bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells
Authors: Choi Hyun Ju , Lim Do Young , Park Jung Han Yoon 
Published: June 2009

AbstractBackground3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in bothin vivoandin vitromodels. We have previously determined that DIM (0 – 30 μmol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells.MethodsHT-29 cells were cultured with various concentrations of DIM (0 – 30 μmol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation andin vitrokinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted.ResultsThe percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1.ConclusionHere, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.
A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth
Authors: Mita Hiroaki , Toyota Minoru , Aoki Fumio , Akashi Hirofumi , Maruyama Reo , Sasaki Yasushi , Suzuki Hiromu , Idogawa Masashi , Kashima Lisa , Yanagihara Kazuyoshi , Fujita Masahiro , Hosokawa Masao , Kusano Masanobu , Sabau Sorin Vasile , Tatsumi Haruyuki , Imai Kohzoh , Shinomura Yasuhisa , Tokino Takashi 
Published: June 2009

AbstractBackgroundGastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations ofKRASare infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells.MethodsDGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors forKRASamplification by quantitative PCR, and investigatedKRASamplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect ofKRASknock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively.ResultsDGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains theKRASgene locus. Amplification of theKRASlocus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification).KRASmutations were identified in two of the three cell lines in whichKRASwas amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increasedKRAScopy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-typeKRAS, but not in cells with amplified mutantKRAS. Knock-down ofKRASin gastric cancer cells that carried amplified wild-typeKRASresulted in the inhibition of cell growth and suppression of p44/42 MAP kinase and AKT activity.ConclusionOur study highlights the utility of DGS for identification of copy-number alterations. Using DGS, we identifiedKRASas a gene that is amplified in human gastric cancer. We demonstrated that gene amplification likely forms the molecular basis of overactivation of KRAS in gastric cancer. Additional studies using a larger cohort of gastric cancer specimens are required to determine the diagnostic and therapeutic implications ofKRASamplification and overexpression.
Health beliefs about bottled water: a qualitative study
Authors: Ward Lorna A , Cain Owen L , Mullally Ryan A , Holliday Kathryn S , Wernham Aaron GH , Baillie Paul D , Greenfield Sheila M 
Published: June 2009

Abstract

Background
There has been a consistent rise in bottled water consumption over the last decade. Little is known about the health beliefs held by the general public about bottled water as this issue is not addressed by the existing quantitative literature. The purpose of this study was to improve understanding of the public's health beliefs concerning bottled mineral water, and the extent to which these beliefs and other views they hold, influence drinking habits.

Methods
A qualitative study using semi-structured interviews, with 23 users of the Munrow Sports Centre on the University of Birmingham campus.

Results
Health beliefs about bottled water could be classified as general or specific beliefs. Most participants believed that bottled water conferred general health benefits but were unsure as to the nature of these. In terms of specific health beliefs, the idea that the minerals in bottled water conferred a health benefit was the most commonly cited. There were concerns over links between the plastic bottle itself and cancer. Participants believed that bottled water has a detrimental effect on the environment. Convenience, cost and taste were influential factors when making decisions as to whether to buy bottled water; health beliefs were unimportant motivating factors.

Conclusion
The majority of participants believed that bottled water has some health benefits. However, these beliefs played a minor role in determining bottled water consumption and are unlikely to be helpful in explaining recent trends in bottled water consumption if generalised to the UK population. The health beliefs elicited were supported by scientific evidence to varying extents. Most participants did not feel that bottled water conferred significant, if any, health benefits over tap water.
Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons
Authors: Schutgens Christine AE , Schuring Merel , Voorham Toon AJ , Burdorf Alex 
Published: June 2009

Abstract

Background
The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health.

Methods
A longitudinal, non-controlled design was used. The programme consisted of two weekly exercise sessions and one weekly cognitive session during 12 weeks. The main outcome measures were body mass index, blood pressure, cardiorespiratory fitness, abdominal muscle strength, and low back and hamstring flexibility. Potential determinants of change in physical health were demographic variables, psychological variables (self-esteem, mastery, and kinesiophobia), and self-perceived health.

Results
The initial response was 73% and 252 persons had complete data collection at baseline. In total, 36 subjects were lost during follow-up. Participants were predominantly low educated, long-term unemployed, and in poor health. Participation in the programme was not influenced by demographic and psychological factors or by self-reported health. Drop-outs were younger and had a lower body mass index at baseline than subjects who completed the programme. At post-test, participants' cardiorespiratory fitness, abdominal muscle strength, and flexibility had increased by 6.8%–51.0%, whereas diastolic and systolic blood pressures had decreased by 2.2%–2.5%. The effect sizes ranges from 0.17–0.68.

Conclusion
Participants with the poorest physical health benefited most from the programme and gender differences in improvement were observed. Physical health of unemployed persons with health complaints improved after participation in this health promotion programme, but not sufficiently, considering their poor physical health at baseline.
Effectiveness of physical training for self-employed persons with musculoskeletal disorders: a randomized controlled trial
Authors: Heinrich Judith , Anema Johannes R , de Vroome Ernest MM , Blatter Birgitte M 
Published: June 2009

Abstract

Background
Despite the fact that the population of self-employed persons is still growing and at risk for long term disability due to a number of risk factors, there is still a lack of information on the effectiveness of interventions for this specific group.

Methods
To determine the effectiveness of physical training without a cognitive behavioral component and workplace specific exercises (PT) and physical training with a cognitive behavioral component and workplace specific exercises (PTCBWE), we conducted a pragmatic Randomized Controlled Trial, stratified into two groups. Self-employed persons with a new work disability claim because of musculoskeletal disorders were randomized to PT (n = 53) or PTCBWE (n = 76), or to a corresponding usual care group (n = 50 and n = 75 respectively). Both types of training consisted of cardiovascular training, strengthening, relaxation and posture exercises and took place two or three times a week, for 1–1.5 hours, during three months, also if someone had already returned to work full-time. The primary outcome measure was claim duration (in days) during 12 months follow-up. Pain severity and functional status were secondary outcome measures. All data were assessed at baseline and at 6 and 12 months follow-up. The data with regard to claim duration were analyzed by survival analysis and Cox regression analysis. Secondary outcome measures were analyzed by means of linear regression analysis.

Results
After 12 months of follow-up there was no difference in claim duration between PT and usual care (Hazard Ratio 0.7; 95%CI, 0.4–1.1; p = 0.12) or PTCBWE and usual care (Hazard Ratio 0.9; 95%CI, 0.6–1.4; p = 0.72). Both types of physical training and usual care improved in pain and functional status over time, but there was only a statistically significant difference in favor of PT on pain improvement at 6 months.

Conclusion
In this study, physical training with and without a cognitive behavioral component and workplace specific exercises for self-employed persons with musculoskeletal disorders was not shown to be effective on claim duration, pain severity and functional status at 12 months follow-up.

Trial registration
Current Controlled Trials ISRCTN67766245.
Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women
Authors: Zaros Pedro R , Pires Carla EM Romero , Bacci Mauricio , Moraes Camila , Zanesco Angelina 
Published: June 2009

Abstract

Background
Evidences have showed that the incidence of arterial hypertension is greater in postmenopausal women as compared to premenopausal. Physical inactivity has been implicated as a major contributor to weight gain and abdominal obesity in postmenopausal women and the incidence of cardiovascular disease increases dramatically after menopause. Additionally, more women than men die each year of coronary heart disease and are twice as likely as men to die within the first year after a heart attack. A healthy lifestyle has been strongly associated with the regular physical activity and evidences have shown that physically active subjects have more longevity with reduction of morbidity and mortality. Nitric oxide (NO) produced by endothelial cells has been implicated in this beneficial effect with improvement of vascular relaxing and reduction in blood pressure in both laboratory animals and human. Although the effect of exercise training in the human cardiovascular system has been largely studied, the majority of these studies were predominantly conducted in men or young volunteers. Therefore, the aim of this work was to investigate the effects of 6 months of dynamic exercise training (ET) on blood pressure and plasma nitrate/nitrite concentration (NOx-) in hypertensive postmenopausal women.

Methods
Eleven volunteers were submitted to the ET consisting in 3 days a week, each session of 60 minutes during 6 months at moderate intensity (50% of heart rate reserve). Anthropometric parameters, blood pressure, NOx- concentration were measured at initial time and after ET.

Results
A significant reduction in both systolic and diastolic blood pressure values was seen after ET which was accompanied by markedly increase of NOx- levels (basal: 10 ± 0.9; ET: 16 ± 2 μM). Total cholesterol was significantly reduced (basal: 220 ± 38 and ET: 178 ± 22 mg/dl), whereas triglycerides levels were not modified after ET (basal: 141 ± 89 and ET: 147 ± 8 mg/dl).

Conclusion
Our study shows that changing in lifestyle promotes reduction of arterial pressure which was accompanied by increase in nitrite/nitrate concentration. Therefore, 6-months of exercise training are an important approach in management arterial hypertension and play a protective effect in postmenopausal women.
Plasmodium falciparum genotypes diversity in symptomatic malaria of children living in an urban and a rural setting in Burkina Faso
Authors: Soulama Issiaka , Nébié Issa , Ouédraogo Alphonse , Gansane Adama , Diarra Amidou , Tiono Alfred B , Bougouma Edith C , Konaté Amadou T , Kabré Gustave B , Taylor Walter RJ , Sirima Sodiomon B 
Published: June 2009

Abstract

Background
The clinical presentation of malaria, considered as the result of a complex interaction between parasite and human genetics, is described to be different between rural and urban areas. The analysis of the Plasmodium falciparum genetic diversity in children with uncomplicated malaria, living in these two different areas, may help to understand the effect of urbanization on the distribution of P. falciparum genotypes.

Methods
Isolates collected from 75 and 89 children with uncomplicated malaria infection living in a rural and an urban area of Burkina Faso, respectively, were analysed by a nested PCR amplification of msp1 and msp2 genes to compare P. falciparum diversity.

Results
The K1 allelic family was widespread in children living in the two sites, compared to other msp1 allelic families (frequency >90%). The MAD 20 allelic family of msp1 was more prevalent (p = 0.0001) in the urban (85.3%) than the rural area (63.2%). In the urban area, the 3D7 alleles of msp2 were more prevalent compared to FC27 alleles, with a high frequency for the 3D7 300bp allele (>30%). The multiplicity of infection was in the range of one to six in the urban area and of one to seven in the rural area. There was no difference in the frequency of multiple infections (p = 0.6): 96.0% (95% C.I: 91.6–100) in urban versus 93.1% (95%C.I: 87.6–98.6) in rural areas. The complexity of infection increased with age [p = 0.04 (rural area), p = 0.06 (urban area)].

Conclusion
Urban-rural area differences were observed in some allelic families (MAD20, FC27, 3D7), suggesting a probable impact of urbanization on genetic variability of P. falciparum. This should be taken into account in the implementation of malaria control measures.
Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells
Authors: Liu Tongzheng , Schneider Ryan A , Shah Vaibhav , Huang Yongcheng , Likhotvorik Rostislav I , Keshvara Lakhu , Hoyt Dale G 
Published: June 2009

Abstract

Background
The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1), regulates turnover of inducible nitric oxide synthase (iNOS) in murine aortic endothelial cells (MAEC) stimulated with E. coli endotoxin (LPS) and interferon-γ (IFN). Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX)-2, in MAEC.

Methods
MAEC, transduced with lentivirus encoding an inactive control short hairpin (sh) RNA or one targeting PIN1 that reduced PIN1 by 85%, were used. Cells were treated with LPS/IFN, calpain inhibitors (carbobenzoxy-valinyl-phenylalaninal (zVF), PD150606), cycloheximide and COX inhibitors to determine the effect of PIN1 depletion on COX-2 and calpain.

Results
LPS or IFN alone did not induce COX-2. However, treatment with 10 μg LPS plus 20 ng IFN per ml induced COX-2 protein 10-fold in Control shRNA MAEC. Induction was significantly greater (47-fold) in PIN1 shRNA cells. COX-2-dependent prostaglandin E2 production increased 3-fold in KD MAEC, but did not increase in Control cells. The additional increase in COX-2 protein due to PIN1 depletion was post-transcriptional, as induction of COX-2 mRNA by LPS/IFN was the same in cells containing or lacking PIN1. Instead, the loss of COX-2 protein, after treatment with cycloheximide to block protein synthesis, was reduced in cells lacking PIN1 in comparison with Control cells, indicating that degradation of the enzyme was reduced. zVF and PD150606 each enhanced the induction of COX-2 by LPS/IFN. zVF also slowed the loss of COX-2 after treatment with cycloheximide, and COX-2 was degraded by exogenous μ-calpain in vitro. In contrast to iNOS, physical interaction between COX-2 and PIN1 was not detected, suggesting that effects of PIN1 on calpain, rather than COX-2 itself, affect COX-2 degradation. While cathepsin activity was unaltered, depletion of PIN1 reduced calpain activity by 55% in comparison with Control shRNA cells.

Conclusion
PIN1 reduced calpain activity and slowed the degradation of COX-2 in MAEC, an effect recapitulated by an inhibitor of calpain. Given the sensitivity of COX-2 and iNOS to calpain, PIN1 may normally limit induction of these and other calpain substrates by maintaining calpain activity in endothelial cells.
Conflicting priorities: evaluation of an intervention to improve nurse-parent relationships on a Tanzanian paediatric ward
Authors: Manongi Rachel N , Nasuwa Fortunata R , Mwangi Rose , Reyburn Hugh , Poulsen Anja , Chandler Clare IR 
Published: June 2009

Abstract

Background
Patient, or parent/guardian, satisfaction with health care provision is important to health outcomes. Poor relationships with health workers, particularly with nursing staff, have been reported to reduce satisfaction with care in Africa. Participatory research approaches such as the Health Workers for Change initiative have been successful in improving provider-client relationships in various developing country settings, but have not yet been reported in the complex environment of hospital wards. We evaluated the HWC approach for improving the relationship between nurses and parents on a paediatric ward in a busy regional hospital in Tanzania.

Methods
The intervention consisted of six workshops, attended by 29 of 31 trained nurses and nurse attendants working on the paediatric ward. Parental satisfaction with nursing care was measured with 288 parents before and six weeks after the workshops, by means of an adapted Picker questionnaire. Two focus-group discussions were held with the workshop participants six months after the intervention.

Results
During the workshops, nurses demonstrated awareness of poor relationships between themselves and mothers. To tackle this, they proposed measures including weekly meetings to solve problems, maintain respect and increase cooperation, and representation to administrative forces to request better working conditions such as equipment, salaries and staff numbers. The results of the parent satisfaction questionnaire showed some improvement in responsiveness of nurses to client needs, but overall the mean percentage of parents reporting each of 20 problems was not statistically significantly different after the intervention, compared to before it (38.9% versus 41.2%). Post-workshop focus-group discussions with nursing staff suggested that nurses felt more empathic towards mothers and perceived an improvement in the relationship, but that this was hindered by persisting problems in their working environment, including poor relationships with other staff and a lack of response from hospital administration to their needs.

Conclusion
The intended outcome of the intervention was not met. The priorities of the intervention – to improve nurse-parent relationships – did not match the priorities of the nursing staff. Development of awareness and empathy was not enough to provide care that was satisfactory to clients in the context of working conditions that were unsatisfactory to nurses.
Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models
Authors: Xie Ke , Bai Rui-Zhen , Wu Yang , Liu Quan , Liu Kang , Wei Yu-Quan 
Published: June 2009

AbstractBackgroundVascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (Flk-1/KDR), play a key role in tumor angiogenesis. Blocking the VEGF-VEGFR-2 pathway may inhibit tumor growth. Here, we used human VEGFR-2 as a model antigen to explore the feasibility of immunotherapy with a plasmid DNA vaccine based on a xenogeneic homologue of this receptor.MethodsThe protective effects and therapeutic anti-tumor immunity mediated by the DNA vaccine were investigated in mouse models. Anti-angiogenesis effects were detected by immunohistochemical staining and the alginate-encapsulate tumor cell assay. The mechanism of action of the DNA vaccine was primarily explored by detection of auto-antibodies and CTL activity.ResultsThe DNA vaccine elicited a strong, protective and therapeutic anti-tumor immunity through an anti-angiogenesis mechanism in mouse models, mediated by the stimulation of an antigen-specific response against mFlk-1.ConclusionOur study shows that a DNA vaccine based on a xenogeneic homologue plasmid DNA induced autoimmunity against VEGFR-2, resulting in inhibition of tumor growth. Such vaccines may be clinically relevant for cancer immunotherapy.