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Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured vascular endothelial cells produce several mitogens including a platelet-derived growth factor-like protein (PDGF-c). We previously reported that acetylated low density lipoprotein (acetyl-LDL) caused accumulation of cholesterol and specific inhibition of PDGF-c production by bovine aortic endothelial cells (Fox, P. L., and DiCorleto, P. E. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 4774-4778). We have now examined the role of cholesterol and other lipids on the inhibition of production of PDGF-c. Incubation of endothelial cells with free cholesterol/albumin complexes resulted in a large increase in cellular cholesterol content but did not inhibit PDGF-c production, demonstrating that cholesterol itself is not inhibitory. Involvement of lipid peroxides in the suppression of PDGF-c production was indicated by three observations. LDL modified in vitro by free radical lipid peroxidation quantitatively inhibited PDGF-c production. The inhibition was dependent on the level of LDL oxidation (as measured by thiobarbituric acid reactivity) and was specific since total protein synthesis was not affected. Inhibition of PDGF-c production by acetyl-LDL was also dependent on peroxidation. A lipid extract from oxidized LDL, but not from native LDL, specifically inhibited PDGF-c production. Chloroquine, monensin, and NH4Cl, inhibitors of lysosomal hydrolytic activity, did not prevent acetyl-LDL-mediated inhibition of PDGF-c production, indicating that cellular metabolism of the lipoprotein was not required for the inhibition. Furthermore, acetyl-LDL suppressed PDGF-c production by endothelial cells even in the presence of butylated hydroxytoluene, an inhibitor of lipid peroxidation, suggesting that cellular propagation of free radicals was not required for the inhibition. Finally, inhibition of PDGF-c production may be regulated at the post-transcriptional level since Northern blot analysis using a v-sis probe showed that the PDGF B-chain mRNA amounts were unaffected by oxidized or acetylated LDL. In summary, levels of an oxidized lipoprotein that have no effect on endothelial cell viability or protein synthetic rates can completely suppress production of a growth factor which may act as a paracrine mitogen in normal and pathological vascular processes.
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PMID:Lipoprotein-mediated inhibition of endothelial cell production of platelet-derived growth factor-like protein depends on free radical lipid peroxidation. 357 Dec 45

Weight loss and nutritional deterioration are associated with adverse outcomes in terms of cancer prognosis (response rate and survival) as well as increased complications, prolonged hospitalizations, increased risk of unplanned hospitalization, increased disability, and increased overall cost of care. The nutritional oncology service at Fox Chase Cancer Center defined a proactive, standardized assessment and interventional approach from 1987-1994. In 186 consecutive patients referred to the nutrition clinic and managed solely by oral intervention and aggressive symptom management, the team demonstrated a 50%-80% success rate in getting patients to maintain or gain weight during therapy, with a similar success in maintaining or improving visceral protein status as determined by serum transferrin and/or albumin. Evaluation of the home parenteral nutrition program (n = 65, from 1987-1993) demonstrated similar success when appropriate triaging was carried out, with 58% of patients able to be tapered off parenteral nutrition (PN) entirely or with transition to enteral tube feeding. The assessment of success for a nutritional intervention (e.g., a disease-specific nutritional supplement) requires the standardization of definitions, assessment tools, criteria for nutritional intervention, and appropriate end points for the assessment of outcomes. The Patient-Generated Subjective Global Assessment of nutritional status is used in conjunction with the nutritional risk of planned cancer therapy to define a standardized interventional approach in oncology patients, which can be used in clinical practice, cooperative oncology group protocols, and clinical trials of nutritional intervention regimens.
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PMID:Definition of standardized nutritional assessment and interventional pathways in oncology. 885 Feb 13

The extravascular matrix is believed to carry negative charge due to its glycosaminoglycans (GAGs) composition. In the present study, we developed an electrodiffusion-convection model to investigate the mechanisms by which this negative charge affects the charged molecule transport through the interstitial space. The model predictions demonstrate that the apparent tissue diffusion coefficient of negatively charged albumin (net charge = -19) in rat mesentery should be comparable to that of neutral dextran with equivalent hydrodynamic radius. The discrepancy in their concentration distributions in the mesenteric tissue, which was observed by Fox and Wayland [1], may be explained by the charge effect of the tissue matrix, especially by the partitioning between the vascular and extravascular compartments, instead of different apparent diffusion coefficients. The charge effect induces equivalent to about two-fold difference in apparent tissue diffusion coefficients of charged albumin and neutral dextran with same free diffusion coefficients. Furthermore, our results indicate that the more negative charge the interstitium has, the smaller the interstitial fluid flow is when the same tissue-lymph pressure gradient is applied.
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PMID:A model for charged molecule transport in the interstitial space. 1728 9