Isotopic determination of fibronectin synthesis in humans

Fibronectin is an opsonic protein that, among other functions, activates the reticuloendothelial system. Accurate measurement of its rate of synthesis is necessary to more fully understand its physiological role in normal and pathological conditions. We have determined the rate of fibronectin synthesis in three normal volunteers using a primed-constant infusion of 15N-glycine and 1,2-13C-leucine, and measuring the incorporation of the isotopes into the protein over 5 days of infusion. In nine additional subjects, the fractional synthetic rate (FSR) of fibronectin was calculated during a 24-hour infusion using urinary hippurate and plasma alpha-ketoisocaproic acid enrichment to represent the precursors for incorporation of labeled glycine and leucine, respectively, into fibronectin. The FSR using glycine and leucine was 1.56 +/- 0.14 and 1.29 +/- 0.04 (%/h), respectively, in the 5-day infusion study, and 1.56 +/- 0.10 versus 1.83 +/- 0.09 (%/h), respectively, in the 24-hour study. The results of the 5-day infusion of 15N-glycine justify the use of urinary hippurate to reflect the precursor enrichment for the determination of the FSR of fibronectin during a shorter (less than 24 hour) infusion period

Effect of dichloroacetate on lactate concentration in exercising humans

The precise mechanism responsible for the increase in plasma lactate concentration during exercise in humans is not known. We have used dichloroacetate to test the hypothesis that a limitation in pyruvate dehydrogenase activity is responsible for the rise in plasma lactate. Dichloroacetate stimulates the activity of pyruvate dehydrogenase, which is normally the regulatory enzyme in the oxidation of glucose when tissue oxygenation is adequate. Six subjects were studied twice according to a randomized, crossover protocol, involving one test with saline infusion and another with dichloroacetate infusion. Exercise load on a bicycle ergometer was increased progressively until exhaustion. Blood samples were drawn each minute throughout exercise and periodically throughout 120 min of recovery. Dichloroacetate significantly lowered the lactate concentration during exercise performed at less than 80% of the average maximal O2 consumption. The peak concentration of lactate at exhaustion was not affected by dichloroacetate treatment, but dichloroacetate did lower lactate concentration throughout recovery. These results suggest that a limitation in pyruvate dehydrogenase activity contributes to the increase in plasma lactate during submaximal exercise and recovery

Communication as an emergent metaphor for neuronal operation

The original publication is available at www.springerlink.com . Copyright Springer --DOI : 10.1007/3-540-48834-0_19The conventional computational description of brain operations has to be understood in a metaphorical sense. In this paper arguments supporting the claim that this metaphor is too restrictive are presented. A new metaphor more accurately describing recently discovered emergent characteristics of neuron functionality is proposed and its implications are discussed. A connectionist system fitting the new paradigm is presented and its use for attention modelling briefly outlined.Peer reviewe