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Biomedical subjects

J Leighton

Publications and source records attributed to J Leighton.

At least 55 records · Page 3Linked to original sources
PubMed1983

Mitral valve E point to ventricular septal separation in infants and children.

This investigation establishes heretofore unavailable norms that permit clinical application of mitral valve E point to ventricular septal separation (EPSS) as an ejection phase index in infants and children. The study consisted of 105 normal subjects (1 day through 15 years of age, mean 7.4 years) and 67 patients of comparable age. Fifty-seven patients had increased left ventricular (LV) volume with normal function (ventricular septal defect or patent ductus arteriosus) and 10 patients had increased LV volume with depressed function (dilated cardiomyopathy). In normal subjects, EPSS was 2.5 +/- 1.7 mm and "normalized" EPSS, that is, the ratio of EPSS to end-diastolic dimension (EPSS/EDD), was 0.08 +/- 0.06 (mean +/- standard deviation); there was no correlation between either of these indexes and age, body surface area, height or weight. In patients with ventricular septal defect or patent ductus arteriosus, or both, the EPSS and EPSS/EDD were similar to those of normal subjects (3.2 +/- 2.3 mm and 0.09 +/- 0.06 mm, respectively). In patients with dilated cardiomyopathy, these indexes were significantly increased (p greater than 0.05) (EPSS 16.5 +/- 5.1 mm; EPSS/EDD 0.39 +/- 0.09). The data provide normal values for EPSS and EPSS/EDD in infants and children and show that these indexes are independent of age, body surface area, height or weight. Mitral valve EPSS and EPSS/EDD can now be used in pediatric echocardiography as a simple, practical and accurate means of separating normal from abnormal LV function.

Adolescent↗
PubMed1983

Angiogenesis-dependent tumor spread in reinforced fibrin clot culture.

To investigate the role played by developing microvessels in the spread of tumors, segments of rat aorta were cultured with aggregates of NBT-II-81, a cell line derived from squamous cell carcinoma of rat bladder. Aortic rings cultured in plasma clot gave rise to microvascular networks composed of branching endothelial channels. Aggregates of carcinoma in contract with fibrin clot alone grew slowly and by expansion. When the proliferating branching endothelial sprouts and channels contacted the tumor aggregates, the pattern of neoplastic growth changes abruptly, as carcinoma cells infiltrated the fibrin clot, migrating and proliferating in periendothelial location. Some vascular channels were disrupted and permeated by cords of invading tumor cells. Ultrastructural studies revealed intimate associated between invading epithelial cells and endothelial cells. Focal fusion of the endothelial basal lamina with the basal lamina of the tumor cells was observed. Our results demonstrate that angiogenesis in vitro, ie., in absence of active circulation, markedly enhanced the spread of a carcinoma in plasma clot and modified its pattern of growth. This indicates that other vascular-related factors beside nutritional gradients from the circulation attract tumor cells along endothelial paths.

Animals↗
PubMed1982

Histotypic angiogenesis in vitro: light microscopic, ultrastructural, and radioautographic studies.

A model for the study of angiogenesis in vitro is described. Rat aortas, cultured in a tridimensional matrix of clotted chick plasma, gave rise to luxuriant outgrowth of vascular channels. We studied this process with light microscopic, radioautographic, and ultrastructural techniques. On the 2nd d of culture, endothelial cells sprouted from the intima of the aorta and its collateral branches into the surrounding clot, forming solid cellular cords. A complex vascular network was established within the 1st wk by spindly, poorly differentiated endothelial cells. At this stage cells were migrating, branching, and proliferating in a longitudinal fashion (labeling index: 67.4% +/- 7.7). Lumens, when present, appeared as slitlike spaces enclosed with junctional complexes. By the end of the 2nd wk the migratory activity decreased and proliferation occurred mostly in a cross-sectional plane, with formation of large patent lumens (labeling index: 48% +/- 3.1). Vascular channels were lined by prominent endothelial cells rich in rough endoplasmic reticulum, polysomes, mitochondria. Golgi apparatuses, and coated vesicles. Cells were enveloped with a ruthenium red positive layer, particularly abundant on the luminal surface and in the interendothelial space. A discontinuous basal lamina was present along the abluminal side. At 28 d the labeling index was reduced to 2.25% +/- 0.9. The still viable endothelium exhibited numerous microfilaments and microtubules, decreased cytoplasmic organelles, and increased pinocytotic activity. This experimental model, histophysiologic gradient culture, provides us with a new tool for the study of vascular morphogenesis, angiogenesis dependent growth of tumors, and neoplastic intravasation.

Animals↗
PubMed1981

3':5'-stimulation of cyst formation by dibutyryl cyclic adenosine monophosphate in human urinary bladder tumors cultured in vitro.

Ten cases of human urinary bladder tumors, varying from histological Grades I to III, were cultured as fragments on a gyratory shaker. Low-grade tumors formed cysts spontaneously, and dibutyryl cyclic adenosine 3':5'-monophosphate stimulated both the number and the size of cysts. Grade III tumors did not form any cysts in culture, and, with light microscopy, dibutyryl cyclic adenosine 3':5'-monophosphate had no visible effect on the fragments. The cells lining the cysts that occurred in the aggregates were characterized by the appearance of zonula occludens on the aspect of the cells facing the culture medium. Two types of cysts were observed: some were lined by a monolayer of cells; and some were lined by a multilayer. In the former, zonula occludens appeared on the aspect facing the culture medium; in the latter, zonula occludens appeared on both the aspect facing the culture medium and that facing the cavities. These specialized structures functioned as tight intercellular junctions as one component of the complex of functions required for effective transport by sheets of epithelium.

Bucladesine↗
PubMed1980

Effect of cell-substratum interaction on hemicyst formation by MDCK cells.

On impermeable substrata MDCK cells, a cell line derived from normal dog kidney, forms a confluent monolayer that is studded with numerous hemicysts. Previous studies with this cell line suggest that thes hemicysts develop as a result of active fluid accumulation between cell sheet and substratum. However, the formation of hemicysts as a multifocal phenomenon is still unexplained. The results presented here show that the hemicysts are not only expressions of active transport of solutes and water, but also of cell-substratum interaction. The increase in number and size of the hemicyst produced by dbcAMP may be explained by a decrease in the adhesive strength to substrata produced by this compound. Moreover, when the strength of the cell-substratum adhesion was increased the number of hemicysts was reduced or abolished. On the contrary, when this strength was reduced, larger hemicysts occurred, covering practically all the area available for growth. Results from cinematographic time lapse studies, showing that 90% of the area of the monolayer is able to produce hemicysts, also suggest that hemicyst formation as a multifocal phenomenon is more an expression of local variations in cell-substratum interaction than of regional changes in transepithelial active transport.

Animals↗
PubMed1979

Hemicyst formation stimulated by cyclic AMP in dog kidney cell line MDCK.

Certain epithelial cell lines have morphologic, physiologic, biochemical and pharmacologic characteristics of transporting epithelia from intact organs. In this paper we show that dibutyryl cyclic AMP, 5' AMP, adenosine and cyclic AMP phosphodiesterase inhibitors stimulate hemicyst formation by the dog kidney cell line MDCK. It is suggested that this effect is explained by elevation of intracellular cyclic AMP levels by means of an exogenous non-metabolizable source of cyclic AMP, phosphodiesterase inhibition or adenyl cyclase stimulation. Since hemicyst formation is in part due to transepithelial fluid transport, these findings raise the possibility that this fraction might be modulated by cAMP in an established cell line. We believe that cultured epithelial cells may provide an exploitable model system to investigate at the cellular and subcellular levels, the mechanism by which cyclic AMP modifies water and solute movements across epithelia.

Adenine Nucleotides↗
PubMed1979

The effect of vitamin A on the migration and DNA synthesis of rat bladder tumor cell line NBT II in culture.

In the presence of vitamin A, NBT II cells, derived from a carcinoma of rat bladder, grew as a monolayer with diminished piling up. Keratinization, which normally appeared within stratified cells in postconfluent cultures, was inhibited. A "wounding" technique suitable for quantitative analysis of cell migration was developed for confluent cultures grown on glass coverslips. Vitamin A treatment enhanced the migration of cells from the wound edge. In dense postconfluent monolayer cultures, vitamin A treatment maintained a higher percentage of cells in DNA synthesis than in the control cultures, as determined by 3H-TdR uptake and autoradiography. In contrast, in sparse cultures vitamin A did not stimulate DNA synthesis or increase the mitotic index. This stimulatory effect, limited to dense cultures, may be attributable to vitamin A causing viable cells to be shed into the medium, thereby maintaining the monolayer just at confluence. Thus vitamin A inhibits squamous cell differentiation, enhances migration, and maintains the culture in the proliferative phase. In a different system of high cell density, NBT II aggregates cultured in a combined matrix of chick plasma clot and collagen-coated sponge, vitamin A also enhanced the migration of cells. These results may explain, in part, the failure of vitamin A to inhibit completely the growth of some established tumors.

Animals↗
PubMed1978

Distribution and characteristics of the occluding junctions in a monolayer of a cell line (MDCK) derived from canine kidney.

On solid substrates MDCK, a cell line derived from normal dog kidney, forms a confluent monolayer that is studded with "blisters". Previous studies with this cell line suggest that these hemicysts develop as a result of active fluid accumulation between cell sheet and substratum. One factor that may determine when and how hemicysts appear only in localized sites is the interruption of occluding junctions in nonhemicyst areas. To study this possibility, we compared the permeability characteristics of the occluding junctions in hemicysts and in an uninterrupted monolayer of MDCK grown on a permeable support of collagen-coated nucleopore filter. The spontaneous electrical potential differences were small, without statistical differences between them. Relative ionic permeability coefficients were evaluated from the voltage deflections to imposed salt gradients or to a single ion substitution across both structures. The results showed that the relative permeability ratios for Na+, K+, choline+, and Cl- were the same in hemicysts and the uninterrupted monolayer. These and other results indicate that the junctional complex encircling the apical surface of a sheet of MDCK cells can provide an effective permeability barrier constituting a true occluding junction with the same properties in hemicyst and nonhemicyst areas.

Cell Line↗
PubMed1978

Clinical bladder cancer in sponge matrix tissue culture: procedures for collection, cultivation, and assessment of viability.

We studied the growth of surgically resected human bladder cancer in three dimensional tissue culture, Observations were made in the living cultures and after the sponge matrix cultures were fixed and prepared as histologic sections. We compared the histologic appearance of each tumor immediately after removal and after a week in culture. In a few instances the donor tumor was kept in medium at room temperature for one day before being inoculated into the matrix. This delay had only slight deleterious effect on the growth in culture. Over 85 consecutive cases have been placed in culture and the first 47 have been evaluated in histologic preparations. Tumors grew into the matrix with distinctly different patterns even when the zero time specimens were of similar histopathology. We also studied several antibiotics to idenify conditions that would suppress the usual urinary bacterial contaminants without producing cytotoxicity to tumor cells by microscopic evaluation. A combination of gentamicin and kanamycin, each at a concentration of 50 microgram/ml was effective.

Culture Media↗
PubMed1977

Cell surface glycosaminoglycans of cell line MDCK derived from canine kidney.

Morphological observations and biochemical analysis were made on glycosaminoglycans produced by MDCK cells of dog kidney origin growing on a glass surface as a mosaic of epithelium with many multicellular hemishperical vesicles. MDCK cells synthesized glycosaminoglycans, which consisted mainly of heparan sulfate and hyaluronic acid. The majority of the substances were contained in a cell-surface component removable with ethylenediaminetetraacetic acid-trypsin. In the radioautograph of tissue sections, high radioactivity of 35SO4 was observed on the medium-bathed cell surface, where Alcian blue-strained material could be observed. Ultrastructurally, the surface of microvillous processes which were abundant on the cell surface in contact with the medium was stained with ruthenium red. A small amount of chondroitin 4- and 6-sulfates were also synthesized. After 24 hr, the majority of chondrotin [35S] sulfates newly formed were secreted into the cultured medium, whereas haparan [35S] sulfate was released much less, remaining as a cellular component. The biological roles of glyconsaminoglycans produced by epithelial cells are discussed.

Animals↗