Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions.

Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells.

Morphoproteomic evidence of constitutively activated and overexpressed mTOR pathway in cervical squamous carcinoma and high grade squamous intraepithelial lesions.

Human papilloma virus (HPV) infection of the uterine cervix is linked to the pathogenesis of cervical cancer. Preclinical in vitro and in vivo studies using HPV-containing human cervical carcinoma cell lines have shown that the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, erlotinib, can induce growth delay of xenografts. Activation of Akt and mTOR are also observed in cervical squamous cell carcinoma and, the expression of phosphorylated mTOR was reported to serve as a marker to predict response to chemotherapy and survival of cervical cancer patients. Therefore, we investigated: a) the expression level of EGFR in cervical squamous cell carcinoma (SCC) and high-grade squamous intraepithelial lesions (HSIL) versus non-neoplastic cervical squamous epithelium; b) the state of activation of the mTOR pathway in these same tissues; and c) any impact of these signal transduction molecules on cell cycle. Formalin-fixed paraffin-embedded tissue microarray blocks containing 20 samples each of normal cervix, HSIL and invasive SCC, derived from a total of 60 cases of cervical biopsies and cervical conizations were examined. Immunohistochemistry was utilized to detect the following antigens: EGFR; mTOR pathway markers, phosphorylated (p)-mTOR (Ser2448) and p-p70S6K (Thr389); and cell cycle associated proteins, Ki-67 and S phase kinase-associated protein (Skp)2. Protein compartmentalization and expression were quantified in regard to proportion (0-100%) and intensity (0-3+). Mitotic index (MI) was also assessed. An expression index (EI) for pmTOR, p-p70S6K and EGFR, respectively was calculated by taking the product of intensity score and proportion of positively staining cells. We found that plasmalemmal EGFR expression was limited to the basal/parabasal cells (2-3+, EI = 67) in normal cervical epithelium (NL), but was diffusely positive in all HSIL (EI = 237) and SCC (EI 226). The pattern of cytoplasmic p-mTOR and nuclear p-p70S6K expression was similar to that of EGFR; all showed a significantly increased EI in HSIL/SCC versus NL (p<0.02). Nuclear translocation of p-mTOR was observed in all SCC lesions (EI = 202) and was significantly increased versus both HSIL (EI = 89) and NL (EI = 54) with p<0.015 and p<0.0001, respectively. Concomitant increases in MI and proportion of nuclear Ki-67 and Skp2 expression were noted in HSIL and SCC. In conclusion, morphoproteomic analysis reveals constitutive activation and overexpression of the mTOR pathway in HSIL and SCC as evidenced by: increased nuclear translocation of pmTOR and p-p70S6K, phosphorylated at putative sites of activation, Ser2448 and Thr389, respectively; correlative overexpression of the upstream signal transducer, EGFR, and increases in cell cycle correlates, Skp2 and mitotic indices. These results suggest that the mTOR pathway plays a key role in cervical carcinogenesis and targeted therapies may be developed for SCC as well as its precursor lesion, HSIL.

The Role of Acidic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor 4 in High Grade Serous Carcinoma

Background: High grade serous carcinoma whether ovarian, tubal or primary peritoneal, continues to be the most lethal gynecologic malignancy in the USA. Although combination chemotherapy and aggressive surgical resection has improved survival in the past decade the majority of patients still succumb to chemo-resistant disease recurrence. It has recently been reported that amplification of 5q31-5q35.3 is associated with poor prognosis in patients with high grade serous ovarian carcinoma. Although the amplicon contains over 50 genes, it is notable for the presence of several members of the fibroblast growth factor signaling axis. In particular acidic fibroblast growth factor (FGF1) has been demonstrated to be one of the driving genes in mediating the observed prognostic effect of the amplicon in ovarian cancer patients. This study seeks to further validate the prognostic value of fibroblast growth receptor 4 (FGFR4), another candidate gene of the FGF/FGFR axis located in the same amplicon. The emphasis will be delineating the role the FGF1/FGFR4 signaling axis plays in high grade serous ovarian carcinoma; and test the feasibility of targeting the FGF1/FGFR4 axis therapeutically. Materials and Methods: Spearman and Pearson correlation studies on data generated from array CGH and transcriptome profiling analyses on 51 microdissected tumor samples were used to identify genes located on chromosome 5q31-35.3 that showed significant correlation between DNA and mRNA copy numbers. Significant correlation between FGF1 and FGFR4 DNA copy numbers was further validated by qPCR analysis on DNA isolated from 51 microdissected tumor samples. Immunolocalization and quantification of FGFR4 expression were performed on paraffin embedded tissue samples from 183 cases of high-grade serous ovarian carcinoma. The expression was then correlated with clinical data to assess impact on survival. The expression of FGF1 and FGFR4 in vitro was quantified by real-time PCR and western blotting in six high-grade serous ovarian carcinoma cell lines and compared to those in human ovarian surface epithelial cells to identify overexpression. The effect of FGF1 on these cell lines after serum starvation was quantified for in vitro cellular proliferation, migration/invasion, chemoresistance and survival utilizing a combination of commercially available colorimetric, fluorometric and electrical impedance assays. FGFR4 expression was then transiently silenced via siRNA transfection and the effects on response to FGF1, cellular proliferation, and migration were quantified. To identify relevant cellular pathways involved, responsive cell lines were transduced with different transcription response elements using the Cignal-Lenti reporter system and treated with FGF1 with and without transient FGFR4 knock down. This was followed by western blot confirmation for the relevant phosphoproteins. Anti-FGF1 antibodies and FGFR trap proteins were used to attempt inhibition of FGF mediated phenotypic changes and relevant signaling in vitro. Orthotopic intraperitoneal tumors were established in nude mice using serous cell lines that have been previously transfected with luciferase expressing constructs. The mice were then treated with FGFR trap protein. Tumor progression was then followed via bioluminescent imaging. The FGFR4 gene from 52 clinical samples was sequenced to screen for mutations. Results: FGFR4 DNA and mRNA copy numbers were significantly correlated and FGFR4 DNA copy number was significantly correlated with that of FGF1. Survival of patients with high FGFR4 expressing tumors was significantly shorter that those with low expression(median survival 28 vs 55 month p< 0.001) In a multivariate cox regression model FGFR expression significantly increased risk of death (HR 2.1, p<0.001). FGFR4 expression was significantly higher in all cell lines tested compared to HOSE, OVCA432 cell line in particular had very high expression suggesting amplification. FGF1 was also particularly overexpressed in OVCA432. FGF1 significantly increased cell survival after serum deprivation in all cell lines. Transient knock down of FGFR4 caused significant reduction in cell migration and proliferation in vitro and significantly decreased the proliferative effects of FGF1 in vitro. FGFR1, FGFR4 traps and anti-FGF1 antibodies did not show activity in vitro. OVCA432 transfected with the cignal lenti reporter system revealed significant activation of MAPK, NFkB and WNT pathways, western blotting confirmed the results. Reverse phase protein array (RPPA) analysis also showed activation of MAPK, AKT, WNT pathways and down regulation of E Cadherin. FGFR trap protein significantly reduced tumor growth in vivo in an orthotopic mouse model. Conclusions: Overexpression and amplification of several members of the FGF signaling axis present on the amplicon 5q31-35.3 is a negative prognostic indicator in high grade serous ovarian carcinoma and may drive poor survival associated with that amplicon. Activation of The FGF signaling pathway leads to downstream activation of MAPK, AKT, WNT and NFkB pathways leading to a more aggressive cancer phenotype with increased tumor growth, evasion of apoptosis and increased migration and invasion. Inhibition of FGF pathway in vivo via FGFR trap protein leads to significantly decreased tumor growth in an orthotopic mouse model.

A study of the impact of cigarette advertising on adolescent susceptibility to smoking among 5th-, 8th-, and 12th-grade students in Hempstead and Hitchcock Independent School Districts

This study assessed the impact of cigarette advertising on adolescent susceptibility to smoking in the Hempstead and Hitchcock Independent School Districts. A convenience sample of 217 youths, 10-19 years of age was recruited in the study. Students completed both a paper-and-pencil and a computer-aided questionnaire in April 1996. Adolescents were defined as susceptible to smoking if they could not definitely rule out the possibility of future smoking. For the analysis, an index was devised: a 5-point index of an individual's receptivity to cigarette advertising. The index is determined by the number of positive responses to five survey items (recognizing cigarette brand logos, recognizing cigarette advertisement's pictures, recognizing cigarette brand slogans, evaluating adolescent attitudes toward cigarette advertising, and the degree to which adolescents were exposed to cigarette advertisements). Using logistic regression, we assessed the independent importance of the index in predicting susceptibility to smoking and ever smoking after adjusting for sociodemographic variables, perceived school performance and family composition. Of students surveyed, 54.4% of students appeared to have started the smoking uptake process as measured by susceptibility to smoking. Camel was recognized by the majority of students (88%), followed by Marlboro (41.5%) and Newport (40.1%). The pattern for recognition of the cigarette advertisements was the same as the pattern of market for cigarette. Advertisement featuring the cartoon character Joe Camel was significantly more appealing to adolescents than were advertisements with human models, with animal models, and with text only (p $<$ 0.001). Text only advertisement was significantly less appealing than other types of advertisements. The cigarette advertisement with White models (Marlboro) had significantly higher appeal to White students than to African-American students (p $<$ 0.001). The cigarette advertisement featuring African-American models (Virginia Slims) was significantly more appealing to African-American students than other ethnic groups (p $<$ 0.001). Receptivity to cigarette advertising was to be an important concurrent predictor of past smoking experience and intention to smoke in the future. Adolescents who scored in the fourth quartile of the Index of Receptivity to Cigarette Advertising were 7.54 (95% confidence interval (CI) = 1.92-29.56) times as likely to be susceptible to smoking, and were 4.56 (95% CI = 1.55-13.38) times as likely to have tried smoking, as those who scored in the first quartile of the Index. The findings confirmed the hypothesis that cigarette advertising may be a strong current influence in encouraging adolescents to initiate the smoking uptake process than sociodemographic variables, perceived school performance and family composition. ^

Team: Bee Me. A formulative evaluation of a negative eating attitudes and behaviors primary prevention curriculum targeted at 5 th grade elementary school girls

Objective. To evaluate a school-based intervention aimed at the primary prevention of negative eating attitudes and behaviors among preadolescent girls, and to revise curriculum lessons based on quantitative and qualitative findings. ^ Intervention Design. A formative evaluation was conducted on four Team: Bee Me curriculum lessons at a Houston elementary school. Evaluation focused on program satisfaction and short-term effect on knowledge and eating attitudes and behaviors. ^ Results. Sixteen girls participated in the five-day project. Statistically significant improvements in overall knowledge were observed (p<0.05), however only modest changes were observed in eating attitudes and behaviors. Program satisfaction was high among student participants and the teacher who implemented it. Insight for future modifications to this program and for similar interventions was provided by the students and teacher. ^ Conclusions. This program led to positive trends in outcome variables; however longer and more intensive testing of this program is needed to better evaluate its effectiveness.^

The Skip To Breakfast project: Development, implementation, and feasibility evaluation of an intervention to increase healthful breakfast consumption among fifth grade students and their families

Children and adults frequently skip breakfast and rates are currently increasing. In addition, the food choices made for breakfast are not always healthy ones. Breakfast skipping, in conjunction with unhealthy breakfast choices, leads to impaired cognitive functioning, poor nutrient intake, and overweight. In response to these public health issues, Skip To Breakfast, a behaviorally based school and family program, was created to increase consistent and healthful breakfast consumption among ethnically diverse fifth grade students and their families, using Intervention Mapping™. Four classroom lessons and four parent newsletters were used to deliver the intervention. For this project, a healthy, "3 Star Breakfast" was promoted, and included a serving each of dairy product, whole grain, and fruit, each with an emphasis on being low in fat and sugar. The goal of this project was to evaluate the feasibility and acceptability of the intervention. A pilot-test of the intervention was conducted in one classroom, in a school in Houston, during the Fall 2007 semester. A qualitative evaluation of the intervention was conducted, which included focus groups with students, phone interviews of parents, process evaluation data from the classroom teacher, and direct observation. Sixteen students and six parents participated in the study. Data were recorded and themes were identified. Initial results showed there is a need for such programs. Based on the initial feedback, edits were made to the intervention and program. Results showed high acceptability among the teacher, students, and parents. It became apparent that students were not reliably getting the parent newsletters to their parents to read, so a change to the protocol was made, in which students will receive incentives for having parents read newsletters and return signed forms, to increase parent participation. Other changes included small modifications to the curriculum, such as, clarifying instructions, changing in-class assignments to homework assignments, and including background reading materials for the teacher. The main trial is planned to be carried out in Spring 2008, in two elementary schools, utilizing four, fifth grade classes from each, with one school acting as the control and one as the intervention school. Results from this study can be used as an adjunct to the Coordinated Approach To Child Health (CATCH) program. ^

Does parental monitoring influence the use of alcohol and drugs among inner city 7th grade students?

Objective. To examine associations between parental monitoring and adolescent alcohol/drug use. ^ Methods. 981 7th grade students from 10 inner-city middle schools were surveyed at the 3 month follow-up of an HIV, STD, and pregnancy prevention program. Data from 549 control subjects were used for analyses. Multinomial logistic regression was used to examine associations between five parental monitoring variables and substance use, coded as: low risk [never drank alcohol or used drugs (0)], moderate risk [drank alcohol, no drug use (1)], and high risk [both drank alcohol and used drugs or just used drugs (2)]. ^ Results. Participants were 58.3% female, 39.6% African American, 43.8% Hispanic, mean age 13.3 years. Lifetime alcohol use was 47.9%. Lifetime drug use was 14.9%. Adjusted for gender, age, race, and family structure, each individual parental monitoring variable (perceived parental monitoring, less permissive parental monitoring, greater supervision (public places), greater supervision (teen clubs), and less time spent with older teens) was significant and protective for the moderate and high risk groups. When all 5 variables were entered into a single model, only perceived parental monitoring was significantly associated (OR=0.40, 95% CI 0.29-0.55) for the moderate risk group. For the high risk group, 3 variables were significantly protective (perceived parental monitoring OR=0.28, CI 0.18-0.42, less time spent with older teens OR=0.75, CI 0.60-0.93, and greater supervision (public places) OR=0.79, CI 0.64-0.99). ^ Conclusion. The association between parental monitoring and substance abuse is complex and varied for different risk levels. Implications for intervention development are addressed. ^

Psychosocial variables associated with sexual risk behavior among an urban seventh grade population

This dissertation examines the psychosocial factors associated with sexual risk behavior among low socio-economic, minority middle school students in a large urban school district in Houston, Texas and is presented in the form of three articles. Article One examines the association between knowledge, perceived risk of HIV/STD, and self-reported lifetime engagement in vaginal sex among seventh grade students. The purpose of Article Two is to examine the association between knowledge about condoms, condom use attitudes, perceived peer norms about condom use, condom use negotiation self-efficacy, condom use self-efficacy, condom use intentions and actual condom use among seventh grade middle school adolescents. Finally, Article Three examines the association between attitudes, perceived peer norms, refusal self-efficacy about sex, sexual and abstinence intentions among seventh grade adolescents. By providing a better understanding of factors influencing sexual intentions and sexual behaviors among this population, these articles will enable practitioners to develop effective evidence-based interventions to delay sexual initiation and prevent youth from engaging in risky sexual behaviors, including risk of HIV/STDs and unintended pregnancy.^

If we call them, will they change? Feasibility of a telephone adaptation of motivational interviewing aimed at parents to reduce television time among 2nd and 4th grade children

Television viewing is a sedentary behavior that is modifiable. Reducing media-related behaviors via parent-focused interventions may hold promise for decreasing childhood obesity. This feasibility study examines a novel parent-centered brief telephone-delivered Motivational Enhancement Interview (MEI) to encourage parents of 2nd and 4th graders to set a rules limiting TV time or remove the TV from the child's bedroom. This quasi-experimental sub-study was part of the larger CATCH: En Vivo pilot study conducted in a Hispanic population in the Texas Rio Grande Valley. Parents in the MEI condition were contacted via telephone and encouraged to meet the American Academy of Pediatrics (AAP) recommended 2 hours per day or less of TV. Unconditional logistic regression was used to analyze the data. At post-test, 85% of parents of 4th graders in the MEI group (compared to 71% at pre-test) reported having a rule limiting TV time. The adjusted odds ratio for the MEI group compared to the control group was 3.88, 95% CI (0.72-20.99). At pre-test, 63.16% of 2nd graders had a television in their bedrooms. The 2nd grade MEI intervention reduced that number to 41.03% (OR=0.25, 95%CI (0.08-0.82)). This first look at using MEI to target parents of children to modify TV behavior presents evidence on a promising strategy for modifying children's home media environment and warrants further investigation. ^

An investigation into the relationship between screen time, consumption of advertised foods, and physical activity among Texas 4th grade elementary school children

Background. The high prevalence of obesity among children has spurred creation of a list of possible causative factors, including the advertising of foods of minimal nutritional value, a decrease in physical activity, and increased media use. Few studies show prevalence rates of these factors among large cohorts of children. ^ Methods. Using data from the 2004-2005 School Physical Activity and Nutrition project (SPAN), a secondary analysis of 7907 4th-grade children (mean age 9.74 years) was conducted. In addition, a comic-book–based intervention that addressed advertised food consumption, physical activity, and media use was developed and evaluated using a pre-post test design among 4th-grade children in an urban school district. ^ Results. Among a cohort of 4th-grade children across the state of Texas, children who had more than 2 hours of video game or computer time the previous day were more than twice as likely to drink soda and eat candy or pastries. In addition, children who watched more than 2 hours of TV the previous day were more than three times as likely to consume chips, punch, soda, candy, frozen desserts, or pastries (AOR 3.41, 95% CI: 1.58, 7.37). A comic-book based intervention held great promise and acceptance among 4th-grade children. Outcome evaluation showed that while results moved in a positive direction, they were not statistically significant. ^ Conclusion. Statistically significant associations were found between screen time and eating various types of advertised food. The comic book intervention was widely accepted by the children exposed to it, and pre-post surveys indicated they moved constructs in a positive direction. Further research is needed to look at more specific ways in which children are exposed to TV, and the relationship of the TV viewing time with their consumption of advertised foods. In addition, researchers should look at comic book interventions more closely and attempt to utilize them in more in studies with a longer follow-up time. ^

Estrogen-induced gene expression and patient survival in high-grade serous carcinoma of the ovary

Background. Assessment of estrogen receptor (ER) expression has inconsistent utility as a prognostic marker in epithelial ovarian carcinoma. In breast and endometrial cancers, the use of estrogen-induced gene panels, rather than ER expression alone, has shown improved prognostic capability. Specifically, over-expression of estrogen-induced genes in these tumors is associated with a better prognosis and signifies estrogen sensitivity that can be exploited with hormone antagonizing agents. It was therefore hypothesized that estrogen-induced gene expression in ovarian carcinoma would successfully predict outcomes and differentiate between tumors of varying estrogen sensitivities. Methods. Two hundred nineteen (219) patients with ovarian cancer who underwent surgery at M. D. Anderson between 2004 and 2007 were identified. Of these, eighty-three (83) patients were selected for inclusion because they had advanced stage, high-grade serous carcinoma of the ovary or peritoneum, had not received neoadjuvant chemotherapy, and had readily available frozen tissue for study. All patients had also received adjuvant treatment with platinum and taxane agents. The expression of seven genes known to be induced by estrogen in the female reproductive tract (EIG121, sFRP1, sFRP4, RALDH2, PR, IGF-1, and ER) was measured using qRT-PCR. Unsupervised cluster analyses of multiple gene permutations were used to categorize patients as high or low estrogen-induced gene expressors. QPCR gene expression results were then compared to ER and PR immunohistochemical (IHC) expression. Cox proportional hazards models were used to evaluate the effects of both individual genes and selected gene clusters on patient survival. Results. Median follow-up time was 38.7 months (range 1-68 months). In a multivariate model, overall survival was predicted by sFRP1 expression (HR 1.10 [1.02-1.19], p=0.01) and EIG121 expression (HR 1.28 [1.10-1.49], p<0.01). A cluster defined by EIG121 and ER was further examined because that combination appeared to reasonably segregate tumors into distinct groups of high and low estrogen-induced gene expressors. Shorter overall survival was associated with high estrogen-induced gene expressors (HR 2.84 [1.11-7.30], p=0.03), even after adjustment for race, age, body mass index, and residual disease at debulking. No difference in IHC ER or PR expression was noted between gene clusters. Conclusion. In sharp contrast to breast and endometrial cancers, high estrogen-induced gene expression predicts shorter overall survival in patients with high-grade serous ovarian carcinoma. An estrogen-induced gene biomarker panel may have utility as prognostic indicator and may be useful to guide management with estrogen antagonists in this population.^

Relating one's social support network to one's mid term grade

Much has been written about the relation of social support to health outcomes. Support networks were found to be predictive of health status. Not so clear was the manner in which social support helped the individual to avoid health complications. Whereas some aspects of the support network were protective, others were burdensome. Duties to one's network could serve as a stressor and duties outside one's network might stress the support system itself. Exposure to one's network was associated with certain health risks while disruption in one's social support network was associated with other health risks.^ Many factors contributed to the impact of a social support network upon the individual member: the characteristics of the individual, the individual's role or position within the network, qualities of the network and duties or indebtedness of the individual to the network. This investigation considered the possibility that performance could serve as a stressor in a fashion similar to an exposure to a health hazard.^ Because the literature includes many examples of studies in which the subjects were college students, academic progress is a performance common to most subjects. A profile of the support networks of successful students was contrasted with those of less successful students in this correlational study.^ What was uncovered in this investigation was a very complex web of interrelated constructs. Most aspects of the social support network did not significantly predict academic performance. Only a limited number of characteristics were associated with academic success: the frequency of support, student age, the existence of a 'mentor' within one' s network, and the extent to which one received a predominant source of support. Other factors had a tendency to be negatively correlated with midterm grade, suggesting those factors may impede academic performance.^ Medical status did not predict grades, but was correlated with many aspects of the network. Disruptions in particular parts of one's network were correlated with particular health categories. In fact, disruption in social support was more predictive of academic outcomes than medical complications. Whereas the individual's values were related to the contributing factors, only the individual's satisfaction with certain aspects of the support network were predictive of higher midterm grades in a psychology class. Dissatisfaction was associated with lower grades, suggesting a disruptive effect within the network. Associations among the features of support networks which predicted academic progress were considered. ^

Associations between exposure to violence and depression in 5th grade students: Results from the Healthy Passages study

Purpose. To describe the prevalence of violence exposure and depression and their association among 5th grade students. ^ Methods.. Students (n=5,147) attending 5th grade (mean age 11.12) from three major metropolitan areas in the United States were surveyed on various health-related measures including experience with being a victim of violence (adapted from YRBS and Traumatic Events Screening Inventory) and depressive symptoms (from the DISC Predictive Scale). Prevalence was calculated for rates of violence exposure as well as depression defined as having five or more depressive symptoms. Logistic regression was used to examine the association between exposure to violence and depression. ^ Results. This study found that over 35% of students were exposed to some form of violence such as being threatened, hit, punched, kicked, beaten up, or threatened/injured with a gun or knife. Male students had a higher prevalence than female students on almost all exposure types. Over 7% of students also reported having 5 or more depressive symptoms. All forms of violence were significantly associated with depression. Students who had been a victim of violence were between 2.5 and 6.5 more likely to have five or more depression symptoms. Conslusion. The results of this study underscore the urgent need of collaborative prevention and treatment efforts for children exposed to violence. By preventing such exposure, serious effects including physical injury, mental health problems, and other detrimental outcomes may be mitigated.^

The heart challenge: The effect of regular aerobic exercise on body fat distribution in third and fourth grade school children: A randomized clinical trial

The pattern of body fat distribution known as "centralized", and characterized by a predominance of subcutaneous fat on the trunk and a "pot belly", has been associated with an increased risk of chronic disease. These patterns of fat distribution, as well as the lifestyle habit variables associated with adult fatness and chronic morbidity clearly begin to develop during childhood, indicating the need for intervention and primary prevention of obesity, particularly the centralized form, during childhood or adolescence. The purpose of this study was to determine whether regular aerobic exercise could beneficially alter the distribution of body fat in 8 and 9 year old children. One hundred and eighty-eight participants were randomized into either a regular aerobic exercise treatment group or a standard physical education program control group. A variety of aerobic activities was used for intervention 5 days per week during physical education class for a period of 12 weeks. Fat distribution was measured by a number of the most commonly used indices, including ratios of body circumferences and skinfolds and indices derived from a principal components analysis. Change over time in average pulse rate was used to determine if intervention actually occurred. Approximately 10% of the students were remeasured, allowing the calculation of intra- and interexaminer measurement reliability estimates for all indices.^ This study group was comparable to the U.S. population, though the study children were slightly larger for certain measures. No effect of the exercise intervention was found. The most likely explanation for this was inadequacy of the intervention, as indicated by the lack of any change in average pulse rate with treatment. The results of the measurement reliability analysis are reported and indicate that body circumference ratios are more precise than skinfold ratios, particularly when multiple observers are used. Reliability estimates for the principal component indices were also high.^ It remains unclear whether the distribution of body fat can be altered with exercise. It is likely that this issue will remain undecided until one highly reliable, valid, and sensitive measure of fat distribution can be found. ^

Molecular studies of human high grade B cell non -Hodgkin's lymphomas

The non-Hodgkin's B cell lymphomas are a diverse group of neoplastic diseases. The incidence rate of the malignant tumors has been rising rapidly over the past twenty years in the United States and worldwide. The lack of insight to pathogenesis of the disease poses a significant problem in the early detection and effective treatment of the human malignancies. These studies attempted to investigate the molecular basis of pathogenesis of the human high grade B cell non-Hodgkin's lymphomas with a reverse genetic approach. The specific objective was to clone gene(s) which may play roles in development and progression of human high grade B cell non-Hodgkin's lymphomas.^ The messenger RNAs from two high grade B cell lymphoma lines, CJ and RR, were used for construction of cDNA libraries. Differential screening of the derived cDNA libraries yielded a 1.4 kb cDNA clone. The gene, designated as NHL-B1.4, was shown to be highly amplified and over-expressed in the high grade B cell lymphoma lines. It was not expressed in the peripheral blood lymphoid cells from normal donors. However, it was inducible in peripheral blood T lymphocytes by a T cell mitogen, PHA, but could not be activated in normal B cells by B cell mitogen PMA. Further molecular characterization revealed that the gene may have been rearranged in the RR and some other B cell lymphoma lines. The coding capacity of the cDNA has been confirmed by a rabbit reticulocyte lysate and wheat germ protein synthesis system. A recombinant protein with a molecular weight of approximate 30 kDa was visualized in autoradiogram. Polyclonal antisera have been generated by immunization of two rabbits with the NHL-B1.4 recombinant protein produced in the E. coli JM109. The derived antibody can recognize a natural protein with molecular weight of 49 kDa in cell lysate of activated peripheral T lymphocytes of normal donors and both the cell lysate and supernatant of RR B cell lymphoma lines. The possible biologic functions of the molecule has been tested preliminarily in a B lymphocyte proliferation assay. It was found that the Q-sepharose chromatograph purified supernatant of COS cell transfection could increase tritiated thymidine uptake by B lymphocytes but not by T lymphocytes. The B cell stimulatory activity of the supernatant of COS cell tranfection could be neutralized by the polyclonal antisera, indicating that the NHL-B1.4 gene product may be a molecule with BCGF-like activity.^ The expression profiles of NHL-B1.4 in normal and neoplastic lymphoid cells were consistent with the current B lymphocyte activation model and autocrine hypothesis of high grade B cell lymphomagenesis. These results suggested that the NHL-B1.4 cDNA may be a disease-related gene of human high grade B cell lymphomas, which may codes for a postulated B cell autocrine growth factor. ^