Search PubMed⌕ Search

Biomedical subjects

R Ross

Publications and source records attributed to R Ross.

At least 325 records · Page 18Linked to original sources
PubMed1983

Interactions between the receptors for platelet-derived growth factor and epidermal growth factor.

Preincubation of Swiss 3T3 cells or human fibroblasts with purified platelet-derived growth factor (PDGF) at 4 degrees C or 37 degrees C rapidly inhibits subsequent binding of 125I-epidermal growth factor (125I-EGF). The effect does not result from competition by PDGF for binding to the EGF receptor since (a) very low concentrations of PDGF are effective, (b) cells with EGF receptors but no PDGF receptors are not affected, and (c) the inhibition persists even if the bound PDGF is eluted before incubating the cells with 125I-EGF. PDGF does not affect 125I-insulin binding nor does EGF affect 125I-PDGF binding under these conditions. Endothelial cell-derived growth factor also competes for binding to PDGF receptors and inhibits 125I-EGF binding. The inhibition demonstrated by PDGF seems to result from an increase in the Kd for 125I-EGF binding with no change in the number of EGF receptors.

Animals↗
PubMed1983

Effects of amitriptyline, desipramine and zimeldine, alone and in combination with ethanol, on information processing and memory in healthy volunteers.

Interactions of three antidepressants--amitriptyline, desipramine and zimeldine--with a single 0.8 g/kg body weight dose of alcohol were studied in healthy male volunteers. The dependent variables were performance measurements in the Continuous Performance Task and a cognitive memory task. Alcohol and desipramine showed different and specific deleterious effects on cognitive and memory functions, whereas amitriptyline produced a more generalized impairment. Zimeldine slightly improved performance in the Continuous Performance Task and antagonized effects of alcohol in both tasks.

Adult↗
PubMed1983

Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons.

The effect of sulfinpyrazone on endothelial injury induced by homocysteine has been studied both in vitro, using cultured human umbilical vein endothelial cells, and in vivo, using a primate model of homocysteine-induced arteriosclerosis. Oral sulfinpyrazone (250 mumol/kg body weight per day in three divided doses) in eight chronically homocystinemic baboons (0.14 +/- 0.04 mM plasma homocystine) decreased the extent of aortic endothelial injury as measured morphometrically by silver staining techniques, compared with six untreated comparably homocystinemic animals (denuded surface averaged 0.5% with range 0-2.1 vs 7.7 +/- 1.6%, respectively; P less than 0.001). Sulfinpyrazone therapy to homocystinemic baboons also normalized platelet survival and turnover measurements (5.1 +/- 0.4 days and 70,000 +/- 11,000 platelets/microliter per day vs. 2.8 +/- 0.6 days and 179,000 +/- 19,000 platelets/microliter per day in untreated homocystinemic controls; P less than 0.001). Sulfinpyrazone therapy also reduced the size and frequency of homocysteine-induced intimal lesion formation (P less than 0.001). Although sulfinpyrazone reduced the amount of specific 51Cr release from cultured human umbilical vein endothelial cells induced by 10 mM homocysteine after 24 hours of co-incubation, no effect was observed in assays of endothelial cell detachment when sulfinpyrazone (10(-5) M) or its thioether metabolite were pre- or co-incubated during 24 hours with homocysteine (2.5-10 mM). These data suggest that sulfinpyrazone may protect endothelial cells from injury in vivo by some apparently indirect mechanism.

Animals↗
PubMed1983

Coronary thrombosis in the absence of angiographically-evident obstructive coronary disease.

A 31-year-old man with an acute myocardial infarction underwent intracoronary thrombolysis with streptokinase. Post-thrombolytic angiography revealed no underlying obstructive coronary disease. This particular syndrome of a documented thrombus in a normal vessel causing infarction has not previously been described. Such a sequence may explain the occurrence of myocardial infarction in some patients with normal coronary arteries. The mechanism by which thrombus occurs in an angiographically-normal coronary artery is at present undefined.

Adult↗
PubMed1982

Growth factors from platelets, monocytes, and endothelium: their role in cell proliferation.

Of the various biological roles assigned to growth factors at the beginning of this article, the factors described here are largely associated with the response to injury. These represent a special type of factor since two of them, PDGF and MDGF, are carried in the circulation by the platelet and the monocyte respectively, and can therefore be delivered to sites where a proliferative response would be an important event in the restitution of tissue continuity. The role of the endothelial-derived growth factor in these phenomena is not clear at present. Atherosclerosis has been suggested to represent a protective proliferative response that has gone awry and become disease. In this instance both PDGF and MDGF could play important roles, since platelets have been associated with the early injury phenomenon and macrophages appear to be present in virtually all phases of the development of the lesions of atherosclerosis from the fatty streak to the fibrous plaque and the complicated lesion. In each of these circumstances the macrophage may be important in lesion progression and possibly in lesion initiation. PDGF may also be important in initiation of some lesions, and in some instances would undoubtedly participate in the fibroproliferative response that occurs during organization of a thrombus.

Animals↗
PubMed1982

Asbestos exposure and lymphomas of the gastrointestinal tract and oral cavity.

An epidemiological case-control study of non-Hodgkin's lymphomas revealed an excess of male patients with large-cell lymphomas primary to the gastrointestinal tract and oral cavity who had evidence of substantial exposure to asbestos. Between 1977 and 1981, 28 men with large-cell lymphomas primary to these sites were interviewed about previous environmental exposure. Pathology slides from 26 of these cases were reviewed by haematopathologists, who confirmed each to be non-Hodgkin's lymphoma of large-cell type. Neighbourhood controls were matched to patients for age, race, and sex. 13 matched pairs were discordant for asbestos exposure, and in 12 of these the exposed individual was a lymphoma patient. 10 patients and 1 control also reported a history of malaria.

Adult↗
PubMed1982

Domperidone elevates rat plasma beta-endorphin-immunoreactivity when administered peripherally but not intracerebroventricularly.

Domperidone, a dopamine receptor antagonist which apparently does not penetrate the blood-brain barrier in rats was administered to adult males. Domperidone 500 micrograms and 100 micrograms, given through intracarotid cannula, significantly elevated plasma beta-endorphin-immunoreactivity (beta-EP-I) at +15 min. To show that only a peripheral site(s) of action is implicated, domperidone was given to rats by cannulae implanted into both lateral ventricles. Plasma beta-EP-I was unaffected by this route of administration. These results suggest that plasma beta-EP-I is tonically inhibited by dopamine acting at site(s) outside of the blood-brain barrier.

Animals↗
PubMed1982

Platelet-derived growth factor. II. Specific binding to cultured cells.

We have prepared radioiodinated purified platelet-derived growth factor (125I-PDGF) which retains full mitogenic activity. The binding of 125I-PDGF to Swiss 3T3 cells is saturable and highly competed by whole blood serum, purified unlabeled PDGF, and by material from each stage in the purification of PDGF from platelet-rich plasma. Other purified mitogens and substances tested do not compete. 125I-PDGF binding to fibroblasts, 3T3 cells, and arterial smooth muscle cells shows an apparent dissociation constant of 10(-11) M, comparable to the range in which PDGF is mitogenic. A clone of Swiss 3T3 cells obtained from a population selected repeatedly against mitogenic response to PDGF shows a greatly reduced mitogenic response to PDGF and binds only 5% as much 125I-PDGF/cell. The binding capacity of the different cell types tested ranges from 2,500 binding sites/cell on the poorly responding variant to 390,000 binding sites/cell on one strain of Swiss 3T3 cells. Cell types that do not respond to PDGF do not show specific high affinity binding of 125I-PDGF. At 4 degrees C, 125I-PDGF binding to monolayer cultures is relatively slow. Equilibrium binding of low concentrations of 125I-PDGF is not achieved during 7 h unless the binding medium is constantly mixed. 125I-PDGF binding at 4 degrees C shows a broad pH optimum between 6.3 and 8.0. Binding does not seem to require Ca2+ or Mg2+ but is reduced more than 6-fold if both monovalent and divalent salts are omitted. The initial rate of 125I-PDGF binding is greater at 37 degrees C than at 4 degrees C but cell-associated 125I begins to decline soon after reaching a peak value at 30-60 min. Coincident with this decline, trichloroacetic acid-soluble 125I appears in the medium and the binding capacity of the cells declines. These phenomena suggest that PDGF and its receptor may be internalized and degraded.

Animals↗
PubMed1982

Platelet-derived growth factor. III. Identification of a platelet-derived growth factor receptor by affinity labeling.

Two homobifunctional cross-linking reagents have been used to cross-link 125I-platelet-derived growth factor (PDGF) to a cell surface component with an approximate Mr = 164,000 that has many characteristics of a specific PDGF receptor. Excess unlabeled PDGF competed for labeling of this component, while high concentrations of fibroblast growth factor, insulin, epidermal growth factor, low density lipoprotein or acetylated low density lipoprotein had no effect. Preincubation of cells with 125I-PDGF at 37 degrees C reduced specific 125I-PDGF binding (down regulation) and produced a parallel decrease in the amount of the 164,000-dalton receptor available for labeling. The 164,000-dalton component contains at least some protein that is accessible to trypsin in the extracellular medium. A complex of comparable Mr is seen on all PDGF-responsive cell types examined, but not on a nonresponsive cell type. 125I-PDGF does not become covalently cross-linked to this component in the absence of a cross-linking reagent.

Affinity Labels↗
PubMed1982

Platelet-derived growth factor. I. High yield purification and evidence for multiple forms.

Platelet-derived growth factor has been purified from human outdated platelet-rich plasma with a 21% overall yield. This five-step procedure represents a 500,000-fold purification over serum. 6.4 ng/ml (2 X 10(-10) M) of purified platelet-derived growth factor stimulated DNA synthesis in quiescent, density arrested cultures of Swiss 3T3 cells to a level equivalent to that produced by 5% calf serum. The growth-promoting activity and specific binding to 3T3 cells has been shown to be associated with four entities of molecular weights: 31,000, 29,000, 28,500, and 27,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. In the presence of 2-mercaptoethanol, the four molecular species are converted to three inactive chains of lower molecular weights: 17,500, 16,000, and 14,400. Other methods of chemically cleaving the disulfide bonds were investigated: reductive cleavage by S-sulfonation, reductive cleavage with dithiothreitol, and performic acid oxidation. In all cases, mitogenic activity was reduced by 80-100%. Attempts to restore mitogenic activity after reduction were unsuccessful. Two-dimensional 125I-peptide mapping of the nonreduced and reduced multiple forms was also investigated. The four nonreduced moieties gave basically identical maps. The maps of the reduced 17,500- and 16,000-dalton chains were also essentially identical, but the map of the reduced 14,400-dalton chain was significantly different. We propose that platelet-derived growth factor consists of two polypeptide chains: a 14,400-dalton chain and either a 17,500- or a 16,000-dalton chain.

Animals↗
PubMed1982

Similar effects of platelet-derived growth factor and epidermal growth factor on the phosphorylation of tyrosine in cellular proteins.

Platelet-derived growth factor (PDGF) stimulates the phosphorylation of proteins at tyrosine when added to quiescent 3T3 cells, as evidenced by the increase in the amount of phosphotyrosine, relative to phosphoserine and phosphothreonine, in cellular proteins. The increase was detected within 1 min of adding PDGF and was maximal by 5 min. This effect showed the same dependence on PDGF concentration as did association of 125I-PDGF with the cells. In different 3T3 cell lines the magnitude of the increase was approximately proportional to the number of PDGF receptors per cell. A number of proteins phosphorylated at tyrosine in response to PDGF have been detected by two-dimensional gel electrophoresis. They include a pair of related 45 kilodalton phosphoproteins, a pair of related 43 kilodalton phosphoproteins and a 42 kilodalton phosphoprotein. Similar changes were noted when quiescent 3T3 cells were incubated with epidermal growth factor. Possibly, these phosphoproteins are primary substrates of the tyrosine protein kinases activated by the receptors for PDGF and epidermal growth factor, and are involved in physiological effects common to the two growth factors.

Amino Acids↗
PubMed1982

Effects of dietary phosphorus and calcium on the intestinal absorption of Ca in sheep.

1. Wether sheep were used, some of which were prepared with a Thiry-Vella loop of jejunum. The long-term use of these loops was ensured by regular perfusion with fresh nutrient solution. 2. The net calcium absorption rate from a Thirty-Vella loop of jejunum increased with increasing intraluminal Ca concentration and was increased by the addition of 1 alpha-hydroxy-cholecalciferol (3 micrograms/l) to the loop fluid. 3. When the diet of sheep was changed from one which was normal in Ca to a diet low in Ca there was an increase in the efficiency of net Ca absorption from the jejunal loop. This dietary change was accompanied by an increase in the circulating concentration of 1,25-dihydroxy-cholecalciferol (1,25(OH)2D3). 4. An intravenous infusion of the Ca chelating agent EDTA increased the efficiency of net Ca absorption from the jejunal loop. The use of 47Ca demonstrated that this reflected an increase in the true absorption rate of Ca. 5. Dietary phosphorus deficiency reduced the efficiency of intestinal Ca absorption and was associated with a reduction in the plasma concentration of 1,25(OH)2D3.

Animals↗
PubMed1982

A study of the Influence of mevalonic acid and its metabolites on the morphology of swiss 3T3 cells.

We used two model systems to investigate the effect of compactin, a competitive inhibitor of beta-hydroxy beta-methylglutarylcoenzyme A reductase, on the shape of Swiss 3T3 cells. We maintained cells in a quiescent state in medium deficient in platelet-derived growth factor (PDGF), or we added PDGF to quiescent cells to initiate traverse through a single cell cycle. In both systems, the cells responded to compactin by acquiring a characteristic rounded shape. Cell rounding seemed to depend on an induced deficiency of mevalonic acid (MVA) since the response could be prevented or reversed by adding MVA to the culture medium. Compactin-induced rounding appeared in PDGF-stimulated cells concomitantly with a compactin-mediated inhibition of DNA synthesis, and both effects had similar sensitivities to exogenous compactin and MVA. However, cell rounding seemed to be unrelated to other, previously observed effects of MVA deficiency. Compactin did not influence the total content of cell cholesterol, and little cholesterol was formed when we added radioactive MVA to round cells to effect shape change reversal. Measurement of the dolichol-dependent glycosylation of cell protein revealed no evidence of dolichol deficiency. In addition, reversal of cell rounding by MVA was not prevented by concentrations of tunicamycin that effectively blocked the incorporation of radioactive mannose into cell protein or by concentrations of cycloheximide that blocked protein synthesis. Taken together, our results suggest a new role for MVA or its products in the maintenance of cell shape.

Animals↗