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Objective— The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques. Methods and Results— Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes; inflammatory in low-shear stress regions and fibrous in oscillatory shear stress regions. Electron microscopy showed that collagen fibrils were thicker and more heterogeneous in oscillatory shear stress lesions from ApoE/fibromodulin-null mice. Low-shear stress lesions were smaller in ApoE/fibromodulin-null mice and contained less lipids. Total plaque burden in aortas stained en face with Oil Red O, as well as lipid accumulation in aortic root lesions, was also decreased in ApoE/fibromodulin-null mice. In addition, lipid accumulation in RAW264.7 macrophages cultured on fibromodulin-deficient extracellular matrix was decreased, whereas levels of interleukin-6 and -10 were increased. Our results show that an abnormal plaque collagen fibril structure can influence atherosclerotic plaque development. Conclusion— The present findings suggest a more complex role for collagen in plaque stability than previously anticipated, in that it may promote lipid-accumulation and inflammation at the same time as it provides mechanical stability.

Resident dendritic cells (DC) within the T cell area of the lymph node take up soluble antigens that enter via the afferent lymphatics before antigen carrying DC arrive from the periphery. The reticular network within the lymph node is a conduit system forming the infrastructure for the fast delivery of soluble substances from the afferent lymph to the lumen of high endothelial venules (HEVs). Using high-resolution light microscopy and 3D reconstruction, we show here that these conduits are unique basement membrane-like structures ensheathed by fibroblastic reticular cells with occasional resident DC embedded within this cell layer. Conduit-associated DC are capable of taking up and processing soluble antigens transported within the conduits, whereas immigrated mature DC occur remote from the reticular fibers. The conduit system is, therefore, not a closed compartment that shuttles substances through the lymph node but represents the morphological equivalent to the filtering function of the lymph node.

Background and Objectives 5-fluorouracil (5-FU) exerts its effects mainly by its incorporation into RNA and inhibition of DNA synthesis. Its toxicity may therefore be estimated by measuring its incorporation into RNA. Protein malnutrition has been considered to increase the toxicity of 5-FU. Methods Rats with a hepatoma implanted into the liver were fed on either a 25% or a 0% casein diet for 1 week. On the last day, they were infused via the hepatic artery with a therapeutic dose of 3H-5-FU. Its incorporation into RNA was measured in hepatoma and several normal tissues. Results Protein deprivation increased the incorporation of 5-FU into liver and intestinal RNA. Incorporation into hepatoma RNA did not increase significantly, but the ratio, liver/hepatoma RNA incorporation, remained unchanged. Conclusions Protein deprivation might increase the toxicity of 5-FU on liver and intestine. J. Surg. Oncol. 1997;65:155–158. © 1997 Wiley-Liss, Inc.

The cytotoxicity of 5-FUra has been related to its incorporation into RNA. In a model of secondary liver cancer in the rat, the incorporation of 5-FUra into the acid-soluble fraction, RNA and DNA of several normal tissues and an adenocarcinoma of the colon transplanted to the liver was determined. A therapeutic labelled dose of the drug was infused via the hepatic artery for 2 hr and the rats killed 1 hr later. Half of the rats were starved overnight before treatment. The incorporation of 5-FUra into liver and intestinal RNA increased at starvation. It was unchanged in kidney and bone marrow.The incorporation into tumor RNA decreased insignificantly. The incorporation into tumor RNA was significantly higher than in hepatic, intestinal, and renal RNA at ad libitum feeding. This difference disappeared at overnight starvation. © 1993 Wiley-Liss, Inc.