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CJC Open Nov 2020Tetralogy of Fallot is a congenital heart disease comprised of a tetrad of ventricular septal defect, pulmonary stenosis, overriding aorta, and right ventricular...
Tetralogy of Fallot is a congenital heart disease comprised of a tetrad of ventricular septal defect, pulmonary stenosis, overriding aorta, and right ventricular hypertrophy. In developed countries, most cases are diagnosed in babies; mortality is high if not surgically corrected in a timely manner. We describe herein a woman who was diagnosed at age 73 years. Several factors accounted for her unusual longevity. We highlight the importance of multimodal imaging to look for other associated anomalies of tetralogy of Fallot in cases of apparent simple ventricular septal defect when the echocardiographic images are either suggestive or suboptimal.
PubMed: 33305230
DOI: 10.1016/j.cjco.2020.06.011 -
Developmental Biology Aug 2005Several syndromes characterized by defects in cardiovascular and craniofacial development are associated with a hemizygous deletion of chromosome 22q11 in humans and... (Comparative Study)
Comparative Study
Several syndromes characterized by defects in cardiovascular and craniofacial development are associated with a hemizygous deletion of chromosome 22q11 in humans and involve defects in pharyngeal arch and neural crest cell development. Recent efforts have focused on identifying 22q11 deletion syndrome modifying loci. In this study, we show that mouse embryos deficient for Gbx2 display aberrant neural crest cell patterning and defects in pharyngeal arch-derived structures. Gbx2(-/-) embryos exhibit cardiovascular defects associated with aberrant development of the fourth pharyngeal arch arteries including interrupted aortic arch type B, right aortic arch, and retroesophageal right subclavian artery. Other developmental abnormalities include overriding aorta, ventricular septal defects, cranial nerve, and craniofacial skeletal patterning defects. Recently, Fgf8 has been proposed as a candidate modifier for 22q11 deletion syndromes. Here, we demonstrate that Fgf8 and Gbx2 expression overlaps in regions of the developing pharyngeal arches and that they interact genetically during pharyngeal arch and cardiovascular development.
Topics: Animals; Arteries; Body Patterning; Branchial Region; Fibroblast Growth Factor 8; Gene Expression Regulation, Developmental; Homeodomain Proteins; Immunohistochemistry; In Situ Hybridization; Mice; Microscopy, Confocal; Neural Crest
PubMed: 15996652
DOI: 10.1016/j.ydbio.2005.05.023 -
The Journal of Biological Chemistry Mar 1996Activation of the platelet-derived growth factor (PDGF) beta-receptor leads to cell growth and chemotaxis. The PDGF alpha-receptor also mediates a mitogenic signal, but... (Comparative Study)
Comparative Study
Activation of the platelet-derived growth factor (PDGF) beta-receptor leads to cell growth and chemotaxis. The PDGF alpha-receptor also mediates a mitogenic signal, but fails to induce cell migration in certain cell types. To examine this difference in signal transduction, a series of point-mutated PDGF alpha-receptors were analyzed. Porcine aortic endothelial cells expressing mutant PDGF alpha-receptors, in which tyrosine residues 768, 993, or 1018 were changed to phenylalanine residues migrated toward PDGF, whereas wild-type alpha-receptors and mutant alpha-receptors changed at tyrosine residues 720, 944, or 988 failed to migrate. All mutant receptors were mitogenically active and their capacity to activate phosphatidylinositol 3'-kinase and phospholipase C-gamma was not different from that of the wild-type receptor. Tyr-768 was found to be phosphorylated in PDGF-stimulated cells; in the Y768F mutant, there was a considerable increase in phosphorylation of Ser-767. Tyr-993 was not phosphorylated, but mutation of this tyrosine residue to a phenylalanine residue resulted in increased efficiency of phosphorylation on Tyr-988. Tyr-1018 is known to be an autophosphorylation site. Phosphorylated Tyr-768 and Tyr-1018 may bind signal transduction molecules involved in negative modulation of the chemotactic signaling capacity, whereas phosphorylated Tyr-988 may mediate increased chemotaxis. Thus our data indicate that the PDGF alpha-receptor has an intrinsic ability to transduce a chemotactic signal, and that this signal is counteracted by overriding negative signals.
Topics: Amino Acid Sequence; Animals; Aorta; Base Sequence; Becaplermin; Cell Line; Chemotaxis; Endothelium, Vascular; Enzyme Activation; Humans; Inositol Phosphates; Isoenzymes; Kinetics; Molecular Sequence Data; Mutagenesis, Site-Directed; Oligodeoxyribonucleotides; Peptide Fragments; Phenylalanine; Phosphatidylinositol 3-Kinases; Phosphopeptides; Phosphotransferases (Alcohol Group Acceptor); Platelet-Derived Growth Factor; Point Mutation; Proto-Oncogene Proteins c-sis; Receptor, Platelet-Derived Growth Factor alpha; Receptors, Platelet-Derived Growth Factor; Recombinant Proteins; Signal Transduction; Swine; Transfection; Type C Phospholipases; Tyrosine
PubMed: 8617789
DOI: 10.1074/jbc.271.9.5101 -
Annals of Medicine and Surgery (2012) Jan 2024Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys,...
INTRODUCTION AND IMPORTANCE
Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys, patent ductus arteriosus, central nervous system dysgenesis, distinctive craniofacial deformities, and overriding or overlapping fingers. Klinefelter syndrome (47, XXY) is found in 1 in 660 newborn males. It is considered to be one of the most common genetic causes of infertility. It manifests with small firm testes, androgen insufficiency, and azoospermia.
CASE PRESENTATION
A 2-month-old male infant with a history of weakness in feeding, frequent convulsions, and an increase in cyanosis two days ago. There were multiple skeletal deformities and a tendency to spasm in the extremities, left ventricular atrophy, mitral atresia, atrial septal defect, ventricular septal defect with dilated right cavities, tricuspid valve regurgitation, pulmonary valve stenosis; and the aorta exits in the right ventricle. There is a widening of the subdural space, which was observed in the left frontal-parietal side with cortical atrophy in that area and a widening of the Sylvian fissure. A karyotype test confirmed the presence of Edward and Klinefelter syndromes.
CLINICAL DISCUSSION
Aneuploidy is a chromosomal issue characterized by an abnormal number of a chromosome copies. The coexistence of two aneuploidies is called "double aneuploidy" which is a rare occurrence. Herein, we report a case of a 2-month-old male with Edward syndrome and Klinefelter syndrome.
CONCLUSION
This publication aims to highlight the challenges in diagnosing and treating a complicated genetic disease.
PubMed: 38222680
DOI: 10.1097/MS9.0000000000001468 -
American Journal of Physiology. Heart... Sep 2009A multilayered model of the aortic wall is introduced to investigate the transport of low-density lipoprotein (LDL) under hypertension, taking into account the...
A multilayered model of the aortic wall is introduced to investigate the transport of low-density lipoprotein (LDL) under hypertension, taking into account the influences of increased endothelial cell turnover and deformation of the intima at higher pressure. Meanwhile, the thickness and properties of the endothelium, intima, internal elastic lamina (IEL), and media are affected by the transmural pressure. The LDL macromolecules enter the intima through leaky junctions over the endothelium, which are created by dying or dividing cells. Water molecules enter the intima via the paracellular pathway through breaks in tight junctions after passing the glycocalyx as well as through leaky junctions. The glycocalyx is modeled as a Brinkman porous medium to describe the fluid filtration associated with its structure. Combined Navier-Stokes and Brinkman equations are solved for the transmural flow, and the convective-diffusion equation is employed for LDL transport. The permeation of LDL over the surface of smooth muscle cells is modeled through a uniform reaction evenly distributed in the macroscopically homogeneous media layer. Simulations are performed in an axisymmetric plane centered at a leaky cell. The overriding issue addressed is that LDL fluxes across the leaky junction, the intima, fenestral pores in the IEL, and the media layer are highly affected by the transmural pressure, which affects the endothelial cell turnover rate and the compaction of intima. The present model, for the first time and with no adjustable parameters, is capable of making many realistic predictions including the proper magnitudes for the permeability of endothelium and intimal layers and the hydraulic conductivity of all layers as well as their trends with pressure. Results for the volume flux through the wall and the hydraulic conductivity of the entire arterial wall, the endothelium, and subendothelial layers at 70 and 180 mmHg are in good agreement with previous experimental studies.
Topics: Aorta; Atherosclerosis; Blood Pressure; Cell Division; Cholesterol, LDL; Computational Biology; Diffusion; Endothelium, Vascular; Humans; Hypertension; Models, Cardiovascular; Predictive Value of Tests
PubMed: 19592615
DOI: 10.1152/ajpheart.00324.2009 -
Developmental Biology Aug 2005Recent studies in chick and mouse embryos have identified a previously unrecognized secondary heart field (SHF), located in the ventral midline splanchnic mesenchyme,... (Comparative Study)
Comparative Study
Recent studies in chick and mouse embryos have identified a previously unrecognized secondary heart field (SHF), located in the ventral midline splanchnic mesenchyme, which provides additional myocardial cells to the outflow tract as the heart tube lengthens during cardiac looping. In order to further delineate the contribution of this secondary myocardium to outflow development, we labeled the right SHF of Hamburger-Hamilton (HH) stage 14 chick embryos via microinjection of DiI/rhodamine and followed the fluorescently labeled cells over a 96-h time period. These experiments confirmed the movement of the SHF into the outflow and its spiraling migration distally, with the right side of the SHF contributing to the left side of the outflow. In contrast, when the right SHF was labeled at HH18, the fluorescence was limited to the caudal wall of the lengthening aortic sac. We then injected a combination of DiI and neutral red dye, and ablated the SHF in HH14 or 18 chick embryos. Embryos were allowed to develop until day 9, and harvested for assessment of outflow alignment. Of the embryos ablated at HH14, 76% demonstrated cardiac defects including overriding aorta and pulmonary atresia, while none of the sham-operated controls were affected. In addition, the more severely affected embryos demonstrated coronary artery anomalies. The embryos ablated at HH18 also manifested coronary artery anomalies but maintained normal outflow alignment. Therefore, the myocardium added to the outflow by the SHF at earlier stages is required for the elongation and appropriate alignment of the outflow tract. However, at later stages, the SHF contributes to the smooth muscle component of the outflow vessels above the pulmonary and aortic valves which is important for the development of the coronary artery stems. This work suggests a role for the SHF in a subset of congenital heart defects that have overriding aorta and coronary artery anomalies, such as tetralogy of Fallot and double outlet right ventricle.
Topics: Animals; Carbocyanines; Chick Embryo; Fluorescent Dyes; Heart; Immunohistochemistry; In Situ Hybridization; Models, Biological; Morphogenesis; Myocardium; Pulmonary Atresia; Tetralogy of Fallot
PubMed: 15950213
DOI: 10.1016/j.ydbio.2005.05.003 -
Circulation Research Aug 2014The E3 ubiquitin ligase inducible degrader of the low-density lipoprotein receptor (IDOL) triggers lysosomal degradation of the low-density lipoprotein receptor. The...
RATIONALE
The E3 ubiquitin ligase inducible degrader of the low-density lipoprotein receptor (IDOL) triggers lysosomal degradation of the low-density lipoprotein receptor. The tissue-specific effects of the IDOL pathway on plasma cholesterol and atherosclerosis have not been examined.
OBJECTIVE
Given that the liver is the primary determinant of plasma cholesterol levels, we sought to examine the consequence of effect of chronic liver-specific expression of a dominant-active form of IDOL in mice.
METHODS AND RESULTS
We expressed a degradation-resistant, dominant-active form of IDOL (super IDOL [sIDOL]) in C57Bl/6J mice from the liver-specific albumin promoter (L-sIDOL transgenics). L-sIDOL mice were fed a Western diet for 20 or 30 weeks and then analyzed for plasma lipid levels and atherosclerotic lesion formation. L-sIDOL mice showed dramatic reductions in hepatic low-density lipoprotein receptor protein and increased plasma low-density lipoprotein cholesterol levels on both chow and Western diets. Moreover, L-sIDOL mice developed marked atherosclerotic lesions when fed a Western diet. Lesion formation in L-sIDOL mice was more robust than in apolipoprotein E*3 Leiden mice and did not require the addition of cholate to the diet. Western diet-fed L-sIDOL mice had elevated expression of liver X receptor target genes and proinflammatory genes in their aortas.
CONCLUSIONS
Liver-specific expression of dominant-active IDOL is associated with hypercholesterolemia and a marked elevation in atherosclerotic lesions. Our results show that increased activity of the IDOL pathway in the liver can override other low-density lipoprotein receptor regulatory pathways leading to cardiovascular disease. L-sIDOL mice are a robust, dominantly inherited, diet-inducible model for the study of atherosclerosis.
Topics: Albumins; Animals; Aorta; Aortic Diseases; Apolipoprotein E3; Atherosclerosis; Cholesterol, LDL; Diet, High-Fat; Diet, Western; Disease Models, Animal; Humans; Hypercholesterolemia; Inflammation Mediators; Liver; Liver X Receptors; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Orphan Nuclear Receptors; Plaque, Atherosclerotic; Promoter Regions, Genetic; Receptors, LDL; Time Factors; Ubiquitin-Protein Ligases
PubMed: 24935961
DOI: 10.1161/CIRCRESAHA.115.304440 -
Cureus Jan 2024Tetralogy of Fallot (TOF) is a common cyanotic congenital heart disease characterized by four distinct anatomical features. While surgical repair has significantly...
Tetralogy of Fallot (TOF) is a common cyanotic congenital heart disease characterized by four distinct anatomical features. While surgical repair has significantly improved long-term outcomes, some individuals, particularly those from low socioeconomic backgrounds who lack access to medical care, may suffer from complications such as pulmonary hypertension (pHTN) and heart failure. We present a case report of a young female with unrepaired TOF who presented with acute-on-chronic hypoxic respiratory failure and heart failure, highlighting the complex nature and challenges associated with this condition.
PubMed: 38371077
DOI: 10.7759/cureus.52407 -
The Journal of Thoracic and... Jun 1995We examined 13 hearts with concordant atrioventricular and ventriculoarterial connections and interruption of the aortic arch to establish and describe the morphologic...
We examined 13 hearts with concordant atrioventricular and ventriculoarterial connections and interruption of the aortic arch to establish and describe the morphologic features of the outflow tracts in relation to axial deviation and malalignment of the outlet septum as opposed to overriding of the arterial valvular orifices. Interruption in all cases but one was between the left common carotid and left subclavian arteries; the other arch was interrupted at the isthmus. A patent arterial duct and ventricular septal defect were universally present. When its borders were viewed from the right ventricle, the ventricular septal defect was perimembranous in seven hearts, had exclusively muscular borders in four hearts, and was doubly committed and juxta-arterial in the remaining two hearts. Malalignment between the muscular ventricular septum and outlet septum, or a fibrous raphe, as judged when the heart was viewed in its short axis, was found in 12 of the hearts. Posterior and leftward axial deviation of the outlet septum in its long axis was found in 4 of the 12 hearts and also in one heart that did not have short-axis malalignment. Attachments of the leaflets of the pulmonary valve in both right and left ventricles, however, were present in only one of the specimens, this being a case with a doubly committed and juxta-arterial defect. These separate features of the outflow tract in hearts with interruption of the aortic arch, therefore, require thorough assessment when surgical management is planned. All these variable features can be assessed preoperatively by cross-sectional echocardiography, which should be directed toward defining the degree of development and alignment of the outlet septum, as well as the length of the subpulmonary infundibulum.
Topics: Aorta, Thoracic; Echocardiography; Female; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Humans; Infant, Newborn; Male; Ventricular Outflow Obstruction
PubMed: 7776687
DOI: 10.1016/S0022-5223(95)70207-5 -
American Journal of Physiology.... Sep 2009The relationship between cardiac energy metabolism and the depression of myocardial performance during oxygen deprivation has remained enigmatic. Here, we combine in...
The relationship between cardiac energy metabolism and the depression of myocardial performance during oxygen deprivation has remained enigmatic. Here, we combine in vivo (31)P-NMR spectroscopy and MRI to provide the first temporal profile of in vivo cardiac energetics and cardiac performance of an anoxia-tolerant vertebrate, the freshwater turtle (Trachemys scripta) during long-term anoxia exposure (approximately 3 h at 21 degrees C and 11 days at 5 degrees C). During anoxia, phosphocreatine (PCr), unbound levels of inorganic phosphate (effective P(i)(2-)), intracellular pH (pH(i)), and free energy of ATP hydrolysis (dG/dxi) exhibited asymptotic patterns of change, indicating that turtle myocardial high-energy phosphate metabolism and energetic state are reset to new, reduced steady states during long-term anoxia exposure. At 21 degrees C, anoxia caused a reduction in pH(i) from 7.40 to 7.01, a 69% decrease in PCr and a doubling of effective P(i)(2-). ATP content remained unchanged, but the free energy of ATP hydrolysis (dG/dxi) decreased from -59.6 to -52.5 kJ/mol. Even so, none of these cellular changes correlated with the anoxic depression of cardiac performance, suggesting that autonomic cardiac regulation may override putative cellular feedback mechanisms. In contrast, during anoxia at 5 degrees C, when autonomic cardiac control is severely blunted, the decrease of pH(i) from 7.66 to 7.12, 1.9-fold increase of effective P(i)(2-), and 6.4 kJ/mol decrease of dG/dxi from -53.8 to -47.4 kJ/mol were significantly correlated to the anoxic depression of cardiac performance. Our results provide the first evidence for a close, long-term coordination of functional cardiac changes with cellular energy status in a vertebrate, with a potential for autonomic control to override these immediate relationships.
Topics: Adaptation, Physiological; Adenosine Triphosphate; Animals; Aorta; Autonomic Nervous System; Energy Metabolism; Heart; Heart Rate; Hydrogen-Ion Concentration; Hydrolysis; Hypoxia; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Myocardial Contraction; Myocardium; Phosphates; Phosphocreatine; Pulmonary Circulation; Regional Blood Flow; Temperature; Time Factors; Turtles
PubMed: 19587113
DOI: 10.1152/ajpregu.00102.2009