This chapter discusses the genetic mechanisms that underlie the ultraviolet response. During the early characterization of the UV response in cultured human fibroblasts, it became apparent that treatment of these cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) leads to induction of most of the same peptides induced by UV or mitomycin C. Treatment of cultured mammalian cells with phorbol ester tumor promoters such as TPA causes a variety of pleiotropic effects, most of which are probably mediated by the activation of protein kinase C, the major cellular target for these agents. Many of the genes are also induced after treatment of cells with agents such as phorbol esters, serum growth factors, and lymphokines, which in most cases do not lead to direct deoxyribonucleic acid damage. However, based on genetic analysis, it appears that common cis- and trans-acting elements participate in mediating the transcriptional response to these agents.
PURPOSE We assessed physical activity (PA) tracking in a Euro- and Mexican-American cohort from ages 4 to 17 using both objective and subjective measures. METHODS 1 Objective PA data were obtained from direct observation in children's homes using BEACHES (12 occasions; ages 4–7), CALTRAC accelerometer (4 occasions; ages 11–12), and CSA accelerometer (4 occasions; ages 15–17). Listwise analyses for objective measures included 147 children (N=76 boys, 71 girls). Log transformations of CALTRAC and CSA measures corrected for skewed distributions. Best Linear Unbiased Predictors (BLUPs) were computed for each measure to accommodate subjects with missing data. Partial correlations were conducted separately for boys and girls, controlling for ethnicity. RESULTS 1 Significant correlations (i.e., tracking) among the three PA measures (i.e., across the three time periods) were not found for either gender. METHODS 2 Subjective PA data were obtained via Physical Activity Recall (PAR) interviews in children's homes on 4 occasions (2 interviews, 6-months apart at ages 11–12, and 2 interviews, 6-months apart at ages 16–17). Listwise analyses for PAR included 177 children (N=88 boys, 89 girls). BLUPs were computed for each measurement period. Partial correlations were conducted separately for boys and girls, controlling for ethnicity. RESULTS 2 Significant relationships in self-reported PA across time periods for both boys (r=.372, p = .000) and girls (r=.311, p = .000) were found. CONCLUSIONS Similar to other studies, PA tracking was higher using subjective than objective measures. Studying the tracking of PA as children move from early childhood through adolescence faces numerous challenges, including (1) rapid changes in the type of PA and its contexts (e.g., location) as children age, and (2) the need for technological advancements that will provide a valid samples of PA at different developmental levels. Supported by HL52449
In addition to being a central coordinator of immune responses, NF-kappaB signaling also plays a critical role in cancer development and progression and it may determine the response to therapy. NF-kappaB activation was shown to provide a critical mechanistic link between inflammation and cancer and is a major factor that controls the ability of both preneoplastic and malignant cells to resist apoptosis-based tumor surveillance mechanisms. NF-kappaB may also be involved in regulation of tumor angiogenesis and invasiveness. Importantly, NF-kappaB and the signaling pathways that mediate its activation have become attractive targets for development of new chemopreventive and chemotherapeutic approaches.
No abstract is provided for this article.
Cancer development and its response to therapy are strongly influenced by innate and adaptive immunity, which either promote or attenuate tumorigenesis and can have opposing effects on therapeutic outcome. Chronic inflammation promotes tumor development, progression, and metastatic dissemination, as well as treatment resistance. However, cancer development and malignant progression are also associated with accumulation of genetic alterations and loss of normal regulatory processes, which cause expression of tumor-specific antigens and tumor-associated antigens (TAAs) that can activate antitumor immune responses. Although signals that trigger acute inflammatory reactions often stimulate dendritic cell maturation and antigen presentation, chronic inflammation can be immunosuppressive. This antagonism between inflammation and immunity also affects the outcome of cancer treatment and needs to be considered when designing new therapeutic approaches.
Purpose. The study examines the relationship between children's television (TV) viewing and physical fitness. Design. Cross-sectional data from questionnaires and objective measures were analyzed. Setting. Data were collected during the fall of 1990 from public elementary school students in a suburban California city. Subjects. Approximately 98% of eligible students participated. Of these, 10% were dropped due to missing data, yielding a final sample of 284 girls and 304 boys. Measures. Children reported their amount of TV viewing on a typical summer day; parents reported their child's TV viewing on a typical weekday during the school year. Cardiovascular fitness was the 1-mile run/walk. Body fat was both the child's body mass index (BMI) and skinfolds. Additional measures included muscular strength/endurance and flexibility. Results. Mile run/walk times were associated with both parental (η 2 = . 051 and . 031 for boys and girls, respectively) and child reports (η 2 = . 020 and . 028) of the child's amount of TV viewing. Parental reports, but not child reports, of the child's TV viewing were related to BMI (η 2 = .041 and .058) and skinfolds (η 2 = .050 and .029). Neither measure of children's TV viewing was related to muscular strength/endurance or flexibility. Conclusions. Children's TV viewing seems to be weakly and inconsistently related to various components of physical fitness. However, given the tracking of cardiovascular disease risk factors from childhood into adulthood and the high proportion of children who watch television, these relationships are worthy of further study.
Correlates of physical activity were examined in young people in grades 1 through 12, and analyses were conducted separately for eight age/grade and sex subgroups. Twenty-one explanatory variables were assessed by parental report. Physical activity was assessed in 781 young people via parent report, and 200 wore an accelerometer for seven days. Between 11% and 36% of parent-reported child vigorous physical activity was explained. The most consistent correlates were peer support and use of afternoon time for active rather than sedentary recreation. Peer support was the only significant correlate of objectively monitored activity in multiple subgroups.
1318 Data from an 18-month phone and mail intervention, Project GRAD (Graduate Ready for Activity Daily), were examined to determine to what extent use of behavior change skills explains change in physical activity outcomes. An innovation of this study was assessing use of skills contemporaneously rather than retrospectively. Recent college graduates (N=170; M age=24.1; 51% female) who had participated in the semester-long GRAD intervention were included in this follow-up study. Behavioral skills included goal setting, decisional balance, self-talk, stress management, time management, enjoyment, social support, activism, and relapse prevention. Use of skills was measured by structured telephone interviews throughout the 18-month intervention. Strength, vigorous, and moderate intensity activities, as well as total physical activity, were assessed using the 7-Day PAR (Blair, 1984). Women reported using a significantly greater number of skills than men (p<.01); specifically, more positive self-talk, decisional balance, enjoyment, social support, and relapse prevention (p<.05). Regressions revealed that women who reported more goal setting and relapse prevention reported more vigorous activity (p<.05). For women, strength, moderate, and total activity were not significantly predicted by the total number of skills used or any specific skill. Men who reported increasing enjoyment reported more moderate intensity activity (p<.05). Surprisingly, men who reported using more relapse prevention reported less vigorous activity (p<.01), and men who reported using more stress management reported less strength activity (p<.05). Results indicate that women may use more behavioral skills than men, and these skills differentially predict physical activity outcomes. This may have important implications for tailoring physical activity interventions for men and women, and may be useful for identifying which components of an intervention may be most related to physical activity outcomes. Supported by NIH #HL49505.
A review of 41 clinical and 54 analogue studies was undertaken to evaluate the relationship between anxiety response channels—physiological, behavioral and cognitive. The results indicated that congruence among response channels tended to be higher for the clinical populations than for the analogue populations. The data tend best to support Hodgson and Rachman's (1974) theory that anxiety channel congruence increases as a function of intensity of the anxiety. Tentative support was found for Bernstein and Paul's (1971) assertion that analogue and clinical subjects are sufficiently dissimilar as to obstruct the generalization of findings from one population to the other. Lastly, the congruence patterns suggest that behavioral and cognitive measures are less reliable indices of anxiety than physiological measures, especially in analogue samples.
Nearly two decades after the initial cloning and identification of the founding father of the tumor necrosis factor receptor (TNFR) family, much has been learned about the mechanisms by which these receptors signal to critical transcription factors and other targets that regulate gene expression and cellular physiology. Mitogen-activated protein kinases (MAPKs) and inhibitor of nuclear factor (NF)-kappaB (I kappaB) kinases (IKKs) were identified early on as the upstream kinases responsible for activation of activator-protein 1 (AP-1) and NF-kappaB, respectively, and later on for their ability to control life-or-death decisions in TNF-stimulated cells. Both of these critical pathways are regulated at the level of MAPK kinase kinases (MAP3Ks), after which point they diverge. Recent work, however, illustrates that protein ubiquitination cascades play a critical initiating role in TNFR signaling and account for spatial and temporal separation of IKK and MAPK signaling cascades and thereby determine biological specificity and outcome. Cellular inhibitors of apoptosis (cIAPs) 1 and 2 are ubiquitin (Ub) ligases (E3s) that mediate canonical Lys48-linked ubiquitination of TNFR-associated factor 3 (TRAF3), marking it for subsequent degradation by the proteasome. TRAF3 degradation releases the brake on TRAF2/6:MAP3K signaling complexes responsible for MAPK activation, leading to their translocation from the cytoplasmic segment of the receptor to the cytosol where they initiate MAPK phosphorylation and activation. By contrast, IKK activation proceeds considerably faster than MAPK activation, takes place at the receptor, and is independent of cIAP1/2 activity and TRAF3 degradation. This arrangement may be important for ensuring the proper delivery of NF-kappaB-dependent survival signals and conversion of JNK-promoted death signals to proliferative ones.
The strongest health benefit of physical activity for young people may be improved psychological health ((1)). Because psychological health affects the daily well-being of young people and the adults in their lives, this may be reason enough to ensure that young people are active. In addition, physical activity constitutes part of effective weight loss programs for obese youth, and it can affect risk factors for cardiovascular disease and diabetes such as high-density lipoprotein cholesterol levels, blood pressure, and insulin resistance ((1)). The ultimate effects on disease in adulthood, however, are not known.
