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Biomedical subjects

Daniel R Anderson

Publications and source records attributed to Daniel R Anderson.

5 recordsLinked to original sources

The role of complement in the adherence of microbubbles to dysfunctional arterial endothelium and atherosclerotic plaque.

OBJECTIVE: To determine whether serum complement C3 mediates adherence of albumin-encapsulated microbubbles to vascular endothelium in the development of atherosclerotic plaques. METHODS: Adherence of microbubbles to aortic endothelium was examined with scanning electron microscopy following intravenous injection of 20% intralipid in wild-type mice, genetic complement-deficient mice (C3-/-), and in pharmacologic C3-depleted wild-type mice. In a second experimental model, atherosclerostic plaque was induced in apolipoprotein E-deficient mice (apoE-/-), and adherence of microbubbles to atherosclerotic plaques was evaluated using fluorescent microscopy of fluorescein isothiocynate-conjugated microbubbles. Finally, imaging of aortas was performed in eight rats (four JCR:LA-cp atherosclerosis-prone rats on high cholesterol diets; four controls) following intravenous albumin microbubble injections (PESDA) to determine whether microbubble adherence to the endothelium could be detected with low mechanical index pulse sequence schemes. RESULTS: Scanning electron microscopy confirmed the adherence of microbubbles to the endothelial cells of the aorta in wild-type mice following induction of hypertriglyceridemia but not in C3-depleted mice. Microbubble adherence to the endothelial surface of atherosclerotic plaque was confirmed in all apoE-/- mice (median 172 microbubbles/field; compared to a median of 3 microbubbles/field in cobra venom factor-treated apoE-/- mice; p < 0.001). Low mechanical index ultrasound imaging detected microbubble adherence in all JCR atherosclerosis prone rats even in the absence of vasomotor or phenotypical evidence of endothelial dysfunction. The numbers of adherent microbubbles correlated with serum triglyceride levels, and were seen in conjunction with increased endothelial nitric oxide synthase activity. CONCLUSIONS: Complement C3 binds to albumin-encapsulated microbubbles and mediates microbubble adherence to vascular endothelium both early and late in the atherosclerotic process.

Albumins↗

On the road to obesity: Television viewing increases intake of high-density foods.

Television viewing (TVV) has been linked with obesity, possibly through increased sedentary behavior and/or through increased ingestion during TVV. The proposition that TVV causes increased feeding, however, has not been subjected to experimental verification until recently. Our objective was to determine if the amount eaten of two familiar, palatable, high-density foods (pizza and macaroni and cheese) was increased during a 30-min meal when watching TV. In a within-subjects design, one group of undergraduates (n = 10) ate pizza while watching a TV show of their choice for one session and when listening to a symphony during the other session. A second group of undergraduates (n = 10) ate macaroni and cheese (M&C). TVV increased caloric intake by 36% (one slice on average) for pizza and by 71% for M&C. Eating patterns also differed between conditions. Although the length of time to eat a slice of pizza remained stable between viewing conditions, the amount of time before starting another slice was shorter during TVV. In contrast, M&C was eaten at a faster rate and for a longer period of time during TVV. Thus, watching television increases the amount eaten of high-density, palatable, familiar foods and may constitute one vector contributing to the current obesity crisis.

Adult↗

A shine-dalgarno-like sequence mediates in vitro ribosomal internal entry and subsequent scanning for translation initiation of coxsackievirus B3 RNA.

Translation initiation of coxsackievirus B3 (CVB3) RNA is directed by an internal ribosome entry site (IRES) within the 5' untranslated region. However, the details of ribosome-template recognition and subsequent translation initiation are still poorly understood. In this study, we have provided evidence to support the hypothesis that 40S ribosomal subunits bind to CVB3 RNA via basepairing with 18S rRNA in a manner analogous to that of the Shine-Dalgarno (S-D) sequence in prokaryotic systems. We also identified a new site within both the 18S rRNA and the polpyrimidine-tract sequence of the IRES that allows them to form stronger sequence complementation. All these data were obtained from in vitro translation experiments using mutant RNAs containing either an antisense IRES core sequence at the original position or site-directed mutations or deletions in the polypyrimidine tract of the IRES. The mutations significantly reduced translation efficiency but did not abolish protein synthesis, suggesting that the S-D-like sequence is essential, but not sufficient for ribosome binding. To determine how ribosomes reach the initiation codon after internal entry, we created additional mutants: when the authentic initiation codon at nucleotide (nt) 742 was mutated, a 180-nt downstream in-frame AUG codon at nt 922 is able to produce a truncated smaller protein. When this mutation was introduced into the full-length cDNA of CVB3, the derived viruses were still infectious. However, their infectivity was much weaker than that of the wild-type CVB3. In addition, when a stable stem-loop was inserted upstream of the initiation codon in the bicistronic RNA, translation was strongly inhibited. These data suggest that ribosomes reach the initiation codon from the IRES likely by scanning along the viral RNA.

Base Sequence↗