Suppressor T-cell activity in responder x nonresponder (C57BL/10 x DBA/1)F(1) spleen cells responsive to l-glutamic acid(60)-L-alanine(30)-L-tyrosine (10)

The ability of spleen cells from (responder X nonresponder)F(1) mice immunized with various GAT-Mφ, GAT-MBSA, and soluble GAT to develop IgG GAT-specific PFC responses in vitro after stimulation with responder and nonresponder parental and F(1) GAT-Mφ, was investigated. F(1) spleen cells from mice immunized with F(1) GAT-Mφ or GAT-MBSA developed secondary responses to responder and nonresponder parental and F(1) GAT- Mφ, but not to unrelated third party GAT-Mφ. Spleen cells from F(1) mice immunized with either parental GAT-Mφ developed secondary responses to F(1) GAT-Mφ and only the parental GAT-Mφ used for immunization in vivo. Soluble GAT-primed F(1) spleen cells responded to F(1) and responder parental, but not nonresponder parental, GAT-Mφ. Simultaneous immunization in vivo with the various GAT-Mφ or GAT-MBSA plus soluble GAT modulated the response pattern of these F(1) spleen cells such that they developed secondary responses only to F(1) and parental responder GAT-Mφ regardless of the response pattern observed after immunization with the various GAT-Mφ or GAT-MBSA alone. These observations demonstrate the critical importance of the physical state of the GAT used for immunization in determining the subsequent response pattern of immune F(1) spleen cells to the parental and F(1) GAT-Mφ. Further, suppressor T cells, capable of inhibiting primary responses to GAT by virgin F(1) spleen cells stimulated by nonresponder parental GAT-Mφ, were demonstrated in spleens of F(1) mice immunized with soluble GAT, but not those primed with F(1) GAT-Mφ. Because responder parental mice develop both helper and suppressor T cells after immunization with GAT-Mφ, and soluble GAT preferentially stimulates suppressor T cells whereas GAT-Mφ stimulate helper T cells in nonresponder parental mice, these observations suggest that distinct subsets of T cells exist in F(1) mice which behave phenotypically as responder and nonresponder parental T cells after immunization with soluble GAT and GAT- Mφ

A Model of Temporal Intensity Modulation for Laser Generated Ultrasound

Q-switched lasers are often used as a non-contact ultrasound source in non-destructive evaluation (NDE) of materials [1]. Q-switched lasers typically have ns pulse durations and generate broadband ultrasound waves, though longer laser pulses, of 100 microseconds or greater, have also been used [2] for NDE. These longer pulses tend to produce somewhat lower center frequencies than do Q-switched pulses, though they are still a broadband source. But it would be desirable in some NDE applications to narrow the signal bandwidth to improve the signal to noise ration (SNR), and also to have direct control over the center frequency of the generated ultrasound. In principle, this may be achieved by temporal [3,4] or spatial modulation [5,6] of the laser pulse, or both [7]. The purpose of this work was to develop a numerical model of a single, temporally modulated laser source of ultrasound in the thermoelastic regime, for isotropic metals

Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development

Evaluation of the use of Global Youth Tobacco Survey (GYTS) data for developing evidence-based tobacco control policies in Turkey

Introduction The tobacco control effort in Turkey has made significant progress in recent years. Turkey initiated its tobacco control effort with the passing of Law 4207 (The Prevention of Harmful Effects of Tobacco Products) in 1996 and ratified the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) in 2004. It is important to base policy decisions on valid and reliable evidence from population-based, representative studies that are periodically repeated to enable policy makers to monitor the results of their interventions and to appropriately tailor anti-tobacco activities towards future needs. Methods The Global Youth Tobacco Survey (GYTS) was developed to track tobacco use among young people and enhance the capacity of countries to design, implement, and evaluate tobacco control and prevention programs. Turkey conducted the GYTS in 2003 and data from this survey can be used as baseline measures for evaluation of the tobacco control programs implemented by the Ministry of Health (MOH) of the Turkish government. Results The GYTS was conducted in 2003 on a representative sample of students aged 13 to 15 years. It indicated that almost 3 in 10 students in Turkey had ever smoked cigarettes, with significantly higher rates among boys. Current cigarette smoking rates were lower, at 9% for boys and 4% for girls. The prevalence of current use of other tobacco products was about half these figures for each gender. About 80% were exposed to secondhand smoke. Exposure to pro-smoking media messages was not rare. Almost half of the smokers 'usually' bought their tobacco from a store, despite the law prohibiting this. Exposure to teaching against smoking in schools was not universal. Conclusion Findings from the GYTS, with periodic repeats of the survey, can be used to monitor the impact of enforcing various provisions of the present law (No: 4207), the progress made in achieving the goals of the WHO FCTC, and the effectiveness of various preventive interventions against smoking. Such data would inform and help in the development of public health strategy.PubMedWoSScopu

Tobacco use among students aged 13–15 years in Greece: the GYTS project

BACKGROUND: Data on the prevalence of tobacco use among teenagers in Greece are limited. We examined the prevalence of smoking among middle-school students in Greece using the Global Youth Tobacco Survey (GYTS). METHODS: The Global Youth Tobacco Survey was implemented in Greece during the academic year 2004 – 2005 by the University of Thessaly and the National School of Public Health. Data were collected using the GYTS self-administered anonymous questionnaire, which was distributed by specifically trained field workers to a nationally representative sample of middle-school students aged 13–15 years (through randomly selected schools and classes), randomly selected through a two-stage cluster sample design. Data processing and statistical analyses were performed at the Centers for Disease Control and Prevention (CDC). RESULTS: About one third of the students 32.1% (29.4 – 35.0) reported that they had tried tobacco in the past, while 16.2% (14.3 – 18.4) reported being current users of tobacco products. In addition, 1 in 4 of ever smokers reported that they began smoking before the age of 10 years old. Almost 1 in 5 never smokers reported being susceptible to initiate smoking in the next year and about 89.8% (88.3 – 91.1) of the respondents were exposed to environmental tobacco smoke in their homes and 94.1% (93.2 – 94.9) in public places. Finally, a strikingly high number of students 95% (89.5 – 97.7) reported that they were able to buy their own cigarettes without restrictions. CONCLUSION: The results of the GYTS show that the prevalence of smoking in middle-school children is alarmingly high in Greece. Smoking among young people constitutes a significant problem that is destined to worsen in the absence of any comprehensive efforts focused on strict anti-smoking legislation, policies and tobacco control interventions targeting children at a young age

Dosimetric consequences of the shift towards computed tomography guided target definition and planning for breast conserving radiotherapy

Background: The shift from conventional two-dimensional (2D) to three-dimensional (3D)conformal target definition and dose-planning seems to have introduced volumetric as well as geometric changes. The purpose of this study was to compare coverage of computed tomography (CT)-based breast and boost planning target volumes (PTV), absolute volumes irradiated, and dose delivered to the organs at risk with conventional 2D and 3D-conformal breast conserving radiotherapy. Methods: Twenty-five patients with left-sided breast cancer were subject of CT-guided target definition and 3D-conformal dose-planning, and conventionally defined target volumes and treatment plans were reconstructed on the planning CT. Accumulated dose-distributions were calculated for the conventional and 3D-conformal dose-plans, taking into account a prescribed dose of 50 Gy for the breast plans and 16 Gy for the boost plans. Results: With conventional treatment plans, CT-based breast and boost PTVs received the intended dose in 78% and 32% of the patients, respectively, and smaller volumes received the prescribed breast and boost doses compared with 3D-conformal dose-planning. The mean lung dose, the volume of the lungs receiving > 20 Gy, the mean heart dose, and volume of the heart receiving > 30 Gy were significantly less with conventional treatment plans. Specific areas within the breast and boost PTVs systematically received a lower than intended dose with conventional treatment plans. Conclusion: The shift towards CT-guided target definition and planning as the golden standard for breast conserving radiotherapy has resulted in improved target coverage at the cost of larger irradiated volumes and an increased dose delivered to organs at risk. Tissue is now included into the breast and boost target volumes that was never explicitly defined or included with conventional treatment. Therefore, a coherent definition of the breast and boost target volumes is needed, based on clinical data confirming tumour control probability and normal tissue complication probability with the use of 3D-conformal radiotherapy

Survival in Norwegian BRCA1 mutation carriers with breast cancer

Several studies of survival in women with BRCA1 mutations have shown either reduced survival or no difference compared to controls. Programmes for early detection and treatment of inherited breast cancer, have failed to demonstrate a significant improvement in survival in BRCA1 mutation carriers

Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

e Glasgow and Manchester Experimental Cancer Medicine Centres (ECMC), which are funded by CR-UK and the Chief Scientist’s Office (Scotland). We acknowledge the funders who have contributed to this work: MRC stratified medicine infrastructure award (A.D.W.), CR-UK C11074/A11008 (F.P., L.E.M.H., T.L.H., A.D.W.); LLR08071 (S.A.A., E.C.); LLR11017 (M.C.); SCD/04 (M.C.); LLR13035 (S.A.A., K.D., A.D.W., and A.P.); LLR14005 (M.T.S., D.V.); KKL690 (L.E.P.); KKL698 (P.B.); LLR08004 (A.D.W., A.P. and A.J.W.); MRC CiC (M.E.D.); The Howat Foundation (FACS support); Friends of Paul O’Gorman (K.D. and FACS support); ELF 67954 (S.A.A.); BSH start up fund (S.A.A.); MR/K014854/1 (K.D.)

Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells

authorHypoxia inducible factor-1 (HIF-1) is considered a crucial mediator of the cellular response to hypoxia through its regulation of genes that control angiogenesis^1, ^2, ^3, ^4. It represents an attractive therapeutic target^5, ^6 in colon cancer, one of the few tumor types that shows a clinical response to antiangiogenic therapy^7. But it is unclear whether inhibition of HIF-1 alone is sufficient to block tumor angiogenesis^8, ^9. In HIF-1_α knockdown DLD-1 colon cancer cells (DLD-1^HIF-kd), the hypoxic induction of vascular endothelial growth factor (VEGF) was only partially blocked. Xenografts remained highly vascularized with microvessel densities identical to DLD-1 tumors that had wild-type HIF-1_α (DLD-1^HIF-wt). In addition to the preserved expression of VEGF, the proangiogenic cytokine interleukin (IL)-8 was induced by hypoxia in DLD-1^HIF-kd but not DLD-1^HIF-wt cells. This induction was mediated by the production of hydrogen peroxide and subsequent activation of NF-_KB. Furthermore, the KRAS oncogene, which is commonly mutated in colon cancer, enhanced the hypoxic induction of IL-8. A neutralizing antibody to IL-8 substantially inhibited angiogenesis and tumor growth in DLD-1^HIF-kd but not DLD-1^HIF-wt xenografts, verifying the functional significance of this IL-8 response. Thus, compensatory pathways can be activated to preserve the tumor angiogenic response, and strategies that inhibit HIF-1α may be most effective when IL-8 is simultaneously targeted