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S A Reynolds

Publications and source records attributed to S A Reynolds.

14 recordsLinked to original sources

In vitro incubation of low-density lipoproteins with inflammatory cells causes enhanced degradation by macrophages in culture.

Utilizing the polyvinyl sponge-implant model, we have reported in vivo modification of low-density lipoproteins (LDL) isolated from interstitial inflammatory fluid (IF) of the rabbit. Further studies on the metabolism of IF-LDL by resident mouse peritoneal macrophages (MPM), demonstrated enhanced uptake and degradation of these modified lipoproteins by scavenger mechanisms. Based upon these studies, we attempted to examine the mechanisms of these observed in vivo modifications in IF-LDL by in vitro incubation of plasma LDL with inflammatory fluid subfractions. Incubation of LDL with inflammatory cells at 37 degrees C resulted in an increased anodal electrophoretic mobility and alteration in apolipoprotein (APO) composition. Subsequent incubation of this modified plasma LDL with MPM resulted in a significant increase in cell surface binding and an increase in the appearance of degradation products in the medium. The formation of lipid peroxides, measured as thiobarbituric acid-reacting substances (T Bars), increased with the time of LDL incubation with inflammatory cells. Conversely, incubation of LDL with cell-free, lipoprotein-deficient IF (LPDIF, d greater than 1.210 g/ml) significantly inhibited LDL degradation by MPM. LPDIF did not alter the electrophoretic mobility of LDL or result in the appearance of T Bars in the medium. These results implicate peroxidative reactions associated with an inflammatory response as mediators of the in vivo modifications in IF-LDL which facilitates enhanced uptake via the scavenger receptor in MPM.

Animals

The effect of oral l-carnitine on lipoprotein composition in the Watanabe Heritable Hyperlipidemic Rabbit (Oryctolagus cuniculus).

1. We have recently reported the ability of orally administered l-carnitine to lower plasma triglyceride in the Watanabe Heritable Hyperlipidemic Rabbit (WHHL), an animal model of familial hyperlipoproteinemia. 2. In the present studies we examined the effect of l-carnitine administration upon individual lipoprotein subfractions in this animal model. 3. Carnitine feeding resulted in a reduction in very low density lipoproteins (VLDL) and high density lipoprotein (HDL). 4. Compositional analysis revealed a reduction in core triglyceride content with a concomitant increase in protein and phospholipid in VLDL and low density lipoproteins (LDL). 5. Conversely, electrophoretic mobility and apolipoprotein composition were unchanged with l-carnitine. 6. These results further demonstrate the ability of l-carnitine to modulate lipoprotein lipid composition in this animal model of familial hyperlipoproteinemia.

Animals

Turnover of low-density lipoprotein isolated from interstitial inflammatory fluid of the rabbit.

Utilizing the polyvinyl sponge-implant model in the rabbit, we have described in vivo modification of low-density lipoproteins (LDL) in interstitial inflammatory fluid (IF). In the present studies, plasma clearance rates of IF-LDL were determined and compared with normal whole plasma LDL (WP-LDL) as well as plasma LDL modified by chemical reaction with acetic anhydride (Ac-LDL). Lipoproteins were labeled with 125I and injected into the lateral ear vein of recipient rabbits. At 10 min after injection, only 51.5% of IF-LDL could be accounted for in recipient plasma, as compared to 91.9% for WP-LDL, and 2.4% of Ac-LDL. Subsequent log-linear decay rates were similar for IF-LDL and WP-LDL (t 1/2 = 9.5 vs. 11.0 h). Autoradiography of plasma obtained from recipient animals at 15 min and 1 h after injection revealed a return to normal electrophoretic mobility of [125I]IF-LDL. These results indicate that IF-LDL is a mixture of both modified and essentially unmodified particles. We propose that the modified particles may be removed from the circulation by mechanisms described for Ac-LDL.

Animals

Lipoproteins of the extravascular space: enhanced macrophage degradation of low density lipoproteins from interstitial inflammatory fluid.

Current evidence has demonstrated that cholesteryl ester-loaded macrophages are important components of the atherosclerotic lesion. Additional studies have implicated low density lipoproteins (LDL) and circulating monocytes as central to the origin of lipid-laden foam cells found in the arterial wall. This is a result of the finding of accelerated macrophage uptake of LDL chemically modified by reaction with malondialdehyde (MDA-LDL), acetic anhydride (Ac-LDL), or incubation with arterial cells in vitro. In concert with these chemical modifications, we have previously demonstrated selective in vivo modification of LDL isolated from interstitial inflammatory fluid (IF) of the rabbit. Utilizing the polyvinyl sponge implant model, we reported that IF-LDL had an altered chemical composition, electrophoretic mobility, and particle size distribution when compared to LDL isolated from homologous plasma (WP-LDL). In this study reported herein, we examined the metabolism of IF-LDL by resident mouse peritoneal macrophages (MPM) in culture. IF-LDL was degraded substantially faster by MPM, and resulted in a substantial increase in cellular cholesteryl ester when compared to cells incubated with WP-LDL. IF-LDL binding to MPM was inhibited by Ac-LDL derived from WP-LDL, but only minimally by unmodified WP-LDL. Transmission electron microscopy of MPM revealed extensive lipid deposition in cells incubated with Ac-LDL and IF-LDL. These results implicate LDL from interstitial inflammatory fluid as an in vivo modified lipoprotein that can enhance uptake via the acetyl LDL receptor pathway in resident macrophages.

Acetic Anhydrides

Direct modification of plasma low-density lipoproteins in interstitial inflammatory fluid of the rabbit.

Utilizing the polyvinyl sponge-implant model in the rabbit, we have previously demonstrated modification in low-density lipoproteins (LDL) in the extravascular space in association with a cellular inflammatory response. In an attempt to isolate the source of these modifications, plasma LDL was labeled with 125I, and introduced directly into the extravascular space at the time of sponge implantation. [125I] plasma LDL recovered from interstitial inflammatory fluid (IF) at 24 h after implantation demonstrated increased electrophoretic mobility as well as heterogeneity in particle size and hydrated density. These results are in agreement with our previous observations and indicate that modification in IF-LDL probably occurs after it has entered the extravascular space across the vascular wall.

Animals

Effect of cholesterol feeding on lipoprotein distribution in interstitial inflammatory fluid of the rabbit.

Utilizing the polyvinyl sponge-implant model in the rabbit we have previously demonstrated modification in low density lipoproteins (LDL) of interstitial tissue fluid obtained in association with a cellular inflammatory response. In order to examine the interaction between the inflammatory response and lipoproteins from hypercholesterolemic rabbits, 30 male, New Zealand White rabbits were fed standard chow supplemented with 0.5% cholesterol for 4 weeks prior to sponge implantation. Lipoproteins were prepared from interstitial inflammatory fluid (IF) as well as homologous whole plasma (WP). Total IF cholesterol was positively correlated with plasma cholesterol (459 +/- 43 vs. 1485 +/- 130 mg/dl, means +/- SEM, r = 0.81, P less than 0.01). Distribution of lipoproteins in IF was similar to WP in both particle size and density. Beta-migrating VLDL were the predominant particles in both WP and IF, containing 43.7 +/- 3.4 and 42.2 +/- 5.1% of WP and IF cholesterol, respectively. IF-VLDL were similar to WP-VLDL in lipid and apoprotein composition, morphology and particle size distribution. We conclude from these data that the observed dramatic alterations in lipoprotein distribution in response to a dietary cholesterol challenge in rabbit plasma is essentially unaltered in interstitial inflammatory fluid obtained from these animals.

Animals

Lipoprotein metabolism in the extravascular space. Cyclophosphamide inhibits modification of low-density lipoproteins in interstitial inflammatory fluid of the rabbit.

We have recently reported preferential modification and reduction in low-density lipoproteins (LDL) of inflammatory exudates in the rabbit. In an attempt to establish the role of inflammatory cells in these specific alterations, using the sponge-implanted rabbit model we characterized extravascular lipoproteins in animals with severely induced leukopenia. Under these conditions we were unable to demonstrate alterations in the distribution of lipoproteins in inflammatory fluid as compared to homologous plasma. Characterization of LDL from both plasma and inflammatory fluids revealed close similarity in molecular composition and electrophoretic mobility. These studies further implicate the role of scavenger cell systems as a significant component of daily lipoprotein homeostasis.

Animals

Lipoproteins of the extravascular space: alterations in low density lipoproteins of interstitial inflammatory fluid.

Although extrahepatic degradation of low density lipoproteins (LDL) by peripheral cells is considered to be a significant component of daily cholesterol homeostasis, the nature of lipoproteins in the extravascular space has not been well described. Using a sponge implantation model in the rabbit, we examined lipoproteins prepared from interstitial inflammatory fluid. Inflammatory fluid cholesterol is correlated with plasma values, (r = 0.735, P less than 0.01), but triglyceride values are not. Examination of inflammatory fluid lipoproteins by agarose gel electrophoresis, column chromatography, and density gradient centrifugation revealed a marked reduction in LDL concentration as compared to plasma LDL. Inflammatory fluid low density lipoproteins prepared by sequential density flotation had a larger mean diameter, they were erratic in shape, and contained more triglyceride and less cholesterol and cholesteryl ester than plasma LDL. Total cholesterol to protein ratio was significantly reduced in inflammatory fluid LDL (0.73 vs. 1.10, P less than 0.05). Inflammatory fluid LDL migrated further than plasma LDL on agarose electrophoresis, despite similar apoprotein patterns. These data concur with findings of altered composition and electrophoretic mobility of plasma LDL modified in vitro by exposure to acetylating agents, malondialdehyde, or aortic cells in culture, and they may represent the actual form of LDL in the extravascular space.

Animals

Circulating phospholipids in interstitial inflammatory fluid of the rabbit.

Using a sponge implantation model in the rabbit, we have examined the distribution and fatty acid composition of extravascular phospholipids in interstitial inflammatory fluid. Inflammatory fluid contained less phosphatidylserine and -inositol and a complete absence of phosphatidylethanolamine as compared to autologous plasma. Inflammatory fluid phospholipids contained an increased amount of oleic acid, decreased linoleic acid, and undetectable levels of arachidonic acid, despite unaltered levels of these fatty acids in other extravascular lipid classes as compared to plasma. Potential metabolic consequences of these findings are discussed.

Animals

Comparative results of postmastectomy rehabilitation in a specialized and a community hospital.

This article describes results of postmastectomy rehabilitation program as operating at Mt. Sinai Hospital of Cleveland, a general community facility. Common physical and emotional problems following mastectomy are documented, as well as barriers to effective rehabilitation--particularly the fact that such programs are usually associated with specialized oncology settings and not seen as feasible in the community hospital. An analysis of outcomes of a program operated at both Mt. Sinai and Memorial Sloan-Kettering Cancer Center demonstrates that comparable and positive patient outcomes can be achieved in terms of range of motion, resumption of prior activities, and emotional stress. Recommendations are made regarding ways to overcome common problems in implementing such programs in an inexpensive and effective manner.

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