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C R Chapman

Publications and source records attributed to C R Chapman.

78 records · Page 5Linked to original sources
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Quantification of the close association between DNA haplotypes and specific beta-thalassaemia mutations in Mediterraneans.

It has been suggested that there is a close linkage between specific restriction fragment polymorphism patterns, defined as haplotypes, in the beta-globin gene cluster and specific mutations in Mediterranean people with thalassaemia. This association formed the basis of a strategy for the efficient characterization of beta-thalassaemia mutations from the DNA sequence of one or two beta-thalassaemia genes derived from each haplotype in each ethnic group. Subsequently, Robertson and Hill argued that this strategy greatly underestimates the number of mutations on haplotypes which are frequent among normal chromosomes. We have therefore now analysed the proposed association and strategy quantitatively by the use of oligonucleotide hybridization and direct restriction analysis. Our results suggest that: (1) the association of specific haplotypes with specific mutations is high, but not invariant; (2) a different beta-thalassaemia mutation has arisen within each haplotype in Mediterraneans; and (3) mutation spread from one haplotype to another occurs mainly through meiotic recombination within a 9-kilobase region 5' to the beta-globin gene.

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Pain perception and assessment.

Our inability to measure pain effectively is a major barrier to progress in pain research and advancement in clinical interventions for pain. Historically, the mind-body dichotomy has constrained our thinking about pain and its quantification. One line of work has pursued pain as the sensory end product of nociception: pain is the realization of signals of tissue injury arriving at the cortex. At the other extreme, some clinicians contend that pain is ''what the patient says it is''. In other words, it is a purely mental and entirely subjective phenomenon. Research on functional brain imaging, psychophysiological research and recent neurophysiological research on animal models provide confluent evidence that both of these positions are misleading oversimplifications. Pain is the emergent product of massive, parallel, distributed processing in the brain that engages structures involved in emotion and cognition as well as in sensation. To advance pain measurement, our research team has examined Sokolov's defense response in human subjects experiencing repeated, brief painful electrical shocks delivered to a fingertip through a tiny electrode. Sokolov proposed that threatening events elicit a hypothalamically-orchestrated pattern of arousal that prepares the organism to cope with threat. Measures of sympathetic nervous system arousal and brain evoked potentials in our subjects reveal a stable pattern of this sort when we subject the data to structural equation modeling. When subjects undergo equally intense shocks delivered through a large electrode, they experience a strong vibration-like, unpleasant sensation that causes discomfort but not nociception. The non-painful shock elicits broad levels of arousal equal to those obtained with painful shocks in subjects, but structural equation modeling demonstrates that such arousal does not conform to the defense response pattern. Moreover, multivariate measures of sympathetic arousal and evoked potentials can discriminate painful from non-painful stimuli more accurately than can subjective pain reports. These observations suggest that pain may have a unique psychophysiological signature. More importantly, perhaps, this approach suggests that the combination of psychophysiological research and multivariate statistics provides an avenue for advancing pain research outside of the mind-body dichotomy.

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