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Chronic Maternal Protein Deprivation In Mice Is Associated With Overexpression Of The Cohesin-Mediator Complex In Liver Of Their Offspring, Alfred Balasa, Amarilis Sanchez-Valle, Bekim Sadikovic, Haleh Sangi-Haghpeykar, Jaclyn Bravo, Liang Chen, Wei Liu, Shu Wen, Marta L. Fiorotto, Ignatia B. Van Den Veyver
Chronic Maternal Protein Deprivation In Mice Is Associated With Overexpression Of The Cohesin-Mediator Complex In Liver Of Their Offspring, Alfred Balasa, Amarilis Sanchez-Valle, Bekim Sadikovic, Haleh Sangi-Haghpeykar, Jaclyn Bravo, Liang Chen, Wei Liu, Shu Wen, Marta L. Fiorotto, Ignatia B. Van Den Veyver
Paediatrics Publications
Epigenetic mechanisms may play an important role in the developmental programming of adult-onset chronic metabolic diseases resulting from suboptimal fetal nutrition, but the exact molecular mechanisms are incompletely understood. Given the central role of the liver in metabolic regulation, we investigated whether chronic maternal dietary protein restriction has long-term effects on liver gene expression in the offspring. We fed adult C57BL/6J dams ad libitum an 8% maternal lowprotein (MLP) or 20% protein control diet (C) from 4 wk prior to mating until the end of lactation. Male pups were weaned to standard nonpurified diet and singly housed at 21 d …
Inhibition Of Rho Kinase Regulates Specification Of Early Differentiation Events In P19 Embryonal Carcinoma Stem Cells, Roman J. Krawetz, Jaymi Taiani, Alexis Greene, Gregory M. Kelly, Derrick E. Rancourt
Inhibition Of Rho Kinase Regulates Specification Of Early Differentiation Events In P19 Embryonal Carcinoma Stem Cells, Roman J. Krawetz, Jaymi Taiani, Alexis Greene, Gregory M. Kelly, Derrick E. Rancourt
Paediatrics Publications
Background: The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined. Methodology/Principal Findings: …
Clinical And Genetic Determinants Of Warfarin Pharmacokinetics And Pharmacodynamics During Treatment Initiation, Inna Y. Gong, Ute I. Schwarz, Natalie Crown, George K. Dresser, Alejandro Lazo-Langner, Guang Yong Zou, Dan M. Roden, C. Michael Stein, Marc Rodger, Philip S. Wells, Richard B. Kim, Rommel G. Tirona
Clinical And Genetic Determinants Of Warfarin Pharmacokinetics And Pharmacodynamics During Treatment Initiation, Inna Y. Gong, Ute I. Schwarz, Natalie Crown, George K. Dresser, Alejandro Lazo-Langner, Guang Yong Zou, Dan M. Roden, C. Michael Stein, Marc Rodger, Philip S. Wells, Richard B. Kim, Rommel G. Tirona
Paediatrics Publications
Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (I max) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for I max were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status …
A Unique Role Of Gata1s In Down Syndrome Acute Megakaryocytic Leukemia Biology And Therapy, Ana C. Xavier, Holly Edwards, Alan A. Dombkowski, Tugce B. Balci, Jason N. Berman, Graham Dellaire, Chengzhi Xie, Steven A. Buck, Larry H. Matherly, Yubin Ge, Jeffrey W. Taub
A Unique Role Of Gata1s In Down Syndrome Acute Megakaryocytic Leukemia Biology And Therapy, Ana C. Xavier, Holly Edwards, Alan A. Dombkowski, Tugce B. Balci, Jason N. Berman, Graham Dellaire, Chengzhi Xie, Steven A. Buck, Larry H. Matherly, Yubin Ge, Jeffrey W. Taub
Paediatrics Publications
Background: Acute megakaryocytic leukemia (AMkL) in Down syndrome (DS) children is uniformly associated with somatic GATA1 mutations, which result in the synthesis of a shorter protein (GATA1s) with altered transactivation activity compared to the wild-type GATA1. It is not fully established whether leukemogenesis and therapeutic responses in DS AMkL patients are due to loss of the wild-type GATA1 or due to a unique function of GATA1s. Methodology: Stable clones of CMK cells with decreased GATA1s or Bcl-2 levels were generated by using GATA1- or BCL-2-specific lentivirus shRNAs. In vitro ara-C, daunorubicin, and VP-16 cytotoxicities of the shRNA stable clones were …
Role And Expression Of Frs2 And Frs3 In Prostate Cancer, Tania Valencia, Ajay Joseph, Naveen Kachroo, Steve Darby, Susan Meakin, Vincent J. Gnanapragasam
Role And Expression Of Frs2 And Frs3 In Prostate Cancer, Tania Valencia, Ajay Joseph, Naveen Kachroo, Steve Darby, Susan Meakin, Vincent J. Gnanapragasam
Paediatrics Publications
Background: FGF receptor substrates (FRS2 and FRS3) are key adaptor proteins that mediate FGF-FGFR signalling in benign as well as malignant tissue. Here we investigated FRS2 and FRS3 as a means of disrupting global FGF signalling in prostate cancer.Methods: FRS2 and FRS3 manipulation was investigated in vitro using over-expression, knockdown and functional assays. FRS2 and FRS3 expression was profiled in cell lines and clinical tumors of different grades.Results: In a panel of cell lines we observed ubiquitous FRS2 and FRS3 transcript and protein expression in both benign and malignant cells. We next tested functional redundancy of FRS2 and FRS3 in …
Targeted Inhibition Of Calpain Reduces Myocardial Hypertrophy And Fibrosis In Mouse Models Of Type 1 Diabetes, Ying Li, Jian Ma, Huaqing Zhu, Manpreet Singh, David Hill, Peter A. Greer, J. Malcolm Arnold, E. Dale Abel
Targeted Inhibition Of Calpain Reduces Myocardial Hypertrophy And Fibrosis In Mouse Models Of Type 1 Diabetes, Ying Li, Jian Ma, Huaqing Zhu, Manpreet Singh, David Hill, Peter A. Greer, J. Malcolm Arnold, E. Dale Abel
Paediatrics Publications
OBJECTIVE - Recently we have shown that calpain-1 activation contributes to cardiomyocyte apoptosis induced by hyperglycemia. This study was undertaken to investigate whether targeted disruption of calpain would reduce myocardial hypertrophy and fibrosis in mouse models of type 1 diabetes. RESEARCH DESIGN AND METHODS - Diabetes in mice was induced by injection of streptozotocin (STZ), and OVE26 mice were also used as a type 1 diabetic model. The function of calpain was genetically manipulated by cardiomyocyte-specific knockout Capn4 in mice and the use of calpastatin transgenic mice. Myocardial hypertrophy and fibrosis were investigated 2 and 5 months after STZ injection …
Type I Collagen Cleavage Is Essential For Effective Fibrotic Repair After Myocardial Infarction, Zengxuan Nong, Caroline O'Neil, Ming Lei, Robert Gros, Alanna Watson, Amin Rizkalla, Kibret Mequanint, Shaohua Li, Matthew J. Frontini, Qingping Feng, J. Geoffrey Pickering
Type I Collagen Cleavage Is Essential For Effective Fibrotic Repair After Myocardial Infarction, Zengxuan Nong, Caroline O'Neil, Ming Lei, Robert Gros, Alanna Watson, Amin Rizkalla, Kibret Mequanint, Shaohua Li, Matthew J. Frontini, Qingping Feng, J. Geoffrey Pickering
Paediatrics Publications
Efficient deposition of type I collagen is fundamental to healing after myocardial infarction. Whether there is also a role for cleavage of type I collagen in infarct healing is unknown. To test this, we undertook coronary artery occlusion in mice with a targeted mutation (Col1a1 r/r) that yields collagenase-resistant type I collagen. Eleven days after infarction, Col1a1 r/r mice had a lower mean arterial pressure and peak left ventricular systolic pressure, reduced ventricular systolic function, and worse diastolic function, compared with wild-type littermates. Infarcted Col1a1 r/r mice also had greater 30-day mortality, larger left ventricular lumens, and thinner infarct walls. …
Master Transcription Factors Determine Cell-Type-Specific Responses To Tgf-Β Signaling, Alan C. Mullen, David A. Orlando, Jamie J. Newman, Jakob Lovén, Roshan M. Kumar, Steve Bilodeau, Jessica Reddy, Matthew G. Guenther, Rodney P. Dekoter, Richard A. Young
Master Transcription Factors Determine Cell-Type-Specific Responses To Tgf-Β Signaling, Alan C. Mullen, David A. Orlando, Jamie J. Newman, Jakob Lovén, Roshan M. Kumar, Steve Bilodeau, Jessica Reddy, Matthew G. Guenther, Rodney P. Dekoter, Richard A. Young
Paediatrics Publications
Transforming growth factor beta (TGF-β) signaling, mediated through the transcription factors Smad2 and Smad3 (Smad2/3), directs different responses in different cell types. Here we report that Smad3 co-occupies the genome with cell-type-specific master transcription factors. Thus, Smad3 occupies the genome with Oct4 in embryonic stem cells (ESCs), Myod1 in myotubes, and PU.1 in pro-B cells. We find that these master transcription factors are required for Smad3 occupancy and that TGF-β signaling largely affects the genes bound by the master transcription factors. Furthermore, we show that induction of Myod1 in nonmuscle cells is sufficient to redirect Smad3 to Myod1 sites. We …
Suppression Of The Imprinted Gene Nnat And X-Chromosome Gene Activation In Isogenic Human Ips Cells, Jonathan H. Teichroeb, Dean H. Betts, Homayoun Vaziri
Suppression Of The Imprinted Gene Nnat And X-Chromosome Gene Activation In Isogenic Human Ips Cells, Jonathan H. Teichroeb, Dean H. Betts, Homayoun Vaziri
Paediatrics Publications
Genetic comparison between human embryonic stem cells and induced pluripotent stem cells has been hampered by genetic variation. To solve this problem, we have developed an isogenic system that allows direct comparison of induced pluripotent stem cells (hiPSCs) to their genetically matched human embryonic stem cells (hESCs). We show that hiPSCs have a highly similar transcriptome to hESCs. Global transcriptional profiling identified 102-154 genes (>2 fold) that showed a difference between isogenic hiPSCs and hESCs. A stringent analysis identified NNAT as a key imprinted gene that was dysregulated in hiPSCs. Furthermore, a disproportionate number of X-chromosome localized genes were …
Dompep-A General Method For Predicting Modular Domain-Mediated Protein-Protein Interactions, Lei Li, Bing Zhao, Jun Du, Kaizhong Zhang, Charles X. Ling, Shawn Shun Cheng Lishawn
Dompep-A General Method For Predicting Modular Domain-Mediated Protein-Protein Interactions, Lei Li, Bing Zhao, Jun Du, Kaizhong Zhang, Charles X. Ling, Shawn Shun Cheng Lishawn
Paediatrics Publications
Protein-protein interactions (PPIs) are frequently mediated by the binding of a modular domain in one protein to a short, linear peptide motif in its partner. The advent of proteomic methods such as peptide and protein arrays has led to the accumulation of a wealth of interaction data for modular interaction domains. Although several computational programs have been developed to predict modular domain-mediated PPI events, they are often restricted to a given domain type. We describe DomPep, a method that can potentially be used to predict PPIs mediated by any modular domains. DomPep combines proteomic data with sequence information to achieve …
The Potential For Misusing "Genetic Predisposition" In Canadian Courts And Tribunals, Roxanne Mykitiuk, Mark Pioro, Lilith Finkler, Jeff Nisker
The Potential For Misusing "Genetic Predisposition" In Canadian Courts And Tribunals, Roxanne Mykitiuk, Mark Pioro, Lilith Finkler, Jeff Nisker
Paediatrics Publications
No abstract provided.
The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault
The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault
Paediatrics Publications
This study aimed to determine the effect of varying degrees of intermittent umbilical cord occlusion (UCO) on arterial elastin composition. Over 4 days, chronically catheterized late gestation fetal sheep received 5 total UCO per day lasting 1 min/h (mild group: n = 6), 2 min/h (moderate group: n = 4), 3 min/h (severe group; n = 6); or no occlusion (control group: n = 7). Each group was evaluated for elastin content of the carotid and superior mesenteric artery (SMA), the arterial pressure response to UCO, and plasma cortisol concentration. Elastin content of the carotid artery was significantly increased by …
Specific Language Or Working Memory Impairments: A Small Scale Observational Study, Lisa Md Archibald, Marc Joanisse, Alan Edmunds
Specific Language Or Working Memory Impairments: A Small Scale Observational Study, Lisa Md Archibald, Marc Joanisse, Alan Edmunds
Paediatrics Publications
Study of the developmental relationship between language and working memory skills has only just begun, despite the prominent role of their interdependency in some theoretical accounts of developmental language impairments. Recently, Archibald and Joanisse (2009) identified children with specific language impairment (SLI), or specific working memory impairment (SWMI), or mixed language and working memory impairment (Mixed) based on standardized testing. In the present study, we report a first effort to provide clinical verification of these profiles by describing the social, behavioral, and academic characteristics of individual group members. Two each of children with SLI, SWMI, or Mixed impairments, individually paired …
Inducible Nitric Oxide Synthase-Nitric Oxide Signaling Mediates The Mitogenic Activity Of Rac1 During Endochondral Bone Growth, Guoyan Wang, Qian Yan, Anita Woods, Laura A. Aubrey, Qingping Feng, Frank Beier
Inducible Nitric Oxide Synthase-Nitric Oxide Signaling Mediates The Mitogenic Activity Of Rac1 During Endochondral Bone Growth, Guoyan Wang, Qian Yan, Anita Woods, Laura A. Aubrey, Qingping Feng, Frank Beier
Paediatrics Publications
Coordinated proliferation and differentiation of growth plate chondrocytes controls endochondral bone growth and final height in humans, and disruption of this process results in diseases of the growing and adult skeleton, such as chondrodysplasias or osteoarthritis. We had shown recently that chondrocyte-specific deletion of the gene Rac1 in mice leads to severe dwarfism due to reduced chondrocyte proliferation, but the molecular pathways involved remained unclear. Here, we demonstrate that Rac1-deficient chondrocytes have severely reduced levels of inducible nitric oxide synthase (iNOS) protein and nitric oxide (NO) production. NO donors reversed the proliferative effects induced by Rac1 deficiency, whereas inhibition of …
Time To Focus On Outcome Assessment Tools For Childhood Vasculitis, Erkan Demirkaya, Raashid Luqmani, Nuray A. Ayaz, Abdulbaki Karaoglu, Seza Ozen
Time To Focus On Outcome Assessment Tools For Childhood Vasculitis, Erkan Demirkaya, Raashid Luqmani, Nuray A. Ayaz, Abdulbaki Karaoglu, Seza Ozen
Paediatrics Publications
Childhood systemic vasculitides are a group of rare diseases with multi-organ involvement and potentially devastating consequences. After establishment of new classification criteria (Ankara consensus conference in 2008), it is now time to establish measures for proper definition of activity and damage in childhood primary vasculitis. By comparison to adult vasculitis, there is no consensus for indices of activity and damage assessment in childhood vasculitis. Assessment of disease activity is likely to become a major area of interest in pediatric rheumatology in the near future. After defining the classification criteria for primary systemic childhood vasculitis, the next step was to perform …
Deletion Of Genes Encoding Pu.1 And Spi-B In B Cells Impairs Differentiation And Induces Pre-B Cell Acute Lymphoblastic Leukemia, Kristen M. Sokalski, Stephen K.H. Li, Ian Welch, Heather Anne T. Cadieux-Pitre, Marek R. Gruca, Rodney P. Dekoter
Deletion Of Genes Encoding Pu.1 And Spi-B In B Cells Impairs Differentiation And Induces Pre-B Cell Acute Lymphoblastic Leukemia, Kristen M. Sokalski, Stephen K.H. Li, Ian Welch, Heather Anne T. Cadieux-Pitre, Marek R. Gruca, Rodney P. Dekoter
Paediatrics Publications
The E26 transformation-specific (Ets) transcription factor PU.1 is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors.We hypothesized that PU.1 function in B-cell differentiation is complemented by the related Ets transcription factor Spi-B. To test this hypothesis, mice were generated lacking both PU.1 and Spi-B in the B-cell lineage. Unlike mice lacking PU.1 or Spi-B, mice deficient in both PU.1 and Spi-B in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation. Strikingly, all PU.1 and Spi-B-deficient mice developed …
Quantification Of Renal Perfusion: Comparison Of Arterial Spin Labeling And Dynamic Contrast-Enhanced Mri, Jeff D. Winter, Keith S. St. Lawrence, Hai Ling Margaret Cheng
Quantification Of Renal Perfusion: Comparison Of Arterial Spin Labeling And Dynamic Contrast-Enhanced Mri, Jeff D. Winter, Keith S. St. Lawrence, Hai Ling Margaret Cheng
Paediatrics Publications
Purpose: To provide the first comparison of absolute renal perfusion obtained by arterial spin labeling (ASL) and separable compartment modeling of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Moreover, we provide the first application of the dual bolus approach to quantitative DCE-MRI perfusion measurements in the kidney. Materials and Methods: Consecutive ASL and DCE-MRI acquisitions were performed on six rabbits on a 1.5 T MRI system. Gadolinium (Gd)-DTPA was administered in two separate injections to decouple measurement of the arterial input function and tissue uptake curves. For DCE perfusion, pixel-wise and mean cortex region-of-interest tissue curves were fit to a …
Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, And Platelet Activation, Kieran L. Quinn, Melanie Henriques, Arata Tabuchi, Bing Han, Hong Yang, Wei Erh Cheng, Soumitra Tole, Hanpo Yu, Alice Luo, Emmanuel Charbonney, Elizabeth Tullis, Alan Lazarus, Lisa A. Robinson, Heyu Ni, Blake R. Peterson, Wolfgang M. Kuebler, Arthur S. Slutsky, Haibo Zhang
Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, And Platelet Activation, Kieran L. Quinn, Melanie Henriques, Arata Tabuchi, Bing Han, Hong Yang, Wei Erh Cheng, Soumitra Tole, Hanpo Yu, Alice Luo, Emmanuel Charbonney, Elizabeth Tullis, Alan Lazarus, Lisa A. Robinson, Heyu Ni, Blake R. Peterson, Wolfgang M. Kuebler, Arthur S. Slutsky, Haibo Zhang
Paediatrics Publications
Objective-: Neutrophils are involved in the inflammatory responses during atherosclerosis. Human neutrophil peptides (HNPs) released from activated neutrophils exert immune modulating properties. We hypothesized that HNPs play an important role in neutrophil-mediated inflammatory cardiovascular responses in atherosclerosis. Methods and results-: We examined the role of HNPs in endothelial-leukocyte interaction, platelet activation, and foam cell formation in vitro and in vivo. We demonstrated that stimulation of human coronary artery endothelial cells with clinically relevant concentrations of HNPs resulted in monocyte adhesion and transmigration; induction of oxidative stress in human macrophages, which accelerates foam cell formation; and activation and aggregation of human …
Adenovirus E1a Directly Targets The E2f/Dp-1 Complex, Peter Pelka, Matthew S. Miller, Matthew Cecchini, Ahmed F. Yousef, Dawn M. Bowdish, Fred Dick, Peter Whyte, Joe S. Mymryk
Adenovirus E1a Directly Targets The E2f/Dp-1 Complex, Peter Pelka, Matthew S. Miller, Matthew Cecchini, Ahmed F. Yousef, Dawn M. Bowdish, Fred Dick, Peter Whyte, Joe S. Mymryk
Paediatrics Publications
Deregulation of the cell cycle is of paramount importance during adenovirus infection. Adenovirus normally infects quiescent cells and must initiate the cell cycle in order to propagate itself. The pRb family of proteins controls entry into the cell cycle by interacting with and repressing transcriptional activation by the E2F transcription factors. The viral E1A proteins indirectly activate E2F-dependent transcription and cell cycle entry, in part, by interacting with pRb and family members to free the E2Fs. We report here that an E1A 13S isoform can unexpectedly activate E2F-responsive gene expression independently of binding to the pRb family of proteins. We …
Comment On: Interest Of B-Blockers In Patients With Right Ventricular Systemic Dysfunction, Kambiz Norozi, Herschel C. Rosenberg, Reiner Buchhorn
Comment On: Interest Of B-Blockers In Patients With Right Ventricular Systemic Dysfunction, Kambiz Norozi, Herschel C. Rosenberg, Reiner Buchhorn
Paediatrics Publications
No abstract provided.
Evaluation Of Adipose Tissue Volume Quantification With Ideal Fat-Water Separation, Abdullah Alabousi, Salam Al-Attar, Tisha R. Joy, Robert A. Hegele, Charles A. Mckenzie
Evaluation Of Adipose Tissue Volume Quantification With Ideal Fat-Water Separation, Abdullah Alabousi, Salam Al-Attar, Tisha R. Joy, Robert A. Hegele, Charles A. Mckenzie
Paediatrics Publications
Purpose: To validate iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) for adipose tissue volume quantification. IDEAL allows MRI images to be produced only from adipose-containing tissues; hence, quantifying adipose tissue should be simpler and more accurate than with current methods. Materials and Methods: Ten healthy controls were imaged with 1.5 Tesla (T) Spin Echo (SE), 3.0T T1-weighted spoiled gradient echo (SPGR), and 3.0T IDEAL-SPGR. Images were acquired from the abdomen, pelvis, mid-thigh, and mid-calf. Mean subcutaneous and visceral adipose tissue volumes were compared between the three acquisitions for each subject. Results: There were no …
Once Were Farmers: Occupation, Social Mobility, And Mortality During Industrialization In Saguenay-Lac-Saint-Jean, Quebec 1840-1971, Alain Gagnon, Marc Tremblay, Hélène Vézina, Jamie A. Seabrook
Once Were Farmers: Occupation, Social Mobility, And Mortality During Industrialization In Saguenay-Lac-Saint-Jean, Quebec 1840-1971, Alain Gagnon, Marc Tremblay, Hélène Vézina, Jamie A. Seabrook
Paediatrics Publications
We study men's adult mortality and longevity by socio-occupational status during industrialization in Saguenay-Lac-Saint-Jean, Quebec. Data were extracted from the BALSAC database (Université du Québec à Chicoutimi), which comprehensively traces the demographic history of the region since the beginning of the French Canadian settlement in 1840 up to the early 1970s. Using five occupational classes and controlling for year, age at marriage, urban/rural residence, and literacy, we found no evidence for the emergence of a socioeconomic gradient in mortality. At least until the early 1970s, mortality in the region is the lowest for farmers and appears to be driven by …
Chronic Intrauterine Hypoxia Interferes With Aortic Development In The Late Gestation Ovine Fetus, Jennifer A. Thompson, Bryan S. Richardson, Robert Gagnon, Timothy R.H. Regnault
Chronic Intrauterine Hypoxia Interferes With Aortic Development In The Late Gestation Ovine Fetus, Jennifer A. Thompson, Bryan S. Richardson, Robert Gagnon, Timothy R.H. Regnault
Paediatrics Publications
This study explored arterial remodelling in fetuses growth restricted by hypoxia. Chronically catheterized fetal sheep were made moderately or severely hypoxic by placental embolization for 15 days starting at gestational age 116-118 (term ∼147 days). Cross-sections of the aorta were analysed for collagen and elastin content using histological procedures, while immunofluorescence was applied to measure markers of vascular smooth muscle cell (VSMC) type. In frozen aortae quantitative PCR was used to measure mRNA levels of extracellular matrix (ECM) precursor proteins as well as molecular regulators of developmental and pathological remodelling. Relative to Control (n= 6), aortic wall thickness was increased …
Diagnostic Accuracy Of Cystatin C-Based Egfr Equations At Different Gfr Levels In Children, Ajay P. Sharma, Abeer Yasin, Amit X. Garg, Guido Filler
Diagnostic Accuracy Of Cystatin C-Based Egfr Equations At Different Gfr Levels In Children, Ajay P. Sharma, Abeer Yasin, Amit X. Garg, Guido Filler
Paediatrics Publications
Background and objectives The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation. Design, setting, participants, & measurements We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium- 99m-diethylene-triamine penta-acetic acid (99mTc DTPA). Results We compared various cystatin C equations across GFR strata <60, <90, ≥135, and ≥150 ml/min per 1.73 m2 for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli- CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective 99mTc DTPA, in the GFR categories <60 and <90 ml/min per 1.73 m2, whereas the Bökenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories ≥135 and ≥150 ml/min per 1.73 m2. The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR <60 and <90 ml/min per 1.73 m2, whereas the Bökenkamp equation had a higher sensitivity for GFR ≥135 and ≥150 ml/min per 1.73 m2. Conclusions The diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations. © 2011 by the American Society of Nephrology.
Diagnostic Accuracy Of Cystatin C-Based Egfr Equations At Different Gfr Levels In Children, Ajay P. Sharma, Abeer Yasin, Amit X. Garg, Guido Filler
Diagnostic Accuracy Of Cystatin C-Based Egfr Equations At Different Gfr Levels In Children, Ajay P. Sharma, Abeer Yasin, Amit X. Garg, Guido Filler
Paediatrics Publications
Background and objectives The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation. Design, setting, participants, & measurements We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium- 99m-diethylene-triamine penta-acetic acid (99mTc DTPA). Results We compared various cystatin C equations across GFR strata <60, <90, ≥135, and ≥150 ml/min per 1.73 m2 for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli- CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective 99mTc DTPA, in the GFR categories <60 and <90 ml/min per 1.73 m2, whereas the Bökenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories ≥135 and ≥150 ml/min per 1.73 m2. The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR <60 and <90 ml/min per 1.73 m2, whereas the Bökenkamp equation had a higher sensitivity for GFR ≥135 and ≥150 ml/min per 1.73 m2. Conclusions The diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations. © 2011 by the American Society of Nephrology.
The Authors Reply:, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark
The Authors Reply:, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark
Paediatrics Publications
No abstract provided.
A Preliminary Examination Of The Psychometric Properties Of The Coparenting Questionnaire And The Diabetes-Specific Coparenting Questionnaire In Families Of Children With Type I Diabetes, Mor Barzel, Graham J. Reid
A Preliminary Examination Of The Psychometric Properties Of The Coparenting Questionnaire And The Diabetes-Specific Coparenting Questionnaire In Families Of Children With Type I Diabetes, Mor Barzel, Graham J. Reid
Paediatrics Publications
Objectives: To examine the structure and psychometric properties of a general childrearing [Coparenting Questionnaire (CQ)] and an adapted Diabetes-Specific Coparenting Questionnaire (DCQ) and compare general and diabetes-specific coparenting among two-parent families caring for a child with type I diabetes. Methods: Mothers and fathers of children (N=61) aged 8-12 years with type I diabetes completed self-report measures of marital functioning, parenting, and coparenting, including the CQ and DCQ. Results: Confirmatory factor analyses favored the hypothesized 3-factor model for mothers and fathers for the CQ and DCQ. The internal consistencies and convergent validities of the CQ and DCQ were adequate. Coparenting conflict …
Coparenting In Relation To Children's Psychosocial And Diabetes-Specific Adjustment, Mor Barzel, Graham J. Reid
Coparenting In Relation To Children's Psychosocial And Diabetes-Specific Adjustment, Mor Barzel, Graham J. Reid
Paediatrics Publications
Objective: To explore the potential utility of a general and diabetes-specific measure of coparenting by evaluating linkages between coparenting and both the psychosocial and medical adjustment of children with type 1 diabetes (TID). Method: Mothers and fathers of children (ages 8-12 years; n=61) with TID completed questionnaires including measures of general and diabetes-specific coparenting, and children's internalizing and externalizing problems. Medical adjustment included parent-reported diabetes management behaviors, children's self-reported diabetes quality of life (QOL), and metabolic control (HbA1c) assessed during clinic appointments. Results: Coparenting conflict around general child rearing tasks was significantly related to children's internalizing and externalizing problems. Diabetes-specific …
Integrin-Linked Kinase: A Scaffold Protein Unique Among Its Ilk, Lina Dagnino
Integrin-Linked Kinase: A Scaffold Protein Unique Among Its Ilk, Lina Dagnino
Paediatrics Publications
Integrin-linked kinase (ILK) is a scaffolding protein with central roles in tissue development and homeostasis. Much debate has focused on whether ILK is a bona fide or a pseudo- kinase. This aspect of ILK function has been complicated by the large volumes of conflicting observations obtained from a wide variety of experimental approaches, from in vitro models, to analyses in invertebrates and in mammals. Key findings in support or against the notion that ILK is catalytically active are summarized. The importance of ILK as an adaptor protein is well established, and defining its role as a signaling hub will be …
In Vitro And In Vivo Germ Line Potential Of Stem Cells Derived From Newborn Mouse Skin, Paul W. Dyce, Jinghe Liu, Chandrakant Tayade, Gerald M. Kidder, Dean H. Betts, Julang Li
In Vitro And In Vivo Germ Line Potential Of Stem Cells Derived From Newborn Mouse Skin, Paul W. Dyce, Jinghe Liu, Chandrakant Tayade, Gerald M. Kidder, Dean H. Betts, Julang Li
Paediatrics Publications
We previously reported that fetal porcine skin-derived stem cells were capable of differentiation into oocyte-like cells (OLCs). Here we report that newborn mice skin-derived stem cells are also capable of differentiating into early OLCs. Using stem cells from mice that are transgenic for Oct4 germline distal enhancer-GFP, germ cells resulting from their differentiation are expected to be GFP+. After differentiation, some GFP+ OLCs reached 40-45 μM and expressed oocyte markers. Flow cytometric analysis revealed that ∼0.3% of the freshly isolated skin cells were GFP+. The GFP-positive cells increased to ∼7% after differentiation, suggesting that the GFP+ cells could be of …