factor of activated T-cell isoform expression and regulation in humanmyometrium
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Additional file 2: Figure S1. Schematic of Otolith Application. To measure the distance between radial glial fibres the Otolith Application was used. In each of the images assessed, three 1000 µm transect lines (red line) were drawn at... more
Additional file 2: Figure S1. Schematic of Otolith Application. To measure the distance between radial glial fibres the Otolith Application was used. In each of the images assessed, three 1000 µm transect lines (red line) were drawn at different points on the edge of each scan. The outer reference circle was formed at the endpoint of each transect line (blue arrow). The application identified the circuli or radial structures (µm). The number of circulii and the distances between each radial projection was calculated and this data was analysed. Scale bar = 30 µm.
Additional file 2: Figure S2. GFAP and Vimentin in late gestation. (A, C) GFAP and (B, D) Vimentin in the late gestation brain in (A, B) euploid age-matched (38+4 weeks PMA) and (C, D) DS (38+6 weeks PMA). DS case had Hypoxic-Ischemic... more
Additional file 2: Figure S2. GFAP and Vimentin in late gestation. (A, C) GFAP and (B, D) Vimentin in the late gestation brain in (A, B) euploid age-matched (38+4 weeks PMA) and (C, D) DS (38+6 weeks PMA). DS case had Hypoxic-Ischemic Encephalopathy, with evidence of reactive astrocytes (C). Scale bar indicate 100 µm.
doi: 10.3389/fphys.2014.00169 STIM and Orai isoform expression in pregnant human myometrium: a potential role in calcium signaling during pregnancy
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Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide... more
Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks ’ gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (,25 mm) by 24 weeks ’ and 38 women did not. Women who developed a short cervix had 2.71 times higher concentrations of CVF trappin2/ elafin from 14 weeks ’ versus those who did n...
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Purpose. Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency. The extent to which STK4 deficiency impairs immune signaling and host defenses is unclear. We... more
Purpose. Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency. The extent to which STK4 deficiency impairs immune signaling and host defenses is unclear. We assessed the functional consequences of a novel, homozygous nonsense STK4 mutation (NM_006282.2:c.871C>T, p.Arg291*) found in a pediatric patient by comparing the patient’s innate and adaptive cell-mediated and humoral immune responses with those of three heterozygous relatives and unrelated controls.Methods. The genetic etiology was identified by whole genome sequencing and confirmed by Sanger sequencing. STK4 gene and protein expression was measured by quantitative RT-PCR and immunoblotting, respectively. Cellular abnormalities were assessed by high-throughput RT-RCR, RNA-Seq, ELISA and polychromatic flow cytometry. Finally, antibody responses were delinated by ELISA and phage immunoprecipitation-sequencing.Results. The affected patient exhibi...
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Introduction Elafin, a natural antimicrobial peptide, is an important component of the innate immune system. It is hypothesised that elafin production in cervico-vaginal fluid (CVF) will be altered in women at risk of spontaneous preterm... more
Introduction Elafin, a natural antimicrobial peptide, is an important component of the innate immune system. It is hypothesised that elafin production in cervico-vaginal fluid (CVF) will be altered in women at risk of spontaneous preterm birth (sPTB) associated with inflammation/infection. Aim To determine the relationship between CVF elafin concentrations and cervical length in women at high risk of sPTB. Methods Elafin concentrations were measured in 437 CVF samples (taken two-weekly between 14-28 weeks') from 74 pregnant women (asymptomatic, high risk for sPTB). Controls women who did not develop a short cervix (n=38); cases: women who developed a short cervix <25mm, n=36) and were randomised to either cerclage or vaginal progesterone (400 mg/od). Elafin was measured by ELISA. Logged data were analysed using random-effects interval regression. Results Concentrations of elafin were higher in the CVF of the short cervix group, regardless of gestation and treatment (ratio 2.71, CI 1.94 to 3.79, p<0.0005). Elafin concentrations predicted cervical shortening from 14 weeks' (n=11, ROC area = 1.00, p=0.0082), and remained high when cervical shortening was first detected (ratio 3.03 CI 1.92-4.81, p<0.0005). Elafin concentrations were unaltered by cerclage or progesterone (ratio 1.28, CI: 0.88-1.87, p=0.196). Raised elafin concentrations <24 weeks' were associated with SPTB <37 weeks (ratio 1.79, CI: 1.05-3.05, p=0.034). Conclusion These data suggest that CVF elafin concentrations may be useful for the early prediction of sPTB prior to cervical shortening.
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Hypothesis / aims of study There is increasing evidence that different isoforms of the IGF-1 gene responding to mechanical stimuli are involved in smooth and skeletal muscle regeneration. Studies looking at average voided volumes in the... more
Hypothesis / aims of study There is increasing evidence that different isoforms of the IGF-1 gene responding to mechanical stimuli are involved in smooth and skeletal muscle regeneration. Studies looking at average voided volumes in the presence of urinary frequency in OAB patients have shown a significant statistical reduction in voided volume (mean 170 ml) when compared with healthy asymptomatic volunteers (1) . We hypothesize that in the absence of normal physiological bladder distension leading to insufficient mechanical stimuli, the IGF-1 gene related muscle repair mechanism will fail to activate preventing further regeneration of the detrusor muscle. Several studies to date have shown that during regeneration of adult muscle, the IGF-1 gene undergoes alternative splicing within the E domain generating two distinct isoforms in humans: IGF-1Ea and IGF-1Ec (also known as Mechano Growth Factor, MGF). Although both isoforms are directly involved in muscle regeneration, they also ha...
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Purpose Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency; however, the extent to which immune signaling and host defense are impaired is unclear. We... more
Purpose Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency; however, the extent to which immune signaling and host defense are impaired is unclear. We assessed the functional consequences of a novel, homozygous nonsense STK4 mutation (NM_006282.2:c.871C > T, p.Arg291*) identified in a pediatric patient by comparing his innate and adaptive cell-mediated and humoral immune responses with those of three heterozygous relatives and unrelated controls. Methods The genetic etiology was verified by whole genome and Sanger sequencing. STK4 gene and protein expression was measured by quantitative RT-PCR and immunoblotting, respectively. Cellular abnormalities were assessed by high-throughput RT-RCR, RNA-Seq, ELISA, and flow cytometry. Antibody responses were assessed by ELISA and phage immunoprecipitation-sequencing. Results The patient exhibited partial loss of STK4 expression and complete loss of STK4 fun...
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There is much interest in the role of innate immune system proteins (antimicrobial peptides) in the inflammatory process associated with spontaneous preterm birth (sPTB). After promising pilot work, we aimed to validate the association... more
There is much interest in the role of innate immune system proteins (antimicrobial peptides) in the inflammatory process associated with spontaneous preterm birth (sPTB). After promising pilot work, we aimed to validate the association between the antimicrobial peptides/proteins elafin and cathelicidin and sPTB. An observational cohort study of 405 women at high-risk, and 214 women at low-risk of sPTB. Protein concentrations of elafin and cathelicidin, and the enzyme human neutrophil elastase (HNE) were measured in over 1,000 cervicovaginal fluid (CVF) samples (10 to 24 weeks’ gestation). Adjusted CVF cathelicidin and HNE concentrations (but not elafin) were raised in high-risk women who developed cervical shortening and who delivered prematurely and were predictive of sPTB
Host defense peptides (HDPs) in the pregnant female reproductive tract provide protection against infection. The relationship between HDPs and infection/inflammation is poorly understood. Therefore, we investigated the regulation of HDPs... more
Host defense peptides (HDPs) in the pregnant female reproductive tract provide protection against infection. The relationship between HDPs and infection/inflammation is poorly understood. Therefore, we investigated the regulation of HDPs by 1α, 25-dihydroxyvitamin D3 (1,25-(OH)2) in the presence/absence of infectious/inflammatory agents. Endocervical epithelial cells (END1/E6E7, n = 6) were exposed to 1,25-(OH)2, calcipotriol, interleukin 1β (IL-1β), granulate-macrophage colony-stimulating factor (GM-GSF), and lipopolysaccharide (LPS). Elafin, human beta defensin (hBD2), cathelicidin, secretory leucocyte protease inhibitor, interleukin 8, 1,25-(OH)2 receptor, and toll-like receptor 4 (TLR4) expression was determined using quantitative polymerase chain reaction and/or enzyme-linked immunosorbent assay. Host defense peptide gene and protein expression was assessed in cervicovaginal cells/fluid, respectively, from first trimester pregnant women (n = 8-12). Interleukin 1β induced elafin...
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Research Interests: Nursing, Treatment Outcome, Adolescent, United Kingdom, Pregnancy, and 13 moreProgesterone, Humans, Female, Young Adult, Adult, Public health systems and services research, Clinical Protocols, Pessaries, Progestins, Pregnancy Outcome, Premature Birth, Pregnancy complications, and Paediatrics and reproductive medicine
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BackgroundThe involvement of natural antimicrobial peptides in infection-associated preterm birth is unknown. Our aim was to assess regulation by granulocyte-macrophage colony-stimulating factor, monocyte-chemotactic-protein-1 (GM-CSF and... more
BackgroundThe involvement of natural antimicrobial peptides in infection-associated preterm birth is unknown. Our aim was to assess regulation by granulocyte-macrophage colony-stimulating factor, monocyte-chemotactic-protein-1 (GM-CSF and MCP-1, interleukin-1 (IL) and lipopolysaccharide (LPS) in cultured human vaginal epithelial cells.MethodsVK2/E6E7 cells were treated with IL-1, MCP-1 and GM-CSF (20/100/200/500 pg/ml and 1 ng/ml) at 2 h, 4 h, 6 h and 24 h