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Biomedical subjects

R Ross

Publications and source records attributed to R Ross.

At least 379 records · Page 21Linked to original sources
PubMed1978

Physiological quiescence in plasma-derived serum: influence of platelet-derived growth factor on cell growth in culture.

A platelet-derived growth factor can be shown to be the principal stimulant of DNA synthesis in whole blood serum for those cells that require serum for maintenance and growth in culture. Cell free plasma-derived serum lacks such platelet-derived material. 3T3 cells and primate arterial smooth muscle cells can be maintained in a quiescent state in culture for as long as six weeks in plasma-derived serum. Such cells can grow logarithmically after exposure to 5% whole blood serum or as little as 100 ng/ml of partially purified platelet factor. The cell cycle of smooth muscle cells has been studied in the quiescent (5% plasma-derived serum) and growing state (5% whole blood serum or 5% plasma-derived serum plus platelet factor). The generation time of smooth muscle cells is 16 to 18 hours as shown by autoradiographic frequency of labelled mitoses. The generation time is the same for cells in the growth fraction in either 5% whole blood serum or 5% plasma-derived serum. Thus, platelet factor acts by recruiting cells into the growth fraction rather than effecting a change in the duration of the cell cycle. Flow microfluorimetry studies on cells growing logarithmically in 5% whole blood serum give the following phase durations: G1 = 5.6 hours; S = 7.6 hours; and G2 + M = 3.8 hours. Based on these studies the argument is presented that cells cultured in 5% plasma-derived serum provide a more physiological base for the study of quiescence than do cells in low concentrations of whole blood serum or confluent, density inhibited cells at high (5% or greater) concentrations of whole blood serum. Furthermore, 5% plasma-derived serum represents an appropriate state to examine the perturbation of quiescent cells.

Animals↗
PubMed1978

Vessel injury, thrombosis, and platelet survival.

Vascular injury triggers platelet reactions of adhesion, aggregation, and release, and these reactions play important roles in hemostasis, thrombosis and thromboembolism, and atherogenesis. Measurement of platelet and fibrinogen turnover rates are indicators of the relative involvement of platelets and fibrin in the thrombotic process, and also provide an objective means of assessing antithrombotic therapy. Isotopic methods are preferred over chemical methods to measure platelet survival time; 51Cr is used most widely to label platelets. Problems of analysis and interpretation of platelet disappearance curves are reviewed briefly.

Animals↗
PubMed1978

Platelets, endothelium, and smooth muscle cells in atherosclerosis.

A factor derived from platelets stimulates the proliferation of smooth muscle cells in culture, and is likely important in stimulating smooth muscle proliferative lesions of atherogenesis in vivo. The platelet factor is produced during platelet aggregation when serum is made from whole blood. In vitro, smooth muscle cells are potent aggregating agents for platelets, while endothelial cells can inhibit this aggregating effect. Better understanding of the interactions of platelets, smooth muscle cells, and endothelium would facilitate developing effective means of intervening in or preventing the smooth muscle proliferative lesions of atherosclerosis.

Animals↗
PubMed1978

Coordinate control of 3T3 cell proliferation by platelet-derived growth factor and plasma components.

DNA synthesis and cell division were measured in Swiss mouse 3T3 cells cultured in different concentrations of cell-free plasma-derived serum and increasing amounts of a platelet-derived growth factor. In plasma-derived serum alone, the cells were quiescent and they were arrested in the Go/G1 phase of the cell cycle. Addition of a platelet-derived growth factor to quiescent cells maintained in plasma-derived serum stimulated both DNA synthesis and cell division. When plasma components were present at high concentration (5%, vol/vol), the amount of platelet factor added to the cultures determined the number of cell doublings. Plasma-derived molecules were required for the platelet factor to stimulate DNA synthesis and cell division in the maximal number of cells. In addition, plasma components had to be present for recently divided cells to respond to the platelet factor. When 3T3 cells were cultured in excess platelet factor and limiting amounts of plasma-derived serum (0.5%, vol/vol), the cells underwent one doubling and then ceased to proliferate. Addition of fresh plasma-derived serum to these cells induced a second round of cell division. Plasma components and the platelet-derived growth factor acted in a coordinate fashion to regulate the proliferation of Swiss 3T3 cells.

Blood Platelets↗
PubMed1978

Mediation of pinocytosis in cultured arterial smooth muscle and endothelial cells by platelet-derived growth factor.

Pinocytosis was measured in monkey aortic smooth muscle cells (SMC), bovine aortic endothelial cells, and Swiss 3T3 cells in culture as cellular uptake of [U-(14)C]sucrose and horseradish peroxidase (HRP) from the tissue culture medium. Monkey arterial SMC and Swiss 3T3 cells were maintained in a quiescent state of growth at low cells density in medium containing 5 percent monkey plasma-derived serum (PDS). Replacement of PDS with 5 percent monkey whole blood serum (WBS) from the same donor, or addition to PDS of partially purified platelet-derived growth factor(s) (PF), resulted in a marked stimulation of pinocytosis as well as of cellular proliferation. In SMC, enhancement of the rate of pinocytosis occurred 4-6 h after exposure to WBS or PF, and the rate was up to twofold higher than the rate in medium containing PDS. In contrast, [(3)H]thymidine uptake by SMC did not increase until 12-16 h after exposure to PF. In endothelial cells the presence of PF or WBS did not enhance either the rate of pinocytosis or the rate of proliferation over that in PDS. Thus, endothelial cells did not become quiescent at subconfluent densities in PDS but maintained rates of proliferation and pinocytosis that were equivalent to those in WBS. By autoradiography, the fraction of labeled nuclei in SMC cultures 24 h after change of medium increased from 0.061 +/- 0.004 in quiescent cultures to 0.313 +/- 0.028 after exposure to WBS or PF. In contrast, labeling indices of endothelial cells were similar for cultures grown in PDS, WBS, or PF at any single time point after change of medium. These findings suggest that the rate of pinocytosis maybe be coupled in some fashion to growth regulation, which may be mediated in part by specific growth factors, such as that derived from the thrombocyte.

Animals↗
PubMed1978

Fine structure alterations of elastic fibers in pseudoxanthoma elasticum.

Examination by electron microscopy of the elastic fibers of individuals with Pseudoxanthoma Elasticum (PXE) revealed that the principal alterations were in the elastin moiety of the elastic fibers. The elastin had a granular appearance, an increased affinity for cationic stains, and it often demonstrated sites of increased density presumed to represent foci of calcification. In contrast to the elastin, the microfibrillar component of the elastic fibers was unchanged, both in morphologic appearance and in distribution. There was no clear correlation between the extent of the morphologic alteration in the elastic fiber and the level of clinical severity. Morphologically altered fibers were often found together with unaltered fibers. Changes similar to those seen in patients with PXE were also found in biopsies obtained from clinically unaffected consanguinous relatives. The pattern of inheritance in several of the families examined was compatible with autosomal recessive, whereas in at least one family a more complex mode of transmission seems likely. The electron microscopic data therefore provide further support for the genetic heterogeneity of PXE.

Adolescent↗
PubMed1978

Role of platelet factors in the growth of cells in culture.

The studies reported suggest that the principal mitogen(s) present in sera responsible for the proliferation of diploid cells in culture is derived from the physiologic response of platelet adherence, aggregation, and release upon their exposure to factors present in serum, such as thrombin, or in tissue, such as collagen. Since it is impossible to make whole blood serum without platelet release, all sera contain platelet mitogenic factor(s). In contrast, serum made from platelet-free plasma lacks mitogenic activity and permits maintenance of cells in culture in a quiescent state for long periods if the cells are routinely fed. The platelet factor(s) appears to be a heat-stable, basic polypeptide or protein, that upon exposure to the cells recruits them into the cell cycle, DNA synthesis, and mitosis. The factor(s) has been shown to act not only in cell culture but in vivo as well. Maintaining cells in a culture medium containing platelet-free, plasma-derived serum may be more analogous to the quiescence of adult cells in vivo, since quiescent cells in adult tissues are normally exposed to interstitial fluid that is probably more like a filtrate of plasma or lymph rather than to whole blood serum. In contrast, growth of cells in a culture medium containing whole blood serum would be more analogous to the pathologic situation that occurs during tissue injury accompanied by hemorrhage.

Animals↗
PubMed1977

Two cholesterol ester hydrolases. Distribution in rat tissues and in cultured human fibroblasts and monkey arterial smooth muscle cells.

Hydrolytic activity against acetone-dispersed [4-14C]cholesterol oleate has been assayed as a function of pH in seven parenchymal tissues, blood cells, and plasma of the rat, as well as in cultured human fibroblasts and monkey (Macaca nemestrina) arterial smooth muscle cells. Both acid and neutral hydrolytic activities were present in all of these except rat plasma. The pH optima were in all cases close to pH 4.5 and pH 6.8. Acid activity was quite constant from tissue to tissue, while neutral activity varied greatly, being greatest in adrenal, testis, and adipose tissue. Subcellular fractionation of human fibroblasts allowed demonstration that activities at pH 4.5 and pH 6.8 were concentrated in different fractions, apparently lysosomal and polysomal, respectively. It appears most cell types, including fibroblasts and smooth muscle cells, contain two separate enzymes capable of hydrolyzing cholesterol esters. The neutral pH polysomal enzyme, which is especially prominent in certain tissues, may have a function related to the specialized roles of these tissues.

Animals↗
PubMed1977

Quantitation of dimethylnitrosamine in the whole mouse after biosynthesis in vivo from trace levels of precursors.

A simple and highly sensitive procedure is described for the recovery and quantitative identification of nanogram quantities of preformed N-nitroso compounds in the whole mouse. This procedure has also been applied to the quantitation of N-nitroso compounds after they have been biosynthesized from trace amounts of precursors. The whole animal is frozen in liquid nitrogen and homogenized to a frozen powder; the powder is then extracted and analyzed by a thermal energy analyzer interfaced to a gas-liquid and a high-pressure liquid chromatograph.

Animals↗
PubMed1977

Synthesis of types I and III procollagen and collagen by monkey aortic smooth muscle cells in vitro.

Analysis of pepsin-resistant proteins produced in culture by monkey aortic smooth muscle cells (SMC) indicates the synthesis of types I and III collagen. As determined by carboxymethylcellulose chromatography and disc gel electrophoresis, SMC cultures synthesize more type III collagen than monkey skin fibroblast cultures; aortic adventitial cell cultures (a mixture of SMC and fibroblasts) synthesize an intermediate amount of type III collagen. Both types I and III procollagens can also be isolated from the culture medium of SMC and skin fibroblasts. The procollagens were separated by diethylaminoethylcellulose (DEAE-cellulose) chromatography in identified by electrophoresis and after cleavage with pepsin and cyanogen bromide. Quantitation of the procollagen by DEAE-cellulose chromatography suggests that 68% of the SMC procollagens and less than 10% of the skin fibroblast procollagens are type III. On the other hand, estimation of the proportions of collagen types secreted by cells, employing pepsin digestion of cell culture medium at 15 degrees C, leads to an underestimation of the amount of type III collagen relative to type I. SMC and fibroblasts may differ in their ability to convert type I procollagen to collagen ad indicated by the observation that skin fibroblast culture medium contains both pN and pC collagen intermediates after 24 h, while cultures of SMC essentially lack the pC collagen intermediates.

Animals↗