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Biomedical subjects

M E Bates

Publications and source records attributed to M E Bates.

At least 19 recordsLinked to original sources
PubMed2001

Transduction of a dominant-negative H-Ras into human eosinophils attenuates extracellular signal-regulated kinase activation and interleukin-5-mediated cell viability.

Inhibition of eosinophil apoptosis by exposure to interleukin-5 (IL-5) is associated with the development of tissue eosinophilia and may contribute to the inflammation characteristic of asthma. Analysis of the signaling events associated with this process has been hampered by the inability to efficiently manipulate eosinophils by the introduction of active or inhibitory effector molecules. Evidence is provided, using a dominant-negative N17 H-Ras protein (dn-H-Ras) and MEK inhibitor U0126, that activation of the Ras-Raf-MEK-ERK pathway plays a determining role in the prolongation of eosinophil survival by IL-5. For these studies, a small region of the human immunodeficiency virus Tat protein, a protein transduction domain known to enter mammalian cells efficiently, was fused to the N-terminus of dn-H-Ras. The Tat-dn-H-Ras protein generated from this construct transduced isolated human blood eosinophils at more than 95% efficiency. When Tat-dn-H-Ras-transduced eosinophils were treated with IL-5, they exhibited a time- and dosage-dependent reduction in extracellular regulated kinase 1 and 2 activation and an inhibition of p90 Rsk1 phosphorylation and IL-5-mediated eosinophil survival in vitro. In contrast, Tat-dn-H-Ras did not inhibit CD11b up-regulation or STAT5 tyrosine phosphorylation. These data demonstrate that Tat dominant-negative protein transduction can serve as an important and novel tool in studying primary myeloid cell signal transduction in primary leukocytes and can implicate the Ras-Raf-MEK-ERK pathway in IL-5-initiated eosinophil survival.

Cell Survival↗
PubMed2001

Adolescence-limited versus persistent delinquency: extending Moffitt's hypothesis into adulthood.

The authors examined how neuropsychological, personality, and environmental risk factors and their interactions were related to trajectories of delinquent behavior from adolescence to adulthood. Four waves of longitudinal data from 698 male participants, ages 12-18 at Time 1 and ages 25-31 at Time 4, were included in the analyses. Using a growth mixture model approach, 4 trajectories were identified: nondelinquents, adolescence-limited delinquents, adolescence-to-adulthood-persistent delinquents, and escalating delinquents. Five risk factors distinguished escalating from persistent delinquents and 5 also distinguished nondelinquents from the 3 delinquency trajectories. Persistent delinquents scored significantly higher than adolescence-limited delinquents on only one risk factor, disinhibition. Overall, few of the factors that are related to childhood-to-adolescence persistence were associated with persistence in delinquency beyond adolescence.

Adolescent↗
PubMed2001

Granulocyte macrophage colony-stimulating factor and interleukin-5 activate STAT5 and induce CIS1 mRNA in human peripheral blood eosinophils.

In these studies, we examined signaling through the transcription factor STAT5 in human peripheral blood eosinophils after treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin (IL)-5. In response to either cytokine, STAT5 was rapidly tyrosine phosphorylated and acquired interferon gamma activation site (GAS) DNA binding activity. Tyrosine-phosphorylated STAT5 was associated with both cytosolic and nuclear cell fractions. Consistent with activation, the transcription of a STAT5-dependent gene, cytokine inducible, SH2-containing protein (CIS1), was enhanced after cytokine stimulation. This is the first report of IL-5 regulation of CIS1 gene expression in any cell type. Given its role in cytokine signaling, CIS1 upregulation may serve to attenuate IL-5 and GM-CSF modulation of eosinophil function. These data suggest that active nuclear STAT5 participates in the regulation of IL-5 and GM-CSF--inducible genes in stimulated human peripheral blood eosinophils.

Cell Nucleus↗
PubMed2001

Neurotoxicity and neurocognitive impairments with alcohol and drug-use disorders: potential roles in addiction and recovery.

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organisers/chairs were Stephen C. Bowden and Fulton T. Crews. The presentations were (1) Age, genetic and other factors that increase risk of alcoholism also increase alcohol-induced neurotoxicity, by Fulton T. Crews; (2) A neurocognitive moderation model of addictions treatment response, by Marsha E. Bates; (3) The relationship of neurocognitive impairment and longitudinal treatment outcome among substance-abusing patients, by William Fals-Stewart; and (4) Treatment of cognition in detoxifying alcohol-dependent participants, by Margaret L. Ambrose.

Alcoholism↗
PubMed2000

ERK1 and ERK2 activation by chemotactic factors in human eosinophils is interleukin 5-dependent and contributes to leukotriene C(4) biosynthesis.

Eosinophils, the major immune effector cells contributing to allergic inflammation and asthma, are profoundly affected by interleukin (IL) 5 with respect to their differentiation, viability, recruitment, and cytotoxic effector functions. IL-5 enhances eosinophil responsiveness to a variety of chemotactic factors via a process called priming, although the molecular mechanism is unknown. In this study, we report that, following IL-5 priming of eosinophils, chemotactic agents including fMet-Leu-Phe, IL-8, and RANTES, promote vigorous transient activation of ERK1 and ERK2. In contrast, these chemotactic factors stimulate weak or indiscernible ERK activation in unprimed eosinophils. Furthermore, this intracellular marker of priming is selective for IL-5-related cytokines, in that it is observed following exposure to IL-5 and granulocyte macrophage-colony stimulating factor but not to interferon-gamma, stem cell factor, tumor necrosis factor alpha, or IL-4. Interestingly, priming of chemoattractant-induced ERK activation is accompanied by an increase in association of tyrosine-phosphorylated proteins with the adapter protein Grb2. The biological relevance of ERK activation to IL-5 priming is supported by the observation that inhibition of ERK activity by treatment with the MEK inhibitors PD98059 or U0126 inhibited the release of leukotriene C(4) stimulated by fMet-Leu-Phe in IL-5-primed eosinophils. These data provide evidence for a previously undescribed fundamental mechanism by which stimulation of IL-5 family receptors induces a rapid phenotypic alteration in the signal transduction pathways of chemotactic receptors, enabling their activation of the ERK1 and ERK2 pathway and contributing to the capacity of these cells to synthesize LTC(4).

Adaptor Proteins, Signal Transducing↗
PubMed2000

Utility of component-process approaches for understanding complex alcohol-related behavior within an executive functioning framework: comment on Giancola (2000).

P. R. Giancola's (2000) macroconstruct framework of executive functions (EF) characterizes how cognitive processes work together to inhibit aggressive responding in provocative situations, and how alcohol intoxication increases the likelihood of aggression by disrupting these processes. His framework can be considered within contemporary controversies in cognitive neuroscience research: how interrelated EF operate, which brain areas are involved in cognitive control, the specificity of EF impairment to different behaviors, and how to operationalize EF to examine different questions. Giancola highlighted the use of one broad, multidimensional, EF construct for predicting aggressive behavior. His macroconstruct framework can also be used to examine component information-processing operations. Component-process approaches may facilitate integrative research at multiple levels and add to the specificity of EF impairment-aggression linkages.

Aggression↗
PubMed2000

Integrating person-centered and variable-centered approaches in the study of developmental courses and transitions in alcohol use: introduction to the special section.

This special section consists of research from the symposium "Integrating Person-Centered and Variable-Centered Approaches to the Study of Developmental Courses and Transitions in Alcohol Use," presented at the 1999 Annual Meeting of the Research Society on Alcoholism. The section focuses on ways to integrate variable-centered and person-centered approaches to better understand longitudinal trajectories of alcohol use and associated problems. Our aim is to increase awareness and discussion of alternative conceptual and quantitative approaches that involve both a person-centered and a variable-centered component, and to make these methods more accessible to alcohol and other drug researchers. The first paper provides a general latent variable modeling framework within which to conceptualize developmental questions that involve the combination of continuous latent variables and categorical variables that represent classifications of individuals into meaningful subgroups. This is followed by three empirical papers that use integrative methods to examine early adult outcomes of adolescent binge drinking; potential mediators of familial alcoholism effects on alcohol and tobacco use disorder comorbidity; and the ability of psychopathology, substance use, and parental history of alcohol problems to predict individual differences in the likelihood of transitions in drinking behavior during adolescence. The section concludes with a discussion of the statistical basis for integrating person-centered and variable-centered methods, a comparison of study findings, and directions for future research.

Adult↗
PubMed1999

The selective effects of alcohol on automatic and effortful memory processes.

Automatic and effortful memory processes were evaluated in a 2-session, within-subjects design involving an alcohol challenge and a no-alcohol condition. Free recall of a 90-word list measured effortful processing. Estimation of word frequency from the same list measured automatic processing. Acute intoxication was hypothesized to diminish effortful but not automatic memory processes. Healthy, male volunteers (n = 36) completed the 2 conditions 1 week apart. Presentation frequency influenced both free recall and frequency estimation, with both measures increasing as presentation frequency increased. Free recall was significantly lower in the alcohol than in the no-alcohol condition, but frequency estimation was not differentially affected. The data showed that an alcohol challenge dissociated automatic and effortful memory processes in volunteers. The authors discuss potential neurobiological substrates that may account for alcohol's selective disruption of effortful, verbal, episodic memory processing.

Adult↗
PubMed1999

Effects of executive function impairment on change processes and substance use outcomes in 12-step treatment.

OBJECTIVE: A strong clinical rationale exists to hypothesize that neuropsychological impairment interferes with treatment-initiated change, thereby leading to poor outcome. This study examined the relationship of executive function impairment, change process factors and substance use outcomes in a sample of substance users in intensive 12-step treatment. METHOD: Participants were 118 individuals entering residential or intensive day treatment at two traditional treatment programs. Participants were assessed at entry into treatment, at discharge from treatment, and at 1 and 6 months following treatment. Participants were administered a battery of measures to assess executive function impairment, processes hypothesized to mediate change in 12-step treatment, negative prognostic indicators and substance use outcomes. RESULTS: More than half the sample showed some form of executive function impairment. Executive function impairment did not directly predict worse substance use outcomes nor difficulty acquiring or maintaining change processes. However, impairment significantly moderated the relationship between change processes and outcome. Change processes were strongly related to outcome for unimpaired individuals but weakly related for impaired individuals. CONCLUSIONS: Executive function impairment is not a significant predictor of poor treatment response in 12-step treatment. However, analyses suggest that impaired and unimpaired individuals traverse different pathways in achieving equivalent outcomes.

Adult↗
PubMed1998

Interleukin 5 signals through Shc and Grb2 in human eosinophils.

Eosinophils are potent effector cells contributing to allergic inflammation and asthma. The differentiation, recruitment, and effector functions of eosinophils are greatly affected by interleukin (IL)-5. In the eosinophil, signal transduction pathways including Jak-STAT and Ras-Raf-MAP kinase are stimulated by IL-5 and enzymatic activation of tyrosine kinases Jak-2 and Lyn has been demonstrated. The participation of adapter proteins in the responses of the Ras-Raf-MAP kinase pathway has been documented in many cytokine family receptors but the expression and activation of these proteins have not been demonstrated in eosinophils. In these studies, we have found three isoforms of the adapter protein, Shc, to be expressed in eosinophils. One of these isoforms, p52 Shc, was tyrosine phosphorylated following IL-5 treatment of eosinophils. A second adapter protein, Grb2, coimmunoprecipitated with Shc following IL-5 stimulation of eosinophils. Furthermore, p52 Shc was increasingly associated with a cell fraction resistant to detergent solubilization, following IL-5 administration. This cell fraction of limited detergent solubility is a complex mixture of proteins and the adapter protein Grb2, the tyrosine kinases Jak-2 and Lyn, the nucleotide exchange factor Vav, and the serine-threonine kinases p45 MAP kinase, Raf-1, and PKCbeta, were distributed either wholly or partially in the same fraction, as were the cytoskeletal proteins actin and vimentin. Only p52 Shc, however, demonstrated discernibly increased association with this fraction following IL-5 stimulation of eosinophils. These data suggest that IL-5 activates a signal transduction pathway utilizing the adapter proteins Shc and Grb2 in the human eosinophil.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Immediate, quantitative estimation of blood alcohol concentration from saliva.

OBJECTIVE: Reliable, valid, and noninvasive methods to quantitatively estimate blood alcohol concentration (BAC) are important in forensic, work place, medical and research settings. To date, noninvasive methods for quantitatively estimating BAC have primarily used breath testing. This study evaluated a new device for estimating BAC via saliva that is unique in providing on-the-spot, quantitative results in 2 minutes. The Q.E.D-A150 test (STC Technologies, Inc., Bethlehem, Pa.) is based on the enzymatic oxidation of alcohol by alcohol dehydrogenase. Saliva alcohol concentration (SAC) is read directly from the test device. METHOD: In each of three sessions, 24 male and 15 female social drinkers, aged 21-28 years, provided yoked breath and saliva samples prior to, and at five times following, a dose of 1.0 g (men) or 0.9 g (women) alcohol per kg lean body mass. RESULTS: Intertest reliability, determined by two simultaneous saliva samples, was very high for each measurement time (r's = .97 to .99), for each subject (4's = .95 to .99) and across all observations (r = .98). The coefficient of variation was below 5% in 97% of paired observations. The correlation between breath and saliva estimates was .94 across all observations and ranged from .92 to .98 across measurement times. The difference between breath and saliva estimates was significantly larger on the ascending limb than on the descending limb of the blood alcohol curve at comparable BACs. On the average, SAC estimates were 6 mg/dl higher than breath during ascending BACs and 3 mg/dl higher than breath during descending BACs. Individual differences in the ratio of SAC to breath measures of BAC ranged from 0.99 to 1.15 (average = 1.06). Test performance was not affected by gender, drinking pattern or cigarette smoker status. CONCLUSIONS: The Q.E.D.-A150 device had good reliability and validity for the noninvasive, quantitative estimation of BACs.

Adult↗
PubMed1997

Stability of neuropsychological assessments early in alcoholism treatment.

OBJECTIVE: Current trends in managed mental health care have telescoped the assessment and treatment of individuals diagnosed with an alcohol or other drug use disorder. Yet, there is limited empirical information about the short-term stability of neuropsychological status and other person characteristics that are useful to assess early in treatment. This study examined the stability of neuropsychological test scores within the first 3 weeks following diagnosis of an alcohol use disorder. METHOD: An eclectic neuropsychological battery made up of commonly used, sensitive tests of abstraction, executive functions, memory, visuospatial abilities and verbal ability was administered to female and male alcohol use disordered individuals within 3 days of treatment entry (or following detoxification), 3-5 days later and 21 days later. The three test administrations were completed by 35, 32 and 24 subjects, respectively. RESULTS: Across tests, the average stability coefficient (Pearson correlation) was .82 between Days 3 and 5, .86 between Days 5 and 21, and .79 between Days 3 and 21. Intraclass correlations ranged from .79 to .98 across tests (mean = .92). Clinical stability, defined as the likelihood that a test score fell consistently above or below a standardized impairement cutoff score, was also good. Across tests, percent agreement in impairment diagnoses for the same three time intervals averaged 84%, 92% and 87%, respectively. The chance-corrected kappa (Kappa) coefficients of diagnostic agreement were generally moderate to substantial from Day 3 to Days 5 or 21, and mostly substantial from Day 5 to 21. CONCLUSIONS: Early assessments of neuropsychological status were psychometrically stable, and also provided reasonably stable indicants of clinically significant impairment. It was likely that the data provided lower bound estimates of the stability of impairment classifications due to the repeated measures design and power limitations.

Adult↗
PubMed1997

Age of first use: its reliability and predictive utility.

OBJECTIVE: The purpose of this study was: (1) to assess the utility of age of first licit use and age of first illicit use as predictors of alcohol and drug use at ages 20 and 30; and (2) to examine the reliability of retrospectively recalled ages of onset of use. METHOD: Subjects (N = 839) from the Rutgers Health and Human Development Project provided four waves of longitudinal data spanning the age range from 15 to 31. RESULTS: Retrospective recall of age of onset revealed a fair degree of relative agreement but a lack of absolute agreement because of an upward shift in recalled ages as individuals became older. Repeated measures ANOVAS revealed normative declines in alcohol and drug use from 20 to 30 even though individual differences in use remained quite stable across time. Regression analyses indicated that: (1) age of first licit use as recalled at age 18 did not predict alcohol or drug use at age 20; (2) age of first illicit use was a weak predictor of alcohol use at 20 but a fairly strong predictor of drug use at 20; and (3) neither age predicted use or use consequences at age 30. CONCLUSIONS: In the general population, illicit drug use and heavier alcohol use are, regardless of age of onset, adolescence-limited phenomena for most individuals. Findings suggest that intervention efforts need to be aimed simultaneously at delaying the onset of illicit use and reducing use levels among young adult users.

Adolescent↗
PubMed1997

Adolescent risk factors and the prediction of persistent alcohol and drug use into adulthood.

Adolescence is a time of heightened risk for relatively intensive alcohol and other drug use behaviors. However, heavy use is often "adolescence-limited," giving way to moderation or cessation in adulthood. We examined individual differences in risk factors at age 18 that were predictive of alternative alcohol and drug use trajectories from adolescence to adulthood. Data were collected prospectively on four occasions from participants in the Rutgers Health and Human Development Project. Subsets of individuals representing three prototypical trajectories of (1) consistently low alcohol and drug use during adolescence and early adulthood; (2) heavier alcohol or drug use during adolescence, but not during adulthood; and (3) persistent heavier alcohol or drug use from adolescence into adulthood were found to differ significantly on a number of intrapersonal, behavioral, and environmental risk factors, with the adolescence-limited group consistently scoring between the other two groups. Based on these results, a composite risk index was constructed. In the total sample, however, when the effect of alcohol and drug use behaviors at age 18 was controlled, the composite risk index was unrelated to adult (age 28 to 31) levels of alcohol and drug use and consequences. Thus, in this community sample, well-documented risk factors assessed in adolescence did not exhibit any direct, longterm effects on use intensity and problems in adulthood. It is concluded that the assessed risk factors (disinhibition, cognitive structure, play, deviant coping, friends' deviance, and stressful life events) are not immutable, but subject to individual and normative changes during the transition from adolescence to adulthood. More research is needed to determine the long-term stability of risk factors, and how changes in risk factors over time, discontinuities in what constitutes risk in adolescence versus adulthood, and proximal adult protective factors that compensate for early risk contribute to developmental patterns of use.

Adolescent↗
PubMed1996

IL-5 activates a 45-kilodalton mitogen-activated protein (MAP) kinase and Jak-2 tyrosine kinase in human eosinophils.

IL-5 is a member of the hemopoietic cytokine family and has profound effects on the differentiation, survival, migration, and effector function of human eosinophils. Increased tyrosine phosphorylation has been observed as an early event in IL-5 signal transduction in eosinophils; most notably, proteins of 45 and 135 kDa became tyrosine phosphorylated following IL-5 treatment. Some of these phosphotyrosine-containing proteins may represent intermediates in IL-5 signal transduction pathways. This study demonstrates that Jak-2, a tyrosine kinase, is increasingly tyrosine phosphorylated after IL-5 treatment of human eosinophils. Furthermore, we found proteins of 42, 44, and 45 kDa immunoreactive with anti-mitogen-activated protein (MAP) kinase Abs that are expressed in human eosinophils. One of these, the protein of approximately 45 kDa (p45), was tyrosine phosphorylated following treatment of eosinophils with IL-5 and PMA, as seen by anti-phosphotyrosine immunoprecipitation and immunoblotting with anti-MAP kinase Abs. In addition, anti-phosphotyrosine immunoprecipitates of IL-5-treated eosinophils contained enhanced phosphotransferase activity toward a myelin basic protein (MBP) peptide substrate when compared with control-treated eosinophils. In contrast to cytokine-stimulated MAP kinase activation in other cells, there is no evidence of tyrosine phosphorylation or enzymatic activation of p42 MAP kinase in eosinophils after IL-5 treatment. These data suggest that Jak-2 kinase and an activated isoform of MAP kinase, p45, are detected following incubation with IL-5, and may mediate some of this cytokine's effects on eosinophils in a manner unique to the activation pathways previously described for other cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1996

Carbon dioxide exchange of lettuce plants under hypobaric conditions.

Growth of plants in a Controlled Ecological Life Support System (CELSS) may involve the use of hypobaric pressures enabling lower mass requirements for atmospheres and possible enhancement of crop productivity. A controlled environment plant growth chamber with hypobaric capability designed and built at Ames Research Center was used to determine if reduced pressures influence the rates of photosynthesis (Ps) and dark respiration (DR) of hydroponically grown lettuce plants. The chamber, referred to as a plant volatiles chamber (PVC), has a growing area of about 0.2 m2, a total gas volume of about 0.7 m3, and a leak rate at 50 kPa of <0.1%/day. When the pressure in the chamber was reduced from ambient to 51 kPa, the rate of net Ps increased by 25% and the rate of DR decreased by 40%. The rate of Ps increased linearly with decreasing pressure. There was a greater effect of reduced pressure at 41 Pa CO2 than at 81 Pa CO2. This is consistent with reports showing greater inhibition of photorespiration (Pr) in reduced O2 at low CO2 concentrations. When the partial pressure of O2 was held constant but the total pressure was varied between 51 and 101 kPa, the rate of CO2 uptake was nearly constant, suggesting that low pressure enhancement of Ps may be mainly attributable to lowered partial pressure of O2 and the accompanying reduction in Pr. The effects of lowered partial pressure of O2 on Ps and DR could result in substantial increases in the rates of biomass production, enabling rapid throughput of crops or allowing flexibility in the use of mass and energy resources for a CELSS.

Atmosphere Exposure Chambers↗