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Biomedical subjects

D C Howell

Publications and source records attributed to D C Howell.

17 recordsLinked to original sources
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2001

Direct thrombin inhibition reduces lung collagen, accumulation, and connective tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis.

Dramatic activation of the coagulation cascade has been extensively documented for pulmonary fibrosis associated with acute and chronic lung injury. In addition to its role in hemostasis, thrombin exerts profibrotic effects via activation of the major thrombin receptor, protease-activated receptor-1. In this study, we examined the effect of the direct thrombin inhibitor, UK-156406 on fibroblast responses in vitro and on bleomycin-induced pulmonary fibrosis in rats. UK-156406 significantly inhibited thrombin-induced fibroblast proliferation, procollagen production, and connective tissue growth factor (CTGF) mRNA levels when used at equimolar concentration to the protease. Thrombin levels in bronchoalveolar lavage fluid and expression of thrombin and protease-activated receptor-1 in lung tissue were increased after intratracheal instillation of bleomycin. The characteristic doubling in lung collagen in bleomycin-treated animals (38.4 +/- 2.0 mg versus 17.1 +/- 1.4 mg, P < 0.01) was preceded by significant elevations in alpha1(I) procollagen and CTGF mRNA levels (3.0 +/- 0.4-fold and 6.3 +/- 0.4-fold respectively, (P < 0.01), and total inflammatory cell number. UK-156406, administered at an anticoagulant dose, attenuated lung collagen accumulation in response to bleomycin by 35 +/- 12% (P < 0.05), inhibited alpha1(I) procollagen and CTGF mRNA levels by 50% and 35%, respectively (P < 0.05), but had no effect on inflammatory cell recruitment. This is the first report showing that direct thrombin inhibition abrogates lung collagen accumulation in bleomycin-induced pulmonary fibrosis.

Animals↗
PubMed1998

Regression equations in clinical neuropsychology: an evaluation of statistical methods for comparing predicted and obtained scores.

Regression equations are widely used in clinical neuropsychology, particularly as an alternative to conventional normative data. In neuropsychological applications the most common method of making inferences concerning the difference between an individual's test score and the score predicted by a regression equation is to multiply the standard error of estimate by an appropriate value of z to form confidence limits around the predicted score. The technically correct method is to calculate the standard error of a new individual Y and multiply it by the value of t corresponding to the desired limits (e.g., 90% or 95%). These two methods are compared in data sets generated to be broadly representative of data sets used in clinical neuropsychology. The former method produces confidence limits which are narrower than the true confidence limits and fail to reflect the fact that limits become wider as scores on the predictor deviate from the mean. However, for many of the example data sets studied, the differences between the two methods were trivial, thereby providing reassurance for those who use the former (technically incorrect) method. Despite this, it would be preferable to use the correct method particularly with equations derived from samples with modest Ns, and for individuals with extreme scores on the predictor variable(s). To facilitate use of the correct method a computer program is made available for clinical practice.

Algorithms↗
PubMed1998

Payne and Jones revisited: estimating the abnormality of test score differences using a modified paired samples t test.

Payne and Jones (1957) presented a useful formula for estimating the abnormality of differences between an individual's scores on two tests. Extending earlier work by Sokal and Rohlf (1995) and Crawford and Howell (in press), we developed a modified paired samples t test as an alternative to this formula. Unlike the Payne and Jones formula, the new method treats data from a normative or control sample as sample statistics rather than as population parameters. Technically, the new method is more appropriate for any comparison of an individual's difference score against normative data. However, it is most useful when the normative data is derived from samples with modest Ns; in these circumstances the Payne and Jones method overestimates the abnormality of differences. We suggest that the modified t test can be a useful tool in clinical practice and in single-case research. A computer program is made available that automates the calculations involved and can be used to store relevant data for future use.

Humans↗
PubMed1997

Covariation of the anxious-depressed syndrome during adolescence: separating fact from artifact.

Nosological (symptom overlap) and methodological (informant) artifact in the covariation of an empirically derived syndrome of anxious-depressed symptoms with 7 other syndromes of emotional and behavior problems was examined in reports by parents, teachers, and adolescents on a nationally representative sample of 908 adolescents. Although minor symptom overlap was observed and the effects of informant were significant, the anxious-depressed syndrome covaried significantly with all other syndromes after controlling for these effects. Indices of covariation controlling for informant effects were all significant and ranged for all syndromes except for delinquent behavior from .619 to .681, reflecting significant covariation of the anxious-depressed syndrome with both externalizing and internalizing syndromes. Covariation of the anxious-depressed syndrome and delinquent behavior was .470. Implications for research on the comorbidity-covariation of depressive syndromes during childhood and adolescence are highlighted.

Adolescent↗
PubMed1996

When mom or dad has cancer: II. Coping, cognitive appraisals, and psychological distress in children of cancer patients.

Cognitive appraisals and coping were examined in children, adolescents, and young adults (N = 134) faced with the diagnosis of cancer in a parent. All 3 age groups perceived low personal control and high external control over their parent's illness and used relatively little problem-focused coping. Adolescents and young adults reported more emotion-focused coping and dual-focused coping (both problem- and emotion-focused in intent) than did preadolescent children. Stage and prognosis of parent's cancer were related to appraisals of greater seriousness and stressfulness, and to more avoidance; however, only appraisals of stress were related to symptoms of anxiety-depression. Emotion-focused coping was related to greater avoidance and to higher symptoms of anxiety-depression; coping and control beliefs did not interact in their association with anxiety-depression symptoms.

Adaptation, Psychological↗
PubMed1995

Cognitive factors in adjustment to cancer: attributions of self-blame and perceptions of control.

We examined attributions of behavioral and characterological self-blame and perceptions of control over disease progression and recurrence as predictors of symptoms of psychological distress in a sample of adult men and women with cancer. Data were obtained near the time of diagnosis and a 4-month follow-up. Initial levels of behavioral and characterological self-blame were unrelated to concurrent psychological distress. Initial characterological self-blame as well as the interaction of characterological and behavioral self-blame was predictive of psychological distress 4 months later. Perceptions of control over cancer recurrence were unrelated to psychological distress near diagnosis or at follow-up, and control beliefs did not function as a mediator of self-blame. Initial levels of psychological distress predicted characterological but not behavioral self-blame at follow-up, suggesting a reciprocal relationship between characterological self-blame and distress.

Adaptation, Psychological↗
PubMed1994

Predictors of cancer progression in young adult men and women: avoidance, intrusive thoughts, and psychological symptoms.

Psychological symptoms, avoidance, and intrusive thoughts were examined prospectively as predictors of cancer progression over a period of 1 year. Sixty-six male and female cancer patients who differed in their diagnoses and initial disease-severity ratings participated. Measures of psychological factors, disease severity, and type of treatment were obtained near time of diagnosis and disease status (no cancer, continued or recurrent cancer, or deceased) 1 year later. Cross-sectional analyses near the time of diagnosis showed that initial psychological variables were intercorrelated with one another but unrelated to initial disease prognosis. Longitudinal findings revealed that, after controlling for initial disease parameters and age, avoidance predicted disease status 1 year later; however, neither psychological symptoms nor intrusive thoughts and emotions accounted for additional variance in disease outcomes.

Adaptation, Psychological↗
PubMed1994

When mom or dad has cancer: markers of psychological distress in cancer patients, spouses, and children.

This study assessed anxiety/depression and stress response symptoms in adult cancer patients (n = 117), spouses (n = 76), and their children (n = 110, ages 6 to 30 years old) near the patients' diagnoses to identify family members at risk for psychological maladjustment. Patients' and family members' distress was related to appraisals of the seriousness and stressfulness of the cancer but not related to objective characteristics of the disease. Patients and spouses did not differ in anxiety/depression or in stress-response symptoms. Both stress-response and anxiety/depression symptoms differed in children as a function of age, sex of child, and sex of patient. Adolescent girls whose mothers had cancer were the most significantly distressed. Implications for understanding the impact of cancer on the family are highlighted.

Adaptation, Psychological↗
PubMed1991

Correlates of internalizing and externalizing behavior problems: perceived competence, causal attributions, and parental symptoms.

Young adolescents in the clinical range on internalizing, externalizing, and both internalizing and externalizing behavior problems, as well as youth in the normal range on both types of problems, were identified separately using adolescents' self-reports and mothers' reports of behavior problems. In comparisons of groups identified on the basis of either type of informant, differences among the four groups were found in adolescents' self-perceptions of competence and in their fathers' psychological symptoms. Specifically, normals reported a more positive sense of their social acceptance and their behavioral conduct than all clinical groups, and fathers of adolescents in the clinical range on both internalizing and externalizing problems tended to report more psychological symptoms than the fathers of the normal group. Differences were found in mothers' psychological symptoms only when mothers' reports of adolescents' behavior problems were used to identify the groups. No consistent differences among the groups were found on adolescents' causal attributions for success and failure.

Adolescent↗
PubMed1989

Risk factors for emotional/behavioral problems in young adolescents: a prospective analysis of adolescent and parental stress and symptoms.

Stressful events in the lives of 309 10- to 15-year-olds and stressful events and psychological symptoms reported by their parents were examined in a 9-month study. Ss' self-reported emotional/behavioral problems were predicted by their reports of stressful events and their fathers' reports of psychological symptoms in cross-sectional analyses. Analyses at follow-up after controlling for initial reports of emotional/behavioral problems and prospective analyses predicting from first assessment to follow-up yielded significant effects for Ss' self-reported stressful events. Mothers' reports of children's problems were predicted by mothers' psychological symptoms in cross-sectional analyses and at follow-up after controlling for initial emotional/behavioral problems. Only prior levels of maternal reports of emotional/behavioral problems predicted mothers' reports of their children's problems 9 months later.

Adolescent↗
PubMed1988

Daily and major life events: a test of an integrative model of psychosocial stress.

The hypothesis that negative daily events mediate the relationship between major negative events and psychological symptomatology was tested using a three-wave, three-variable panel design. Measures of major and daily life events and psychological symptomatology were administered to 58 older adolescents at three time points during the transition from high school to college. The results indicated that the pathways from major life events to daily events and from daily events to psychological symptomatology were significant at each of the time points, but that the direct pathways from major events to psychological symptomatology were not significant at any time point. Thus, the hypothesis was fully supported. The findings are discussed in light of their implications for an integrative theory of the process by which major and daily events have an effect on psychological symptomatology.

Adaptation, Psychological↗
PubMed1985

Fifteen-year follow-up of a behavioral history of attention deficit disorder.

A 15-year longitudinal study of 369 children originally classified in second grade as exhibiting or not exhibiting behaviors commonly associated with attention deficit disorder was made. Diagnostic data were collected on these children in second, fourth, and fifth grades and subsequent school performance was evaluated after ninth and twelfth grades. Interviews were conducted 3 years after their graduation from high school. The ninth and twelfth grade records reveal that those who had previously been identified as showing behavior related to attention deficit disorder later performed significantly more poorly in school and had poorer social adjustment. Interviews in early adulthood continued to reveal differences in outcome between normal subjects and those earlier classified as having attention deficit disorder. Many of these differences could not be directly attributed to poor academic performance. A subgroup of students who were rated favorably by their elementary school teachers were found to perform better during high school than other members of the normal group in academic areas, but they generally did not differ from normal subjects in nonacademic areas.

Achievement↗