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R R Markwald

Publications and source records attributed to R R Markwald.

At least 91 records · Page 5Linked to original sources
PubMed1979

Glycosaminoglycans: potential determinants in cardiac morphogenesis.

Treatment of the embryonic heart shortly after looping with 6-diazo-5-oxo-L-norleucine (DON) primarily inhibited the secretion of hyaluronate by the myocardium, an event accompanied by delayed and reduced formation of AV cushion cells (valvular and septal primordia). Sulfated glycosaminoglycan synthesis (primarily chondroitin-6-sulfate and heparan sulfate) was not significantly reduced until after cushion cell formation, an event accompanied by their altered migratory behavior. Results thus support a causal relationship between the morphogenesis of cushion tissue and extracellular glycosaminoglycans.

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PubMed1979

Effects of hyaluronic acid on cardiac cushion tissue cells in collagen matrix cultures.

To initiate the experimental exploration of the role of extracellular macromolecules in influencing developmental events in the heart, a 3-dimensional substrate culture model of the developing cardiac cushion was devised. One cardiac jelly component, hyaluronic acid, was tested for its effects on morphology and migratory capacity of cushion tissue cells within the collagen matrix substrate. Hyaluronate treatment resulted in: (1) an increase in the number and extent of filopodia, reflected as an increase in cell surface area, and (2) an increase in migratory capacity, reflected as an increase in maximum depth to which cells migrate through the collagen lattice. These results suggest one major role for hyaluronate in the early cardiac cushion is the promotion of a high level of motility capability in the newly seeded cushion tissue cells, required for the key event of cell migration across the developing cushion.

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PubMed1979

Matrical ordering in the morphogenesis of tunica media.

The cells which will form the smooth muscle tunica media are derived embryologically from the cardiac mesenchyme referred to as endocardial cushion tissue. These progenitor smooth muscle cells, however, are derived primarily from aortic arch mesenchyme as opposed to the endocardium in the prevalvular areas. The matrical microenvironments of these cells begin to change at approximately 5 days of development when the progenitor smooth muscle cells acquire a more fibrillar matrix. The prospective adventitia and valvular areas still maintain an environment rich in hyaluronate and proteoglycans. By Day 6, the 110Ao microfibril, characteristic of smooth muscle cells, appears in the matrix well in advance of the amorphous elastin component seen at Days 8 and 9. The orientation of the collagenous microfibrils and elastic microfibrils is non-random with respect to the layers of cells, and this precludes a simple substrate alignment model in establishing the characteristic laminarity of this tissue.

Animals↗
PubMed1977

Structural development of endocardial cushions.

Development of chick and rat endocardial cushions (cardiac mesenchyme) was studied histologically (using Nomarski differential interference optics on living and unfixed tissue), ultrastructurally (scanning and transmission electron microscopy), cytochemically (using acidified dialyzed iron as a visual probe for polyanionic material) and autoradiographically (using 35S) to elucidate the origin of the mesenchyme, the morphologic sequences leading to cushion formation and secretion of sulfated glycosaminoglycans, if any, by migrating mesenchymal cells. Cushion formation was similar for both species. Mesenchymal cells appeared initially, in 16- to 18-somite embryos, beneath the endothelium (which lacked a basal lamina) of the future atrioventricular canal and outflow tract. The cytoplasm of cushion mesenchymal cells was structurally similar to the ensothelium; probably these cells arose by proliferation of the endothelium. Mitotic figures among the "seeded" cells were also numerous. Cushion cells were initially attached to the endothelium by desmosomes but acquired motile apparatus (pseudopodia and filopodia containing microtubules and microfilamentous bundles). Serial sectioning of successively-aged embryos (20-44 somites) indicated a centrifugal migratory direction. Interaction of the cell processes with extracellular matrix suggested that the latter was used as a migratory substrate. Contact of the advancing wedge of cushion cells with the myocardium produced no alteration in cell structure or mitotic activity. Localization of hyaluronidase-sensitive, dialyzed iron (DI) precipitates in 250-nm Golgi vacuoles and hyaluronidase-sensitive 35S-endangendered silver grains over cushion cells indicated that this tissue contributed sulfated macromolecules to the matrix. Localization of hyaluronidase-labile, DI material in coated, endocytic-like vesicles and caveolae also suggested potential modification or conditioning of the matrix by migrating mesenchymal cells. Altogether, the study established loci in developing cushions where disruption where disruption of the developmental sequence could engender valvular or septal defects.

Animals↗
PubMed1975

An ultrastructural and radioimmunoassay study of anterior pituitary somatotrophs following pituitary portal vessel infusion of growth hormone releasing factor.

The hypophysial portal vessels and anterior pituitary glands of adult male rats were surgically exposed, cannulated and infused for 1 min with saline, growth hormone-releasing factor (GH-RF), and dbcAMP. After cessation of infusion, anterior pituitary glands were collected at 1, 5, 15, 30 or 60 min for electron microscopic and ultrastructural cytochemical examination. Before and after cannulation of a portal vessel a 1-ml sample of blood was collected at 1, 5, 15, 30 or 60 min from the femoral vein for RIA of growth hormone. When viewed ultrastructurally, the initial response following the infusion of GH-RF into a portal vessel was one of granule release. Emiocytic activity was observed at all time intervals studied. This response was followed 30 min later by evidence of increased protein synthesis. Significant increases in plasma GH levels were present at 1, 5, and 15 min following infusion of GH-RF but not at 30 or 60 min. Preliminary analysis of the RIA data suggests that dbcAMP was significantly more potent than GH-RF in elevating radioimmunoassayable plasma GH levels. The results suggest that similar mechanisms of synthesis and release were involved.

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PubMedDate not supplied

Morphogenetic alterations during endocardial cushion development in the trisomy 16 (Down syndrome) mouse.

Atrioventricular septal defect occurs with a high prevalence in both human Down syndrome (trisomy 21) and the animal model for this disorder, murine trisomy 16 (Ts-16). The embryologic basis of this defect is the failure of the endocardial cushions to fuse. Quantitatively, Ts-16 hearts, when compared to normal mouse embryos, were not significantly different in either the estimates of whole heart volume or endocardial cushion volume. However, both the raw number of cardiac mesenchyme cells and the cellular density were reduced significantly. Qualitatively, endocardial cushion shape was elongated. Immunohistochemistry revealed an apparent delay in the temporally regulated expression of cytotactin and fibronectin during cushion development. Also, anti-heparan sulfate staining was noted on newly formed cardiac mesenchymal cells. These results suggest that the failure of endocardial cushion fusion in the Ts-16 mouse may be related to an elongated shape of the cushions and an inhibition or delay in the induction, transformation, or seeding of cardiac mesenchymal cells.

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