Erythroblast iron metabolism and serum soluble transferrin receptor values in the anemia of rheumatoid arthritis.

OBJECTIVES: We have investigated in vitro erythroblast iron metabolism in the anemia of rheumatoid arthritis (RA). We also have examined the results in relation to bone marrow iron status in an attempt to explain the reported difference between serum soluble transferrin receptor (sTfR) values in anemia of chronic disease (ACD) and iron deficiency anemia (IDA) in patients with RA. METHODS: Bone marrow was examined in 29 anemic patients with RA, 9 healthy volunteers, and 6 patients with simple IDA. High purity erythroblast fractions were prepared from these bone marrow samples. Erythroblast surface TfR expression and iron uptake was assessed in vitro using (125)I-transferrin (Tf) and (59)Fe-Tf, respectively. The efficiency of erythroblast surface TfR function for Tf-iron uptake was determined by relating total iron uptake at 4 hours to surface TfR number. Serum sTfR values were measured for the RA anemia group, which was subdivided as RA-ACD (marrow iron present) or RA-IDA (marrow iron absent) on the basis of visible reticuloendothelial (RE) marrow iron stores. RESULTS: High purity (87 +/- 5%) erythroblast fractions were obtained from 35 of the 44 marrow samples. Erythroblasts obtained from patients with simple IDA showed a significant increase in surface TfR expression (P = 0.0003) and Tf-iron uptake (P = 0.001). RA anemia also led to a significant increase in erythroblast Tf-iron uptake (P = 0.016). This increase was not associated with an increase in surface TfR expression (P = 0.5), but was seen to occur as a result of a significant increase in the efficiency of surface TfR for Tf-iron uptake (P = 0.027). Within the RA anemia group, the increase in erythroblast Tf- iron uptake at 4 hours was more evident for RA-IDA (3.96 +/- 1.73 versus 1.66 +/- 0.66; P = 0.03) than for RA-ACD (2.69 +/- 1.18 versus 1.66 +/- 0.66; P = 0.057). This additional erythroblast response to absent RE iron stores led to a highly significant difference in serum sTfR values between RA-IDA and RA-ACD (40.2 +/- 14.0 versus 23.9 +/- 5.3 nmoles/liter; P = 0.001) CONCLUSIONS: An increase in erythroblast surface TfR efficiency for Tf-iron uptake compensates for the low plasma iron levels associated with anemia in RA and helps to maintain RA erythroblast iron uptake. With adequate RE iron stores, this increased efficiency limits intracellular iron deprivation and consequently reduces the need to increase surface TfR expression. As a result, serum sTfR levels in RA-ACD remain within the normal range. RA erythroblasts, however, are still able to respond to any additional worsening of the iron supply caused by absent RE iron stores. This additional response causes the highly significant increase in serum sTfR values seen between RA-IDA and RA-ACD.

Analysis of the elements of attention: a neuropsychological approach.

A model for conceptualizing the components or elements of attention is presented. The model substitutes for the diffuse and global concept of "attention" a group of four processes and links them to a putative system of cerebral structures. Data in support of the model are presented; they are derived from neuropsychological test scores obtained from two samples, the first consisting of 203 adult neuropsychiatric patients and normal control subjects, and the second, an epidemiologically-based sample of 435 elementary school children. Principal components analyses of test scores from these two populations yielded similar results: a set of independent elements of attention that are assayed by different tests. This work presents a heuristic for clinical research in which the measurement of attention is essential.

Prestimulation effects on blink and cardiac reflexes of 15-month human infants.

Reduction of reflex startle by brief changes in prestimulation is a robust phenomenon in adults of several species. Although the phenomenon does not require structures above midbrain, it has a long and uneven developmental course. This study of human infants assessed prestimulus effects at 15 months, within a period which has failed, in past work, to show the usual inhibitory modulation. Magnitude and onset latency of the startle blink and concurrent changes in heart rate were measured under four conditions: 2 single-stimulus conditions, 25-msec, 84-dB, 1000-Hz tone or 50-msec, 109-dB white noise; 2 paired-stimulus conditions, noise bursts preceded by tone at lead times of 125 msec or 225 msec. Compared to noise-alone, paired conditions elicited insignificant increases in blink size, significant shortening of blink onset latency, and significant attenuation of heart rate responses. The findings add to growing evidence of a dissociation between modulating effects on blink magnitude and latency and of a dissociation between modulating effects on somatic and autonomic reflexes.

Stimulus duration as an age-dependent factor in reflex blinking.

Alternative hypotheses of differential development of auditory and visual systems versus temporal-processing systems were tested to explain prior adult-infant differences in reflex blink latency. The present study removed a confound between stimulus modality and duration, present in prior work, and determined whether age interacted with modality or with duration when they were varied orthogonally. Reflexes were elicited from human adults and infants under 4 stimulus conditions: flash and click, delivered singly and in trains. Age interacted only with duration to affect latency and elicitation probability, reflex characteristics which depend on adequate triggering by a transient change at onset. In contrast, age did not interact with duration to affect peak amplitude which presumably depends on temporal integration. Findings are compatible with the hypothesis that processes or structures, specialized for differentiation of transient stimulus change, mature at a different rate than those specialized for integration of stimulus energy over time.

Blink reflex modification by selective attention: evidence for the modulation of 'automatic' processing.

Probe stimuli which elicit activity reflexly provide a means of assessing 'top-down' effects of attentional manipulations while minimizing the perhaps insolvable problem of determining whether effects are due to post-perceptual selection or to changes in the input pathway. Parallel experiments on adults and infants presented acoustic and visual probes unpredictably while subjects attended to acoustic and visual foregrounds: Attention was indexed by heart rate deceleration. When probe and foreground modality matched, probe-elicited reflex blinks were significantly facilitated in magnitude (infants) or latency (adults) relative to reflexes elicited when probe and foreground modality mismatched. Further, facilitation was greater when modality-matching probes were presented over foregrounds judged a priori to be more 'interesting' than 'dull' foregrounds. Because acoustic and visual blink reflexes have a common efferent path, modulating effects must have occurred earlier, in modality-specific paths. As such, the results suggest that attention can influence 'automatic' sensory-perceptual analysis.

Evidence for sensory-selective set in young infants.

The existence of low-level filtering of sensory input is a point of debate among cognitive theorists. This present study suggests that filtering by modality exists at levels low enough to modulate the brainstem blink reflex and that it is evident as early as the 16th week of life. During foreground listening or looking conditions, blinks elicited by acoustic or visual probes were larger when probe and foreground modality matched than when they mismatched. "Interesting" foregrounds, by comparison with "dull" ones, intensified the modality-selective effect.