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Activation of programmed cell death by recombinant human tumor necrosis factor plus topoisomerase II-targeted drugs in L929 tumor cells.

The mechanism of death induced by recombinant human tumor necrosis factor (rHuTNF) in L929 tumor cells of C3H mice was investigated. Treatment with rHuTNF led to fragmentation of DNA into nucleosomal oligomers and to induction of the expression of TRPM-2, a programmed cell death-associated gene. Both events preceded cell death by several hours. Treatment with DNA topoisomerase II inhibitors accelerated both the rHuTNF-mediated DNA fragmentation and the elevation in TRPM-2 messenger RNA levels. These results suggest that rHuTNF exerts its cytotoxicity on L929 cells by activating programmed cell death, leading to apoptosis, and that topoisomerase II inhibitors enhance rHuTNF-mediated cytotoxicity by accelerating this process.

Animals↗

Programs and services to prevent pregnancy, childbearing, and poor birth outcomes among adolescents in rural areas of the southeastern United States.

PURPOSE: To illustrate how rural adolescents' needs for pregnancy prevention and improved birth outcomes are currently being addressed, and to suggest strategies for future programs. METHODS: Local and state-level informants knowledgeable about services to adolescents in the Southeastern United States were identified. Semistructured interviews were used to determine the program start date and time frame, funding sources, target population, participating counties, implementing agency or organization, specific program services, and status of program activities. These programs were categorized by the type of services offered and the population targeted. RESULTS: The most common adolescent services in the rural Southeast attempt either to improve life options of youth, reduce sexual activity, or provide prenatal and postnatal care. Unlike urban areas where there are a variety of family planning providers, in the rural Southeast, health departments are the primary source of family planning for adolescents. There are no abortion providers in most rural areas of the Southeast. The majority of rural programs that include adolescents among the population served are developed for all women rather than specifically for adolescents. Programs specific to rural adolescents are described. CONCLUSIONS: The majority of programs in the rural Southeast address only selected adolescent health issues. Successful interventions require locally supported, multipronged, intensive approaches with consistent messages targeted to high-risk populations. Evaluation tools are needed to determine the effectiveness of each component of prevention programs.

Adolescent↗

FK506 augments activation-induced programmed cell death of T lymphocytes in vivo.

FK506 is an immunosuppressive drug that inhibits T cell receptor-mediated signal transduction. This drug can induce immunological tolerance in allograft recipients. In this study, we investigated the in vivo effects of FK506 on T cell receptor-mediated apoptosis induction. Injection of anti-CD3 antibody (Ab) in mice resulted in the elimination of CD4+ CD8+ thymocytes by DNA fragmentation. FK506 treatment significantly augmented thymic apoptosis induced by in vivo anti-CD3 Ab administration. Increased thymic apoptosis resulted in the disappearance of CD4+ CD8+ thymocytes after anti-CD3 Ab/FK506 treatment. DNA fragmentation triggered by FK506 was induced exclusively in antigen-stimulated T cells, since enhanced DNA fragmentation induced by in vivo staphylococcal enterotoxin B (SEB) injection was confirmed in SEB-reactive V beta 8+ thymocytes but not in SEB-nonreactive V beta 6+ thymocytes. In addition to thymocytes, mature peripheral T cells also die by activation-induced programmed cell death. A similar effect of FK506 on activation-induced programmed cell death was observed in SEB-activated peripheral spleen T cells. In contrast, cyclosporin A treatment did not enhance activation-induced programmed cell death of thymocytes and peripheral T cells. Apoptosis is required for the generation and maintenance of self-tolerance in the immune system. Our findings suggest that FK506-triggered apoptosis after elimination of antigen-activated T cells may represent a potential mechanism of the immunological tolerance achieved by FK506 treatment.

Animals↗

'Make a move' falls prevention project: an area health service collaboration.

ISSUE ADDRESSED: Since a lack of physical activity is a risk factor for falling, effective interventions to increase participation rates among older people need to be found. This project assessed the viability of a metropolitan Area Health Service collaboration to increase physical activity rates among older people. METHODS: A collaboration involving six Area Health Services in the Sydney metropolitan area, central coast of New South Wales (NSW), and NSW Department of Health was established. Interventions included a communication strategy to raise awareness of the benefits of physical activity for preventing falls and enhancement of local physical activity programs for older people. A repeated measures cross-sectional design was used to assess increases in physical activity programs and older people's participation, and data of fall-related hospital admissions were examined. Annual activity logs were completed to track local project activities. Semi-structured interviews with key stakeholders and workshops were used to review the collaborative management model. RESULTS: Response to the communication strategy and gains in physical activity programs for older people varied among Area Health Services. Overall, approximately 2,929 people called the campaign inquiry hotlines in response to the media campaign, Area Health Service-supported exercise programs for older people increased by 19%, participation rates increased by 16%, and fall-related hospital admissions were observed to plateau. The collaborative management model used was somewhat effective, but had difficulties for the issue being addressed. CONCLUSION: 'Make a Move' added value to local physical activity programs for older people and increased the number of older people participating in Area Health Service-supported exercise programs. Collaborative projects are worthwhile if they address the right issue, involve the right partners and have sound management processes.

Accidental Falls↗

Crk synergizes with epidermal growth factor for epithelial invasion and morphogenesis and is required for the met morphogenic program.

Activation of the Met receptor tyrosine kinase through its ligand, hepatocyte growth factor, stimulates cell spreading, cell dispersal, and the inherent morphogenic program of various epithelial cell lines. Although both hepatocyte growth factor and epidermal growth factor (EGF) can activate downstream signaling pathways in Madin-Darby canine kidney epithelial cells, EGF fails to promote the breakdown of cell-cell junctional complexes and initiate an invasive morphogenic program. We have undertaken a strategy to identify signals that synergize with EGF in this process. We provide evidence that the overexpression of the CrkII adapter protein complements EGF-stimulated pathways to induce cell dispersal in two-dimensional cultures and cell invasion and branching morphogenesis in three-dimensional collagen gels. This finding correlates with the ability of CrkII to promote the breakdown of adherens junctions in stable cell lines and the ability of EGF to stimulate enhanced Rac activity in cells overexpressing CrkII. We have previously shown that the Gab1-docking protein is required for branching morphogenesis downstream of the Met receptor. Consistent with a role for CrkII in promoting EGF-dependent branching morphogenesis, the binding of Gab1 to CrkII is required for the branching morphogenic program downstream of Met. Together, our data support a role for the CrkII adapter protein in epithelial invasion and morphogenesis and underscores the importance of considering the synergistic actions of signaling pathways in cancer progression.

Animals↗

Signaling pathways engaged by NK cell receptors: double concerto for activating receptors, inhibitory receptors and NK cells.

Despite the absence of antigen-specific receptors at their surface, NK cells can selectively eliminate virus-infected cells, tumor cells and allogenic cells. A dynamic and precisely coordinated balance between activating and inhibitory receptors governs NK cell activation programs. Multiple activating and inhibitory NK cell surface molecules have been described, a group of them acting as receptors for MHC class I molecules. In spite of their heterogeneity, activating NK cell receptors present remarkable structural and functional homologies with T cell- and B cell-antigen receptors. Inhibitory NK cell receptors operate at early stages of activating cascades by recruiting protein tyrosine phosphatases via intra- cytoplasmic motifs (ITIM), a strategy which is widely conserved in hematopoietic and non-hematopoietic cells.

Cytotoxicity, Immunologic↗

Challenging residents to assume maximal responsibilities in homes for the aged.

A program for activating residents of homes for the aged to assume maximal responsibilities is described. Promoting maximal physical and mental health through various modalities including activity programs, appropriate exercise and participation in democratic self-government mechanisms, will result in a happier, healthier population of residents in institutions for the aged. The increased demands on staff time and patience will be compensated for by relief of the too-frequent feelings of hopelessness and boredom endemic among the staff of long-term care facilities. Such programs demand constant effort by all staff members, patients, volunteers and relatives because if they succumb to the usual human dislike of persistency, short-term gains can easily be lost.

Aged↗

[The effects of a physical activity reinforcement program on exercise compliance, depression, and anxiety in continuous ambulatory peritoneal dialysis patients].

PURPOSE: This study was to evaluate the effects of a physical activity reinforcement program on exercise compliance, depression, and anxiety in continuous ambulatory peritoneal dialysis(CAPD) patients. METHOD: A nonequivalent control group with a pre-post test was designed. Data collection was done from December, 2002 to June, 2003 at a hospital. The degree of depression and anxiety of the patients was assessed by the score of SCL-90-R, and exercise compliance was measured by exercise period, frequency, time and intensity. The experimental group was composed of 19 participants who were educated based on an exercise education protocol and carried out walking exercises two to four times a week after hearing verbal persuasion biweekly through the telephone or a face-to-face interview for 12 weeks, while 17 participants in control group received no intervention. RESULT: 1. The experimental group showed significant improvement in self-efficacy of exercise compliance (U=79.00, p=.01), exercise period (chi2=20.84, p=.00), exercise frequency (chi2=9.03, p=.01), exercise time (chi2=9.03, p=.01) and exercise intensity (chi2=11.09, p=.00) compared to those of the control group. 2. The experimental group showed a lower depression score (U=84.50, p=.01) than the results of the control group. 3. However, there were no changes in anxiety level compared to the control group. CONCLUSION: The physical activity reinforcement program was found to have an effect on exercise compliance and the depression score of CAPD patients. The results provided evidence for the importance of physical activity and verbal persuasion in CAPD patients.

Adolescent↗

Outcome for court-referred drug-abusing male adolescents of an alternative activity treatment program in a vocational high school setting.

This is a report of outcome of an alternative activity treatment program, consisting of off-campus supportive life skill activities, in a private vocational high school for court-adjudicated delinquent boys. A total of 130 adolescent male drug abusing student-clients were evaluated at follow-up, 22 months after admission to the day school treatment program. The determination of graduation vs. dropping out was made 3 years after admission to the study. The sample was 75% white, 21% black, and 4% Hispanic. Eighty-two percent were from 16 to 18 years of age, but only 24% had completed the 10th grade. The mean number of different types of drugs "ever used" was 5.87, and the mean number of drug sale offenses was 4.4. Sixty-one percent had been incarcerated (overnight or longer). A comprehensive assessment was administered at admission and at follow-up. The findings developed by paired t-test, comparing the student-clients' self-reports at follow-up evaluation with their self-reports at pretreatment, indicated significant improvement in numerous problem areas of behavior, adjustment, and attitude measured, except that no significant reduction in illicit drug use occurred. The improvement, however, was more related to the vocational training and job placement program and the general milieu of the school than to the off-campus supportive life skills program. The latter was shown to have a highly significant positive association with outcome as measured by success in graduating from high school and a significant positive association to improvement in "personal adjustment" (reduction in personal problems and increase in interpersonal maturity).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Physical activity among minority populations: what health promotion practitioners should know--a commentary.

Leisure time and moderate-level physical activity participation in the United States is low among the majority of the population. Minority populations are especially inactive and report having fewer opportunities and access to be physically active. Physical activity programs utilizing a strong health promotion framework (including needs assessment, program plan and design, program implementation, and evaluation) are limited, particularly among minority populations. The purpose of this article is to discuss the importance of physical activity, briefly review and describe current literature, identify the need for physical activity programs among minority populations, and relate the concepts of a health promotion framework to physical activity programs that are usable among practitioners. The article also provides health promotion practitioners with various resources for improving physical activity programs.

Adolescent↗

Active treatment programs for patients with chronic low back pain: a prospective, randomized, observer-blinded study.

Several new studies have indicated that an active approach to patients with chronic disabling low back pain (LBP) seems effective. Some of these studies emphasize the importance of dealing with the patient's total situation in comprehensive multidisciplinary programs--the bio-psycho-social model. However, these programs are expensive. The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of: (1) return-to-work rate, (2) days of sick leave, (3) health-care contacts, (4) pain and disability scores, and (5) staying physically active. The subjects included 132 patients randomized to the study, of whom 123 started one of the treatment programs. They had all had at least 6 months of chronic LBP. The patients were randomized into one of three programs: group 1--a full-time, intensive 3-week multidisciplinary program, including active physical and ergonomic training and psychological pain management, followed by 1 day weekly for the subsequent 3 weeks; group 2--active physical training, twice a week for 6 weeks, for a total of 24h; group 3--psychological pain management combined with active physical training, twice a week for 6 weeks, also for a total of 24h. The results presented here are based on data collected 4 months following treatment, which shows an 86% response rate. The initial examination and the follow-up evaluation were performed by a blinded observer. The results show that 4 months after treatment, the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate, health-care contacts, pain and disability scores, and staying physically active.(ABSTRACT TRUNCATED AT 250 WORDS)

Absenteeism↗

The GENE-TOX program: genetic activity evaluation.

The GENE-TOX program, a two-phase evaluation from the existing literature of selected bioassays for detecting mutagenicity and presumptive carcinogenicity, is described. Sponsored and directed by the Office of Testing and Evaluation within the U.S. Environmental Protection Agency's (EPA) Office of Pesticides and Toxic Substances, this program will aid EPA in establishing standard genetic testing and evaluation procedures for the regulation of toxic substances and determining the direction of research and development in the area of genetic toxicology.

Animals↗

Association of obesity with physical activity, television programs and other forms of video viewing among children in Mexico city.

OBJECTIVE: To assess the association of physical activity, television program viewing and other forms of video viewing with the prevalence of obesity among school children. DESIGN: Cross-sectional study. SUBJECTS: 712 children, 9-16 y old, from a low- and a middle-income town in the Mexico City area. MEASUREMENTS: Children completed a self administered questionnaire to assess time spent in physical activity and television viewing, and diet. Height weight and triceps skinfolds were measured. The outcome variable was obesity, and the covariates were hours of television programs and other video viewing, physical activity, energy intake, percentage of energy from fat, town of location of school, age, gender and perception of mother's weight status. RESULTS: Among 461 children with complete information, 24% were classified as obese. Children reported an average of 4.1 +/- 2.2 h/d watching television (2.4 +/- 1.5 h/d for TV programs and 1.7 +/- 1.5 h/d for video cassette recorder (VCR) or videogames), and 1.8 +/- 1.3 h/d in moderate and vigorous physical activities. Odds ratios (OR) of obesity were 12% higher for each hour of television program viewing per day (OR = 1.12, 95% confidence interval (CI) 1.02,-1.22), and 10% lower for each hour of moderate/vigorous physical activity per day (OR = 0.90, 95% CI 0.83-0.98), controlling for age, gender, town and perception of mother's weight status. Children in the middle-income town had higher adjusted odds of obesity (OR = 2.58, 95% CI 1.47-4.54). CONCLUSION: Physical activity and television viewing, but not VCR/videogames use, were related to obesity prevalence in Mexican children 9-16 y old.

Adolescent↗

Does physical activity improve sleep in impaired nursing home residents?

OBJECTIVES: To determine if two physical activity programs of varying intensity would result in improved sleep among incontinent and physically restrained nursing home residents. DESIGN: Controlled trials of two physical activity programs. SETTING: Seven community nursing homes in the Los Angeles area. PARTICIPANTS: Residents were included if they had urinary incontinence or were physically restrained. Sixty-five subjects were studied. Mean age was 84.8 years, 85% were female, mean length of residency in the nursing home was 19.9 months, and mean Mean Mini-Mental State Exam score was 13.1. INTERVENTION: The first physical activity program involved sit-to-stand repetitions and/or transferring and walking or wheelchair propulsion. These activities were performed every 2 hours during the daytime, 5 days per week for 9 weeks. The second, less frequent physical activity program involved rowing in a wheelchair-accessible rowing machine plus walking or wheelchair propulsion once per day three times per week for 9 weeks. MEASUREMENTS: The physical function measures reported here include mobility endurance (maximum time walking or wheeling) and physical activity as measured by motion sensors (Caltrac). Nighttime sleep was estimated by wrist activity monitors. Nighttime sleep measures included total time asleep, percent sleep, average duration of sleep, and peak duration of sleep. Daytime sleep was measured by timed behavioral observations of sleep versus wakefulness performed every 15 minutes during the day. RESULTS: Nighttime sleep was markedly disrupted in both groups at baseline. Across all subjects at baseline, the average total sleep time was 6.2 hours and the percent sleep was 72.0%, but the average duration of sleep episodes was only 21.2 minutes and the peak duration of sleep episode averaged only 83.8 minutes. During the daytime, subjects were observed asleep during 14.5% of observations. Although there was improvement in mobility endurance in the intervention subjects compared with controls (MANOVA F = 4.36, P = .042), there were no differences in the night and day sleep measures at follow-up testing. Even among a subgroup of intervention subjects who showed a 30% or greater improvement in mobility endurance, sleep did not improve at follow-up compared with baseline. CONCLUSION: This study supports our previous findings of marked sleep disruption in impaired nursing home residents. In addition, despite documented improvements in physical function with activity, we did not find improvements in sleep in the intervention versus control groups. These results suggest that increasing daytime physical activity alone is not adequate to improve sleep in impaired NH residents. Future efforts to improve sleep in this population should take into account the multifactorial nature of sleep disruption, including individual health problems that effect sleep and the disruptive nature of the nighttime NH environment.

Aged↗

Differences in psychosocial determinants of physical activity in older adults participating in organised versus non-organised activities.

BACKGROUND: With the introduction of the new consensus on 30 minutes of moderate physical activity preferably on all days of the week, exercise implemented into daily activities is promoted whereas structured activity programs lose importance. Activity levels of most older people don't come up with current recommendations. Therefore strategies to enhance attendance of older adults in physical activities should be developed. Group programs may be more effective in changing exercise behaviour of older adults than non-supervised physical activity. The purpose of this study was to investigate the differences in level of activity and psychosocial determinants of physical activity between seniors involved in an exercise class and seniors not engaged in any organised physical activity. METHODS: Seventy-five elderly who were currently involved in structured exercise classes and 75 elderly who did not participate in any organised physical activity during the previous year were recruited in senior citizens' centres and were asked to fill out a questionnaire. RESULTS: Subjects involved in an exercise program had higher levels of activity and reported more social influences and higher self-efficacy compared to the respondents practising on an individual basis. No differences were found in perceived barriers or benefits. CONCLUSIONS: Exercising in a group program gives the opportunity to accumulate some extra physical activity and positively affects the level of activity outside the program. Stimulating older adults to join a structured activity program in the company of family or friends in order to enhance supporting social influences and perceived competence could be an important intervention strategy.

Aged↗

Physical activities: teaming up patients and programs.

Physical activities programs are suggested for the average deconditioned individual over 35 years of age. They involve noncontact, noncompetitive aerobic activities which require minimal expense. Their purpose is to delay to some degree the progression of the degenerative diseases associated with aging and inactivity. The best activities are walking, running, bicycling, or other exercise in which a sustained cardiac rate of 70% of the individual's work capacity is achieved.

Adult↗

An evaluation of substance abuse aftercare program for homeless women with children using confounding variable-control design.

An outcome evaluation of a substance abuse aftercare program for homeless women with children was conducted using confounding variable-control evaluation design. The confounding variables are chosen from pre-treatment and other contextual variables of the clients that are known to have significant influence on the program outcome, but those that could not have been influenced a priori by the client involvement in in-treatment program activity at Transition House (TH). The latter is the independent variable of this evaluation design. The pre-treatment variables are measured by severity of alcohol and other drug (AOD) problems of the clients, their mental health status, age, and their job status before enrollment in the program. The contextual confounding variables are composed of family and social support available to the clients before and during recovery. While applying multiple regression analysis, we were able to explain 50.8% of the total variance in program outcome by four pre-treatment variables. By adding two contextual variables of family and social support, the total variance in program outcome explained is increased to 64.1%. Finally, by adding the degree of client involvement in in-treatment program activity, we were able to augment the total variance of the program outcome to 69.7%. By estimating the changed variance of program outcome by the in-treatment program activity during the final step, controlling for all other variables previously entered, we were able to establish that client involvement in in-treatment program had unique and positive impact on the program outcome distinct from those explained by the confounding variables. The additional variance uniquely added by in-treatment program activity is 5.6% (p < .001). It has been determined that the degree of client involvement in in-treatment program had positive and systematic impact on the program outcome.

Adult↗