Biomedical subjects

James G Lewis

Publications and source records attributed to James G Lewis.

6 recordsLinked to original sources

PubMed2005

Increases in stimulated secretion of proinflammatory cytokines by blood monocytes following arousal of negative affect: the role of insulin resistance as moderator.

We examined the effect of negative affect on changes in stimulated secretion of cytokines by blood monocytes and determined whether insulin resistance (IR), as indexed by the Homeostasis Model Assessment (HOMA), moderated these associations in 58 healthy men (aged 18-65 years). Blood samples and ratings of negative affect were collected at rest and 15min following subjects' participation in the Anger Recall Interview (ARI). Assessment of lipopolysaccharide (LPS)-stimulated secretion of IL-1beta, IL-6, and TNF-alpha was accomplished by ELISA of supernatant. Regression models controlling for age, body mass index, and race/ethnicity revealed that higher HOMA-IR values were associated with larger stress-induced increases in IL-1beta and TNF-alpha (p<.05). Furthermore, arousal of negative affect during the ARI was differentially associated with stress-induced changes in stimulated secretion of TNF-alpha and IL-6 as a function of HOMA-IR (p<.05). Increases in stimulated cytokine secretion were associated with arousal of negative affect, but only among men with higher HOMA-IR values. Among men with lower HOMA-IR values, arousal of negative affect was associated with diminished cytokine secretion. Collectively, these data suggest that the HOMA-IR moderates the impact that arousal of negative affect has on the ability of blood monocytes to secrete inflammatory cytokines in response to LPS. Stress-induced increases in cytokine secretion among high HOMA-IR men are consistent with the role of inflammation in cardiovascular disease, hypertension, type 2 diabetes as well as the metabolic syndrome and underscore the relevance of negative affect in the etiology of these inflammatory conditions.

Adolescent↗

PubMed2004

Enhanced expression of cytokines and chemokines by blood monocytes to in vitro lipopolysaccharide stimulation are associated with hostility and severity of depressive symptoms in healthy women.

The current study investigated the relation of hostility and severity of depressive symptoms, separately and jointly, to the capacity of blood monocytes to secrete an array of cytokines when stimulated by bacterial lipopolysaccharide (LPS). Subjects were 44 healthy, non-smoking, premenopausal women (aged 23-49 years) not currently taking oral contraceptives. Data were collected during the follicular phase of the menstrual cycle. The Cook-Medley Hostility (Ho) scale and the Beck Depression Inventory (BDI) were used to assess hostility and severity of depressive symptoms, respectively. Dual-color flow cytometry was used to measure the total expression of interleukin (IL)-1alpha, IL-1beta, IL-8, tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1 and monocyte inflammatory protein (MIP)-1alpha in blood monocytes following 4 h in vitro LPS stimulation of whole blood. In analyses adjusting for age, body mass index (BMI), fasting cholesterol, alcohol use, race and 17beta-estradiol (E(2)), higher Ho scores were associated with greater LPS-stimulated expression of IL-1alpha (beta = 0.033, p = 0.02), IL-8 (beta = 0.046, p = 0.01) and IL-1beta (beta = 0.024, p = 0.06). Higher BDI scores were associated with greater expression of TNF-alpha (beta = 0.042, p = 0.02) and IL-8 (beta = 0.045, p = 0.04). The linear combination of Ho and BDI scores was significantly associated with IL-1beta (beta = 0.18, p = 0.057), IL-8 (beta = 0.36, p = 0.01), TNF-alpha (beta = 0.25, p = 0.03), and IL-1alpha (beta = 0.18, p < 0.07). Thus, in healthy women, these psychological risk factors, alone and in combination, induce a proinflammatory phenotype in circulating monocytes characterized by the up-regulation of proinflammatory cytokines, supporting the hypothesis that inflammation may be a key pathway whereby hostility and depressive symptoms contribute to atherosclerosis and subsequent coronary heart disease (CHD).

Cells, Cultured↗

PubMed2004

Beryllium(II) binding to ATP and ADP: potentiometric determination of the thermodynamic constants and implications for in vivo toxicity.

Highly toxic beryllium(II) is divalent metal ion with a high charge density, making it a potential target for binding to bio-molecules rich in O donor groups. In aqueous solution Be2+ binds to ATP and ADP to form 1:1 Be2+:ATP and Be2+:ADP complexes in relatively acidic media. At neutral pH the complex formed undergoes hydrolysis. Be2+ binding to ATP and ADP is much stronger than Ca2+ and Mg2+ binding. The high affinity of Be2+ toward ATP and ADP binding suggests a mechanism relevant to understanding the in vivo chemical toxicity of this metal.

Adenosine Diphosphate↗

PubMed2002

Serotonin-related gene polymorphisms and central nervous system serotonin function.

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.

Adult↗

PubMed2002

The relation of aggression, hostility, and anger to lipopolysaccharide-stimulated tumor necrosis factor (TNF)-alpha by blood monocytes from normal men.

Aggression, hostility, and anger significantly predict morbidity and mortality from atherosclerotic cardiovascular disease (ACVD). ACVD is believed to be an inflammatory disease characterized by increased expression of a number of proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha. This study examined the relation of aggression, hostility, and anger to monocyte-associated TNF-alpha expression following lipopolysaccharide (LPS) stimulation. Participants were 62 healthy, non-smoking men (aged 18-45 years). Hostility, anger, verbal, and physical aggression were assessed using the Buss-Perry aggression questionnaire (BPAQ). LPS-stimulated TNF-alpha expression was determined using dual-color flow cytometry gating for CD14(+) cells. After controlling for age, race, education, and alcohol use, scores on the hostility (p=.013), physical aggression (p=.010), and verbal aggression (p=.034) subscales, and the total score (p=.007) on the BPAQ were positively associated with LPS-stimulated TNF-alpha expression. The results suggest that hostility and aggression are associated with an increased expression of TNF-alpha, a cytokine implicated in ACVD.

Adolescent↗

PubMedDate not supplied

The relation of severity of depressive symptoms to monocyte-associated proinflammatory cytokines and chemokines in apparently healthy men.

OBJECTIVE: We examined the relation of severity of depressive symptoms to lipopolysaccharide-stimulated expression of monocyte-associated proinflammatory cytokines and chemokines in 53 nonsmoking, healthy men. METHODS: Assessments of cytokine and chemokine expression and severity of depressive symptoms were conducted on the same day. The 21-item Beck Depression Inventory (BDI) was used to assess severity of depressive symptoms experienced during the week before study participation. Dual-color flow cytometry was used to determine monocyte-associated (CD14+) expression of interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-8, and monocyte chemotactic protein-1 (MCP-1) after in vitro lipopolysaccharide stimulation of undiluted whole blood. RESULTS: Calculations of partial correlation coefficients controlling for age, race, body mass index, and alcohol use indicated that BDI score was significantly associated with IL-1alpha (r = 0.27), IL-1beta (r = 0.44), TNF-alpha (r = 0.57), MCP-1 (r = 0.52), and IL-8 (r = 0.33). In addition, relative to men with BDI scores below 10, men with BDI scores of 10 or above exhibited an overexpression of IL-1beta (p =.004), TNF-alpha (p =.005), IL-8 (p =.002), and MCP-1 (p =.025). CONCLUSIONS: Relative to men with no or minimal symptoms of depression, men with mild to moderate levels of depressive symptoms showed overexpression of monocyte-associated proinflammatory cytokines and chemokines.

Adolescent↗