16 results on '"Szynal M"'
Search Results
2. CD154 Costimulated Ovine Primary B Cells, a Cell Culture System That Supports Productive Infection by Bovine Leukemia Virus
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Van den Broeke, A., primary, Cleuter, Y., additional, Beskorwayne, T., additional, Kerkhofs, P., additional, Szynal, M., additional, Bagnis, C., additional, Burny, A., additional, and Griebel, P., additional
- Published
- 2001
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3. Complete suppression of viral gene expression is associated with the onset and progression of lymphoid malignancy: observations in Bovine Leukemia Virus-infected sheep
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Burny Arsène, Kerkhofs Pierre, Bagnis Claude, Cleuter Yvette, Szynal Maud, Klener Pavel, Merimi Makram, Martiat Philippe, and Van den Broeke Anne
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background During malignant progression, tumor cells need to acquire novel characteristics that lead to uncontrolled growth and reduced immunogenicity. In the Bovine Leukemia Virus-induced ovine leukemia model, silencing of viral gene expression has been proposed as a mechanism leading to immune evasion. However, whether proviral expression in tumors is completely suppressed in vivo was not conclusively demonstrated. Therefore, we studied viral expression in two selected experimentally-infected sheep, the virus or the disease of which had features that made it possible to distinguish tumor cells from their nontransformed counterparts. Results In the first animal, we observed the emergence of a genetically modified provirus simultaneously with leukemia onset. We found a Tax-mutated (TaxK303) replication-deficient provirus in the malignant B-cell clone while functional provirus (TaxE303) had been consistently monitored over the 17-month aleukemic period. In the second case, both non-transformed and transformed BLV-infected cells were present at the same time, but at distinct sites. While there was potentially-active provirus in the non-leukemic blood B-cell population, as demonstrated by ex-vivo culture and injection into naïve sheep, virus expression was completely suppressed in the malignant B-cells isolated from the lymphoid tumors despite the absence of genetic alterations in the proviral genome. These observations suggest that silencing of viral genes, including the oncoprotein Tax, is associated with tumor onset. Conclusion Our findings suggest that silencing is critical for tumor progression and identify two distinct mechanisms-genetic and epigenetic-involved in the complete suppression of virus and Tax expression. We demonstrate that, in contrast to systems that require sustained oncogene expression, the major viral transforming protein Tax can be turned-off without reversing the transformed phenotype. We propose that suppression of viral gene expression is a contributory factor in the impairment of immune surveillance and the uncontrolled proliferation of the BLV-infected tumor cell.
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- 2007
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4. Occurrence of sleep disorders and the value of body mass index of seniors and the quality of their aging.
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Dąbek J, Szynal M, and Sierka O
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- Humans, Female, Aged, Male, Middle Aged, Aged, 80 and over, Surveys and Questionnaires, Quality of Life, Body Mass Index, Sleep Wake Disorders epidemiology, Aging physiology
- Abstract
Aim: The aim of the study was to assess the occurrence of sleep disorders and the value of body mass index in seniors, taking into account their quality of aging and participation in classes at Universities of the Third Age (UTAs)., Methods: The study involved 631 (100%) seniors from the Silesian Voivodeship, aged 60 to 96 years (𝑥̅ = 70.28 ± 6.09 years). An original survey questionnaire was used, supplemented by the Successful Aging Scale and the Athens Insomnia Scale questionnaires., Results: The median of successful aging index (SAI) points obtained by UTAs "+" seniors was 11.71, while the median of SAI points obtained by UTAs "-" seniors was 11.18. Sleep disorders were more common in women than in men as well as among people aged 71-80 years compared to other groups. There were statistically significant weak negative correlations between the points obtained in Successful Aging Scale questionaire domains and the number of points in the Athens Insomnia Scale as well as body mass index value., Conclusions: The occurrence of sleep disorders and abnormally increased body weight were associated with a deterioration in the quality of aging in the studied seniors. Seniors participating in UTAs activities had a better quality of aging than people who denied participating in the mentioned activity. Actions should be constantly taken to improve the quality of the aging process of seniors, including providing them with access to contacts with other people, treating sleep disorders and educating them on the benefits of a healthy lifestyle and maintaining a proper body weight. Geriatr Gerontol Int 2025; 25: 206-212., (© 2025 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)
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- 2025
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5. Quality of Life of Patients with Heart Failure Due to Myocardial Ischemia.
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Bonek-Wytrych G, Sierka O, Szynal M, and Dąbek J
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Background: Heart failure caused by myocardial ischemia is a common cause encountered in clinical practice. A significant problem in heart failure is its progressive, unfavorable course and the associated increased frequency of repeated hospitalizations, as well as a significant deterioration in the functioning of patients, leading to their inability to function independently and a significant decline in the quality of life. This study aimed to assess the quality of life of patients with heart failure due to myocardial ischemia, considering the left ventricular ejection fraction, the number of "diseased" coronary arteries, co-occurring diseases, and cardiovascular risk factors., Methods: A total of 204 patients with decompensated heart failure due to chronic myocardial ischemia were included in this study and examined twice: A: on the first day of hospitalization; A': from 4 to 8 weeks. For the individual assessment of the quality of life, the WHOQOL-BREF (The World Health Organization Quality of Life - BREF) questionnaire was used., Results: In the group of patients with heart failure in the decompensation stage a statistically significant positive relationship was observed between the number of comorbidities and the social domain (R(A) = 0.197; p (A) = 0.005), the number of diseased coronary arteries and the mental (R(A) = 0.184; p (A) = 0.184) and environmental (R(A) = 0.149; p (A) = 0.034) domains, left ventricular ejection fraction (LVEF%) and quality of life (R(A) = 0.235; p = 0.001) and satisfaction with health (R(A) = 0.235; p = 0.001) and somatic domain (R(A) = 0.194; p = 0.005). A similar result was observed among patients in the long-term follow-up. A statistically significant negative correlation was demonstrated in the mentioned group between the LVEF% value and the social domain (R(A) = -0.235; p = 0.001), as well as in the long-term follow-up (R(A') = -0.191, p = 0.026). The level of self-assessment of quality of life and satisfaction with health was statistically significantly higher among patients with heart failure in the long-term follow-up (3.20 ± 0.62) than in patients in the decompensation stage (1.98 ± 0.69)., Conclusions: The quality of life of the examined patients with heart failure caused by chronic myocardial ischemia was poor, although it improved to average in the long-term follow-up. It was determined by left ventricular ejection fraction, the number of "diseased" coronary arteries, comorbidities, and risk factors., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)
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- 2024
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6. Frequency of back pain occurrence among high school youth including their physical activity.
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Łebek E, Dąbek J, Szynal M, and Knapik A
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- Humans, Adolescent, Male, Female, Surveys and Questionnaires, Sitting Position, Sex Factors, Students statistics & numerical data, Posture, Back Pain epidemiology, Back Pain etiology, Exercise
- Abstract
Background: Back pain diseases are among frequently reported health problems. Unfortunately, more often this problem also affects young people, high school students. Lifestyle that people are representing nowadays has a negative impact on their spine. Development of technology and transportation eliminates daily basic physical activity such as taking a walk to the school. Prolonged and inappropriate sitting posture during classes and using the computer at home are predisposing factors for back pain occurrence. The aim of this paper was to analyze the frequency of back pain occurrence among high school youth and attempt to relate their occurrence frequency with sex, time spent in sitting position, anthropometric parameters and physical activity of examined students., Methods: The examined group initially counted 272 teenagers, but ultimately 218 were taken into account for the analysis and 54 questionnaires were filled in incorrectly and rejected. All of them were high school students. Customized survey consisting of general part and closed questions regarding physical activity (subjective experience of work load) was used as an examination tool., Results: Examined youth spent on average 10.04 hours daily in a sitting position. As much as 195 (89.45%) of examined teenagers declared to experience back pain at least once in their lives. The most of teenagers (117; 53.67%) indicated lumbar spine pain. Girls more often felt spine pain issues in comparison to boys. Short stature of teenagers was often related to back pain occurrence. No correlation between time spent in sitting position and frequency of skeleton axis pain occurrence was noted. Among group of boys a relation between more frequent physical activity and less often spine pain occurrence was observed., Conclusions: Spine pain is an important health problem of examined youth, occurring more frequent among girls than boys. Body height correlate negatively with frequency of spine pain occurrence among youth. Despite spending more than 10 hours daily in sitting position by examined youth, it did not affect the frequency of back pain issues occurrence. Higher physical activity of examined boys was related to less often back pains.
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- 2024
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7. Has learning gone to waste?-Health-promoting behaviors of seniors.
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Dąbek J, Szynal M, Sierka O, Łebek E, and Kulik H
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- Humans, Female, Male, Aged, Middle Aged, Aged, 80 and over, Surveys and Questionnaires, Poland, Alcohol Drinking, Feeding Behavior, Universities, Health Behavior, Exercise, Health Promotion
- Abstract
Objective: Regardless of the fact that Universities of Third Age (UTA's) are becoming more and more popular among seniors there are not many available studies examining the impact of conducted educational activities on seniors' adherence to health-promoting activities. The aim of the study was to compare health behaviors (e.g.,: physical activity, eating habits, alcohol consumption, tobacco smoking, preventive tests performance) between seniors attending and not attending UTA's classes., Methods: The study involved 631 (100%) seniors aged 60-92 years (x =70.28 ± 6.09 years). The majority of the study group were women (475; 75.28%). To conduct the study, a proprietary questionnaire was used, consisting of questions regarding the discussed topic and basic questions including: age, gender, place of residence and education. Polish versions of standardized questionnaire-" My eating behaviors" examine eating behaviors of the respondents. The Chi
2 test was used for qualitative data, and for quantitative data-the Mann-Whitney U test (No normal distribution: T S-W < 0.001). Linear and logistic regression models were used to check whether the associations would remain after adjustments for potential cofounders. The level of statistical significance was set at α < 0.05., Results: Number of seniors participating in UTA's activities was higher in terms of engaging in: actively spending free time (261; 73.73% vs. 93; 26.27%; p < 0.001), regular physical activity (270; 76.27% vs. 133; 48.01%; p < 0.001), self-assessment of physical activity (259; 73.16% vs. 95; 26.84%; p = 0.004), duration of physical activity (< 0.001), past tobacco smoking (133; 37.57 vs. 76; 27.44%; p = 0.007) and alcohol consumption depending on the habit frequency ( p < 0.001). Number of seniors not participating in UTA's classes was lower in terms of: regular annual dental controls (161; 58.12%; vs. 265; 74.86%; p < 0.001), regular self-examination of breasts/testicles (148; 53.43% vs. 218; 61.58%; p = 0.04) and regular laboratory tests (232; 83.75% vs. 318; 89.83%; p = 0.02)., Conclusions: Health-promoting behaviors of seniors attending classes at the UTA's were more correct in terms of physical activity, adequate attendance with preventive test and worst in terms of alcohol consumption. Overall picture allows to conclude that participation in UTA's classes seems to have a positive impact on the examined health-promoting behaviors of the surveyed seniors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dąbek, Szynal, Sierka, Łebek and Kulik.)- Published
- 2024
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8. Do the Gender and the Number of Comorbidities and the Use of Tertiary Prevention Play a Role in the Severity of Anxiety and Depression in Patients with Coronary Artery Disease? A POLASPIRE II Study.
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Dąbek J, Gąsior Z, Styczkiewicz M, Kubica A, Kosior DA, Wolfshaut-Wolak R, Rajzer M, Szynal M, Jankowski P, and Kamiński K
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Background/Objectives: The need to conduct research on anxiety and depression in patients with coronary artery disease in connection with factors such as gender or implemented tertiary prevention is very important for drawing practical conclusions and, consequently, implementing new recommendations and procedures. The aim of the study was to attempt to answer the question whether gender and the number of comorbidities, as well as the application of tertiary prevention principles, play a role in the severity of anxiety and depression in the studied group of patients with coronary artery disease. Material: The study involved 765 patients from 11 Polish cardiology centers. The presented material is part of the multicenter POLASPIRE II study. Methods : All patients completed The Hospital Anxiety and Depression Scale (HADS) questionnaire, and a medical interview was conducted with them. Conclusions: Although the intensity of anxiety and depression in the studied group of patients was low, gender differentiated them, which, however, did not influence undertaking tertiary prevention activities. In the study group of patients, the number of comorbidities and cardiac incidents/procedures after the event qualifying for the study, as well as preventive actions undertaken, were not associated with the severity of anxiety and depression. In the studied group of patients with coronary heart disease, there was still a large group of people who did not take preventive measures. Therefore, there is a need for systematic education regarding the benefits of implementing them to prevent the progression of the disease and premature death.
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- 2024
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9. Quality of Life in Patients with Coronary Artery Disease-Multicenter POLASPIRE II Study.
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Dąbek J, Styczkiewicz M, Kamiński K, Kubica A, Kosior DA, Wolfshaut-Wolak R, Rajzer M, Szynal M, Jankowski P, and Gąsior Z
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Background : The quality of life of patients with coronary heart disease is extremely important for their treatment. The aim of the study was to assess the quality of life of patients with coronary artery disease, considering education and compliance with medical recommendations regarding lifestyle changes, as well as the presence of selected cardiovascular risk factors. Methods: The study involved 763 patients from 11 Polish cardiology centers. The presented material is part of the multicenter POLASPIRE II study. Patients completed a standardized questionnaire EuroQol 5D-5Lm. A medical interview was conducted with each patient. All patients had their body weight and height measured and BMI determined. Results: The quality of life of patients was better in men, younger people, those with lower body weight and those who followed preventive recommendations and intensified their physical activity. Most of the examined patients complied with the medical recommendations regarding lifestyle changes after a cardiac incident, but they mainly concerned dietary modifications. There was still a large group of patients who did not comply with the recommendations, e.g., regarding increasing physical activity. Conclusions: The assessment of quality of life depended on many factors, such as gender, body weight and compliance with medical recommendations. The health education of patients in the presented study group was not sufficient. Therefore, there is a need for better education regarding the benefits of following medical recommendations in terms of leading a healthy lifestyle, which consequently improves its quality and duration.
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- 2024
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10. Selected elements of the lifestyle of Silesian seniors, taking into account their participation in the activities of the Third Age Universities.
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Dąbek J, Szynal M, Łebek E, and Sierka O
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- Humans, Male, Female, Aged, Middle Aged, Universities, Surveys and Questionnaires, Exercise, Life Style, Aging
- Abstract
Introduction: UTA can provide older adult people with the satisfaction of needs and creates the opportunity to pursue youthful interests and passions. The aim of the study was to assess selected elements of the lifestyle of Silesian seniors, taking into account their participation in the activities of Universities of the Third Age., Methods: The study involved 631 (100%) senior residents of the Silesian agglomeration. The majority of the study group were women (475; 75.28%), and the average age of the participants was 70.28 ± 6.09 years. To conduct the study, an original survey questionnaire was used, complemented by PPS-10, PAQE and Yesavage Geriatric Depression Rating Scale., Results: Among the surveyed Silesian seniors who did not attend classes at the University of the Third Age, a statistically significantly higher score on the Yesavage's Geriatric Depression Rating Scale was found compared to those confirming their participation in the mentioned activity ( p = 0.002). Almost 40% (107; 38.63%) of seniors who did not attend classes at the Universities of the Third Age showed a high level of stress, and every fourth (89; 25.14%) Silesian senior taking part in the above-mentioned activity had a low level of stress ( p = 0.04). The median of points obtained on the physical activity assessment scale (PAQE) by seniors attending classes at Universities of the Third Age was statistically higher than seniors who denied participation in the mentioned activity ( p = 0.017)., Conclusion: Participation in the various activities at the Universities of the Third Age influenced positively well-being, reduced stress and raised physical activity of examined seniors. It is important to promote and start actions leading to seniors' better and easier inclusion to the society life. Future research should concentrate on reasons why many seniors do not attend activities in their leisure time - especially on accessibility of various activities and financial reasons, which in the future will play crucial role in the aging societies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dąbek, Szynal, Łebek and Sierka.)
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- 2024
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11. Risky behaviors of adolescents in the Silesian voivodeship: resistance to stress and physical activity.
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Łebek E, Dąbek J, Szynal M, Knapik A, and Gallert-Kopyto W
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- Male, Female, Humans, Adolescent, Students, Surveys and Questionnaires, Sexual Behavior, Exercise, Sports
- Abstract
Background: Movement and physical activity are the natural needs of a living human. Sedentary lifestyle resulting from the development of car communication, improper nutrition, abuse of drugs and addictive substances, constant rush and stress consequently cause destructive health effects. The aim of the study was to analyze risky behaviors among adolescents in the Silesian voivodeship (Poland), taking into account their resistance to stress and physical activity., Methods: Two hundred eleven people were examined (100%). Among them there were 122 girls (57.82%) and 89 boys (42.18%) aged 16 to 18 years (x=17.3, SD=0.53). The participants were students from upper secondary schools in the Silesian voivodeship. The research tool was an original questionnaire consisting of a metric part, closed questions related to the examined problem and a standardized questionnaire of physical activity (Subjective Experience of Work Load [SEWL])., Results: Most of the girls (47, 38.52%) considered themselves to be medically resistant to stress, while boys (30, 33.71%) believed they were rather resistant to stress. On the other hand, there was no correlation between susceptibility to stress of adolescents in relation to age. From the whole group, up to 203 people (96.21%) have already drunk alcohol. Among them there were 117 girls (95.90%) and 86 boys (96.63%). The first cigarette from the studied group of teenagers was ignited by 137 people (64.93%), including 80 girls (65.57%) and 57 boys (64.04%), while psychoactive substances have been already taken by 51 participants (24.17%). Among them there were 23 girls (18.85%) and 28 boys (31.46%). There was no correlation between the self-esteem of susceptibility to stress and the use of stimulants in both boys and girls. The average value of the Sport Index among girls was 2.75, while among boys was 6.37., Conclusions: Boys in comparison to girls considered themselves more resistant to stress, while the age in both sexes did not affect self-assessment of vulnerability to stress. Gender of the adolescents did not affect the frequency of stimulants use.
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- 2023
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12. DOCTORS AND ARCHITECTS - DO THESE PROFESSIONS HAVE ANYTHING IN COMMON?
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Dąbek J, Kulik H, Sierka O, Szynal M, and Gąsior Z
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- Delivery of Health Care, History, Ancient, Humans, Male, Physicians
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Both architecture and medicine have accompanied man for centuries. Both architects and doctors make every effort to ensure that the objects of their interest (buildings and the human body) comply with the Vitruvian principles of ideal construction. Doctors take steps to restore these principles in the event of a disease, and like architects, they try to keep the subject of their activities as long as possible. It can be said that this two professions have a common ancestor: the first physician known by name in general history - Imhotep - was not only an outstanding doctor, but also an architect. He designed and built the funerary complex in Saqqara on the basis of a combination of different types of burials from lower and upper Egypt. He also was the author of the prototype of the Edwin Smith Papyrus, discovered in Luxor, a document containing the rational and scientific approach of ancient physicians to diseases for which science dominates over magic. Historians are debating whether it is Imhotep, and not Hippocrates, who should be called the father of medicine. The 21st century forces both doctors and architects to take up newer and newer challenges and change standards. Both of these professions today are based on the service provider-recipient relationship. According to modern technologies, they both work in accordance with the guidelines displayed on the computer screen. Doctors take responsibility for human health and life, while architects - for interpersonal relationships created in the buildings they have designed.
- Published
- 2021
13. Cytotoxic responses to BLV tax oncoprotein do not prevent leukemogenesis in sheep.
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Van den Broeke A, Oumouna M, Beskorwayne T, Szynal M, Cleuter Y, Babiuk S, Bagnis C, Martiat P, Burny A, and Griebel P
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- Animals, Disease Models, Animal, Female, Gene Products, tax metabolism, Leukemia metabolism, Leukemia prevention & control, Leukemia Virus, Bovine metabolism, Male, Sheep, Vaccines, DNA genetics, Vaccines, DNA immunology, Vaccines, DNA pharmacology, Viral Vaccines genetics, Viral Vaccines immunology, Viral Vaccines pharmacology, Gene Products, tax immunology, Immunity, Cellular, Leukemia immunology, Leukemia virology, Leukemia Virus, Bovine immunology
- Abstract
Delta retrovirus-mediated leukemogenesis is dependent on the oncogenic potential of Tax. It is not clear, however, whether Tax-specific immune responses play a role in leukemia onset and progression. Using the BLV-associated leukemia model in sheep, we found that Tax-specific cytotoxic responses induced by DNA immunization or viral infection of naïve animals were not predictive of disease outcome and did not prevent tumor development. Furthermore, provirus and tax may be absent from blood for extended periods, emphasizing the relevance of surveying other compartments during chronic lymphoproliferative disorders. Our results support the conclusion that Tax-specific cytotoxic responses, even during the initial phase of infection, are not sufficient to prevent leukemogenesis., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
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- 2010
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14. Suppression of viral gene expression in bovine leukemia virus-associated B-cell malignancy: interplay of epigenetic modifications leading to chromatin with a repressive histone code.
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Merimi M, Klener P, Szynal M, Cleuter Y, Kerkhofs P, Burny A, Martiat P, and Van den Broeke A
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- Animals, Cell Line, Tumor, Chromatin genetics, Histones genetics, Leukemia, B-Cell pathology, Leukemia, B-Cell veterinary, Proviruses genetics, Sheep virology, Chromatin pathology, Epigenesis, Genetic, Gene Expression Regulation, Viral physiology, Histones physiology, Leukemia Virus, Bovine genetics, Leukemia, B-Cell virology
- Abstract
Ovine leukemia/lymphoma resulting from bovine leukemia virus infection of sheep offers a large animal model for studying mechanisms underlying leukemogenesis. Silencing of viral information including Tax, the major contributor to the oncogenic potential of the virus, is critical if not mandatory for tumor progression. In this study, we have identified epigenetic mechanisms that govern the complete suppression of viral expression, using a lymphoma-derived B-cell clone carrying a silent provirus. Silencing was not relieved by injection of the malignant B cells into sheep. However, exogenous expression of Tax or treatment with either the DNA methyltransferase inhibitor 5'azacytidine or the histone deacetylase (HDAC) inhibitor trichostatin A rescued viral expression, as demonstrated by in vivo infectivity trials. Comparing silent and reactivated provirus, we found mechanistic connections between chromatin conformation and tumor-associated transcriptional repression. Silencing is associated with DNA methylation and decreased accessibility of promoter sequences. HDAC1 and the transcriptional corepressor mSin3A are associated with the inactive but not the reactivated promoter. Silencing correlates with a repressed chromatin structure marked by histone H3 and H4 hypoacetylation, a loss of methylation at H3 lysine 4, and an increase of H3 lysine 9 methylation. These observations point to the critical role of epigenetic mechanisms in tumor-specific virus/oncogene silencing, a potential strategy to evade immune response and favor the propagation of the transformed cell.
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- 2007
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15. Insights into gene expression changes impacting B-cell transformation: cross-species microarray analysis of bovine leukemia virus tax-responsive genes in ovine B cells.
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Klener P, Szynal M, Cleuter Y, Merimi M, Duvillier H, Lallemand F, Bagnis C, Griebel P, Sotiriou C, Burny A, Martiat P, and Van den Broeke A
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- Animals, Blotting, Northern, Humans, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Sheep, B-Lymphocytes physiology, B-Lymphocytes virology, Cell Transformation, Viral genetics, Gene Expression Profiling, Gene Expression Regulation, Gene Products, tax physiology, Leukemia Virus, Bovine physiology
- Abstract
Large-animal models for leukemia have the potential to aid in the understanding of networks that contribute to oncogenesis. Infection of cattle and sheep with bovine leukemia virus (BLV), a complex retrovirus related to human T-cell leukemia virus type 1 (HTLV-1), is associated with the development of B-cell leukemia. Whereas the natural disease in cattle is characterized by a low tumor incidence, experimental infection of sheep leads to overt leukemia in the majority of infected animals, providing a model for studying the pathogenesis associated with BLV and HTLV-1. Tax(BLV), the major oncoprotein, initiates a cascade of events leading toward malignancy, although the basis of transformation is not fully understood. We have taken a cross-species ovine-to-human microarray approach to identify Tax(BLV)-responsive transcriptional changes in two sets of cultured ovine B cells following retroviral vector-mediated delivery of Tax(BLV). Using cDNA-spotted microarrays comprising 10,336 human genes/expressed sequence tags, we identified a cohort of differentially expressed genes, including genes related to apoptosis, DNA transcription, and repair; proto-oncogenes; cell cycle regulators; transcription factors; small Rho GTPases/GTPase-binding proteins; and previously reported Tax(HTLV-1)-responsive genes. Interestingly, genes known to be associated with human neoplasia, especially B-cell malignancies, were extensively represented. Others were novel or unexpected. The results suggest that Tax(BLV) deregulates a broad network of interrelated pathways rather than a single B-lineage-specific regulatory process. Although cross-species approaches do not permit a comprehensive analysis of gene expression patterns, they can provide initial clues for the functional roles of genes that participate in B-cell transformation and pinpoint molecular targets not identified using other methods in animal models.
- Published
- 2006
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16. Disruption of B-cell homeostatic control mediated by the BLV-Tax oncoprotein: association with the upregulation of Bcl-2 and signaling through NF-kappaB.
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Szynal M, Cleuter Y, Beskorwayne T, Bagnis C, Van Lint C, Kerkhofs P, Burny A, Martiat P, Griebel P, and Van den Broeke A
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- Animals, Apoptosis physiology, B-Lymphocytes cytology, B-Lymphocytes virology, CD40 Ligand pharmacology, CD40 Ligand physiology, Cell Cycle genetics, Cell Division genetics, Cells, Cultured, Clone Cells cytology, Clone Cells metabolism, Clone Cells virology, Cytokines metabolism, Cytokines pharmacology, Gene Products, tax genetics, Gene Transfer Techniques, Interleukin-4 pharmacology, Interleukin-4 physiology, Leukemia Virus, Bovine chemistry, Retroviridae genetics, Sheep, Up-Regulation, B-Lymphocytes metabolism, Gene Products, tax metabolism, NF-kappa B metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Signal Transduction
- Abstract
Transactivating proteins associated with complex onco-retroviruses including human T-cell leukemia virus-1 (HTLV-1) and bovine leukemia virus (BLV) mediate transformation using poorly understood mechanisms. To gain insight into the processes that govern tumor onset and progression, we have examined the impact of BLV-Tax expression on ovine B-cells, the targets of BLV in experimentally infected sheep, using B-cell clones that are dependent on CD154 and gammac-common cytokines. Tax was capable of mediating progression of B-cells from cytokine dependence to cytokine independence, indicating that the transactivator can over-ride signaling pathways typically controlled by cytokine receptor activation in B-cells. When examined in the presence of both CD154 and interleukin-4, Tax had a clear supportive role on B-cell growth, with an impact on B-cell proliferation, cell cycle phase distribution, and survival. Apoptotic B-cell death mediated by growth factor withdrawal, physical insult, and NF-kappaB inhibition was dramatically reduced in the presence of Tax. Furthermore, the expression of Tax was associated with higher Bcl-2 protein levels, providing rationale for the rescue signals mediated by the transactivator. Finally, Tax expression in B-cells led to a dramatic increase of nuclear RelB/p50 and p50/p50 NF-kappaB dimers, indicating that cellular signaling through NF-kappaB is a major contributory mechanism in the disruption of B-cell homeostasis. Although Tax is involved in aspects of pathogenesis that are unique to complex retroviruses, the viral strategies associated with this transactivating oncoprotein may have wide-ranging effects that are relevant to other B-cell malignancies.
- Published
- 2003
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