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Dilip Kumar, Kia Joo Puan, Anand Kumar Andiappan, Bernett Lee, Geertje H A Westerlaken, Doreen Haase, Rossella Melchiotti, Zhuang Li, Nurhashikin Yusof, Josephine Lum, Geraldine Koh, Shihui Foo, Joe Yeong, Alexessander Couto Alves, Juha Pekkanen, Liang Dan Sun, Astrid Irwanto, Benjamin P Fairfax, Vivek Naranbhai, John E A Common, Mark Tang, Chin Keh Chuang, Marjo-Riitta Jarvelin, Julian C Knight, Xuejun Zhang, Fook Tim Chew, Shyam Prabhakar, Liu Jianjun, De Yun Wang, Francesca Zolezzi, Michael Poidinger, E Birgitte Lane, Linde Meyaard, Olaf Rötzschke
BACKGROUND: Expression quantitative trait loci (eQTL) databases represent a valuable resource to link disease-associated SNPs to specific candidate genes whose gene expression is significantly modulated by the SNP under investigation. We previously identified signal inhibitory receptor on leukocytes-1 (SIRL-1) as a powerful regulator of human innate immune cell function. While it is constitutively high expressed on neutrophils, on monocytes the SIRL-1 surface expression varies strongly between individuals...
February 20, 2017: Genome Medicine
Kristof Van Avondt, Maarten van der Linden, Paul H Naccache, David A Egan, Linde Meyaard
In response to microbial invasion, neutrophils release neutrophil extracellular traps (NETs) to trap and kill extracellular microbes. Alternatively, NET formation can result in tissue damage in inflammatory conditions and may perpetuate autoimmune disease. Intervention strategies that are aimed at modifying pathogenic NET formation should ideally preserve other neutrophil antimicrobial functions. We now show that signal inhibitory receptor on leukocytes-1 (SIRL-1) attenuates NET release by human neutrophils in response to distinct triggers, including opsonized Staphylococcus aureus and inflammatory danger signals...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Halina M Zyczynski, Michael E Albo, Howard B Goldman, Clifford Y Wai, Larry T Sirls, Linda Brubaker, Peggy Norton, R E Varner, Maude Carmel, Hae-Young Kim
OBJECTIVE: To assess change in overactive bladder (OAB) symptoms up to 5 years after surgery and to identify associated predictors of change from baseline. METHODS: This is a secondary analysis of data from three multicenter urinary incontinence (UI) surgical trials of women with stress-predominant mixed UI assigned to Burch colposuspension, autologous fascial sling, or retropubic or transobturator midurethral slings. The primary outcome was improvement of 70% or greater from baseline in symptoms measured by the Urinary Distress Inventory-Irritative subscale...
August 2015: Obstetrics and Gynecology
Luis Filipe Mucci, Rubens Pinto Cardoso Júnior, Marcia Bicudo de Paula, Sirle Abdo Salloum Scandar, Márcio Lunardeli Pacchioni, Aristides Fernandes, Cleide Aschenbrenner Consales
BACKGROUND: The reintroduction of sylvatic yellow fever in the state of São Paulo after about six decades was confirmed in the Northwestern region in 2000, where in 2008 there also occurred an important epizootic. The purpose of this study was to investigate the feeding habits of culicids potentially involved in the sylvatic transmission of the virus in this region. METHODS: Specimens were collected in 24 forested localities at ground level with hand nets and mouth aspirators...
2015: Journal of Venomous Animals and Toxins Including Tropical Diseases
Jamie M Bartley, Larry T Sirls, Kim A Killinger, Judith A Boura
OBJECTIVES: To explore the need for secondary surgical procedures after transvaginal prolapse repair with mesh. METHODS: Women that had prolapse repair (Prolift(®) or Elevate(®)) were reviewed for reoperation and clinical/demographic data such as prior prolapse repair, prolapse grade, operative details, length of stay (LOS) and time to reoperation. Pearson's Chi-square, Fisher's exact tests and Wilcoxon rank tests were used. RESULTS: 77/335 women (23%) had 100 additional procedures...
April 2015: International Urology and Nephrology
Philippe E Zimmern, E Ann Gormley, Anne M Stoddard, Emily S Lukacz, Larry Sirls, Linda Brubaker, Peggy Norton, Sallie S Oliphant, Tracey Wilson
AIMS: To examine treatment options selected for recurrent stress urinary incontinence (rSUI) in follow-up after Burch, autologous fascial and synthetic midurethral sling (MUS) procedures. METHODS: We performed a secondary analysis of the SISTER and ToMUS trials of participants who underwent primary stress urinary incontinence (SUI) treatment (without prior SUI surgery or concomitant procedures). Using Kaplan-Meier analysis, retreatment-free survival rates by initial surgical procedure were compared...
March 2016: Neurourology and Urodynamics
Heejo Moon, Woo Sirl Lee, Misook Oh, Huisun Lee, Ji Hoon Lee, Wonpil Im, Hyun-Suk Lim
α-Helices play a critical role in mediating many protein-protein interactions (PPIs) as recognition motifs. Therefore, there is a considerable interest in developing small molecules that can mimic helical peptide segments to modulate α-helix-mediated PPIs. Due to the relatively low aqueous solubility and synthetic difficulty of most current α-helix mimetic small molecules, one important goal in this area is to develop small molecules with favorable physicochemical properties and ease of synthesis. Here we designed phenyl-piperazine-triazine-based α-helix mimetics that possess improved water solubility and excellent synthetic accessibility...
December 8, 2014: ACS Combinatorial Science
Peggy A Norton, Charles W Nager, Linda Brubaker, Gary E Lemack, Larry T Sirls, Robert Holley, Toby C Chai, Stephen R Kraus, Halina Zyczynski, Bridget Smith, Anne Stoddard
AIMS: Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress urinary incontinence (SUI), despite insufficient evidence that it impacts treatment plans or outcomes in patients with uncomplicated SUI. This analysis aimed to calculate the cost incurred when UDS was performed as a supplement to a basic office evaluation and to extrapolate the potential savings of not doing UDS in this patient population on a national basis. METHODS: This is a secondary analysis from the Value of Urodynamic Evaluation (ValUE) trial, a multicenter non-inferiority randomized trial to determine whether a basic office evaluation (OE) is non-inferior in terms of SUI surgery outcomes to office evaluation with addition of urodynamic studies (UDS)...
January 2016: Neurourology and Urodynamics
Kimberly Kenton, Anne M Stoddard, Halina Zyczynski, Michael Albo, Leslie Rickey, Peggy Norton, Clifford Wai, Stephen R Kraus, Larry T Sirls, John W Kusek, Heather J Litman, Robert P Chang, Holly E Richter
PURPOSE: Few studies have characterized longer-term outcomes after retropubic and transobturator mid urethral slings. MATERIALS AND METHODS: Women completing 2-year participation in a randomized equivalence trial who had not undergone surgical re-treatment for stress urinary incontinence were invited to participate in a 5-year observational cohort. The primary outcome, treatment success, was defined as no re-treatment or self-reported stress incontinence symptoms...
January 2015: Journal of Urology
Peggy Norton, Linda Brubaker, Charles W Nager, Gary E Lemack, Halina M Zyczynski, Larry Sirls, Leslie Rickey, Anne Stoddard, R Edward Varner
OBJECTIVE: The aim of our study was to observe pelvic organ prolapse (POP) over time, treated and untreated, in a group of highly characterized women being followed up subjectively and objectively over 5-7 years following continence surgery. STUDY DESIGN: We measured baseline prolapse symptoms and anatomic prolapse in subjects enrolled in the trial of midurethral sling (TOMUS) and E-TOMUS, and measured these same parameters annually for 5-7 years after the index surgery...
November 2014: American Journal of Obstetrics and Gynecology
Misook Oh, Ji Hoon Lee, Wei Wang, Hui Sun Lee, Woo Sirl Lee, Christopher Burlak, Wonpil Im, Quyen Q Hoang, Hyun-Suk Lim
Pharmacological chaperones are small molecules that bind to proteins and stabilize them against thermal denaturation or proteolytic degradation, as well as assist or prevent certain protein-protein assemblies. These activities are being exploited for the development of treatments for diseases caused by protein instability and/or aberrant protein-protein interactions, such as those found in certain forms of cancers and neurodegenerative diseases. However, designing or discovering pharmacological chaperones for specific targets is challenging because of the relatively featureless protein target surfaces, the lack of suitable chemical libraries, and the shortage of efficient high-throughput screening methods...
July 29, 2014: Proceedings of the National Academy of Sciences of the United States of America
Kristof Van Avondt, Ruth Fritsch-Stork, Ronald H W M Derksen, Linde Meyaard
Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of systemic Lupus erythematosus (SLE), since netting neutrophils release potentially immunogenic autoantigens including histones, LL37, human neutrophil peptide (HNP), and self-DNA. In turn, these NETs activate plasmacytoid dendritic cells resulting in aggravation of inflammation and disease. How suppression of NET formation can be targeted for treatment has not been reported yet. Signal Inhibitory Receptor on Leukocytes-1 (SIRL-1) is a surface molecule exclusively expressed on phagocytes...
2013: PloS One
Tessa A M Steevels, Kristof van Avondt, Geertje H A Westerlaken, Femke Stalpers, Jona Walk, Louis Bont, Paul J Coffer, Linde Meyaard
ROS production is an important effector mechanism mediating intracellular killing of microbes by phagocytes. Inappropriate or untimely ROS production can lead to tissue damage, thus tight regulation is essential. We recently characterized signal inhibitory receptor on leukocytes-1 (SIRL-1) as an inhibitory receptor expressed by human phagocytes. Here, we demonstrate that ligation of SIRL-1 dampens Fc receptor-induced ROS production in primary human phagocytes. In accordance, SIRL-1 engagement on these cells impairs the microbicidal activity of neutrophils, without affecting phagocytosis...
May 2013: European Journal of Immunology
J Walk, G H A Westerlaken, N O van Uden, M E Belderbos, L Meyaard, L J Bont
Neonates are born with quantitative and qualitative defects in both adaptive and innate immune responses. The immune system is regulated by several mechanisms, including the signalling of inhibitory receptors. Increased expression of inhibitory receptors may result in a higher threshold for activation and suppressed function of neonatal cells. The aim of this study was to determine whether the expression of seven inhibitory receptors is increased on neonatal immune cells compared to adult immune cells. In a healthy birth cohort, we examined the expression of seven inhibitory immune receptors on neonatal neutrophils, monocytes, natural killer (NK) cells, CD4(+) and CD8(+)T cells...
August 2012: Clinical and Experimental Immunology
Tessa A M Steevels, Robert Jan Lebbink, Geertje H A Westerlaken, Paul J Coffer, Linde Meyaard
Myeloid cells play a crucial role in controlling infection. Activation of these cells needs to be tightly regulated, because their potent effector functions can damage host tissue. Inhibitory receptors expressed by immune cells play an important role in restricting immune cell activation. In this study, we have characterized a hitherto unidentified ITIM-bearing receptor that is highly expressed on human neutrophils and monocytes: signal inhibitory receptor on leukocytes-1 (SIRL-1). The chromosomal location of SIRL-1 is adjacent to the human leukocyte receptor complex on chromosome 19q13...
May 1, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
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