UDP-glucose dehydrogenase required for cardiac valve formation in zebrafish.
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Cardiac valve formation is a complex process that involves cell signaling events between the myocardial and endocardial layers of the heart across an elaborate extracellular matrix. These signals lead to marked morphogenetic movements and transdifferentiation of the endocardial cells at chamber boundaries. Here we identify the genetic defect in zebrafish jekyll mutants, which are deficient in the initiation of heart valve formation. The jekyll mutation disrupts a homolog of Drosophila Sugarless, a uridine 5'-diphosphate (UDP)-glucose dehydrogenase required for heparan sulfate, chondroitin sulfate, and hyaluronic acid production. The atrioventricular border cells do not differentiate from their neighbors in jekyll mutants, suggesting that Jekyll is required in a cell signaling event that establishes a boundary between the atrium and ventricle. (+info)
Surgical management of left-sided carcinoid heart disease.
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BACKGROUND: Carcinoid involvement of left-sided heart valves has been reported in patients with a patent foramen ovale, carcinoid tumor of the lung, and active carcinoid syndrome with high levels of serotonin. The present study details the clinical features and surgical management of patients with carcinoid heart disease affecting both left- and right-sided valves. METHODS AND RESULTS: Eleven patients (7 men, 4 women) with symptomatic carcinoid heart disease underwent surgery for left- and right-sided valve disease between 1989 and 1999. Mean age was 57+/-9 years, and median preoperative NYHA class was 3. All patients had metastatic carcinoid tumors and were on somatostatin analog. Of 11 patients, 5 (45%) had a patent foramen ovale; 1 of these also had a primary lung carcinoid tumor. Surgery included tricuspid valve replacement in all patients, pulmonary valve replacement in 3 and valvectomy in 7, mitral valve replacement in 6 and repair in 1, aortic valve replacement in 4 and repair in 2, CABG in 2, and patent foramen ovale closure in 5. One myocardial metastatic carcinoid tumor was removed. There were 2 perioperative deaths. At a mean follow-up of 41 months, 4 additional patients were dead. All but 1 surgical survivor initially improved >/=1 functional class. No patient required reoperation. CONCLUSIONS: Carcinoid heart disease may affect left- and right-sided valves and occurred without intracardiac shunting in 55% of this surgical series. Despite metastatic disease that limits longevity, operative survivors had improvement in functional capacity. Cardiac surgery should be considered for select patients with carcinoid heart disease affecting left- and right-sided valves. (+info)
Septation and valvar formation in the outflow tract of the embryonic chick heart.
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There is no agreement, in the chick, about the number of the endocardial cushions within the outflow tract or their pattern of fusion. Also, little is known of their relative contributions to the formation of the arterial valves, the subpulmonary infundibulum, and the arterial valvar sinuses. As the chick heart is an important model for studying septation of the outflow tract, our objective was to clarify these issues. Normal septation of the outflow tract was studied in a series of 60 staged chick hearts, by using stained whole-mount preparations, serial sections, and scanning electron microscopy. A further six hearts were examined subsequent to hatching. At stage 21, two pairs of endocardial cushions were seen within the developing outflow tract. One pair was positioned proximally, with the other pair located distally. By stage 25, a third distal cushion had developed. This finding was before the appearance of two further, intercalated, endocardial cushions, also distally positioned, which were first seen at stage 29. In the arterial segment, the aortic and pulmonary channels were separated by the structure known as the aortopulmonary septum. The dorsal limb of this septum penetrated the distal dorsal cushion, whereas the ventral limb grew between the remaining two distal cushions, both of which were positioned ventrally. The three distal endocardial cushions, and the two intercalated endocardial cushions, contributed to the formation of the leaflets and sinuses of the arterial roots. The two proximal cushions gave rise to a transient septum, which later became transformed into the muscular component of the subpulmonary infundibulum. Concomitant with these changes, an extracardiac tissue plane was formed which separated this newly formed structure from the sinuses of the aortic root. Our study confirms that three endocardial cushions are positioned distally, and two proximally, within the developing outflow tract of the chick. The pattern of the distal cushions, and the position of the ventral limb of the aortopulmonary septum, differs significantly from that seen in mammals. (+info)
Alignment maps of tissues: II. Fast harmonic analysis for imaging.
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A methodology for generating polarized light retardation and alignment direction images is presented. A rotated quarter-wave plate changes the linear polarized light to a polarized probe with various degrees of ellipticity by which samples are imaged with the use of a circular analyzer. A harmonic representation of image intensity allows simple analysis, requiring only simple image operations and realizing four orders-of-magnitude computational savings for strongly aligned tissues, where linear birefringence is the dominant optical property. The method is demonstrated for a porcine heart valve leaflet. (+info)
Differential expression of retinoic acid-synthesizing (RALDH) enzymes during fetal development and organ differentiation in the mouse.
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Three retinaldehyde dehydrogenases (RALDH1, RALDH2 and RALDH3), which catalyze the oxidation of retinaldehyde into retinoic acid, have been shown to be differentially expressed during early embryogenesis. Here, we report their differential expression patterns throughout later mouse organogenesis. Raldh1 is prominently expressed in developing lung (notably in bronchial and tracheal epithelia), and shows stage-specific expression in stomach and intestine epithelial and mesenchymal layers. Raldh3 expression is specific to the differentiating intestinal lamina propria. Raldh2 is expressed throughout the kidney nephrogenic zone, whereas Raldh1 and Raldh3 are mostly expressed in collecting duct epithelia. Raldh3 expression is more restricted than that of Raldh1 in the urogenital tract and sex gland epithelia, whereas Raldh2 expression is mesenchymal. Raldh1 is coexpressed with Raldh2 in the early heart epicardium, and is later specifically expressed in developing heart valves. All three genes exhibit distinct expression patterns in respiratory and olfactory epithelia and/or mesenchymes, and in developing teeth. Only Raldh1 expression is seen after birth in specific brain structures. These data indicate a requirement for regulated RA synthesis in various differentiating organs. (+info)
Expression of bone morphogenetic protein-5 gene during chick heart development: possible roles in valvuloseptal endocardial cushion formation.
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The bone morphogenetic protein (BMP) family, comprising multifunctional peptide growth factors, regulates many developmental processes in a variety of tissues. We examined the spatiotemporal expression of BMP5 by in situ hybridization in chick embryonic hearts from stages 5 to 33. The BMP5 gene was first expressed in the endoderm underlying the precardiac mesoderm at stages 5 to 8. Thereafter, BMP5 expression was restricted to the myocardium of the atrioventricular (AV) canal and outflow tract (OT) regions, where the valvuloseptal endocardial cushion tissue is induced. These results suggest that BMP5 may play important roles not only in myocardial differentiation, but also in the formation and maintenance of endocardial cushion tissue. (+info)
In vitro susceptibility to thrombin-induced platelet microbicidal protein is associated with reduced disease progression and complication rates in experimental Staphylococcus aureus endocarditis: microbiological, histopathologic, and echocardiographic analyses.
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BACKGROUND: Mammalian platelets contain small, cationic, staphylocidal peptides, termed thrombin-induced platelet-microbicidal proteins (tPMPs). Evidence suggests that tPMPs play a key role in host defense against endovascular infections, such as infective endocarditis (IE). In the present study, we evaluated the influence of differences in staphylococcal tPMP-susceptibility profiles in vitro on disease severity in experimental IE. METHODS AND RESULTS: Experimental IE was induced in rabbits with either a tPMP-susceptible or an isogenic tPMP-resistant Staphylococcus aureus strain. Vegetation size, left ventricular fractional shortening, and onset of aortic valvular regurgitation were serially assessed by echocardiography over an 11-day postinfection period. In addition, blood cultures were performed daily. Parameters delineated at autopsy included vegetation weights; bacterial densities in vegetations, myocardium, and kidneys; extent of valvular and perivalvular tissue damage; and renal embolization. The following significant differences were observed in animals infected with the tPMP-susceptible versus the tPMP-resistant S aureus strain: substantially lower bacteremia rates (P=0.02); reduced vegetation growth (P<0.001) and weight (P<0.001); a later onset of aortic valvular regurgitation (P=0.0039); increased preservation of left ventricular function (P<0.001); reduced valvular tissue damage (P=0.01) and perivalvular inflammation (P=0.015); and reduced bacterial densities in vegetations (P<0.001) and kidneys (P<0.01). CONCLUSIONS: The in vitro tPMP-susceptibility profile in S aureus substantially affects a number of well-defined cardiac and microbiological parameters related to disease severity and prognosis in IE. These findings underscore the likelihood that platelets mitigate the pathogenesis of endovascular infections via local secretion of antimicrobial peptides. (+info)
Normal cardiac flow velocities at 14-16 weeks of gestation measured by transvaginal ultrasound.
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OBJECTIVE: Doppler ultrasound has been used to study the flow velocities through the valves and arteries of the fetal heart. Using transvaginal sonography, we sought to determine normal values for flow velocities through the fetal heart valves at 14-16 weeks of gestation. METHODS: Eighty-seven normal fetuses were examined. The flow velocity waveforms were visualized using Doppler ultrasound with the sample volume calipers placed just distally to the four fetal valves. Peak E- and A-wave velocities were recorded for the tricuspid and mitral valves and peak systolic flow velocities were recorded for the ascending aorta and pulmonary arteries. Linear regression for comparison of flow velocities with gestational age was performed. RESULTS: There was no significant correlation between any of the velocities and gestational age. CONCLUSIONS: Flow velocities through the fetal cardiac valves remain unchanged at 14-16 weeks of gestation as measured by transvaginal Doppler sonography. (+info)