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Biomedical subjects

R E Roberts

Publications and source records attributed to R E Roberts.

At least 19 recordsLinked to original sources
PubMed2005

Role of cytosolic phospholipase A2 in the enhancement of alpha2-adrenoceptor-mediated vasoconstriction by the thromboxane-mimetic U46619 in the porcine isolated ear artery: comparison with vasopressin-enhanced responses.

Pre-contraction with the thromboxane-mimetic U46619 enhances the subsequent alpha(2)-adrenoceptor-mediated vasoconstriction in the porcine ear artery through an enhanced activation of ERK-MAP kinase. In this study we determined the role of cPLA(2) in this enhanced response, and determined whether vasopressin is also able to enhance alpha(2)-adrenoceptor-mediated vasoconstriction through the same pathway. The cPLA(2) inhibitors AACOCF3 (50 microM) and MAFP (50 microM) both inhibited the U46619-enhanced alpha(2)-adrenoceptor response, but had no effect on the direct alpha(2)-adrenoceptor response. AACOCF3 also inhibited the enhanced ERK activation associated with the enhanced alpha(2)-adrenoceptor-mediated vasoconstriction. Pre-contraction with arachidonic acid mimicked the effect of U46619 by enhancing the contractile response to the alpha(2)-adrenoceptor agonist UK14304 (1 microM) and enhancing the alpha(2)-adrenoceptor-mediated ERK activation. Pre-contraction with vasopressin also enhanced the contractile response to UK14304, but neither PD98059 (50 microM) nor AACOCF3 (50 microM) had any effect this vasopressin-enhanced response, indicating that neither the ERK pathway, nor cPLA(2) are involved in vasopressin-enhanced responses. The alpha(2)-adrenceptor-stimulated activation of ERK was also unaffected by pre-contraction with vasopressin. On the other hand, inhibition of PKCzeta inhibited the enhanced alpha(2)-adrenoceptor contraction after pre-contraction with both U46619 and vasopressin. This study demonstrates that alpha(2)-adrenoceptor-mediated vasoconstriction can be enhanced through two different pathways-one dependent upon the enhanced activation of ERK-MAP kinase through activation of cPLA(2), and the other through a different, ERK/cPLA(2)-independent pathway.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2005

Social threat and novel cage stress-induced sustained extracellular-regulated kinase1/2 (ERK1/2) phosphorylation but differential modulation of brain-derived neurotrophic factor (BDNF) expression in the hippocampus of NMRI mice.

The extracellular signal-regulated kinase1/2 (ERK1/2) pathway has a key role in cell survival and brain plasticity, processes that are impaired following exposure to stressful situations. We have recently validated two repeated intermittent stress procedures in male NMRI mice, social threat and repeated exposure to a novel cage, which result in clear behavioral effects following 4 weeks of application. The present results demonstrate that both repeated intermittent stress procedures alter the activity of the ERK1/2 pathway in the brain, as shown by changes in phosphorylated ERK1/2 (phospho-ERK1/2) protein expression and in the expression of downstream proteins: phosphorylated cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF), in the hippocampus, the frontal cortex and the hypothalamus. The hippocampus showed greater responsiveness to stress as the two stressors increased phospho-ERK1/2 and BDNF expression under acute condition. Following repeated stress, hyperphosphorylation of ERK1/2 was associated with up-regulation of hippocampal BDNF expression in the social threat group but not in mice exposed to novel cage. This lack of a pro-survival effect of ERK1/2 with repeated novel cage exposure may constitute an early event in stress-mediated brain pathology. The sustained BDNF up-regulation in the hippocampi of mice subjected to repeated social threat could be related to rewarding aspects of aggressive interactions, suggested by our previous studies.

Analysis of Variance↗
PubMed2003

Alpha 2 adrenoceptor-mediated vasoconstriction in porcine palmar lateral vein: role of phosphatidylinositol 3-kinase and EGF receptor transactivation.

1 Alpha(2) adrenoceptors cause vasoconstriction in the porcine palmar lateral vein through a mechanism involving the ERK signal transduction cascade, calcium influx, and a Src tyrosine kinase. The aim of the present study was to determine if phosphatidylinositol 3-kinase (PI 3-kinase) and/or epidermal growth factor (EGF) receptor transactivation are also involved. 2 alpha(2) Adrenoceptor-mediated vasoconstriction and ERK2 activation in the porcine palmar lateral vein was inhibited in the presence of either the PI 3-kinase inhibitor LY294002, or the EGF receptor tyrosine kinase inhibitor AG1478 suggesting the involvement of both PI 3-kinase and EGF receptor transactivation. 3 Akt phosphorylation was increased in segments of porcine palmar lateral vein contracted with UK14304 indicating an increase in Akt activation. This is a further indication that PI 3-kinase is involved in alpha(2) adrenoceptor-mediated vasoconstriction. Akt activation was inhibited by the Src tyrosine kinase inhibitor PP2, and removal of extracellular calcium. 4 UK14304 (10 microM) stimulated an increase in intracellular calcium in segments of palmar lateral vein. This was inhibited by removal of extracellular calcium, but not by nifedipine suggesting the rise in calcium is due to influx of calcium through non-L type calcium channels. The increase in calcium was also inhibited by LY294002 indicating that PI 3-kinase is upstream of calcium influx. 5 These data indicate that alpha(2) adrenoceptor-mediated vasoconstriction in the porcine palmar lateral vein is dependent upon stimulation of PI 3-kinase, leading to an influx of calcium. This results in activation of the EGF receptor tyrosine kinase, and finally activation of ERK-MAP kinase.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2003

Enhancement of alpha2-adrenoceptor-mediated vasoconstriction by the thromboxane-mimetic U46619 in the porcine isolated ear artery: role of the ERK-MAP kinase signal transduction cascade.

1. Alpha(2)-adrenoceptor-mediated contractions in porcine blood vessels can be enhanced in the presence of the thromboxane-mimetic U46619, and forskolin. The aim of this study was to determine the role of U46619 in the enhanced contractions, and to determine whether signalling through the ERK-MAP kinase pathway is involved. 2. Responses to the alpha(2)-adrenoceptor agonist UK14304 (1 micro M) were increased from 22+/-3% of the response to 60 mM KCl to 68+/-12% (n=8, mean+/-s.e.m.) in the presence of a low concentration of U46619 (< 20% of the 60 mM KCl response). 3. Both the direct and the U46619-enhanced UK14304 responses were inhibited by 50 microM PD98059, an inhibitor of the ERK-MAP kinase pathway. UK14304-induced contractions were associated with an increase in ERK2 phosphorylation, indicating an increased activity. In the presence of U46619, there was an enhanced phosphorylation of ERK2. U46619 on its own had no effect on ERK phosphorylation. 4. Both the direct and enhanced UK14304 contractions were inhibited in the absence of extracellular calcium. These conditions also prevented the increase in ERK2 phosphorylation. This indicates a role for calcium influx in the enhanced contractions. 5. In conclusion, this study demonstrates that precontraction with the thromboxane-mimetic U46619 enhances alpha(2)-adrenoceptor-mediated vasoconstriction through the enhancement of the ERK-MAP kinase pathway, and influx of extracellular calcium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2003

Prospective association between obesity and depression: evidence from the Alameda County Study.

OBJECTIVE: To examine the temporal relation between obesity and depression to determine if each constitutes a risk factor for the other. DESIGN: A two-wave, 5-y-observational study with all measures at both times. SUBJECTS: A total of 2123 subjects, 50 y of age and older, who participated in the 1994 and 1999 waves of the Alameda County Study. MEASUREMENTS: Obesity defined as body mass index (BMI)> or =30. Depression assessed using DSM-IV symptom criteria for major depressive episodes. Covariates include indicators of age, gender, education, marital status, social support, life events, physical health problems, and functional limitations. RESULTS: Obesity at baseline was associated with increased risk of depression 5 y later, even after controlling for depression at baseline and an array of covariates. The reverse was not true; depression did not increase the risk of future obesity. CONCLUSION: These results, the first ever on reciprocal effects between obesity and depression, add to a growing body of evidence concerning the adverse effects of obesity on mental health. More studies are needed on the relation between obesity and mental health and implications for prevention and treatment.

Aged↗
PubMed2001

Comparability of sleep disorders diagnoses using DSM-IV and ICSD classifications with adolescents.

STUDY OBJECTIVES: The use of diagnostic classifications to define sleep disorders is still unusual in epidemiological studies assessing the prevalence of sleep disorders in an adolescent population. DESIGN: Cross-sectional study. Representative samples of general populations in United Kingdom, Germany and Italy were selected and interviewed by telephone about their sleep habits, sleep and mental disorder diagnoses. Overall, 724 adolescents ages 15-18 years and 1447 young adults ages 19 to 24 years were interviewed. ICSD-90 and DSM-IV diagnoses provided by the Sleep-EVAL expert system were used for the comparisons. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 8% of the adolescents and 12.6% of the young adults had ICSD dyssomnia or sleep disturbances associated with a mental disorder. According to the DSM-IV classification, 5.7% of the adolescents and 8.1% of the young adults had a dyssomnia diagnosis. The comparison between the two classifications show that 73.2% of adolescents and young adults with a DSM-IV dyssomnia diagnosis also had similar ICSD diagnosis. The reverse comparison, ICSD vs. DSM-IV, shows that 39.8% of the subjects with an ICSD diagnosis had a DSM-IV diagnosis. DSM-IV primary insomnia was the most frequent diagnosis. Subjects with such a diagnosis were found in about 10 different ICSD diagnoses, mainly inadequate sleep hygiene, psychophysiological or idiopathic insomnia and insufficient sleep syndrome. CONCLUSIONS: ICSD-90 classification provided higher prevalence of sleep disorder diagnoses than the DSM-IV classification. In adolescents and young adults, DSM-IV primary insomnia is two times more often associated with ICSD inadequate sleep hygiene than with ICSD psychophysiological or idiopathic insomnia.

Adolescent↗
PubMed2001

Role of the extracellular signal-regulated kinase (Erk) signal transduction cascade in alpha(2) adrenoceptor-mediated vasoconstriction in porcine palmar lateral vein.

The mechanism of alpha(2) adrenoceptor-mediated vasoconstriction is unknown, but may involve activation of voltage-sensitive calcium channels, and/or a protein tyrosine kinase. Recently the extracellular signal-regulated kinase (Erk) cascade, often an event downstream of tyrosine kinase activation, has been shown to mediate vasoconstriction to a variety of agents. The aim of this present study was to determine the involvement of the Erk signal transduction cascade in alpha(2) adrenoceptor-mediated vasoconstriction, and to confirm the involvement of activation of voltage-sensitive calcium channels, and protein tyrosine kinase. Contractions to the alpha(2) adrenoceptor agonist UK14304 in the porcine palmar lateral vein in vitro were reduced 70 - 80% by the MEK inhibitors PD98059 (10 - 50 microM) and U0126 (10 - 50 microM), indicating the involvement of the Erk signal transduction cascade. Immunoblots also demonstrated an increase in the phosphorylated (activated) form of Erk in palmar lateral vein segments after contraction with UK14304, which was inhibited by PD98059 and U0126. The calcium channel blockers nifedipine and verapamil, or removal of extracellular calcium inhibited UK14304-induced contractions and phosphorylation of Erk, demonstrating the importance of an influx of extracellular calcium. UK14304-induced contractions were inhibited by PP2 (1 - 10 microM), a selective inhibitor of Src tyrosine kinases, but not by PP3, an inactive analogue. PP2 also prevented the phosphorylation of Erk by UK14304. These data demonstrate that alpha(2) adrenoceptor-mediated vasoconstriction in the porcine palmar lateral vein is dependent upon activation of the Erk signal transduction cascade, which is downstream of an influx of extracellular calcium, and activation of Src tyrosine kinases.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2001

Multiethnic comparison of adolescent major depression based on the DSM-IV criteria in a U.S.-Japan study.

OBJECTIVES: To compare the prevalence rates of major depression based on the DSM-IVcriteria with data from a multiethnic sample of adolescents drawn from the same U.S.-Japan study and to investigate the relation of adolescent major depression to ethnicity. METHOD: Adolescents aged 12-15 years (N= 2,046; 539 Anglo-American, 636 African-American, 409 Mexican-American, and 462 Japanese adolescents) were studied in 1994 (response rates: 85.3% for U.S. students and 95.5% for Japanese students). The DSM Scale for Depression, a self-administered checklist developed from the Diagnostic Interview Schedule for Children questions on major depression, was used to estimate the prevalence of DSM-IV major depression. RESULTS: The overall prevalence rates of major depression without/with impairment were 9.6% and 4.3% for Anglo-American, 13.4% and 6.1 % for African-American, 16.9% and 9.0% for Mexican-American, and 5.6% and 1.3% for Japanese adolescents. The significant association between adolescent major depression and ethnicity disappeared after sociodemographic adjustments. Only fathers' educational attainment and family financial status remained significant (odds ratios: 3.28-5.30 for grade school for fathers and 2.62-2.78 for being worse off economically). CONCLUSION: These findings imply ethnicity does not have a significant impact on the risk of adolescent major depression after sociodemographic adjustments.

Adolescent↗
PubMed2001

Differences in nonfatal suicide behaviors among Mexican and European American middle school children.

This report describes ethnic and gender differences in suicide ideation among two large samples of middle school students in New Mexico (n = 2,140) and Texas (n = 1,302). Students completed a self-administered questionnaire on suicide ideation and psychosocial risk factors. Mexican Americans in both samples reported significantly higher prevalence of suicide ideation than did their European American counterparts. Mexican Americans were 1.8 times more likely to have high suicide ideation than European Americans. The suicide ideation risk for Mexican Americans remained unchanged in both samples after adjusting for gender, age, family structure, depression, low social support, and self-esteem. This study indicates that ethnicity plays an important role in suicidal ideation, but the mechanism remains unclear.

Adolescent↗
PubMed2000

Are the obese at greater risk for depression?

Two waves of data from a community-based study (Alameda County Study, 1994-1995) were used to investigate the association between obesity and depression. Depression was measured with 12 items covering Diagnostic and Statistical Manual of Mental Disorders: DSM-IV diagnostic criteria for major depressive episode. Following US Public Health Service criteria, obese subjects were defined as those with body mass index scores at the 85th percentile or higher. Covariates were age, sex, education, marital status, social isolation and social support, chronic medical conditions, functional impairment, life events, and financial strain. Results were mixed. In cross-sectional analyses, greater odds for depression in 1994 were observed for the obese, with and without adjustment for covariates. When obesity and depression were examined prospectively, controlling for other variables, obesity in 1994 predicted depression in 1995 (odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.04, 2.87). When the data were analyzed with obesity defined as a body mass index of > or = 30, cross-sectional results were the same. However, the prospective multivariate analyses were not significant (OR = 1.43, 95% CI: 0.85, 2.43). Although these data do not resolve the role of obesity as a risk factor for depression, overall the results suggest an association between obesity and depression. The authors found no support for the "jolly fat" hypothesis (obesity reduces risk of depression). However, there has been sufficient disparity of results thus far to justify continued research.

Aged↗
PubMed2000

Fatalism and risk of adolescent depression.

This research examined fatalism, the belief in external control over life chances, as a risk factor for adolescent depression. Data were analyzed from a large (N = 5,423) sample of adolescents attending middle school in an ethnically diverse community in the southwest. It was hypothesized that adolescents who demonstrated greater fatalism would have a higher risk for depression. Bivariate associations between fatalism and depression were substantial, with an odds ratio (OR) of nearly 25 for depression with impairment and nearly 13 for depression without impairment. Adjustment for the effects of 10 covariates drawn from three domains (status attributes, stressors, and personal/social resources) essentially eliminated the association between fatalism and depression with impairment. However, the OR was still 2.6. The significant association between fatalism and depression without impairment (OR = 2.7) remained after adjustment for covariates. The results provide further support for models of depression which emphasize the role of psychosocial deficits. In this case, we found depression was associated not only with greater fatalism but also greater pessimism, lower self-esteem, more passive coping, and less social support.

Adaptation, Psychological↗
PubMed2000

Prevalence and patterns of problematic sleep among older adolescents.

OBJECTIVE: Despite many constraints on time schedules among teenagers, epidemiological data on sleep complaints in adolescence remain limited and are nonexistent for sleep disorders. This study provides additional data on sleep habits and DSM-IV sleep disorders in late adolescence. METHOD: A representative sample of 1,125 adolescents aged 15 to 18 years was interviewed by telephone using the Sleep-EVAL system. These adolescents came from 4 European countries: France, Great Britain, Germany, and Italy. Information was collected about sociodemographic characteristics, sleep/wake schedule, sleep habits, and sleep disorders and was compared with information from 2,169 young adults (19-24 years of age). RESULTS: Compared with young adults, adolescents presented with a distinct sleep/wake schedule: they went to sleep earlier, they woke up later, and they slept longer than young adults did. On weekends and days off, they also slept more than young adults did. However, the prevalence rates of sleep symptoms and sleep disorders were comparable in both groups. Approximately 25% reported insomnia symptoms and approximately 4% had a DSM-IV insomnia disorder. Fewer than 0.5% had a circadian rhythm disorder. CONCLUSIONS: Prevalence of insomnia disorders is lower in the adolescent population than in middle-aged or elderly adults. However, a rate of 4% in this young population is important given their young age and the consequences for daytime functioning.

Adolescent↗
PubMed2000

Ethnocultural differences in sleep complaints among adolescents.

Data from a school survey (N = 5423) were used to examine differences in sleep complaints among adolescents from nine ethnocultural groups. Compared with Anglo youths, Chinese American youths were at significantly lower risk for insomnia, whereas Mexican American youths had an elevated risk, adjusting for the effects of age, gender, and socioeconomic status. Adjusting for the same three covariates, African, Mexican and Central American youths were at elevated risk for hypersomnia. No group was at lower risk for hypersomnia than the Anglos. The results suggest minority status may affect risk for sleep problems but that the direction and the magnitude of the effects vary depending on the outcome examined, severity of the problem, and the ethnic group studied. Given the paucity of data on culture and risk for disturbed sleep among adolescents, more research is needed on the role of ethnocultural background on sleep.

Adolescent↗
PubMed2000

Sleep complaints and depression in an aging cohort: A prospective perspective.

OBJECTIVE: Most research on the association between sleep disturbances and depression has looked at cross-sectional data. The authors used two waves of data from a panel study of community residents aged 50 years or more to investigate this issue prospectively. METHOD: Data on symptoms of major depressive episodes and sleep problems were examined for a subgroup of the 1994 and 1995 surveys of the Alameda County (California) Study (N=2,370). The authors examined the effects of age, gender, education, marital status, social isolation, functional impairment, financial strain, and alcohol use. Depression was measured with 12 items that covered the DSM-IV diagnostic criteria for major depressive episodes, including insomnia and hypersomnia. RESULTS: The prevalences were 23. 1% for insomnia and 6.7% for hypersomnia in 1994. Sleep was a significant correlate of depression, as were being female, older age, social isolation, low education, financial strain, and functional impairment. When sleep problems and depression were examined prospectively, with controls for the effects of the other variables, sleep problems in 1994 predicted depression in 1995. However, other symptoms of major depressive episodes-anhedonia, feelings of worthlessness, psychomotor agitation/retardation, mood disturbance, thoughts of death-were much stronger predictors of future major depression. CONCLUSIONS: Sleep disturbance and other symptoms that are diagnostic for major depression are strongly associated with the risk of future depression. Sleep disturbance appears to be a less important predictor of depression. More epidemiologic research is needed on the relative contributions of the range of depressive symptoms to the risk of clinical depression.

Age Factors↗
PubMed1999

A study of NPY-mediated contractions of the porcine isolated ear artery.

Enhanced contractions of the porcine isolated ear artery by the alpha2-adrenoceptor agonist UK14304 are uncovered by pharmacological manipulation. As both neuropeptide Y (NPY) receptors and alpha2-adrenoceptors are negatively-coupled to adenylyl cyclase in this tissue, we determined whether NPY is also able to produce an enhanced contraction in the same tissue, under the same conditions. NPY (0.1 microM) produced a small contraction of porcine isolated ear arteries which was 5.1+/-0.8% of the response to 60 mM KCl (n = 14). An enhanced NPY response was uncovered if the tissue was pre-contracted with 0.1 microM U46619, and relaxed back to baseline with 1-2 microM forskolin before the addition of NPY (49.8+/-5.3%, n = 14). Forskolin (1 microM) stimulated cyclic AMP accumulation in porcine ear artery segments in the presence of 0.1 microM U46619 and 1 mM isobutylmethylxanthine (IBMX), NPY (0.1 microM) inhibited this response by 40%, but had no effect on basal levels of cyclic AMP. An enhanced response to 0.1 microM NPY was also obtained after pre-contraction with 0.1 microM U46619 and relaxation with either SNP (28.9+/-5.7%, n = 14), or dibutyryl cyclic AMP (21.2+/-4.6%, n = 14). This indicates that at least part of the enhanced response to NPY is independent of the agonist's ability to inhibit adenylyl cyclase. In conclusion, an enhanced contraction to NPY in the porcine isolated ear artery can be obtained by prior pharmacological manipulation. The enhanced responses are mediated through adenylyl cyclase-dependent and independent pathways similar to those reported for alpha2-adrenoceptors in this preparation.

Adenylyl Cyclases↗
PubMed1999

alpha(2)-adrenoceptor and NPY receptor-mediated contractions of porcine isolated blood vessels: evidence for involvement of the vascular endothelium.

1. Enhanced contractions to the alpha(2)-adrenoceptor agonist UK14304 and neuropeptide Y (NPY) in the porcine ear artery can be uncovered by pharmacological manipulation. The aim of this study was to determine whether similar pharmacological manipulation can uncover enhanced contractions in the porcine splenic artery, and to determine whether the endothelium modulates these responses. 2. UK14304 (0.3 microM) and NPY (0.1 microM) produced small contractions of the porcine splenic artery. After pre-contraction of the tissue with U46619, followed by relaxation with forskolin, the responses to both UK14304 and NPY were enhanced. Enhanced contractions to both UK14304 and NPY were also obtained after relaxation with SNP. These results demonstrate that, as in the porcine ear artery, alpha(2)-adrenoceptors and NPY receptors are able to produce enhanced contractile responses through both adenylyl cyclase-dependent and -independent signal transduction pathways. 3. Removal of the endothelium had no significant effect on responses to UK14304 either alone or in the presence of U46619 and forskolin in the porcine splenic artery. On the other hand, responses to UK14304 after relaxation with SNP were reduced after endothelium-denudation in both the porcine splenic artery and ear artery. Similar results were obtained with NPY in the porcine ear artery. 4. In conclusion, enhanced contractile responses to UK14304 and NPY in the porcine splenic artery can be uncovered using methods similar to those employed in the porcine ear artery. Under certain conditions the responses to both agents are modulated by the endothelium. These data highlight further the similarities in the signal transduction pathways used by both alpha(2)-adrenoceptors and NPY receptors to induce vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Generalised uridine diphosphate galactose-4-epimerase deficiency.

The generalised form of epimerase deficiency galactosaemia has been described in only two children from unrelated families. Their progress is reported and three other affected children from these families are described. The initial presentation was similar to classic galactosaemia. Despite treatment all have shown poor growth and moderate learning difficulties. Three have sensorineural deafness and four have pronounced dysmorphic features. The two older female patients have normal pubertal development.

Adolescent↗