Visual EEG differences in abstinent alcohol dependence and ethnicity.
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Adult↗
Biomedical subjects
Michael Irwin
Publications and source records attributed to Michael Irwin.
Macrophage colony-stimulating factor expression in retrovirally transduced cells is dependent upon both the adherence status of the target cells and its 5' flanking untranslated region.
Numerous cell types retrovirally transduced with macrophage colony-stimulating factor (M-CSF) using LXSN-based vectors showed a variable expression of the transgene. Expression of M-CSF correlated with the cells' adherent status. Transduced adherent cells produced the M-CSF, whereas the non-adherent cells synthesized little M-CSF. Studies showed that the 5'-UTR of the M-CSF gene regulated transgenic M-CSF gene expression. Ligation of this 5'-UTR to the enhanced green fluorescent protein gene (EGFP) caused the expression of EGFP to show the same dichotomy as previously seen with the M-CSF. Transgenic M-CSF was expressed within non-adherent cells when the 5'-UTR was removed from the LXSN vector. Quantitative real-time polymerase chain reaction analysis confirmed that lesser production of M-CSF mRNA occurred within the non-adherent cells than in the adherent cells. This difference was eliminated when the 5'-UTR was removed from the retroviral vector. Our work suggests that this 5'-UTR of the M-CSF gene could be an important way to get transgenic expression within adherent cells, but not in non-adherent cells.
5' Untranslated Regions↗
Shingles Immunity and Health Functioning in the Elderly: Tai Chi Chih as a Behavioral Treatment.
Both the incidence and severity of herpes zoster (HZ) or shingles increase markedly with increasing age in association with a decline in varicella zoster virus (VZV)-specific immunity. Considerable evidence shows that behavioral stressors, prevalent in older adults, correlate with impairments of cellular immunity. Moreover, the presence of depressive symptoms in older adults is associated with declines in VZV-responder cell frequency (VZV-RCF), an immunological marker of shingles risk. In this review, we discuss recent findings that administration of a relaxation response-based intervention, tai chi chih (TCC), results in improvements in health functioning and immunity to VZV in older adults as compared with a control group. TCC is a slow moving meditation consisting of 20 separate standardized movements which can be readily used in elderly and medically compromised individuals. TCC offers standardized training and practice schedules, lending an important advantage over prior relaxation response-based therapies. Focus on older adults at increased risk for HZ and assay of VZV-specific immunity have implications for understanding the impact of behavioral factors and a behavioral intervention on a clinically relevant end-point and on the response of the immune system to infectious pathogens.
Journal Article↗
Cellular adhesion molecule expression, nocturnal sleep, and partial night sleep deprivation.
Sleep is hypothesized to have a role in the regulation of the immune system. This study evaluated the nocturnal expression of cellular adhesion molecules, Mac-1 and L-selectin on monocytes and lymphocytes during a full nights sleep and following a partial night of sleep deprivation (PSD). Healthy male subjects (n=16) had an increase in the percentage of Mac-1 positive lymphocytes across the baseline night. Whereas, the percentage of Mac-1 positive lymphocytes was reduced and L-selectin positive lymphocytes and monocytes were greater during the PSD night as compared to the baseline night. These data indicate that acute sleep disruption is associated with alterations in cellular adhesion molecule expression, with implications for the regulation of immune cell trafficking.
Adult↗
Nocturnal proinflammatory cytokine-associated sleep disturbances in abstinent African American alcoholics.
Animal studies reveal that cytokines play a key role in the regulation of sleep. Alcoholic patients show profound alterations of sleep and a defect in the homeostatic recovery of sleep following sleep loss. In this study, we investigated whether nocturnal plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF) were associated with disordered sleep in alcohol dependence by testing the temporal relationships between these inflammatory cytokines and sleep, before and after sleep deprivation. All-night polysomnography and serial blood sampling at 23:00, 03:00, and 06:30 h were conducted across baseline, partial sleep deprivation, and recovery nights in abstinent African American alcoholics (n=16) and matched controls (n=15). Coupled with prolonged sleep latency and increased rapid eye movement sleep, alcoholics showed nocturnal elevations of IL-6 and TNF as compared to controls after adjustment for alcohol consumption and body mass index. Following sleep deprivation, alcoholics showed greater nocturnal levels of IL-6 and greater nocturnal increases of TNF as compared to controls. Pre-sleep IL-6 levels at 23:00 h correlated with prolonged sleep latency after adjustment for potential confounders whereas IL-6 levels at 03:00 h correlated with rapid eye movement sleep in the second half of the night. Taken together, these findings indicate that circulating levels of proinflammatory cytokines may have a negative influence on sleep initiation. These findings have implications for determining why sleep is disordered in alcoholics and may aid in the development of novel treatments to optimize sleep in this population.
Adult↗
The association between major depression and levels of soluble intercellular adhesion molecule 1, interleukin-6, and C-reactive protein in patients with recent acute coronary syndromes.
OBJECTIVE: This study was conducted to determine whether or not depression is associated with higher levels of inflammatory markers in patients recovering from acute coronary syndromes. METHOD: Plasma levels of soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin-6 (IL-6) and the serum level of C-reactive protein were measured in 481 patients 2 months after hospitalization for acute coronary syndromes. Diagnosis of major depression was based on the Structured Clinical Interview for DSM-IV. RESULTS: Depressed patients showed significantly higher sICAM-1 levels, a difference that remained significant after adjustment for potential confounders (gender, smoking, presence of metabolic syndrome). Although there was no significant association between depression and IL-6, there was an interaction between depression and statin therapy for levels of C-reactive protein. Depressed patients not taking statins had markedly higher C-reactive protein levels than did nondepressed patients. There was no relationship with depression in those receiving statins. CONCLUSIONS: These results suggest chronic endothelial activation among depressed patients after acute coronary syndromes. Further research is needed to determine whether or not higher levels of sICAM-1 may identify a subgroup of depressed patients at particularly high risk for cardiac events among patients with established coronary artery disease or among those without previous coronary artery disease.
Acute Disease↗
Home or hospital: choices at the end of life.
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Choice Behavior↗
Immune activation and depression in women with rheumatoid arthritis.
OBJECTIVE: We examined markers of immune activation during periods of stress and depressive symptoms in 45 female patients with rheumatoid arthritis (RA) in comparison to 106 controls with no autoimmune disease. METHODS: Depressive symptoms were recorded, clinician ratings of disease activity were made, and blood was drawn for RA patients and controls at baseline and during a designated stressful week. RESULTS: Counts of T cell subpopulations revealed significant differences between RA and control groups in proportions of CD8 and CD4 cells, with higher CD4 and lower CD8 counts for the RA participants. Significant depression by diagnosis interactions were found, revealing greater CD4 activation among RA patients who were depressed in comparison to other groups. Only marginally significant effects of stress were found on T cell counts. Interleukin 6 (IL-6) concentrations also differentiated groups, with the highest levels of IL-6 observed for depressed RA patients under stress. CONCLUSION: These findings provide new evidence that psychosocial factors play a significant role in autoimmune processes that underlie RA.
Aged↗
Pro-choice living wills.
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Advance Directive Adherence↗
Arrested--for showing compassion?
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Humans↗
Nocturnal catecholamines and immune function in insomniacs, depressed patients, and control subjects.
Insomnia predicts cardiovascular and non-cardiovascular disease mortality. This study evaluated EEG sleep, nocturnal sympathetic activity, and daytime measures of immune function in subjects with primary insomnia (n = 17) and patients with current major depression (n = 14) as compared to controls (n = 31). Insomniacs showed disordered sleep continuity along with nocturnal increases of average levels of circulating norepinephrine and decreases of natural killer cell responses, whereas depressed patients showed declines of natural killer cell activity, but no differences of EEG sleep or nocturnal catecholamines as compared to controls. Impairments of sleep efficiency correlated with nocturnal elevations of norepinephrine in the insomniacs but not in the depressives or controls. These data indicate that insomnia is associated with nocturnal sympathetic arousal and declines of natural immunity, and further support the role of sleep in the regulation of sympathetic nervous and immune system functioning.
Analysis of Variance↗
Sleep deprivation as a probe of homeostatic sleep regulation in primary alcoholics.
BACKGROUND: Alcoholic patients show prominent disturbances of sleep electroencephalograms (EEGs) with a marked loss of slow wave sleep that is even more profound in African American alcoholics as compared to European Americans. Using partial sleep deprivation, this study examined the extent to which abnormal sleep is reversible in alcoholic subjects. METHODS: In a sample stratified on ethnicity, polysomnographic and spectral sleep EEG measures were compared in male primary alcoholic in patients (n=46) and age-matched comparison controls (n=32) at baseline-and recovery sleep following a night of partial sleep deprivation. RESULTS: As compared to controls, alcoholic patients showed a loss of slow wave sleep and more spectral power in beta frequencies. Following sleep deprivation, slow wave sleep and delta power differentially changed between the groups. European American controls showed increases of slow wave sleep that were more robust than responses found in African American controls, whereas both alcoholic groups failed to show increases of slow wave sleep from baseline to recovery. Spectral EEG analyses revealed similar results; sleep deprivation induced significant increases of delta power during NREM-1 in the controls, but not in the alcoholics. CONCLUSIONS: Alcohol dependence compromises the augmentation of slow wave sleep and delta power seen in healthy adults following sleep deprivation. The differential effect of alcoholism on sleep stage physiology suggests a defect in the regulation or plasticity of slow wave sleep with implications for theories linking sleep depth to morbidity and outcome in alcoholics.
Adult↗
Psychoneuroimmunology of depression: clinical implications.
Psychoneuroimmunology is a field that investigates the interactions between the brain and the immune system. One important goal of this field of research is to translate basic research in order to understand how behavior affects health and resistance to disease in humans. This review evaluates the impact of depression on morbidity and mortality risk and asks whether neuroimmune mechanisms contribute to this association. Examples are drawn from three diseases: cardiovascular disease, infectious disease, and rheumatoid arthritis. Finally, the potential for biobehavioral interventions to impact psychological adaptation and the course of immune related disease is discussed.
Behavior Therapy↗
Effects of sleep and sleep loss on immunity and cytokines.
Sleep is hypothesized to be a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed- and alcoholic subjects correlates with declines in natural- and cellular immunity and is associated with alterations in the complex cytokine network. Sleep loss has a role in mediating these immune changes as experimentally induced partial night sleep deprivation replicates the kind of sleep loss found in clinical samples and induces a pattern of immune alterations similar to that found in depressed- and alcoholic patients. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the clinical significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep in patient populations.
Alcoholism↗
Disordered sleep, nocturnal cytokines, and immunity in alcoholics.
OBJECTIVE: Alcoholics who are at risk for infectious disease show profound disturbances of sleep along with decrements of cellular immunity. This study examined the relationships between sleep, nocturnal expression of immunoregulatory cytokines, and natural killer (NK) cell activity in alcoholic patients as compared with control subjects. METHODS: Alcoholic patients (N = 24) and comparison control subjects (N = 23) underwent all-night polysomnography and serial blood sampling at 23:00, 03:00, and 06:30 hours. Stimulated expression of T(H)1 (interferon gamma, IFN-gamma), anti-inflammatory/T(H)2 (interleukin 10, IL-10), and proinflammatory cytokines (IL-6) was measured along with NK cell activity across the night. RESULTS: Alcoholic patients showed lower levels of IL-6 production, suppression of the IL-6/IL-10 ratio, and a reduction of NK cell activity, coupled with losses of delta sleep and increases of rapid eye movement sleep, as compared with control subjects. In addition, alcoholics showed a persistent low ratio of IFN-gamma/IL-10 and reduced levels of NK cell activity, whereas controls had increases of these two immune measures across the night. IL-6 also differentially changed in the two groups; alcoholics showed increases and controls had decreases of IL-6 from 03:00 hours to 06:30 hours. At 06:30 hours, rapid eye movement sleep predicted increases of IL-6 and decreases of NK cell activity independent of the relative contribution of age and chronic alcohol consumption. At 23:00 hours before sleep onset, levels of IL-10 predicted subsequent amounts of delta sleep. CONCLUSIONS: These data further implicate sleep in the regulation of immune function and suggest that disordered sleep contributes to immune alterations in patients with chronic alcoholism. Moreover, the association between awake levels of the anti-inflammatory/T(H)2 cytokine IL-10 and subsequent amounts of delta sleep support the notion of a bidirectional interplay between cytokines and sleep in humans.
Adult↗
Acute psychological stress: effects on chemotaxis and cellular adhesion molecule expression.
OBJECTIVE: Activation of a psychological stress response increases autonomic activity and enhances immune function by inducing a significant increase in numbers of leukocytes at sites of inflammation. Chemotaxis and cellular adhesion are thought to mediate leukocyte trafficking. In this study, we examine the effects of an acute psychological stress on chemotactic responses of PBMCs and on CAM expression in relation to measures of sympathetic activation. METHODS: Subjects underwent either a public speaking task (N = 24) or a control condition (N = 13). Blood was drawn before the task, immediately after, and 20 minutes after, the task for changes in percentage of cells expressing cellular adhesion molecules, chemotaxis to chemokines, HR, blood pressure, and E and NE levels. RESULTS: In response to the laboratory stressor, increases of PBMC chemotaxis to FMLP and SDF-1 were found, which were coupled with increases in the percentages of lymphocytes expressing the integrin Mac-1. Autonomic activity, including blood pressure and circulating levels of catecholamines, increased after administration of the stressor, and correlated with increases of Mac-1. CONCLUSIONS: These data show that acute stress induces increase of chemotaxis and expression of CAM expression, which may contribute to increased migration and recruitment of immune cells to sites of infection and/or inflammation.
Acute Disease↗