Effects of chronic exposure to 12‰ saltwater on the endocrine physiology of juvenile American alligator (Alligator mississippiensis).

American alligator (Alligator mississippiensis) habitats are prone to saltwater intrusion following major storms, hurricanes or droughts. Anthropogenic impacts affecting hydrology of freshwater systems may exacerbate saltwater intrusion into freshwater habitats. The endocrine system of alligators is susceptible to changes in the environment but it is currently not known how the crocodilian physiological system responds to environmental stressors such as salinity. Juvenile alligators were exposed to 12‰ saltwater for 5 weeks to determine the effects of chronic exposure to saline environments. Following 5 weeks, plasma levels of hormones [e.g. progesterone, testosterone, estradiol, corticosterone, aldosterone (ALDO), angiotensin II (ANG II)] were quantified using liquid chromatography and tandem mass spectrometry. Compared with freshwater-kept subjects, saltwater-exposed alligators had significantly elevated plasma levels of corticosterone, 11-deoxycortisol, 17α-hydroxyprogesterone, testosterone, 17ß-estradiol, estrone and estriol whereas pregnenolone and ANG II were significantly depressed and ALDO levels were unchanged (slightly depressed). On the one hand, saltwater exposure did not affect gene expression of renal mineralocorticoid and glucorticoid and angiotensin type 1 (AT-1) receptors or morphology of lingual glands. On the other hand, saltwater exposure significantly reduced plasma glucose concentrations whereas parameters diagnostic of perturbed liver function (aspartate aminotransferase and alanine aminotransferase) and kidney function (creatinine and creatine kinase) were significantly elevated. Except for plasma potassium levels (K+), plasma ions Na+ and Cl- were significantly elevated in saltwater alligators. Overall, this study demonstrated significant endocrine and physiological effects in juvenile alligators chronically exposed to a saline environment. Results provide novel insights into the effects of a natural environmental stressor (salinity) on the renin-angiotensin-aldosterone system and steroidogenesis of alligators.

Temperature and species-specific effects on ß3-adrenergic receptor cardiac regulation in two freshwater teleosts: Channel catfish (Ictalurus punctatus) and common carp (Cyprinus carpio).

ß3-adrenergic receptors (AR) are important in teleost cardiovascular regulation. To date, it is unknown whether temperature acclimation changes ß3-AR functionality and consequently the involvement of this AR subtype in teleost cardiac regulation. Common carp (Cyprinus carpio) were acclimated at 12 °C or 23 °C (minimum 3 weeks) after which cardiovascular variables (cardiac output (Q), stroke volume (Sv) and heart rate (fH)) were measured upon injection of the ß3-AR agonist, BRL(37344), and antagonist, SR(59230A). In both 12 °C and 23 °C acclimated carp, BRL(37344) induced significant increases in fH and Q whereas Sv was significantly decreased. While temperature did not affect the change (increase vs. decrease) in cardiac variables, the magnitude and on-set of responses differed. For instance, fH, Sv and Q responded significantly faster to ß3-AR stimulation in 23 °C carp. In contrast, maximum responses of fH and Q were significantly higher in 23 °C carp whereas the maximum response of Sv was significantly greater in 12 °C carp. These findings suggest that temperature acclimation induced changes in ß3-AR receptor functionality (e.g. density and/or affinity). Stimulation of ß3-ARs in 23 °C acclimated channel catfish (Ictalurus punctatus) caused significant increases in fH, Sv and Q. The increase in Sv was opposite to the decrease observed in 23 °C acclimated common carp. SR(59230A) induced significant decreases in Sv and Q but had no effect in carp (23 °C). Results suggest species diversity in the density and affinity or structure of ß3-ARs which may explain the different cardiac responses to ß3-AR ligands.

Brainstem mechanisms controlling cardiovascular reflexes in channel catfish.

Microinjections of kynurenic acid and kainic acid into the general visceral nucleus (nGV), homologous to the mammalian nucleus tractus solitarius of the medulla, in anesthestized, spontaneously breathing catfish were used to identify central areas and mechanisms controlling resting normoxic heart rate and blood pressure and the cardiovascular responses to hypoxia. Kynurenic acid, an antagonist of ionotropic glutamate receptors, significantly reduced resting normoxic heart rate but did not block the bradycardia associated with aquatic hypoxia. Kainic acid (an excitotoxic glutamatergic receptor agonist) also significantly reduced normoxic heart rate, but blocked the hypoxia-induced bradycardia. Neither kynurenic acid nor kainic acid microinjections affected blood pressure in normoxia or hypoxia. The results of this study indicate that glutamatergic receptors in the nGV are involved in the maintenance of resting heart rate and the destruction of these neurons with kainic acid abolishes the bradycardia associated with aquatic hypoxia.

Identification of central mechanisms vital for breathing in the channel catfish, Ictalurus punctatus.

To investigate central respiratory control mechanisms in channel catfish, microinjections of kainic acid (causing chemical lesion of neurons) or kynurenic acid (an antagonist of N-methyl-D-aspartate (NMDA), kainate and alpha-amino-3-OH-5-methyl-4-isooxazole-propionic-acid (AMPA) receptors) were made into the general visceral nucleus (nGV) of the medulla in anaesthetised spontaneously breathing animals. Kainic acid abolished the ventilatory movements, indicating that neurons in the nGV are crucial for maintaining normal breathing. Kynurenic acid did not affect normal breathing, but abolished the ventilatory responses to hypoxia, showing that ionotropic glutamate receptors in the nGV are vital for the production of oxygen chemoreceptor activated respiratory reflexes. In addition, immunohistochemistry of brain slices showed that interneurons and nerve fibres in the nGV display NMDA-immunoreactivity, which corroborates the physiological experiments. The results of this study suggest that neurons and glutamatergic pathways in the nGV are essential for ventilatory functions and hypoxic reflexes in channel catfish.

Central nervous control of gill filament muscles in channel catfish.

The gills of fish are innervated by cranial nerves IX and X. There have been a number of studies on the characteristics of sensory activity carried by these nerves but remarkably little is known about motor control of the gills. Efferent, motor activity to the first gill arch was recorded from the glossopharyngeal nerve in spontaneously breathing channel catfish, Ictalurus punctatus. This study addressed two objectives. The first objective was to characterize efferent branchial nerve activity in spontaneously breathing fish. Nerve recordings show bursts of activity firing in synchrony with ventilation. These bursts occurred once during either abduction or adduction of the operculum with each breath. The observed patterns of neural activity indicate that it represents motor control of gill filament abductor and adductor muscles. The data show that rhythmic output from a central pattern generator controls filament musculature during the ventilatory cycle. The second objective was to use this efferent branchial nerve activity as an index of ventilation (fictive ventilation) in fish before and after paralysis to determine if feedback from phasic mechanoreceptors affects ventilatory timing. Breath-to-breath intervals measured before and after paralysis with gallamine were not significantly different, demonstrating that rhythmic feedback from phasic mechanoreceptors in the gills and/or ventilatory musculature is not involved in the breath-to-breath timing of the normal ventilatory cycle. During the course of these experiments many fish exhibited coughing. Coughs were characterized by a distinctive pattern of nerve activity that was not altered by paralysis. Overall, the data indicate that phasic mechanoreceptor feedback during normal breathing has no effect on the pattern of central motor control of gill filament muscles.

Pulmonary receptors in reptiles: discharge patterns of receptor populations in snakes versus turtles.

This study examines the effects of lung inflation/deflation with and without CO2 on the entire population of pulmonary receptors in the vagus nerve in two species of snakes and two species of turtles. We asked the question, "how does the response of the entire mixed population of pulmonary stretch receptors (PSR) and intrapulmonary chemoreceptors (IPC) in species possessing both differ from that in species with only PSR"? This was studied under conditions of artificial ventilation with the secondary goal of extending observations on the presence/absence of IPC to a further three species. Our results indirectly illustrate the presence of IPC in the Burmese python and South American rattlesnake but not the side necked turtle, adding support to the hypothesis that IPC first arose in diapsid reptiles. In both species of snake, CO2-sensitive discharge (presumably from IPC) predominated almost to the exclusion of CO2-insensitive discharge (presumably arising from PSR) while the opposite was true for both species of turtle. The data suggest that for animals breathing air under conditions of normal metabolism there is little to distinguish between the discharge profiles of the total population of receptors arising from the lungs in the different groups. Interestingly, however, under conditions of elevated environmental CO2 most volume-related feedback from the lungs is abolished in the two species of snakes, while under conditions of elevated metabolic CO2, it is estimated that volume feedback from the lungs would be enhanced in these same species.

Branchial mechanoreceptor activity during spontaneous ventilation in channel catfish.

Extracellular afferent neural activity was recorded in vivo from cranial nerve IX (glossopharyngeal) from mechanoreceptors in the first gill arch of anesthetized, spontaneously breathing channel catfish (Ictalurus punctatus). Single unit and paucifiber recordings show that both phasic and tonic receptors were active during normal ventilation. Phasic receptors were characterized as having a burst of activity during some phase of the ventilatory cycle. Most of these occurred during peak adduction or peak abduction. Phasic receptors were not active during spontaneous apnic periods. Tonic receptors were always active, even during apneas, firing frequency was modulated by breathing movements with peak activity occurring during adduction. Flow-sensitive mechanoreceptors were identified in anesthetized, paralyzed catfish. These receptors decreased activity when the ventilatory water flow was stopped. Hypercapnia (5% CO(2) in air) stimulated ventilatory rate and amplitude but had no effect on mechanoreceptor activity. The discharge characteristics of branchial mechanoreceptors indicate that they could be involved in the timing and coordination of ventilatory movements and maintenance of the 'gill curtain' to minimize ventilatory dead space. Unlike ventilatory mechanoreceptors in the air breathing organs of gar and lungs of lungfish and tetrapods, branchial mechanoreceptors were insensitive to hypercapnia.

Cardiovascular and endocrine reactivity in older females: intertask consistency.

Age-related structural and functional changes in the cardiovascular, sympathoadrenomedullary (SAM), and hypothalamic-pituitary-adrenocortical (HPA) systems may affect the ability to reliably identify individual differences in response to stress. Heart rate, preejection period, respiratory sinus arrhythmia, respiratory rate, norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol were assessed in 64 healthy older women (mean = 67 years) in response to a mental arithmetic and public-speaking task. All cardiovascular and endocrine measures changed significantly during the tasks. All measures were consistent across the two tasks (r(s)s = .50 to .97). Moreover, a majority of women in this sample exhibited cross-task consistency in the relative activation of the autonomic, SAM, and HPA systems (i.e., response profiles). Further research is recommended to examine the significance of consistent individual differences in response profile.

Autonomic and neuroendocrine responses to mild psychological stressors: effects of chronic stress on older women.

We investigated autonomic and endocrine responses to acute stressors in 27 women who were or are presently caring for a spouse with a progressive dementia (high chronic stress) and 37 noncaregivers who were category matched for age and family income (low chronic stress). Measures were taken before (low acute stress) and in response to brief laboratory stressors (high acute stress). We replicated prior research showing that caregivers report greater stress, depression, and loneliness than the comparison groups, and acute stressors elevate autonomic and neuroendocrine activity. We also found that caregivers, relative to noncaregivers, exhibited shorter preejection periods and elevated blood pressure and heart rate, but the magnitude of autonomic and neuroendocrine reactivity to the experimental stressors was comparable across these groups. This pattern of autonomic differentiation replicates prior research showing that caregivers are characterized by higher sympathetic activation than noncaregivers and suggests that the effects of chronic stress on physiological reactivity may be a less robust effect in older adults.

Epstein-Barr virus antibodies in whole blood spots: a minimally invasive method for assessing an aspect of cell-mediated immunity.

OBJECTIVE: Study 1: Introduce and validate a method for measuring EBV p18-VCA antibodies in whole blood spots to provide a minimally invasive marker of cell-mediated immune function. Study 2: Apply this method to a large community-based study of psychopathology in children and adolescents. METHODS: The EBV antibody method was evaluated through analysis of precision, reliability, stability, and comparisons with plasma and indirect immunofluorescence methods. The effects of life events on p18-VCA antibody level were considered in a subsample of 9, 11, and 13 year-old children participating in the Great Smoky Mountains Study in North Carolina. The subsample was stratified by age, sex, and degree of overall life strain. RESULTS: Dried blood spots provided a convenient, sensitive, precise, and reliable method for measuring EBV p18-VCA antibody titer. Life events were positively associated with p18-VCA antibodies in girls but not in boys. CONCLUSIONS: The validity of the blood spot EBV p18-VCA antibody assay, as well as the ease of sample collection, storage, and transportation, may provide an opportunity for psychoneuroimmunology to explore a wider range of stress models in larger, community-based studies.

Branchial chemoreceptors mediate ventilatory responses to hypercapnic acidosis in channel catfish.

The effects of hyperoxic hypercapnia on cardiovascular and ventilatory variables and blood gas and acid/base parameters were examined in conscious and anesthetized spontaneously breathing (ASB) channel catfish, Ictalurus punctatus. These separate experiments were designed to determine: (1) if channel catfish show a ventilatory response to hypercapnic acidosis when blood O(2) content is maintained in conscious animals; and (2) whether branchial receptors innervated by cranial nerves IX and X mediate this response. The combination of high O(2) and CO(2) tensions allowed the cardioventilatory effects of hypercapnic acidosis to be assessed independently of Root or Bohr mediated changes in blood O(2) content. In the absence of significant changes in dorsal or ventral aorta O(2) content, hyperoxic hypercapnia significantly stimulated ventilation, relative to hyperoxic exposure. Hypercapnic acidosis, however, had no significant effects on blood pressure or heart rate. Branchial denervation in ASB fish abolished the ventilatory response to hypercapnic acidosis. The results indicate that hypercapnic acidosis independently stimulates ventilation in channel catfish. This response is mediated by CO(2)/pH-sensitive branchial receptors innervated by cranial nerves IX and X.

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Autonomic, neuroendocrine, and immune responses to psychological stress: the reactivity hypothesis.

We examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. Results revealed that psychological stressors heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected the cellular immune response (ps < 0.05). In a replication and extension, 27 women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls category matched for age and family income (low chronic stress) performed the 12-min laboratory stressor. Measures were taken before (low acute stress) and immediately following (high acute stress) exposure to the laboratory stressors as well as 30 min after termination of the stressor (recovery period). Acute stress again heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected cellular immune responses (ps < 0.05), whereas chronic stress was associated with higher reports of negative affect, enhanced cardiac sympathetic activation, elevated blood pressure and plasma levels of ACTH, and diminished production of interleukin-1 beta (ps < 0.05). Correlational analyses in both studies further suggested that individuals who showed the greatest stress-related changes in HPA activation also exhibited the greatest diminution in cellular immune response.

Effect of weight training exercise and treadmill exercise on post-exercise oxygen consumption.

Effect of weight training exercise and treadmill exercise on postexercise oxygen consumption. Med. Sci. Sports Exerc., Vol. 30, No. 4, pp. 518-522, 1998. To compare the effect of weight training (WT) and treadmill (TM) exercise on postexercise oxygen consumption (VO2), 15 males (mean +/- SD) age = 22.7 +/- 1.6 yr; height = 175.0 +/- 6.2 cm; mass = 82.0 +/- 14.3 kg) performed a 27-min bout of WT and a 27-min bout of TM exercise at matched rates of VO2. WT consisted of performing two circuits of eight exercises at 60% of each subject's one repetition maximum with a work/rest ratio of 45 s/60 s. Approximately 5 d after WT each subject walked or jogged on the TM at a pace that elicited an average VO2 matched with his mean value during WT. VO2 was measured continuously during exercise and the first 30 min into recovery and at 60 and 90 min into recovery. VO2 during WT (1.58 L.min-1) and TM exercise (1.55 L.min-1) were not significantly (P > 0.05) different; thus the two activities were matched for VO2. Total oxygen consumption during the first 30 min of recovery was significantly higher (P < 0.05) as a result of WT (19.0 L) compared with that during TM exercise (12.7 L). However, VO2 values at 60 (0.32 vs 0.29 L.min-1), and 90 min (0.33 vs 0.30 L.min-1) were not significantly different (P > 0.05) between WT and TM exercise, respectively. The results suggest that, during the first 30 min following exercise. WT elicits a greater elevated postexercise VO2 than TM exercise when the two activities are performed at matched VO2 and equal durations. Therefore, total energy expenditure as a consequence of WT will be underestimated if based on exercise VO2 only.

Cellular immune responses to acute stress in female caregivers of dementia patients and matched controls.

This study investigated whether the stress of caregiving alters cellular immune responses to acute psychological stressors. Twenty-seven women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls matched for age and family income performed a 12-min laboratory stressor. Cellular immune function was assessed by both functional and quantitative measures taken before (low acute stress), immediately after (high acute stress), and 30 min after (recovery from stress) exposure to the laboratory stressors. The laboratory challenges were associated with diminished proliferative responses but elevated natural killer (NK) cell cytotoxicity; however, subsequent analyses suggested that this elevated cytotoxicity was largely attributable to an increase in the number of NK cells in peripheral blood. The results suggest that although the stress of caregiving diminishes cellular immune function, caregiving appears to have little effect on cellular immune responses to or recovery from brief psychological challenges.

Ventilation and acid-base recovery following exhausting activity in an air-breathing fish

The effects of exhausting activity in normoxic (PO2=20.7 kPa) and hypoxic (PO2<2.7 kPa) water on ventilatory, metabolic and acid-base variables were examined in spotted gar (Lepisosteus oculatus) to determine the role of the air-breathing organ in supporting active metabolism and recovery. The level of aquatic hypoxia used effectively eliminated the gills as a site of O2 uptake, forcing the fish to respire as a unimodal air-breather. Swimming duration (until exhaustion) was not significantly different in normoxic and hypoxic water. Blood gas, acid-base, cardiovascular and ventilatory variables were monitored at intervals from 15 min to 24 h post-exercise. Fish survived exhaustive exercise using a combination of anaerobic metabolism and increased ventilation (aerial and aquatic), despite respiratory and metabolic acidoses. The cardiovascular effects of exercise (heart rate and dorsal aortic blood pressure) were minor. The metabolic effects of exercise were similar to those in unimodal water-breathing fish; however, even hypoxic animals recovered from exhaustive exercise by 24 h. Thus, the results of this study show that air breathing in L. oculatus allows gar to exercise to the same extent in normoxic and hypoxic water and enables them to re-establish blood gas and acid-base balance after exhaustive activity even in hypoxic water.

Postmenopausal hormone replacement: effects on autonomic, neuroendocrine, and immune reactivity to brief psychological stressors.

OBJECTIVE: Postmenopausal status increases some aspects of women's physiological responses to psychological stress; however, the influences of chronic hormone replacement with estrogen and progestogen on these responses are not known. We investigated possible effects of long-term estrogen replacement therapy (ERT), both with and without progestogen, on physiological reactivity to brief laboratory stressors. METHOD: We studied three groups of postmenopausal women: 16 on estrogen alone, 14 on estrogen and progestogen, and 25 control participants receiving no replacement therapy. Cardiovascular, neuroendocrine, and immune data were collected at baseline and after speech and math tasks. RESULTS: In all groups, the stressors reduced vagal cardiac control (indexed by respiratory sinus arrhythmia); increased heart rate and plasma epinephrine, adrenocorticotropic hormone, and cortisol levels; and altered T lymphocyte response (measured by mitogen-induced cell proliferation), natural killer cell lysis, and circulating leukocyte subsets. Women on either type of ERT had higher total cortisol levels (reflecting an estrogen effect on cortisol binding globulin) and greater mitogen-induced blastogenesis across measurement periods than controls. They also showed greater vagal withdrawal and less decline in mitogen-stimulated blastogenesis in response to the stressors. Combined estrogen and progestogen was associated with higher epinephrine and lower circulating total lymphocytes, T cells, and CD4+ T cells across measurement periods, and with intermediate levels of vagal withdrawal in response to the stressors. CONCLUSIONS: Long-term ERT was associated with enhanced parasympathetic responsiveness to stress, suggesting possible reduced demand for potentially detrimental sympathetic activation; and with higher overall levels and smaller stress-induced reductions of mitogen-stimulated blastogenesis, suggesting up-regulated T cell function.

Differential effects of estrogen and medroxyprogesterone on basal and stress-induced growth hormone release, IGF-1 levels, and cellular immunity in postmenopausal women.

We evaluated the influence of continual estrogen replacement therapy (ERT) as presently practiced by postmenopausal women with conjugated estrogens and medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and MPA). In the women receiving only conjugated estrogens, increased GH levels and decreased IGF-1 levels were found, which replicated previous research and probably reflected estrogen inhibition of hepatic IGF-1 production with a secondary increase in GH release because of reduced feedback inhibition. In women taking both MPA and estrogen, GH was increased and the previously observed estrogen induced decrease in IGF-1 levels was inhibited. In order to determine the influence of ERT on psycho-social stress-induced GH release, math (mental stress) and speech (social stress) challenges were utilized, and they produced significant increases in heart rate in all three groups. The heart rate following stress was significantly enhanced by estrogen replacement. These stressors also led to increased GH secretion in the women taking estrogen and MPA, but not in the other two groups. Gonadal steroids and GH can influence cellular immunity. We observed that ERT in both groups was associated with significantly enhanced lymphocyte responsiveness to the T-cell mitogens phytohemaglutinin (PHA) and Conconavalin A (Con A), and basal GH levels were correlated with the PHA response in the estrogen only group. ERT did not influence natural killer (NK) cell activity. We also found significant differences in the steady-state expression of latent Epstein-Barr virus (EBV) with increased antibody titers in the women in the estrogen only group and lower antibody titers in the MPA plus estrogen group. GH levels were correlated with EBV antibody titers in the estrogen plus MPA group. This study supports the hypothesis that GH and immune modulation can be influenced by ERT in postmenopausal woman. Given the extant literature on the immune-enhancing effects of GH, these data suggest that ERT may slow the decline of GH secretion with aging, an event that has been implicated in immunosenescence.

Cardio-ventilatory control in rainbow trout: II. Reflex effects of exogenous neurochemicals.

The effects of various neurochemicals were examined in intact, unanesthetized rainbow trout (Oncorhynchus mykiss) to assess the role of branchial O2-sensitive chemoreceptors in the cardio-ventilatory responses to exogenous neurochemicals. cyanide stimulated ventilation and elicited bradycardia when give externally but only stimulated ventilation when injected internally. Norepinephrine increased heart rate, blood pressure and ventilatory rate but opercular pressure was not affect. Dopamine had no effect on either heart or ventilatory rate but increased blood pressure and decreased opercular pressure. Serotonin stimulated heart rate and ventilation but decreased blood pressure. Acetylcholine and nicotine stimulated all cardio-ventilatory variables. Muscarine decreased heart rate and blood pressure and had a biphasic effect on ventilation. These results, combined with the results from the preceding study, suggest that the cardio-ventilatory effects of exogenously administered (1) cyanide are entirely mediated by gill O2 receptors, (2) serotonin, and cholinergic drugs could be partly mediated by O2 receptors and (3) catecholaminergic drugs are not mediated by O2 receptors.

Arthritis and perceptions of quality of life: an examination of positive and negative affect in rheumatoid arthritis patients.

The utility of measuring both positive and negative affective states for assessing rheumatoid arthritis (RA) patients was examined in 3 independent samples of male and female RA patients (Sample A: 179 women, 48 men; Sample B: 177 women, 24 men; Sample C: 134 women, 38 men). Confirmatory factor analyses of each sample indicated that positive and negative affect constituted separate, negatively correlated factors. The relations among disease variables, coping, and affects were consistent with a model in which coping mediates the relationship between disease variables and positive and negative affect. Patients with higher pain and limitation from RA had higher levels of maladaptive coping, and maladaptive coping was associated with lower positive affect and higher negative affect. Those RAs with higher activity limitation also reported less adaptive coping, which was associated with less positive affect.