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https://www.readbyqxmd.com/read/28924228/an-expanded-role-for-heterozygous-mutations-of-abcb4-abcb11-atp8b1-abcc2-and-tjp2-in-intrahepatic-cholestasis-of-pregnancy
#1
Peter H Dixon, Melissa Sambrotta, Jennifer Chambers, Pamela Taylor-Harris, Argyro Syngelaki, Kypros Nicolaides, A S Knisely, Richard J Thompson, Catherine Williamson
Intrahepatic cholestasis of pregnancy (ICP) affects 1/140 UK pregnancies; with pruritus, hepatic impairment and elevated serum bile acids. Severe disease is complicated by spontaneous preterm delivery and stillbirth. Previous studies have reported mutations in hepatocellular transporters (ABCB4, ABCB11). High throughput sequencing in 147 patients was performed in the transporters ABCB4, ABCB11, ATP8B1, ABCC2 and tight junction protein 2 (TJP2). Twenty-six potentially damaging variants were identified with the following predicted protein changes: Twelve ABCB4 mutations - Arg47Gln, Met113Val, Glu161Gly, Thr175Ala, Glu528Glyfs*6, Arg590Gln, Ala601Ser, Glu884Ter, Gly722Ala, Tyr775Met (x2), Trp854Ter...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28888591/aspre-trial-influence-of-compliance-on-beneficial-effect-of-aspirin-in-prevention-of-preterm-preeclampsia
#2
David Wright, Liona C Poon, Daniel L Rolnik, Argyro Syngelaki, Juan Luis Delgado, Denisa Vojtassakova, Mercedes de Alvarado, Evgenia Kapeti, Anoop Rehal, Andrea Pazos, Ilma Floriana Carbone, Vivien Dutemeyer, Walter Plasencia, Nikos Papantoniou, Kypros H Nicolaides
OBJECTIVE: To examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial. STUDY DESIGN: This was a secondary analysis of data from the ASPRE trial. In this multicenter-study women with singleton pregnancies had screening by means of an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine-artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor) at 11-13 weeks' gestation...
September 6, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28884947/confirmation-of-an-arid2-defect-in-swi-snf-related-intellectual-disability
#3
Ruben Van Paemel, Pauline De Bruyne, Saskia van der Straaten, Marleen D'hondt, Urlien Fränkel, Annelies Dheedene, Björn Menten, Bert Callewaert
We present a 4-year-old girl with delayed neuromotor development, short stature of prenatal onset, and specific behavioral and craniofacial features harboring an intragenic deletion in the ARID2 gene. The phenotype confirmed the major features of the recently described ARID2-related intellectual disability syndrome. However, our patient showed overlapping features with Nicolaides-Baraitser syndrome and Coffin-Siris syndrome, providing further arguments to reclassify these disorders as "SWI/SNF-related intellectual disability syndromes...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28881712/tumor-antigen-ca125-suppresses-antibody-dependent-cellular-cytotoxicity-adcc-via-direct-antibody-binding-and-suppressed-fc-%C3%AE-receptor-engagement
#4
James Bradford Kline, Rina P Kennedy, Earl Albone, Qimin Chao, Shawn Fernando, Jennifer M McDonough, Katherine Rybinski, Wenquan Wang, Elizabeth B Somers, Charles Schweizer, Luigi Grasso, Nicholas C Nicolaides
Cancers employ a number of mechanisms to evade host immune responses. Here we report the effects of tumor-shed antigen CA125/MUC16 on suppressing IgG1-mediated antibody-dependent cellular cytotoxicity (ADCC). This evidence stems from prespecified subgroup analysis of a Phase 3 clinical trial testing farletuzumab, a monoclonal antibody to folate receptor alpha, plus standard-of-care carboplatin-taxane chemotherapy in patients with recurrent platinum-sensitive ovarian cancer. Patients with low serum CA125 levels treated with farletuzumab demonstrated improvements in progression free survival (HR 0...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28833651/major-cardiac-defects-and-placental-dysfunction-at-11-13-weeks-gestation
#5
Ilaria Fantasia, Dila Kasapoglu, Taner Kasapoglu, Argyro Syngelaki, Ranjit Akolekar, Kypros H Nicolaides
OBJECTIVES: To investigate the relationship between fetal major cardiac defects and markers of placental perfusion and function. METHODS: This was a prospective screening study in singleton pregnancies at 11-13 weeks' gestation. Uterine artery pulsatility index (UTPI), serum pregnancy associated plasma protein-A (PAPP-A) and placental growth factor (PLGF) were measured and the values were converted into multiples of the normal median (MoM). Median MoM values in fetuses with isolated major cardiac defects were compared to those in fetuses without major defects...
August 18, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28796394/maternal-haemodynamics-in-normal-pregnancies-and-in-pregnancies-affected-by-pre-eclampsia
#6
Daniel Stott, Obianuju Nzelu, Kypros H Nicolaides, Nikos A Kametas
OBJECTIVES: To determine if in a high risk group in the first half of pregnancy, women who developed pre-eclampsia (PE) with fetal growth restriction (PE-FGR) demonstrate distinct haemodynamics compared to those with PE in the absence of FGR (PE-only). METHODS: Cardiac output (CO), peripheral vascular resistance (PVR) and mean arterial pressure (MAP) were measured at the first hospital visit at 9-24 weeks' gestation in 69 women who had chronic hypertension and 67 who had a hypertensive disorder in a previous pregnancy...
August 10, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28792107/intrafetal-laser-for-embryo-reduction-from-dichorionic-triplets-to-dichorionic-twins
#7
Petya Chaveeva, Gergana Peeva, Savino Gil Pugliese, Atanas Shterev, Kypros H Nicolaides
OBJECTIVE: To report the outcome of dichorionic (DC) triplet pregnancies reduced to DC twins by laser ablation of the pelvic vessels of one of the monochorionic twins. METHODS: Intrafetal laser embryo reduction (ER) from DC triplet to DC twins was carried out in 61 pregnancies at 11(+0) - 14(+3) weeks' gestation. Pregnancy outcome was examined and compared to previous studies in DC triplets managed expectantly or by ER to twins or singleton with fetal intracardiac injection of potassium chloride (KCl)...
August 9, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28783690/cross-talk-between-inkt-cells-and-monocytes-triggers-an-atheroprotective-immune-response-in-sle-patients-with-asymptomatic-plaque
#8
Edward Smith, Sara Croca, Kirsty E Waddington, Reecha Sofat, Maura Griffin, Andrew Nicolaides, David A Isenberg, Ines Pineda Torra, Anisur Rahman, Elizabeth C Jury
Accelerated atherosclerosis is a complication of the autoimmune rheumatic disease systemic lupus erythematosus (SLE). We questioned the role played by invariant natural killer T (iNKT) cells in this process because they not only are defective in autoimmunity but also promote atherosclerosis in response to CD1d-mediated lipid antigen presentation. iNKT cells from SLE patients with asymptomatic plaque (SLE-P) had increased proliferation and interleukin-4 production compared with those from SLE patients with no plaque...
December 2, 2016: Science Immunology
https://www.readbyqxmd.com/read/28782231/re-chronic-hypertension-and-adverse-pregnancy-outcome-a-cohort-study-a-m-panaitescu-a-syngelaki-n-prodan-r-akolekar-and-k-h-nicolaides-ultrasound-obstet-gynecol-2017-50-228-235
#9
https://www.readbyqxmd.com/read/28775968/the-role-of-s-palmitoylation-of-the-human-glucocorticoid-receptor-hgr-in-mediating-the-nongenomic-glucocorticoid-actions
#10
Nicolas C Nicolaides, Tomoshige Kino, Michael L Roberts, Eleni Katsantoni, Amalia Sertedaki, Paraskevi Moutsatsou, Anna-Maria G Psarra, George P Chrousos, Evangelia Charmandari
BACKGROUND: Many rapid nongenomic glucocorticoid actions are mediated by membrane-bound glucocorticoid receptors (GRs). S-palmitoylation is a lipid post-translational modification that mediates the membrane localization of some steroid receptors. A highly homologous amino acid sequence (663YLCM KTLLL671) is present in the ligand-binding domain of hGRα, suggesting that hGRα might also undergo S-palmitoylation. AIM: To investigate the role of the motif 663YLCMKTLLL671 in membrane localization of the hGRα and in mediating rapid nongenomic glucocorticoid signaling...
2017: Journal of Molecular Biochemistry
https://www.readbyqxmd.com/read/28742501/novel-insights-into-the-molecular-mechanisms-underlying-generalized-glucocorticoid-resistance-and-hypersensitivity-syndromes
#11
REVIEW
Nicolas C Nicolaides, Evangelia Charmandari
Glucocorticoids play a fundamental role in many physiologic functions and contribute substantially to the achievement of homeostasis. These pleiotropic glucocorticoid actions are mediated by a ubiquitously expressed transcription factor, the human glucocorticoid receptor (hGR), which may influence the transcription rate of numerous target genes, interact with other transcription factors, trigger the activation of several kinase pathways or modulate mitochondrial DNA expression. Any genetic defects in the NR3C1gene that encodes the hGR may cause Primary Generalized Glucocorticoid Resistance or Hypersensitivity Syndromes, two rare allostatic endocrinologic conditions characterized by partial impaired tissue sensitivity to glucocorticoids...
April 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28741785/aspre-trial-performance-of-screening-for-preterm-pre-eclampsia
#12
Daniel L Rolnik, David Wright, Liona C Poon, Argyro Syngelaki, Neil O'Gorman, Catalina de Paco Matallana, Ranjit Akolekar, Simona Cicero, Deepa Janga, Mandeep Singh, Francisca S Molina, Nicola Persico, Jacques C Jani, Walter Plasencia, George Papaioannou, Kinneret Tenenbaum-Gavish, Kypros H Nicolaides
OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial. METHODS: This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation...
July 25, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28728156/predicting-the-risk-to-develop-preeclampsia-in-the-first-trimester-combining-promoter-variant-98a-c-of-lgals13-placental-protein-13-black-ethnicity-previous-preeclampsia-obesity-and-maternal-age
#13
Liora Madar-Shapiro, Ido Karady, Alla Trahtenherts, Argryo Syngelaki, Ranjit Akolekar, Liona Poon, Ruth Cohen, Adi Sharabi-Nov, Berthold Huppertz, Marei Sammar, Kata Juhasz, Nandor Gabor Than, Zoltan Papp, Roberto Romero, Kypros H Nicolaides, Hamutal Meiri
BACKGROUND: LGALS13 (placental protein 13 [PP13]) promoter DNA polymorphisms was evaluated in predicting preeclampsia (PE), given PP13's effects on hypotension, angiogenesis, and immune tolerance. METHODS: First-trimester plasma samples (49 term and 18 intermediate) of PE cases matched with 196 controls were collected from King's College Hospital, London, repository. Cell-free DNA was extracted and the LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs was determined in BeWo trophoblast-like cells with luciferase assays...
July 21, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28727518/therapeutic-and-prognostic-implications-of-braf-v600e-in-pediatric-low-grade-gliomas
#14
Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara McKeown, Jim Loukides, Ofelia Cruz, Carmen de Torres, Cheng-Ying Ho, Roger J Packer, Ruth Tatevossian, Ibrahim Qaddoumi, Julie H Harreld, James D Dalton, Jean Mulcahy-Levy, Nicholas Foreman, Matthias A Karajannis, Shiyang Wang, Matija Snuderl, Amulya Nageswara Rao, Caterina Giannini, Mark Kieran, Keith L Ligon, Maria Luisa Garre, Paolo Nozza, Samantha Mascelli, Alessandro Raso, Sabine Mueller, Theodore Nicolaides, Karen Silva, Romain Perbet, Alexandre Vasiljevic, Cécile Faure Conter, Didier Frappaz, Sarah Leary, Courtney Crane, Aden Chan, Ho-Keung Ng, Zhi-Feng Shi, Ying Mao, Elizabeth Finch, David Eisenstat, Bev Wilson, Anne Sophie Carret, Peter Hauser, David Sumerauer, Lenka Krskova, Valerie Larouche, Adam Fleming, Shayna Zelcer, Nada Jabado, James T Rutka, Peter Dirks, Michael D Taylor, Shiyi Chen, Ute Bartels, Annie Huang, David W Ellison, Eric Bouffet, Cynthia Hawkins, Uri Tabori
Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180)...
September 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28723764/increased-nuchal-translucency-in-fetuses-with-a-normal-karyotype-diagnosis-and-management-an-observational-study
#15
Demetra Socolov, Razvan Socolov, Vlad Eusebiu Gorduza, Tudor Butureanu, Ruxandra Stanculescu, Alexandru Carauleanu, Ioana Pavaleanu
The use of nuchal translucency (NT) in 1992 by Nicolaides et al was a major breakthrough in screening for chromosomal aneuploidies at the end of the first trimester. However, pathological conditions other than chromosomal aneuploidies are also associated with increased NT, which can also be detected in normal fetuses. This study sought to evaluate the causes of this ultrasound sign in a group of patients from Iasi, Romania.During the decade-long study period, there were 71 certified cases involving increased NT; the patients in these cases underwent diagnostic amniocentesis and karyotyping...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723675/tumor-antigen-ca125-suppresses-antibody-dependent-cellular-cytotoxicity-adcc-via-direct-antibody-binding-and-suppressed-fc-%C3%AE-receptor-engagement
#16
James Bradford Kline, Rina P Kennedy, Earl Albone, Qimin Chao, Shawn Fernando, Jennifer M McDonough, Katherine Rybinski, Wenquan Wang, Elizabeth B Somers, Charles Schweizer, Luigi Grasso, Nicholas C Nicolaides
Cancers employ a number of mechanisms to evade host immune responses. Here we report the effects of tumor-shed antigen CA125/MUC16 on suppressing IgG1-mediated antibody-dependent cellular cytotoxicity (ADCC). This evidence stems from prespecified subgroup analysis of a Phase 3 clinical trial testing farletuzumab, a monoclonal antibody to folate receptor alpha, plus standard-of-care carboplatin-taxane chemotherapy in patients with recurrent platinum-sensitive ovarian cancer. Patients with low serum CA125 levels treated with farletuzumab demonstrated improvements in progression free survival (HR 0...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696243/inhibiting-4ebp1-in-glioblastoma
#17
Qi Wen Fan, Theodore P Nicolaides, William A Weiss
Glioblastoma is the most common and aggressive adult brain cancer. Tumors show frequent dysregulation of the phosphatidylinositol-3 kinase-mechanistic target of rapamycin pathway. While a number of small molecules target the PI3K-AKT-mTOR axis, their preclinical and clinical efficacy has been limited. Reasons for treatment failure include poor penetration of agents into the brain, and observations that blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Clinical trials using allosteric mTOR inhibitors (rapamycin and rapalogs) to treat glioblastoma patients have also been unsuccessful or uncertain, in-part because rapamycin inefficiently blocks the mTORC1 target 4EBP1, and also feeds back to activate PI3K-AKT signaling...
July 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28694782/evaluation-of-abdominal-fetal-electrocardiography-in-early-intrauterine-growth-restriction
#18
Clarissa L Velayo, Kiyoe Funamoto, Joyceline Noemi I Silao, Yoshitaka Kimura, Kypros Nicolaides
Objectives: This descriptive study was performed to evaluate the capability of a non-invasive transabdominal electrocardiographic system to extract clear fetal electrocardiographic (FECG) measurements from intrauterine growth restricted (IUGR) fetuses and to assess whether abdominal FECG parameters can be developed as markers for evaluating the fetal cardiac status in IUGR. Methods: Transabdominal FECG was attempted in 20 controls and 15 IUGR singleton pregnancies at 20+0-33+6 weeks gestation. Standard ECG parameters were compared between the study groups and evaluated for their correlation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28657417/aspirin-versus-placebo-in-pregnancies-at-high-risk-for-preterm-preeclampsia
#19
RANDOMIZED CONTROLLED TRIAL
Daniel L Rolnik, David Wright, Liona C Poon, Neil O'Gorman, Argyro Syngelaki, Catalina de Paco Matallana, Ranjit Akolekar, Simona Cicero, Deepa Janga, Mandeep Singh, Francisca S Molina, Nicola Persico, Jacques C Jani, Walter Plasencia, George Papaioannou, Kinneret Tenenbaum-Gavish, Hamutal Meiri, Sveinbjorn Gizurarson, Kate Maclagan, Kypros H Nicolaides
BACKGROUND: Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation...
August 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28640401/two-stage-approach-for-risk-estimation-of-fetal-trisomy-21-and-other-aneuploidies-using-computational-intelligence-systems
#20
A C Neocleous, A Syngelaki, K H Nicolaides, C N Schizas
OBJECTIVE: To estimate the risk for fetal trisomy 21 (T21) and other chromosomal abnormalities at 11-13 week's gestation using computational intelligence classification methods. METHODS: As a first step, we train the artificial neural networks with 72054 euploid pregnancies, 295 cases of T21 and 305 of other chromosomal abnormalities (OCA). Then, we sort the cases into two categories of "no-risk" and "risk". The cases of "no-risk" are no further examined, while the cases with "risk" are forwarded in Stage 2 for further examination where we classify them in three types of risk, namely "no-risk", "moderate-risk" and "high-risk"...
June 22, 2017: Ultrasound in Obstetrics & Gynecology
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