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E A Sprague

Publications and source records attributed to E A Sprague.

46 records · Page 3Linked to original sources

Evolution of foam cells in subcutaneous rabbit carrageenan granulomas. II. Tissue and macrophage lipid composition.

This study describes the lipid composition of differentiating macrophage-derived foam cells in the inflammatory carrageenan granuloma. In this model, macrophages exposed in vivo to diet-induced hypercholesterolemia progressively accumulate electron-translucent lipid inclusions; and at 14 and 28 days, many assume the morphologic features of arterial plaque foam cells. Subcutaneous carrageenan granulomas were induced in 24 pellet-fed (NC) and 24 cholesterol-fed (HC) rabbits, and tissue was harvested at 4, 14, and 28 days. Total (TC) and free cholesterol (FC), cholesteryl esters (CEs), CE fatty acids, triglycerides (TGs), and phospholipids (PLs) were measured on lipid extracts from tissue. TC, FC, and CEs were also measured on isolated, cultured granuloma macrophages. Tissue TCs and FCs were significantly elevated in HC relative to NC rabbits at both 14 and 28 days (P less than 0.005 and P less than 0.01, respectively). CE accumulation in HC granuloma tissue was 80-fold greater at 14 days and 178-fold greater at 28 days (P less than 0.005), compared with NC granulomas. Oleic acid (18:1), the principal CE fatty acid in both NC and HC granulomas, accounted for significantly more (P less than 0.05) of the total CE fatty acids in HC (48%) relative to NC granulomas (37%). No net accumulation of TG was observed with time in NC or HC animals. Although diet did not influence tissue PL content, significant increases (P less than 0.05) were observed at 14 days in NC rabbits and at 14 and 28 days in HC rabbits relative to 4-day levels. CE accumulation was significantly greater in cultured macrophages isolated from HC granulomas at 14 days (P less than 0.001) and 28 days (P less than 0.01). These findings have demonstrated the significant accumulation of CEs in both HC granuloma tissue and in cultured HC macrophage/foam cells in vivo. The carrageenan granuloma model has, we believe, considerable potential for defining mechanisms responsible for CE accumulation in the differentiating macrophage-derived foam cell.

Animals↗

Stimulation of albumin endocytosis by cationized ferritin in cultured aortic smooth muscle cells.

Anionic microdomains within the aortic smooth muscle cell (SMC) surface glycocalyx represent a potential barrier to the endocytosis of anionic plasma proteins. Cultured SMCs exposed briefly to cationized ferritin (CF) exhibit ultrastructural aggregations of surface anionic sites resulting in intervening areas essentially devoid of anionic charge. Preincubation of cultured aortic medial SMCs with 0.2 mg/ml CF for 1 minute at 37 C resulted in a 4-fold increase in binding and a 13-fold increase in internalization of 125I-human serum albumin (125I-HSA) relative to cells pretreated with native ferritin. When both the CF preincubation and the endocytosis were performed at 4 C, the influence of CF was abolished. Studies at 4 C indicated that CF pretreatment of SMC at 37 C induced high affinity (Kd = 1.5 nM) saturable 125I-HSA binding, in addition to low-affinity nonsaturable binding. These results were further confirmed by binding competition studies using increasing concentrations of unlabeled HSA. In contrast, low-density lipoprotein, a large anionic molecule, failed to compete with 125I-HSA for binding sites on CF-pretreated SMCs at either 4 or 37 C. Pulse-chase studies at 37 C indicated that 20-30% of internalized 125I-HSA was degraded, and 40-50% exocytosed within 24 hours in CF-treated cells. CF pretreatment of the SMCs did not significantly enhance the uptake of 14C-sucrose as a measure of fluid-phase endocytosis at 30 and 60 minutes. The results of these studies emphasize the potentially important regulatory roles of cell-surface anionic charge distribution and cationic molecules in cellular endocytosis.

Animals↗

Initial characterization of a peripheral blood mononuclear cell chemoattractant derived from cultured arterial smooth muscle cells.

A mononuclear cell chemoattractant of high specific activity produced by baboon (Papio cynocephalus) aortic medial smooth-muscle cells (SMCs) in culture has been partially characterized. Smooth-muscle cells, between the third and eighth passage, were grown to confluence in Medium 199 containing 10% fetal calf serum and then incubated for 24 hours in either serumless medium (Neuman and Tytell) or Medium 199 containing 0.2% bovine serum albumin. The 24-hour SMC-conditioned medium was fractionated on Sephadex G100-Superfine and potent chemoattractant activity (SMC-CF) eluted in the 10,000-12,000 dalton region. SMC-CF displayed chemotactic and chemokinetic activity for peripheral blood mononuclear cells but not for polymorphonuclear leukocytes. Production of SMC-CF by the cells was significantly inhibited in the presence of cycloheximide, and its activity was abolished after incubation with the bacterial protease subtilisin. Chromatofocusing experiments indicate that SMC-CF is a cationic protein with a pI of greater than 10.5. The role of SMC-CF may play as an inflammatory mediator in monocyte recruitment to the arterial intima in atherogenesis is discussed.

Animals↗

Branches of the aortic arch in the cynomolgus macaque (Macaca fascicularis).

The aortic arch branching patterns of 49 male macaques (Macaca fascicularis) were described and classified according to the classification systems of DeGaris, and the incidence of each pattern was determined. The most frequent pattern observed was a two-branch type in which a truncus communis of intermediate length (7 to 11 mm) and the left subclavian artery constituted the only aortic arch branches. Five patterns not previously described in the cynomolgus were observed. Comparison of the cynomolgus and the rhesus macaques indicated a significant difference between the two species with the rhesus generally having a shorter truncus communis.

Animals↗

The association of elevated plasma cortisol and early atherosclerosis as demonstrated by coronary angiography.

To study the association of plasma cortisol and coronary atherosclerosis, we elected 71 male outpatients who had coronary angiography as part of their evaluation at our facility. Forty-eight percent of the angiograms showed no evidence of coronary artery disease (CAD), 20% showed mild CAD, and 32% showed moderate to severe CAD. We found significant correlations between elevated serial morning plasma cortisols and moderate to severe coronary atherosclerosis. Using the odds ratio, we compared plasma cortisol to the major risk factors for coronary artery disease. Plasma cortisol was second only to serum cholesterol as a discriminator in our patient population between diseased and non-diseased patients. We found a significant correlation between plasma cortisol and cholesterol, blood pressure, and smoking- the three cardinal risk factors for CAD. The highest degree of correlation was found between cortisol and cholesterol. The possible significance of the association of cortisol and the major risk factors for CAD is discussed.

Adult↗

Psoriasis on tumor.

Indicators of the relative contribution of epidermis and dermis to the pathogenesis of psoriasis may be obtained from clinical observation. We studied a case of clinically characteristic and histologically identifiable plaque of chronic psoriasis occurring over transitional cell carcinoma metastatic to the dermis. The tumor substantially replaced the usual fibrous structure of the dermis, showing that a normally structured dermis is not requisite for the presence of psoriasis.

Carcinoma, Transitional Cell↗

Human aortic endothelial cell migration onto stent surfaces under static and flow conditions.

PURPOSE: The objective of the present study is to establish an in vitro model designed to quantitatively define human aortic endothelial cell (HAEC) migration onto stainless steel stent material under both static and flow conditions of high and low wall shear stress. MATERIALS AND METHODS: To simulate implantation of a stent onto the intact arterial wall, HAECs were seeded and grown to confluence on thick, firm collagen gels. Flat 1 x 1-cm square, stainless steel pieces were implanted on this endothelialized surface and migration of HAECs onto the steel surface was monitored, measured, and compared under static and high (15 dynes/cm2) and low (2 dynes/cm2) wall shear stress flow conditions designed to model wall shear stress levels encountered at different sites within the human arterial system. RESULTS: Under no flow, endothelial cell migration occurred uniformly from the periphery, attaining complete confluence over the square surface within 14 days. The initial migratory rate was approximately 10 micrograms/h +/- 0.5 days 1-3 and increased to a rate near 15 micrograms/h +/- 0.5 between days 10 and 14. High shear stress significantly (P < .002) increased HAEC migration rate to 25 micrograms/h +/- 0.8 in the direction of flow, resulting in an increase in total area endothelial coverage from 59% under no flow to 87% under high shear stress flow conditions when compared at 7 days. CONCLUSIONS: These results indicate the rate and extent of endothelial migration onto a prosthetic material surface are influenced by the level of direction of flow-related wall shear stress. Furthermore, these results demonstrate an in vitro model that provides a method to quantitatively evaluate and possibly predict the relative ability of different prosthetic materials to endothelialize under variable in vivo flow conditions.

Angioplasty↗