul C W; Walker, Sara Imari

2017-04-20

Open-ended evolution (OEE) is relevant to a variety of biological, artificial and technological systems, but has been challenging to reproduce in silico. Most theoretical efforts focus on key aspects of open-ended evolution as it appears in biology. We recast the problem as a more general one in dynamical systems theory, providing simple criteria for open-ended evolution based on two hallmark features: unbounded evolution and innovation. We define unbounded evolution as patterns that are non-repeating within the expected Poincare recurrence time of an isolated system, and innovation as trajectories not observed in isolated systems. As a case study, we implement novel variants of cellular automata (CA) where the update rules are allowed to vary with time in three alternative ways. Each is capable of generating conditions for open-ended evolution, but vary in their ability to do so. We find that state-dependent dynamics, regarded as a hallmark of life, statistically out-performs other candidate mechanisms, and is the only mechanism to produce open-ended evolution in a scalable manner, essential to the notion of ongoing evolution. This analysis suggests a new framework for unifying mechanisms for generating OEE with features distinctive to life and its artifacts, with broad applicability to biological and artificial systems.