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N Sorgente

Publications and source records attributed to N Sorgente.

At least 55 records · Page 3Linked to original sources
PubMed1985

Vitreous stimulates proliferation of fibroblasts and retinal pigment epithelial cells.

In proliferative vitreoretinopathy, retinal pigment epithelial cells and glial cells migrate into the vitreous, proliferate, and assume characteristics of myofibroblasts. The addition of vitreous to the culture media stimulates the proliferation of porcine retinal pigment epithelial cells, bovine and lapine dermal fibroblasts but not the proliferation of bovine aortic endothelial cells and smooth muscle cells. The mitogenic activity is not species-specific, since vitreous from various species stimulates the proliferation of these cells. The mitogenic activity is destroyed by heating at 100 degrees C for 10 min or by trypsin treatment. Since the vitreous, under our assay conditions, was not mitogenic for endothelial cells or smooth muscle cells, the mitogenic activity is probably not derived from leakage into the vitreous of circulating fibroblast, epidermal or platelet-derived growth factor.

Animals↗
PubMed1985

Effect of adriamycin on experimental proliferative vitreoretinopathy in the rabbit.

The cell injection model of proliferative vitreoretinopathy (PVR) in the rabbit was used to study the therapeutic value of intravitreal adriamycin (doxorubicin). Adriamycin in a dose of 10 nmol per eye, if injected at the same time as the cells, controls PVR. At the cell doses used, PVR is not affected if there is a time interval between cell and drug injection. Because of retinal toxicity, as evidenced by electroretinographic and histopathologic changes, the beneficial effects of adriamycin on membrane formation cannot be exploited at this time.

Animals↗
PubMed1985

Altered growth kinetics of dermal fibroblasts and arterial smooth muscle cells from spontaneously diabetic BB rats.

We cultured arterial smooth muscle cells and dermal fibroblasts from spontaneously diabetic BB rats and normoglycemic littermate controls. Although there were no detectable differences in the morphology of cells obtained from diabetic rats, significant differences existed in growth parameters of the diabetic smooth muscle cells. These cells grew more rapidly than smooth muscle cells from normal rats (population doubling times: normal = 42.6 +/- 3.2 h, diabetic = 31.8 +/- 3.7 h) and attained greater densities at confluence. The growth rates of the diabetic smooth muscle cells were dependent on the initial seeding density of cells, a characteristic not observed in cells from normal rats. Although growth rates of the diabetic smooth muscle cells were increased, their plating efficiencies were reduced. Dermal fibroblasts from diabetic rats grew at the same rates as fibroblasts from control animals and the plating efficiencies of the diabetic fibroblasts were increased rather than reduced. In these studies, we have shown that vascular-derived cells from diabetic rats have growth defects not detected in dermal fibroblasts from the same animals. This emphasizes the importance of using blood vessel cells to probe the pathophysiology of diabetic vascular disease. Furthermore, our results establish the validity of using spontaneously diabetic rats as a model system for examining inherent cell defects in insulin-dependent diabetes mellitus.

Animals↗
PubMed1985

Daunomycin in the treatment of experimental proliferative vitreoretinopathy. Effective doses in vitro and in vivo.

In previous studies the authors have shown that daunomycin, an anthracycline antibiotic, when injected into the vitreous effectively controls experimental proliferative vitreoretinopathy. Here we show that by administering daunomycin intravitreally it is possible to achieve in vivo concentrations that prevent fibroblast proliferation in vitro. The authors have also determined that the half-life of daunomycin in the vitreous is 131 min, indicating that a critical concentration is maintained in the eye for longer than 4 hr after a single injection. Using 3H-daunomycin, the authors have found that the drug is eliminated across the retina; no significant binding of the drug to vitreous components occurs. These studies demonstrate that it is possible to define the kinetics of drugs injected into the vitreous; and a knowledge of the distribution of any drug in ocular tissues is necessary to effectively determine whether such drug is of therapeutic value.

Animals↗
PubMed1984

Fibronectin-induced protein carboxy-O-methylation in aortic endothelial cells.

In a previous report (Bowersox, J.C. and Sorgente, N. (1982) Cancer Res. 42, 2547-2551) we demonstrated that the glycoprotein fibronectin is a chemoattractant for vascular endothelial cells. In probing the mechanisms by which fibronectin induces endothelial cell chemotaxis, we have discovered that the carboxy-O-methylation of cellular proteins is stimulated by fibronectin. By measuring the incorporation of L-[methyl-3H]methionine into alkali-labile, [3H]methyl ester linkages, we determined that fibronectin stimulated protein carboxy-O-methylation in aortic endothelial cells in a time- and concentration-dependent manner; the greatest stimulation occurred at 100 micrograms/ml fibronectin (approx. 35% above controls). When inhibitors of carboxymethylation were added, fibronectin-induced stimulation of protein methylation did not occur. Furthermore, inhibitors of methylation prevented the chemotaxis of endothelial cells in response to fibronectin. These data support our hypothesis that fibronectin mediates endothelial cell chemotaxis, such as that occurring during neovascularization. As carboxy-O-methylation of cell proteins is also effected by fibronectin, transmethylation reactions may be an important component of endothelial cell chemotaxis.

Adenosine↗
PubMed1984

Surgical removal of vitreous. Its effect on intraocular fibroblast proliferation in the rabbit.

The effect of surgical removal of vitreous on intraocular fibroblast proliferation was studied in an animal model. Forty-eight young adult pigmented rabbits were vitrectomized; four groups of eight animals subsequently received intravitreal injection of tissue-cultured rabbit dermal fibroblasts in doses of 50,000, 100,000, 250,000, and 750,000 cells. As controls, eight vitrectomized rabbits received intravitreal culture medium alone, and the remaining eight vitrectomized rabbits were left uninjected. An additional 40 normal rabbits received the same injections of the same four doses and served as nonvitrectomized controls. All animals were observed for 28 days after injection. The results were dose related and showed that vitrectomy aggravated intraocular fibroblast proliferation in that traction retinal detachment occurred earlier and was more severe in the vitrectomized than in the nonvitrectomized controls.

Animals↗
PubMed1984

Daunomycin in the treatment of experimental proliferative vitreoretinopathy: retinal toxicity of intravitreal daunomycin in the rabbit.

The retinal toxicity of daunomycin, a drug that effectively suppresses experimental proliferative vitreoretinopathy (PVR), was studied in the rabbit by clinical examination, electroretinography (ERG), light microscopy, and electron microscopy. Although no toxicity was observed at the therapeutically effective dose of 10 nmol per eye, the safety margin is too small to recommend this drug for therapy of proliferative vitreoretinopathy in man.

Animals↗
PubMed1984

Total poly(A+)-messenger RNA from bovine lens cofractionates with sucrose purified fiber cell plasma membrane.

Poly(A+)-messenger RNA was isolated from bovine lens as well as poly(A+)-mRNA from crude and sucrose-purified plasma membrane. Bovine lens MP26 antisera was also propagated in rabbits, from which anti-MP26 IgG was partially purified and used to assay for the specific synthesis of MP26 during in vitro translation of the isolated poly(A+)-mRNAs. We found that membrane-associated poly(A+)-mRNA supported the synthesis of proteins which were identical to those translated from total lens fiber cell poly(A+)-mRNA. These proteins included MP26, as assayed by immunoprecipitation of [35S]-labeled MP26.

Animals↗
PubMed1984

Proliferative vitreoretinopathy: the rabbit cell injection model for screening of antiproliferative drugs.

Injection into the rabbit vitreous of cultured cells results in a condition that mimics some of the features of proliferative vitreoretinopathy (PVR) in man. Because of its simplicity and reproducibility, this model is especially useful for screening drugs that may control or inhibit intraocular cell proliferation. The cell injection model of PVR is reviewed, and some modifications are described.

Animals↗
PubMed1984

Endogenous regulation of endothelial cell proliferation.

Bovine aortic endothelial cells (BAEC) in culture have the ability to regulate their own proliferation. We have found that a fraction below 100,000 daltons obtained from the media of confluent cultures of BAEC inhibits tritiated thymidine [3H]TdR incorporation as well as their proliferation. The inhibition is dose- and time-dependent; maximum inhibition of [3H]TdR incorporation occurs 8 hr after cells are released from synchronization and the inhibitory fraction is added. Inhibition is evident at concentrations as low as 50 micrograms/ml and reaches a maximum at 600 micrograms/ml. The blockage of [3H]TdR incorporation is reflected in the inhibition of cell proliferation. In the presence of 400 micrograms of endogenous inhibitor per ml of media, added at the time of plating, the average population doubling time increases from 19 to 41 hr. These findings indicate that, in culture, BAEC can regulate their own proliferation by synthesizing an endogenous inhibitor(s) of proliferation.

Animals↗
PubMed1984

Effects of cytotoxic drugs on proliferative vitreoretinopathy in the rabbit cell injection model.

The effects of adriamycin, 5-fluorouracil, methotrexate, triamcinolone and Viroptic on an experimental model of proliferative vitreoretinopathy (PVR) produced by the injection of homologous dermal fibroblasts into the rabbit vitreous were studied. Adriamycin and fluorouracil inhibited fibroblast proliferation and prevented the formation of membranes as well as did triamcinolone, whereas methotrexate and Viroptic had no beneficial effect in this model of PVR.

Animals↗
PubMed1983

Control of experimental massive periretinal proliferation by daunomycin: dose-response relation.

A condition similar to massive periretinal proliferation in man can be produced in rabbits by injecting homologous fibroblasts into the vitreous. We have studied the effect of daunomycin, a cytotoxic drug, in this model to determine a dose which would not be toxic to the retina but would be effective in preventing proliferation of the injected fibroblasts and eventual retinal detachment. The results of this study demonstrate that daunomycin at a dose of 9 nmol per eye reduces the incidence of retinal detachment by over 50%. Doses higher than 30 nmol per eye are toxic to the retina.

Animals↗
PubMed1983

Fibronectin and laminin distribution in bovine eye.

Using immunofluorescent techniques we have examined the distribution of the glycoproteins, fibronectin and laminin, in bovine eyes. As expected, both fibronectin and laminin were present in blood vessel walls and in all basement membranes, including the internal limiting membrane of the retina. Fibronectin, but not laminin, was observed arranged in fine fibrillar arrays within the vitreous body. The presence of fibronectin in the vitreous cortex and the occurrence of both proteins in the internal limiting membrane of the retina provide a morphologic suggestion of a role for fibronectin and laminin in vitreoretinal adhesion.

Animals↗
PubMed1982

A comparison of different cellular inocula in an experimental model of massive periretinal proliferation.

We modified a preexisting experimental model of massive periretinal proliferation by injecting cells of differing origins into the rabbit vitreous cavity. These cells included autologous and homologous fibroblasts, homologous chondrocytes, homologous retinal pigment epithelial cells, heterologous bovine endothelial cells, and heterologous murine embryonal cells. All cell injections caused vitreous and retinal membrane formation that resulted in a process similar to massive periretinal proliferation. Clinically the character of the membranes formed and the time course in the development of traction retinal detachments was similar for all the different cell types. The initial cell dosage injected was the critical factor in determining the severity of the traction retinal detachments leading to massive periretinal proliferation.

Animals↗
PubMed1982

Chemotaxis of aortic endothelial cells in response to fibronectin.

We have determined the chemotactic response of bovine aortic endothelial cells to fibronectin and to endothelial cell mitogens (endothelial cell growth supplement, tumor extract), using blind-well chemotaxis chambers. Fibronectin induced a chemotactic response in bovine aortic endothelial cells; at 100 micrograms/ml, chemotaxis increased by 440% above that observed in negative controls (p less than 0.001). The chemotactic response plateaued with time, paralleling the disappearance of the fibronectin concentration gradient in the chambers. As further evidence that chemotaxis was measured, we observed that cell migration did not occur when cells were incubated with fibronectin in the absence of a concentration gradient. Endothelial cell mitogens increased bovine aortic endothelial cell proliferation in our experiments but did not stimulate chemotaxis above background levels. In contrast, fibronectin inhibited cell proliferation by 23%. We present a hypothetical model of the role of fibronectin in evoking endothelial cell chemotaxis during tumor neovascularization.

Animals↗
PubMed1980

Anchorage independent growth and plasminogen activator production by bovine endothelial cells.

Endothelial cells obtained from the aortae of 1- to 2-d-old calves were cloned at high efficiency using fibrin-coated dishes. Primary cultures as well as clones derived from them produced high fibrinolytic activity when grown on 125I-fibrin-coated dishes which was 90% dependent upon the presence of plasminogen. High plasminogen-dependent proteolytic activity was also demonstrated in endothelial cell lysates and in the culture medium of the cells. The production and secretion of the plasminogen activator(s) were found to increase during the log phase of cell growth and to reach a maximum level at confluence. These endothelial cells exhibited morphological phenotypes comparable to those of transformed cells when grown in the presence of acid-treated fetal calf, dog, or human serum. Furthermore, they demonstrated anchorage independent growth, and large colonies were formed in semisolid media. Spontaneous neoplastic transformation of these cells was excluded by karyotypic analysis, lack of tumorigenicity in athymic nude mice, and limited lifespan in culture. Cell clones isolated from colonies grown in agarose demonstrated the same growth characteristics and proteolytic activity as before plating in agarose. High fibrinolytic activity, morphological changes in the appropriate serum, and growth in semisolid media may therefore be indicative of the migratory and/or invasive capacity of both nontransformed endothelial cells as well as tumor cells.

Agar↗