No description available.

The Major Histocompatibility Complex (MHC) is a gene-dense region located on the short arm of chromosome 6 (6p21.31). This region contains the highly polymorphic HLA genes as well as many other genes with immunological and non-immunological function. The susceptibility genes of many human disorders have been mapped to genes within the MHC. However, the genes themselves and indeed the locations of the genes, for many of the disorders, remain a mystery. This is a result of the high degree of linkage disequilibrium (LD) that exists between loci within the MHC. The high LD is explained by the genomic structure of the MHC. The MHC contains several blocks of DNA within which recombination is extremely rare, whereas the boundaries of the blocks are defined as "hotspots" of recombination. Most disease association studies have used the highly polymorphic HLA class I and class II genes which are separated by an, as yet, undefined number of blocks and several hundred kilobases of DNA. The MHC gamma block resides in the central region of the MHC between the blocks that contain the HLA class I and class It genes. As such, typing for polymorphisms in the gamma block is critical for MHC disease gene mapping studies. The gamma block contains approximately 20 known genes including the complement C4 genes. The gamma block can contain between I and 3 tandemly arranged C4 genes. The C4 protein exists as either the C4A or C413 isotype and is polymorphic with up to 40 allotypes being reported. However, the majority of Caucasian haplotypes can be explained by the common C4A3 / C4B1 or C4AQ0 / C4B1 complotypes with the remaining haplotypes explained by just a few other complotypes. For this reason, and because C4 allotyping is a technically difficult procedure, C4 allotyping is rarely used in MHC disease association studies. / The molecular heterogeneity of human C4 genes has not been extensively studied. However, the C4A3 and C4131 genes have been completely sequenced and are >99% identical at the DNA level across 41 exons and 15 kb of DNA. This high degree of homology and the presence of up to 3 C4 genes on any MHC haplotype makes PCR separation of the C4 genes difficult for subsequent genetic studies. The aim of this study was to extensively characterise the molecular heterogeneity of the human C4 genes and thereby: 1. determine the extent of human C4 gene polymorphism 2. confirm previous studies which have defined isotype specific sequences 3. characterise the C4 protein polymorphisms at the DNA level 4. determine if common C4 allotypes can be subtyped on a molecular basis 5. identify C4 gene polymorphisms that can be used as targets for DNA based typing methods 6. apply DNA based C4 typing methods in MHC disease association studies 7. provide insights into MHC haplotype evolution. In contrast to separating the C4 genes, a novel approach whereby the C4 genes were amplified and sequenced simultaneously was applied in this study. The DNA from 24 homozygous workshop cell lines, representing different ancestral haplotypes (AHs), was studied. Comparison of the C4 genes from different AHs revealed that the C4d region of the C4 a-chain is most polymorphic, but that polymorphic amino acid residues are also present in other regions of C4. The highest degree of polymorphisms was seen in the introns. In addition, the presence of the isotype specific sequences in exon 26 was confirmed and primers were designed to specifically amplify, and thereby separate, the C4A and C4B genes. / Comparison of the C4 gene sequences representing the same C4 allotype revealed that most C4 allotypes are heterogeneous and may be split into several subtypes. The polymorphisms observed at the sequence level did not correlate with C4 allotypes defined by electrophoretic mobility. However, it could be shown that the differences in electrophoretic mobility of the C4 allotypes are due to cumulative charge differences. Seven polymorphic amino acids were found to account for the different migration rates of the C4 allotypes analysed in this study. In addition, a number of haplospecific single nucleotide polymorphisms (SNPs) were identified within the C4 genes. Haplospecific SNPs are informative markers enabling the genetic mapping of recombinant AHs, an approach which can be used to identify disease susceptibility genes. Haplospecific SNPs located in the C4 gene region are important markers as they represent a separate block of the MIIC (i.e. the gamma block). The frequency of one such SNP marker has been shown for a diabetes patient group and a control population. Although further studies are required to elucidate the role of the gamma block genes in susceptibility to diabetes, this study demonstrates a possible approach for the mapping of MHC disease susceptibility genes, which can also be applied in studies of other MHC associated diseases. To conclude, the present study adds to our knowledge of the C4 gene polymorphism, provides insights into MHC and C4 gene evolution and enables future studies to examine the significance of the C4 genes and other gamma block genes in susceptibility to MHC associated diseases.

No description available.

Background: The HPV vaccine has been introduced to the public and the medical community since June 2006 for the vaccination of females and since November 2009 for the vaccination of males ages 9-26 years old. The purposes of this research were to explore multiple factors and relationships among Health Belief Model (HBM) constructs (perceived susceptibility, perceived severity, perceived barriers, and perceived benefits) and mediating factors (self-efficacy and cues to action) related to HPV, HPV-associated diseases, and HPV vaccine among Russian college students and to determine which factors were most important when considering who would/would not seek HPV vaccination. Methods: A quantitative, cross-sectional, descriptive, and correlational survey design was used in this study. An existing self-report questionnaire HPV Study Survey was adapted with the permission from the author. One thousand two hundred participants were contacted by Yaroslav-the-Wise Novgorod State University, Veliky Novgorod, Russia registrar's office through e-mails and messaging using two social networks through simple random sampling method using the SQL statement "ORDER BY NEWID" propriety of Microsoft algorithm out of the total student population (9,923 students). The survey was distributed through SurveyMonkeyTM survey software that was activated December 2011 - April 2012. Results: Two hundred seventy students replied to the survey (22.5% response rate) and 117 participants fully completed it out of 270 who responded to the survey (43.33% completion rate). The initial response rate increased 4.4 times using social networks messaging compared to e-mailing invitations. Overall, average knowledge levels were moderate. Participants' behaviors regarding their sexual activity showed that the majority of participants were sexually active. Participants' perceptions (susceptibility, severity, barriers, and benefits) and mediating factors (cues to action and self-efficacy) were moderate. Participants' behavioral intention to get HPV vaccination was moderate. There were statistically significant differences between males and females in perceived susceptibility, perceived barriers, self-efficacy, behavioral intention, and in three behavioral items (having had sexual contact; age of having had sexual contact and sex for the first time). Sixty percent of the variance in behavioral intention getting HPV vaccination could be explained by two HBM constructs (perceived benefits and self-efficacy). Self-efficacy was the number one predictor of behavioral intention (p < 0.001) and perceived benefits were the number two predictor of behavioral intention (p < 0.01).

Ensaio clínico aleatorizado conduzido para avaliar o impacto de intervenção intensiva para mudança de estilo de vida em indivíduos com sobrepeso em um Centro de Saúde-Escola em São José do Rio Preto, Estado de São Paulo, Brasil. Dos 259 voluntários (203 mulheres e 56 homens; idade entre 25 e 72 anos) que concordaram em participar do estudo, 104 foram elegíveis (83 mulheres e 21 homens), sendo distribuídos aleatoriamente em dois grupos: grupo intervenção (10 homens e 41 mulheres), com acompanhamento nutricional individualizado, e grupo controle (11 homens e 42 mulheres), que receberam somente orientações gerais e folheto explicativo sobre estilo de vida saudável. A avaliação da composição corporal, indicadores bioquímicos, consumo alimentar e estilo de vida - incluindo-se a prática de atividades físicas, foi realizada no princípio, após 6 meses e 1 ano de estudo. A intervenção nutricional consistiu de incentivo ao consumo de frutas, vegetais, óleo de oliva e produtos lácteos pobres em gordura, associados com a redução do consumo de gorduras saturadas e doces, bem como o estímulo à prática de atividades físicas por pelo menos 30 minutos ao dia. O programa de intervenção mostrou-se efetivo na redução do consumo de calorias, gorduras totais, gorduras saturadas, colesterol, freqüência de carnes, óleos/gorduras e doces. Além disso, observamos um incremento no consumo de fibra total da dieta, fibras de frutas e vegetais, ß-caroteno, vitamina A, cálcio, freqüência de consumo de frutas em geral, vegetais em geral, vegetais verde escuros e leite/derivados. O programa mostrou-se viável em unidades básicas de saúde e efetivo na redução de peso, índice de massa corporal, pressão arterial, colesterol total, LDL colesterol, ácido úrico, homocisteína, aumento da prática de atividades físicas, contribuindo para a melhoria da qualidade de vida no grupo intervenção. / Randomized Nutritional Intervention trial was carried out to evaluate the impact of intensive intervention in changing life style of overweight adults attending at a primary health care in São José do Rio Preto, São Paulo State, Brazil. Of the 259 volunteers (203 women and 56 men; 25 to 72 years old) that agreed in participating in the study, 104 were eligible (83 women and 21 men), and were randomly allocated in two groups: Nutrition Counseling group (42 women, 11 men) with individualized dietary counseling, and Control Group (41 women, 10 men) who recieved only general information and leaflets about healthy life style. The assessment of body composition, biochemical indicators, food consumption and life style – including practice of physical activity were carried out at baseline, 6 months and 1 year. The dietary interventions included increased intake of fruits, vegetables, olive oil and skimmed dairy products, together with reduced intake of saturated fat and sweets, as well as instructions for regular practice of physical activity for at least 30 minutes per day. The intervention program demonstrated to be effective in reducing consumption of calories, total fat, saturated fat, cholesterol, and frequency of meets, fats/oils and sweet groups. Moreover, we observed an increment in the consumption of dietary fiber, fiber of fruits and vegetables, ß-carotene, vitamin A, calcium, and in the frequency of fruits, vegetables, dark green vegetables and dairy products. The program demonstrated to be feasible at a primary health care unit and was effective in reducing weight, body mass index, blood pressure, total cholesterol, LDL cholesterol, uric acid, homocysteine, and improved the physical activity level and quality of life in the intervention group.

Ensaio clínico aleatorizado conduzido para avaliar o impacto de intervenção intensiva para mudança de estilo de vida em indivíduos com sobrepeso em um Centro de Saúde-Escola em São José do Rio Preto, Estado de São Paulo, Brasil. Dos 259 voluntários (203 mulheres e 56 homens; idade entre 25 e 72 anos) que concordaram em participar do estudo, 104 foram elegíveis (83 mulheres e 21 homens), sendo distribuídos aleatoriamente em dois grupos: grupo intervenção (10 homens e 41 mulheres), com acompanhamento nutricional individualizado, e grupo controle (11 homens e 42 mulheres), que receberam somente orientações gerais e folheto explicativo sobre estilo de vida saudável. A avaliação da composição corporal, indicadores bioquímicos, consumo alimentar e estilo de vida - incluindo-se a prática de atividades físicas, foi realizada no princípio, após 6 meses e 1 ano de estudo. A intervenção nutricional consistiu de incentivo ao consumo de frutas, vegetais, óleo de oliva e produtos lácteos pobres em gordura, associados com a redução do consumo de gorduras saturadas e doces, bem como o estímulo à prática de atividades físicas por pelo menos 30 minutos ao dia. O programa de intervenção mostrou-se efetivo na redução do consumo de calorias, gorduras totais, gorduras saturadas, colesterol, freqüência de carnes, óleos/gorduras e doces. Além disso, observamos um incremento no consumo de fibra total da dieta, fibras de frutas e vegetais, ß-caroteno, vitamina A, cálcio, freqüência de consumo de frutas em geral, vegetais em geral, vegetais verde escuros e leite/derivados. O programa mostrou-se viável em unidades básicas de saúde e efetivo na redução de peso, índice de massa corporal, pressão arterial, colesterol total, LDL colesterol, ácido úrico, homocisteína, aumento da prática de atividades físicas, contribuindo para a melhoria da qualidade de vida no grupo intervenção. / Randomized Nutritional Intervention trial was carried out to evaluate the impact of intensive intervention in changing life style of overweight adults attending at a primary health care in São José do Rio Preto, São Paulo State, Brazil. Of the 259 volunteers (203 women and 56 men; 25 to 72 years old) that agreed in participating in the study, 104 were eligible (83 women and 21 men), and were randomly allocated in two groups: Nutrition Counseling group (42 women, 11 men) with individualized dietary counseling, and Control Group (41 women, 10 men) who recieved only general information and leaflets about healthy life style. The assessment of body composition, biochemical indicators, food consumption and life style – including practice of physical activity were carried out at baseline, 6 months and 1 year. The dietary interventions included increased intake of fruits, vegetables, olive oil and skimmed dairy products, together with reduced intake of saturated fat and sweets, as well as instructions for regular practice of physical activity for at least 30 minutes per day. The intervention program demonstrated to be effective in reducing consumption of calories, total fat, saturated fat, cholesterol, and frequency of meets, fats/oils and sweet groups. Moreover, we observed an increment in the consumption of dietary fiber, fiber of fruits and vegetables, ß-carotene, vitamin A, calcium, and in the frequency of fruits, vegetables, dark green vegetables and dairy products. The program demonstrated to be feasible at a primary health care unit and was effective in reducing weight, body mass index, blood pressure, total cholesterol, LDL cholesterol, uric acid, homocysteine, and improved the physical activity level and quality of life in the intervention group.

L’élimination des cellules sénescentes met en jeu le SASP et les cellules immunitaires de l’immunité innée et adaptative tels que les macrophages (Mφ). Dans le cadre de ce projet, nous rapportons que le SASP a un effet pléiotropique sur l’activité des cellules immunitaires incluant leur recrutement, leur activation et leur différenciation. Nos données montrent que les Mφ humains mis en culture avec le SASP de fibroblastes humains développement un profil inflammatoire spécifique au SASP caractérisé par une sécrétion pro-inflammatoire (M1) (ex : IL- 1β, GM-CSF) et des marqueurs de surface anti-inflammatoires (M2) (cellules CD23+CD206+). Le SASP est aussi capable d’augmenter les capacités d’invasion des Mφ, tel que montré via des essais d’invasion, mais n’a pas d’effet sur la différentiation des monocytes. Nos modèles de co- culture montrent que, quoique les cellules NK sont probablement responsables de l’élimination directe et spécifique des cellules sénescentes, leur activité peut être modulée par d’autres cellules immunitaires tels que les Mφ qui réduisent l’élimination faite par les cellules NK, suggérant un profil M2. Les lymphocytes T CD8+ sont aussi essentiels pour l’élimination des cellules sénescentes puisque leur retrait retarde le processus. De plus, nous démontrons que les cellules T CD4+ mises en culture pendant 48h dans le SASP sécrètent de hauts niveaux d’IL-4, indiquant une polarisation Th2. Somme toute, ces données montrent que le SASP peut moduler l’activité des Mφ tout comme celle d’autres cellules immunitaires impliquées dans l’élimination des cellules sénescentes et peut promouvoir, étonnamment, une réponse immunosuppressive pouvant être importante pendant la réparation tissulaire. / Senescent cell clearance brings into play the senescence-associated secretory phenotype (SASP) and immune cells from the innate and adaptive immunity including macrophages (Mφ). In this study, we report that the SASP has a pleiotropic effect on immune cell activity including recruitment, activation and differentiation. We show that human Mφ exposed to the SASP of human fibroblasts develop a SASP-specific inflammatory profile characterized by pro- inflammatory (M1) secretion (e.g. IL-1β, GM-CSF) and anti-inflammatory (M2) surface markers (CD23 and CD206). The SASP also increases Mφ invasion but has no effect on monocyte differentiation. Co-culture models show that while NK cells are likely the direct effectors of senescent cell specific killing, their activity is modulated by other immune cells including Mφ, which reduced NK-mediated killing, suggesting a M2 profile. Alternatively, CD8+ T lymphocytes are essential for senescent cell killing by NK cells. Finally, CD4+ T cells cultured for 48h in the SASP secrete high-levels of IL-4, indicating a Th2 polarization. Overall, our data reveal that the SASP can modulate Mφ and other immune cells involved in senescent cell clearance and surprisingly promote an immunosuppressive response that could be important in tissue repair.