Biomedical subjects

Robert C MacCallum

Publications and source records attributed to Robert C MacCallum.

8 recordsLinked to original sources

PubMed2003

Chronic stress and age-related increases in the proinflammatory cytokine IL-6.

Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD = 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.

Aged↗

PubMed2002

Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy.

Lymphocytes respond to myelin proteins after spinal cord injury (SCI) and may contribute to post-traumatic secondary degeneration. However, there is increasing evidence that autoreactive T-lymphocytes may also convey neuroprotection and promote functional recovery after CNS injury. To clarify the role of myelin autoreactive lymphocytes after SCI, we performed contusion injuries in the thoracic spinal cord of transgenic (Tg) mice in which >95% of all CD4+ T-lymphocytes are reactive with myelin basic protein (MBP). We observed significantly impaired recovery of locomotor and reflex function in Tg mice compared with non-Tg (nTg) littermates. Measures of functional impairment in Tg mice correlated with significantly less white matter at the injury site, and morphometric comparisons of injured Tg and nTg spinal cords revealed increased rostrocaudal lesion expansion (i.e., secondary degeneration) in Tg mice. Rostrocaudal to the impact site in SCI-nTg mice, demyelination was restricted to the dorsal funiculus, i.e., axons undergoing Wallerian degeneration. The remaining white matter appeared normal. In contrast, lymphocytes were colocalized with regions of demyelination and axon loss throughout the white matter of SCI-Tg mice. Impaired neurological function and exacerbated neuropathology in SCI-Tg mice were associated with increased intraspinal production of proinflammatory cytokine mRNA; neurotrophin mRNA was not elevated. These data suggest that endogenous MBP-reactive lymphocytes, activated by traumatic SCI, can contribute to tissue injury and impair functional recovery. Any neuroprotection afforded by myelin-reactive T-cells is likely to be an indirect effect mediated by other non-CNS-reactive lymphocytes. Similar to the Tg mice in this study, a subset of humans that are genetically predisposed to autoimmune diseases of the CNS may be adversely affected by vaccine therapies designed to boost autoreactive lymphocyte responses after CNS trauma. Consequently, the safe implementation of such therapies requires that future studies define the mechanisms that control T-cell function within the injured CNS.

Animals↗

PubMed2002

Stress-related modulation of matrix metalloproteinase expression.

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), whose expression can be controlled by cytokines, play a role in extracellular matrix remodeling in physiological and pathological processes. Using a blister chamber wound model on UV-B-exposed human forearm skin, we examined whether stress or mood-associated neuroendocrine alteration is sufficient to modulate MMP and TIMP expression. We did not find evidence that depressive symptoms were reliably associated with modulation of either MMP or TIMP expression. However, we did find that activation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes can modulate levels of MMPs. A positive association between plasma norepinephrine levels and MMP-2 protein levels, and a negative correlation between plasma cortisol levels and MMP-2 levels were found. The data suggest that activation of the HPA and SAM axes, even in individuals within the normal range of depressive symptoms, could mediate MMP levels and wound healing in blister wounds.

Adrenal Medulla↗

PubMed2002

Exploratory factor analysis in behavior genetics research: factor recovery with small sample sizes.

Results of a Monte Carlo study of exploratory factor analysis demonstrate that in studies characterized by low sample sizes the population factor structure can be adequately recovered if communalities are high, model error is low, and few factors are retained. These are conditions likely to be encountered in behavior genetics research involving mean scores obtained from sets of inbred strains. Such studies are often characterized by a large number of measured variables relative to the number of strains used, highly reliable data, and high levels of communality. This combination of characteristics has special consequences for conducting factor analysis and interpreting results. Given that limitations on sample size are often unavoidable, it is recommended that researchers limit the number of expected factors as much as possible.

Animals↗

PubMed2002

When fit indices and residuals are incompatible.

Standard chi-square-based fit indices for factor analysis and related models have a little known property: They are more sensitive to misfit when unique variances are small than when they are large. Consequently, very small correlation residuals indicating excellent fit can be accompanied by indications of bad fit by the fit indices when unique variances are small. An empirical example of this incompatibility between residuals and fit indices is provided. For illustrative purposes, an artificial example is provided that yields exactly the same correlation residuals as the empirical example but has larger unique variances. For this example, the fit indices indicate excellent fit. A theoretical explanation for this phenomenon is provided using relationships between unique variances and eigenvalues of the fitted correlation matrix.

Humans↗

PubMed2002

On the practice of dichotomization of quantitative variables.

The authors examine the practice of dichotomization of quantitative measures, wherein relationships among variables are examined after 1 or more variables have been converted to dichotomous variables by splitting the sample at some point on the scale(s) of measurement. A common form of dichotomization is the median split, where the independent variable is split at the median to form high and low groups, which are then compared with respect to their means on the dependent variable. The consequences of dichotomization for measurement and statistical analyses are illustrated and discussed. The use of dichotomization in practice is described, and justifications that are offered for such usage are examined. The authors present the case that dichotomization is rarely defensible and often will yield misleading results.

Humans↗

PubMed2002

Comments on the Meehl-Waller (2002) procedure for appraisal of path analysis models.

P. E. Meehl and N. G. Waller (2002) proposed an innovative method for assessing path analysis models wherein they subjected a given model, along with a set of alternatives, to risky tests using selected elements of a sample correlation matrix. Although the authors find much common ground with the perspective underlying the Meehl-Waller approach, they suggest that there are aspects of the proposed procedure that require close examination and further development. These include the selection of only one subset of correlations to estimate parameters when multiple solutions are generally available, the fact that the risky tests may test only a subset of parameters rather than the full model of interest, and the potential for different results to be obtained from analysis of equivalent models.

Humans↗

PubMed1991

Confirming the theoretical structure of the McGill Pain Questionnaire in acute clinical pain.

Based upon a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. Although a number of exploratory factor analytic studies have failed to consistently support the theoretical structure of the instrument, one previous confirmatory factor analytic study of chronic pain did statistically support the a priori model. Because it has been suggested that acute pain may not involve the same dimensions as chronic pain, this study provided a direct test of the theoretical structure of the MPQ through multi-sample confirmatory factor analysis (CFA) using data provided by women experiencing pain during labor (n = 185) and women experiencing acute postoperative pain (n = 192). Results of the LISREL CFA analysis indicated that the a priori, 3-factor, oblique model originally proposed by Melzack provided the most parsimonious representation of the data across the 2 samples of acute pain.

Acute Disease↗