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DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes  

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Full Text Available Abstract Background Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases. Methods In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ. Results DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete. Conclusion The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases.

Santos Rubens R; Sartori Alexandrina; Lima Deison S; Souza Patrícia RM; Coelho-Castelo Arlete AM; Bonato Vânia LD; Silva Célio L

2009-01-01

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The genomic heterogeneity among Mycobacterium terrae complex displayed by sequencing of 16S rRNA and hsp 65 genes.  

UK PubMed Central (United Kingdom)

The species identification within Mycobacterium terrae complex has been known to be very difficult. In this study, the genomic diversity of M. terrae complex with eighteen clinical isolates, which were initially identified as M. terrae complex by phenotypic method, was investigated, including that of three type strains (M. terrae, M. nonchromogenicum, and M. triviale ). 16S rRNA and 65-kDa heat shock protein (hsp 65) gene sequences of mycobacteria were determined and aligned with eleven other references for the comparison using similarity search against the GenBank and Ribosomal Database Project II (RDP) databases. 16S rRNA and hsp 65 genes of M. terrae complex showed genomic heterogeneity. Amongst the eighteen clinical isolates, nine were identified as M. nonchromogenicum, eight as M. terrae, one as M. mucogenicum with the molecular characteristic of rapid growth. M. nonchromogenicum could be subdivided into three subgroups, while M. terrae could be subdivided into two subgroups using a 5 bp criterion (>1% difference). Seven isolates in two subgroups of M. nonchromogenicum were Mycobacterium sp. strain MCRO 6, which was closely related to M. nonchromogenicum. The hsp 65 gene could not differentiate one M. nonchromogenicum from M. avium or one M. terrae from M. intracellulare. The nucleotide sequence analysis of 16S rRNA and hsp 65 genes was shown to be useful in identifying the M. terrae complex, but hsp 65 was less discriminating than 16S rRNA.

Lee CK; Gi HM; Cho Y; Kim YK; Lee KN; Song KJ; Song JW; Park KS; Park EM; Lee H; Bai GH

2004-01-01

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Pyrosequence Analysis of the hsp65 Genes of Nontuberculous Mycobacterium Communities in Unchlorinated Drinking Water in the Netherlands.  

UK PubMed Central (United Kingdom)

Studies have shown that certain opportunistic pathogenic species of nontuberculous mycobacteria (NTM) can be present in distributed drinking water. However, detailed information about NTM population composition in drinking water is lacking. Therefore, NTM communities in unchlorinated drinking water from the distribution system of five treatment plants in the Netherlands were characterized using 454 pyrosequencing of the hsp65 gene. Results showed high diversities in unchlorinated drinking water, with up to 28 different NTM operational taxonomic units (OTUs) in a single sample. Each drinking water sample had a unique NTM community, and most (81.1%) OTUs were observed only once. One OTU was observed in 14 of 16 drinking water samples, indicating that this NTM species is well adapted to unchlorinated drinking water conditions. A clear influence of season, source type (groundwater, surface water), easily assimilable organic carbon (AOC) concentration, biofilm formation rate, and active biomass in treated water on the establishment of an NTM community in drinking water was not observed. Apparently, local conditions are more important for the development of a specific NTM community in the drinking water distribution system. A low (4.2%) number of hsp65 gene sequences showed more than 97% similarity to sequences of the opportunistic pathogens M. avium, M. genavense, and M. gordonae. However, most (95.8%) NTM hsp65 gene sequences were related to not-yet-described NTM species that have not been linked to disease, indicating that most NTM species in unchlorinated drinking water from distribution systems in the Netherlands have a low public health significance.

van der Wielen PW; Heijnen L; van der Kooij D

2013-10-01

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Pyrosequence Analysis of the hsp65 Genes of Nontuberculous Mycobacterium Communities in Unchlorinated Drinking Water in the Netherlands.  

Science.gov (United States)

Studies have shown that certain opportunistic pathogenic species of nontuberculous mycobacteria (NTM) can be present in distributed drinking water. However, detailed information about NTM population composition in drinking water is lacking. Therefore, NTM communities in unchlorinated drinking water from the distribution system of five treatment plants in the Netherlands were characterized using 454 pyrosequencing of the hsp65 gene. Results showed high diversities in unchlorinated drinking water, with up to 28 different NTM operational taxonomic units (OTUs) in a single sample. Each drinking water sample had a unique NTM community, and most (81.1%) OTUs were observed only once. One OTU was observed in 14 of 16 drinking water samples, indicating that this NTM species is well adapted to unchlorinated drinking water conditions. A clear influence of season, source type (groundwater, surface water), easily assimilable organic carbon (AOC) concentration, biofilm formation rate, and active biomass in treated water on the establishment of an NTM community in drinking water was not observed. Apparently, local conditions are more important for the development of a specific NTM community in the drinking water distribution system. A low (4.2%) number of hsp65 gene sequences showed more than 97% similarity to sequences of the opportunistic pathogens M. avium, M. genavense, and M. gordonae. However, most (95.8%) NTM hsp65 gene sequences were related to not-yet-described NTM species that have not been linked to disease, indicating that most NTM species in unchlorinated drinking water from distribution systems in the Netherlands have a low public health significance. PMID:23913420

van der Wielen, Paul W J J; Heijnen, Leo; van der Kooij, Dick

2013-08-02

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Tissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose administered through intramuscular delivery  

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Full Text Available Abstract In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system.

Coelho-Castelo AAM; Trombone AP; Rosada RS; Santos RR; Bonato VLD; Sartori A; Silva CL

2006-01-01

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hsp65 PCR-restriction enzyme analysis (PRA) for identification of mycobacteria in the clinical laboratory PCR e análise de padrões de restrição do gene hsp65 (PRA) para identificação de micobactérias no laboratório clínico  

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Full Text Available More than 70 species of mycobacteria have been defined, and some can cause disease in humans, especially in immunocompromised patients. Species identification in most clinical laboratories is based on phenotypic characteristics and biochemical tests and final results are obtained only after two to four weeks. Quick identification methods, by reducing time for diagnosis, could expedite institution of specific treatment, increasing chances of success. PCR restriction-enzyme analysis (PRA) of the hsp65 gene was used as a rapid method for identification of 103 clinical isolates. Band patterns were interpreted by comparison with published tables and patterns available at an Internet site (http://www.hospvd.ch:8005). Concordant results of PRA and biochemical identification were obtained in 76 out of 83 isolates (91.5%). Results from 20 isolates could not be compared due to inconclusive PRA or biochemical identification. The results of this work showed that PRA could improve identification of mycobacteria in a routine setting because it is accurate, fast, and cheaper than conventional phenotypic identification.Mais de 70 espécies de micobactérias já foram definidas e algumas delas podem causar enfermidade em humanos, especialmente em pacientes imunocomprometidos. A identificação de espécie, na maioria dos laboratórios clínicos, se baseia em características fenotípicas e testes bioquímicos e resultados definitivos só são obtidos após duas a quatro semanas. Métodos rápidos de identificação reduzem o tempo necessário para o diagnóstico e podem antecipar a instituição do tratamento específico, aumentando as chances de sucesso. A análise de padrões de restrição do gene hsp65 amplificado por PCR (PRA) foi utilizada como método rápido de identificação em 103 isolamentos clínicos. Os padrões de bandas foram interpretados por comparação com tabelas publicadas e padrões disponíveis em um site de Internet (http://www.hospvd.ch:8005). Resultados concordantes de PRA e identificação bioquímica foram obtidos em 76 de 83 isolamentos (91,5%). Os resultados de 20 isolamentos não puderam ser comparados porque a identificação fenotípica ou por PRA foi inconclusiva. Os resultados deste trabalho mostram que PRA pode ser útil para identificação de rotina de micobactérias por ser um método acurado, rápido e mais econômico do que a identificação convencional.

Carolina Feher da SILVA; Suely Yoko Mizuka UEKI; Débora de Cássia Pires GEIGER; Sylvia Cardoso LEÃO

2001-01-01

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Análise de restrição enzimática do gene hsp65 de isolados clínicos de pacientes com suspeita de tuberculose pulmonar em Teresina, Piauí/ Restriction enzyme analysis of the hsp65 gene in clinical isolates from patients suspected of having pulmonary tuberculosis in Teresina, Brazil  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese OBJETIVO: Identificar as espécies de micobactérias encontradas no escarro de pacientes com suspeita de tuberculose pulmonar e analisar o impacto dessas identificações na abordagem terapêutica. MÉTODOS: Foram avaliados 106 pacientes com suspeita de tuberculose pulmonar encaminhados para o serviço de pneumologia de um hospital público em Teresina, Piauí. Espécimes de escarro matinal foram avaliados quanto à presença de micobactérias por baciloscopia e cultura. (more) Foram utilizadas PCR e análise de restrição enzimática do gene hsp65 (PRA-hsp65) para a identificação das cepas de micobactérias isoladas em cultura. RESULTADOS: Foram analisadas 206 amostras de escarro. A idade dos pacientes variou de 15 a 87 anos, sendo 67% do gênero masculino. Tosse ocorreu em 100% dos casos. O padrão radiográfico predominante foi de lesão moderada, observada em 70%. A positividade no esfregaço foi de 76%, e isolamento em cultura ocorreu em 91% das culturas executadas. Testes tradicionais identificaram micobactérias não tuberculosas (MNT) em 9% dos isolados. O método PRA-hsp65 confirmou esses dados, mostrando sete padrões de bandas capazes de identificar as espécies de MNT isoladas: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5 e M. gordonae 7. Todos os pacientes com MNT tinham mais de 60 anos, e observaram-se bronquiectasias em 88% das radiografias. Houve dois casos de reinfecção, identificados inicialmente como infecção por M. abscessus e M. kansasii. CONCLUSÕES: As MNT causam infecção pulmonar em pacientes imunocompetentes, e a identificação das MNT é importante para estabelecer o diagnóstico correto e a decisão terapêutica mais adequada. O método PRA-hsp65 é útil para identificar espécies de MNT e pode ser implantado em laboratórios de biologia molecular não especializados em micobactérias. Abstract in english OBJECTIVE: To identify mycobacterial species in the sputum of patients suspected of having pulmonary tuberculosis and to determine the impact that the acquisition of this knowledge has on the therapeutic approach. METHODS: We evaluated 106 patients suspected of having pulmonary tuberculosis and referred to the pulmonology department of a public hospital in the city of Teresina, Brazil. Morning sputum specimens were evaluated for the presence of mycobacteria by sputum smea (more) r microscopy and culture. We used PCR and restriction enzyme analysis of the hsp65 gene (PRA-hsp65) to identify the strains of mycobacteria isolated in culture. RESULTS: A total of 206 sputum samples were analyzed. Patient ages ranged from 15 to 87 years, and 67% were male. There was cough in 100% of the cases. The predominant radiographic pattern was moderate disease, observed in 70%. Smear positivity was 76%, and isolation in culture occurred in 91% of the cultures. Traditional tests identified nontuberculous mycobacteria (NTM) in 9% of the isolates. The PRA-hsp65 method confirmed these data, showing seven band patterns that were able to identify the isolated species of NTM: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5; and M. gordonae 7. All of the patients with NTM were over 60 years of age, and bronchiectasis was seen in 88% of the X-rays. There were two cases of reinfection, initially attributed to M. abscessus and M. kansasii. CONCLUSIONS: In immunocompetent patients, NTM can infect the lungs. It is important to identify the specific NTM in order to establish the correct diagnosis and choose the most appropriate therapeutic regimen. The PRA-hsp65 method is useful in identifying NTM species and can be implemented in molecular biology laboratories that do not specialize in the identification of mycobacteria.

Bona, Maria das Graças Motta e; Leal, Maria José Soares; Martins, Liline Maria Soares; Silva, Raimundo Nonato da; Castro, José Adail Fonseca de; Monte, Semiramis Jamil Hadad do

2011-10-01

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Análise de restrição enzimática do gene hsp65 de isolados clínicos de pacientes com suspeita de tuberculose pulmonar em Teresina, Piauí Restriction enzyme analysis of the hsp65 gene in clinical isolates from patients suspected of having pulmonary tuberculosis in Teresina, Brazil  

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Full Text Available OBJETIVO: Identificar as espécies de micobactérias encontradas no escarro de pacientes com suspeita de tuberculose pulmonar e analisar o impacto dessas identificações na abordagem terapêutica. MÉTODOS: Foram avaliados 106 pacientes com suspeita de tuberculose pulmonar encaminhados para o serviço de pneumologia de um hospital público em Teresina, Piauí. Espécimes de escarro matinal foram avaliados quanto à presença de micobactérias por baciloscopia e cultura. Foram utilizadas PCR e análise de restrição enzimática do gene hsp65 (PRA-hsp65) para a identificação das cepas de micobactérias isoladas em cultura. RESULTADOS: Foram analisadas 206 amostras de escarro. A idade dos pacientes variou de 15 a 87 anos, sendo 67% do gênero masculino. Tosse ocorreu em 100% dos casos. O padrão radiográfico predominante foi de lesão moderada, observada em 70%. A positividade no esfregaço foi de 76%, e isolamento em cultura ocorreu em 91% das culturas executadas. Testes tradicionais identificaram micobactérias não tuberculosas (MNT) em 9% dos isolados. O método PRA-hsp65 confirmou esses dados, mostrando sete padrões de bandas capazes de identificar as espécies de MNT isoladas: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5 e M. gordonae 7. Todos os pacientes com MNT tinham mais de 60 anos, e observaram-se bronquiectasias em 88% das radiografias. Houve dois casos de reinfecção, identificados inicialmente como infecção por M. abscessus e M. kansasii. CONCLUSÕES: As MNT causam infecção pulmonar em pacientes imunocompetentes, e a identificação das MNT é importante para estabelecer o diagnóstico correto e a decisão terapêutica mais adequada. O método PRA-hsp65 é útil para identificar espécies de MNT e pode ser implantado em laboratórios de biologia molecular não especializados em micobactérias.OBJECTIVE: To identify mycobacterial species in the sputum of patients suspected of having pulmonary tuberculosis and to determine the impact that the acquisition of this knowledge has on the therapeutic approach. METHODS: We evaluated 106 patients suspected of having pulmonary tuberculosis and referred to the pulmonology department of a public hospital in the city of Teresina, Brazil. Morning sputum specimens were evaluated for the presence of mycobacteria by sputum smear microscopy and culture. We used PCR and restriction enzyme analysis of the hsp65 gene (PRA-hsp65) to identify the strains of mycobacteria isolated in culture. RESULTS: A total of 206 sputum samples were analyzed. Patient ages ranged from 15 to 87 years, and 67% were male. There was cough in 100% of the cases. The predominant radiographic pattern was moderate disease, observed in 70%. Smear positivity was 76%, and isolation in culture occurred in 91% of the cultures. Traditional tests identified nontuberculous mycobacteria (NTM) in 9% of the isolates. The PRA-hsp65 method confirmed these data, showing seven band patterns that were able to identify the isolated species of NTM: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5; and M. gordonae 7. All of the patients with NTM were over 60 years of age, and bronchiectasis was seen in 88% of the X-rays. There were two cases of reinfection, initially attributed to M. abscessus and M. kansasii. CONCLUSIONS: In immunocompetent patients, NTM can infect the lungs. It is important to identify the specific NTM in order to establish the correct diagnosis and choose the most appropriate therapeutic regimen. The PRA-hsp65 method is useful in identifying NTM species and can be implemented in molecular biology laboratories that do not specialize in the identification of mycobacteria.

Maria das Graças Motta e Bona; Maria José Soares Leal; Liline Maria Soares Martins; Raimundo Nonato da Silva; José Adail Fonseca de Castro; Semiramis Jamil Hadad do Monte

2011-01-01

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Report of 2 indigenous cases of leprosy from a European country: use of polymerase chain reaction-restriction fragment length polymorphism analysis of hsp65 gene for identification of Mycobacterium leprae directly from a clinical sample.  

UK PubMed Central (United Kingdom)

In this article, we report on 2 indigenous cases of leprosy detected in a European country. We also report on the use of polymerase chain reaction-restriction fragment length polymorphism analysis of hsp65 gene for rapid identification of Mycobacterium leprae directly from the clinical sample.

Neonakis IK; Gitti Z; Kontos F; Baritaki S; Zerva L; Krambovitis E; Spandidos DA

2009-07-01

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Report of 2 indigenous cases of leprosy from a European country: use of polymerase chain reaction-restriction fragment length polymorphism analysis of hsp65 gene for identification of Mycobacterium leprae directly from a clinical sample.  

Science.gov (United States)

In this article, we report on 2 indigenous cases of leprosy detected in a European country. We also report on the use of polymerase chain reaction-restriction fragment length polymorphism analysis of hsp65 gene for rapid identification of Mycobacterium leprae directly from the clinical sample. PMID:19376672

Neonakis, Ioannis K; Gitti, Zoe; Kontos, Fanourios; Baritaki, Stavroula; Zerva, Loukia; Krambovitis, Elias; Spandidos, Demetrios A

2009-04-18

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Purification of clinical-grade recombinant HSP65-MUCI fusion protein.  

UK PubMed Central (United Kingdom)

HSP65-MUCI is a fusion protein between BCG (Bacille Calmette-Guerin)-derived HSP65 (heat-shock protein 65) and human MUCI (mucin I) VNTR (variable number of tandem repeats)-domain peptides that has shown antitumour efficacy. China's Food and Drug Administration has recently approved a Phase I clinical trial using HSP65-MUCI for the treatment of MUCI-positive breast cancer. In order to produce sufficient quantities of clinical-grade HSP65-MUCI, we established a pilot-scale purification scheme comprising two steps of column chromatography: HIC (hydrophobic-interaction chromatography) and IEX (ion-exchange chromatography). The pH values of the buffers used in homogenization and HIC were adjusted to pH 9.0 to maintain protein stability and prevent protein degradation. Using this manufacturing process, we obtained clinical-grade HSP65-MUCI with a yield of 400 mg per 70 g of wet cell pellet and >96% purity.

Cao Z; Feng Y; Wei H; Fang M; Hu X; Yu Y; Wang L; Wan M

2010-09-01

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Purification of clinical-grade recombinant HSP65-MUCI fusion protein.  

Science.gov (United States)

HSP65-MUCI is a fusion protein between BCG (Bacille Calmette-Guerin)-derived HSP65 (heat-shock protein 65) and human MUCI (mucin I) VNTR (variable number of tandem repeats)-domain peptides that has shown antitumour efficacy. China's Food and Drug Administration has recently approved a Phase I clinical trial using HSP65-MUCI for the treatment of MUCI-positive breast cancer. In order to produce sufficient quantities of clinical-grade HSP65-MUCI, we established a pilot-scale purification scheme comprising two steps of column chromatography: HIC (hydrophobic-interaction chromatography) and IEX (ion-exchange chromatography). The pH values of the buffers used in homogenization and HIC were adjusted to pH 9.0 to maintain protein stability and prevent protein degradation. Using this manufacturing process, we obtained clinical-grade HSP65-MUCI with a yield of 400 mg per 70 g of wet cell pellet and >96% purity. PMID:20704567

Cao, Zhao; Feng, Yu; Wei, Hongfei; Fang, Mingli; Hu, Xiaoping; Yu, Yongli; Wang, Liying; Wan, Min

2010-09-01

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DETECÇÃO DO COMPLEXO Mycobacterium tuberculosis NO LEITE PELA REAÇÃO EM CADEIA DA POLIMERASE SEGUIDA DE ANÁLISE DE RESTRIÇÃO DO FRAGMENTO AMPLIFICADO (PRA) DETECTION OF Mycobacterium tuberculosis COMPLEX BY PCR-RESTRICTION FRAGMENT LENGTH POLYMORFISM ANALYSIS OF THE HSP65 GENE  

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Full Text Available Mycobacterium bovis é membro do complexo Mycobacterium tuberculosis (MTBC), grupo este composto por espécies com grande homologia genética. É o agente etiológico da tuberculose bovina, importante zoonose transmissível ao homem, principalmente através da inalação do bacilo e/ou pelo consumo de leite e derivados não-pasteurizados provenientes de vacas tuberculosas. O objetivo deste estudo foi padronizar a identificação de micobactérias do complexo M. tuberculosis presentes no leite, por metodologia molecular. Fez-se a extração de DNA diretamente do leite contaminado e realizou-se a identificação molecular pela reação em cadeia da polimerase seguida de análise de restrição do fragmento amplificado (PRA). Utilizaram-se inhagens de referência e leite cru artificialmente contaminado com M. bovis IP. Um fragmento de 441pb do gene hsp65 foi amplificado, tratado com BstEII e HaeIII e empregou-se o perfil de restrição enzimática obtido para identificar o complexo M. tuberculosis no leite. Com a PRA foi possível detectar com especificidade e sensibilidade a presença de M. bovis em até 10 UFC/mL de leite. A metodologia padronizada poderá auxiliar os métodos microbiológicos e bioquímicos tradicionalmente usados na identificação do bacilo em alimentos suspeitos de contaminação, como, por exemplo, o leite proveniente de animais suspeitos de infecção por M. bovis.Palavras-chaves: Análise de perfil de restrição enzimática (PRA), complexo Mycobacterium tuberculosis, leite, Mycobacterium bovis, limite de detecção (PCR). Mycobacterium bovis is a member of the M. tuberculosis complex, a group composed by species with high genetic homology. The pathogen is the etiological agent of bovine tuberculosis, an important zoonosis that is mainly transmitted by inhalation of infectious droplet nuclei or by ingestion of milk and crude milk derivative products from tuberculosis cows. The definitive identification of M. bovis, up to species level, is time consuming and difficult. In this work, the objective was to standardize a polymerase chain reaction followed by an enzyme restriction analysis in order to identify the M. tuberculosis complex in milk, without a microbiological isolation step. Reference strains and raw milk seeded with M. Bovis, were used as the starting material.  A 441pb fragment of the hsp65 gene was amplified and digested by two restriction enzymes BstEII and HaeIII. The obtained profile was used to identify the M. tuberculosis complex in milk. The minimum limit of detection of M. bovis in milk was 10CFU/mL. PRA methodology proved to be a specific and sensible method. It can be used to assist the microbiological and biochemical methods commonly used to identifying the bacilli in clinical samples, as milk  Key word: Detection limit (PRA), Mycobacterium tuberculosis complex, milk Mycobacterium bovis, Restriction Enzyme Analysis (PCR),

Eduardo Eustáquio de Souza Figueiredo; Marlei Gomes da Silva; Leila de Souza Fonseca; Joab Trajano Silva; Vânia Margaret Flosi Paschoalin

2008-01-01

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Th1 polarized response induced by intramuscular DNA-HSP65 immunization is preserved in experimental atherosclerosis  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardi (more) ovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 µg DNA-HSP65. On day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.

Fonseca, D.M.; Bonato, V.L.D.; Silva, C.L.; Sartori, A.

2007-11-01

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HSP65-PRA identification of non-tuberculosis mycobacteria from 4892 samples suspicious for mycobacterial infections.  

Science.gov (United States)

Various molecular methods have been used for the rapid identification of mycobacterial species. In this survey, evaluation of antibiotic resistance and PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene was carried out for identification of non-tuberculosis mycobacteria (NTM) isolates from different clinical specimens. Forty-eight different mycobacterial isolates were selected and followed by the conventional and PRA of hsp65 for species identification. The antibiotic susceptibility test was carried out according to standard methods. A 439 bp PCR product of hsp65 in all selected isolates was amplified and digested with the BstEII and HaeIII restriction enzymes. The restriction fragment length polymorphism (RFLP) patterns were analyzed for species identification. Using PRA for 48 mycobacterial selected isolates, including 15 M. tuberculosis, one M. bovis and all 32 isolates of NTM, revealed 11 different species among the NTM isolates. The most frequent NTM isolates were M. kansasii, M. gordonae III, M. marinum, M. chelonae, M. scrofluaceum and M. gastri. In most cases, the PRA results were perfectly in accordance with the classical biochemical method. Combination of resistance to rifampin and isoniazid was present among M. kansasi, M. gordoniae III, M. scrofluaceum, M. chelonae, M. marinum, M. gastri, M. gordoniae II and M. trivale isolates. A high incidence of co-resistance to six, five, four and three anti-TB drugs was observed in 18.5%, 9.1%, 6.6% and 11.7% of all NTM isolates, respectively. Our results showed that PRA, in comparison with classical methods, is rapid and accurate enough for the identification of mycobacterial species from LJ medium. Additionally, we found that in Iran we have a highly diverse population of NTM isolates among patients suspected of having TB. PMID:22963505

Saifi, M; Jabbarzadeh, E; Bahrmand, A R; Karimi, A; Pourazar, S; Fateh, A; Masoumi, M; Vahidi, E

2012-09-11

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HSP65-PRA identification of non-tuberculosis mycobacteria from 4892 samples suspicious for mycobacterial infections.  

UK PubMed Central (United Kingdom)

Various molecular methods have been used for the rapid identification of mycobacterial species. In this survey, evaluation of antibiotic resistance and PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene was carried out for identification of non-tuberculosis mycobacteria (NTM) isolates from different clinical specimens. Forty-eight different mycobacterial isolates were selected and followed by the conventional and PRA of hsp65 for species identification. The antibiotic susceptibility test was carried out according to standard methods. A 439 bp PCR product of hsp65 in all selected isolates was amplified and digested with the BstEII and HaeIII restriction enzymes. The restriction fragment length polymorphism (RFLP) patterns were analyzed for species identification. Using PRA for 48 mycobacterial selected isolates, including 15 M. tuberculosis, one M. bovis and all 32 isolates of NTM, revealed 11 different species among the NTM isolates. The most frequent NTM isolates were M. kansasii, M. gordonae III, M. marinum, M. chelonae, M. scrofluaceum and M. gastri. In most cases, the PRA results were perfectly in accordance with the classical biochemical method. Combination of resistance to rifampin and isoniazid was present among M. kansasi, M. gordoniae III, M. scrofluaceum, M. chelonae, M. marinum, M. gastri, M. gordoniae II and M. trivale isolates. A high incidence of co-resistance to six, five, four and three anti-TB drugs was observed in 18.5%, 9.1%, 6.6% and 11.7% of all NTM isolates, respectively. Our results showed that PRA, in comparison with classical methods, is rapid and accurate enough for the identification of mycobacterial species from LJ medium. Additionally, we found that in Iran we have a highly diverse population of NTM isolates among patients suspected of having TB.

Saifi M; Jabbarzadeh E; Bahrmand AR; Karimi A; Pourazar S; Fateh A; Masoumi M; Vahidi E

2013-08-01

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Influência do biofármaco DNA-hsp65 na lesão pulmonar induzida por bleomicina/ Influence of a DNA-hsp65 vaccine on bleomycin-induced lung injury  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese OBJETIVO: Avaliar a influência do biofármaco DNA-hsp65 em um modelo de distúrbio fibrosante pulmonar experimental. MÉTODOS: Foram estudados 120 camundongos machos C57BL/6, divididos em quatro grupos: grupo SS, animais tratados com salina (placebo) e injetados com salina intratraqueal (IT); grupo SB, tratados com salina (placebo) e injetados com bleomicina IT; grupo PB, tratados com plasmídeo, sem gene bacteriano, e injetados com bleomicina IT; e grupo BB, tratados co (more) m DNA-hsp65 e injetados com bleomicina IT. A bleomicina foi injetada 15 dias após a última imunização, e os animais sacrificados seis semanas após o uso da droga IT. O pulmão esquerdo retirado foi utilizado para análise morfológica, e o pulmão direito para dosagens de hidroxiprolina. RESULTADOS: A proporção de camundongos que apresentaram morte não-programada depois de 48 h da injeção IT foi maior no grupo SB em comparação ao grupo SS (57,7% vs. 11,1%). A área percentual média de interstício septal foi maior nos grupos SB e PB (53,1 ± 8,6% e 53,6 ± 9,3%, respectivamente) em comparação aos grupos SS e BB (32,9 ± 2,7% e 34,3 ± 6,1%, respectivamente). Os grupos SB, PB e BB mostraram aumentos nos valores médios da área de interstício septal corada por picrosirius em comparação ao grupo SS (SS: 2,0 ± 1,4%; SB: 8,2 ± 4,9%; PB: 7,2 ± 4,2%; e BB:6,6±4,1%).O conteúdo pulmonar de hidroxiprolina no grupo SS foi inferior ao dos demais grupos (SS: 104,9 ± 20,9 pg/pulmão; SB: 160,4 ±47,8 pg/pulmão; PB:170,0 ± 72,0 pg/pulmão; e BB: 162,5 ± 39,7 pg/pulmão). CONCLUSÕES: A imunização com o biofármaco DNA-hsp65 interferiu na deposição de matriz não-colágena em um modelo de lesão pulmonar induzida por bleomicina. Abstract in english OBJECTIVE: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. METHODS: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo) and then receiving intratracheal (IT) instillation of saline; SB, injected with saline (placebo) and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of (more) bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. RESULTS: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure) was higher in the SB group than in the SS group (57.7% vs. 11.1%). The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6±9.3%, respectively) than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively). The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0±1.4%). The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung) than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung). CONCLUSIONS: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.

Padua, Adriana Ignacio de; Silva, Célio Lopes; Ramos, Simone Gusmão; Faccioli, Lúcia Helena; Martinez, José Antônio Baddini

2008-11-01

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Tissue distribution of DNA-Hsp65/TDM-loaded PLGA microspheres and uptake by phagocytic cells  

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Full Text Available Abstract This study aimed to demonstrate that microspheres, used as delivery vehicle of DNA-Hsp65/TDM [plasmid DNA encoding heat shock protein 65 (Hsp65) coencapsulated with trehalose dimycolate (TDM) into PLGA microspheres], are widely spread among several organs after intramuscular administration in BALB/c mice. In general, we showed that these particles were phagocytosed by antigen presenting cells, such as macrophages and dendritic cells. Besides, it was demonstrated herein that draining lymph node cells presented a significant increase in the number of cells expressing costimulatory molecules (CD80 and CD86) and MHC class II, and also that the administration of the DNA-Hsp65/TDM and vector/TDM formulations resulted in the up-regulation of CD80, CD86 and MHC class II expression when compared to control formulations (vector/TDM and empty). Regarding the intracellular trafficking we observed that following phagocytosis, the microspheres were not found in the late endosomes and/or lysosomes, until 15 days after internalization, and we suggest that these constructions were hydrolysed in early compartments. Overall, these data expand our knowledge on PLGA [poly (lactic-co- glycolic acid)] microspheres as gene carriers in vaccination strategies, as well as open perspectives for their potential use in clinical practice.

Trombone Ana Paula F; Silva Celio L; Almeida Luciana P; Rosada Rogerio S; Lima Karla M; Oliver Constance; Jamur Maria C; Coelho-Castelo Arlete AM

2007-01-01

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Discovery of a novel hsp65 genotype within Mycobacterium massiliense associated with the rough colony morphology.  

UK PubMed Central (United Kingdom)

So far, genetic diversity among strains within Mycobacterium massiliense has rarely been studied. To investigate the genetic diversity among M. massiliense, we conducted phylogenetic analysis based on hsp65 (603-bp) and rpoB (711-bp) sequences from 65 M. massiliense Korean isolates. We found that hsp65 sequence analysis could clearly differentiate them into two distinct genotypes, Type I and Type II, which were isolated from 35 (53.8%) and 30 patients (46.2%), respectively. The rpoB sequence analysis revealed a total of four genotypes (R-I to R-IV) within M. massiliense strains, three of which (R-I, R-II and R-III) correlated with hsp65 Type I, and other (R-IV), which correlated with Type II. Interestingly, genotyping by the hsp65 method agreed well with colony morphology. Despite some exceptions, Type I and II correlated with smooth and rough colonies, respectively. Also, both types were completely different from one another in terms of MALDI-TOF mass spectrometry profiles of whole lipid. In addition, we developed PCR-restriction analysis (PRA) based on the Hinf I digestion of 644-bp hsp65 PCR amplicons, which enables the two genotypes within M. massiliense to be easily and reliably separated. In conclusion, two distinct hsp65 genotypes exist within M. massiliense strains, which differ from one another in terms of both morphology and lipid profile. Furthermore, our data indicates that Type II is a novel M. massiliense genotype being herein presented for the first time. The disparity in clinical traits between these two hsp65 genotypes needs to be exploited in the future study.

Kim BJ; Yi SY; Shim TS; Do SY; Yu HK; Park YG; Kook YH; Kim BJ

2012-01-01

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Discovery of a novel hsp65 genotype within Mycobacterium massiliense associated with the rough colony morphology.  

Science.gov (United States)

So far, genetic diversity among strains within Mycobacterium massiliense has rarely been studied. To investigate the genetic diversity among M. massiliense, we conducted phylogenetic analysis based on hsp65 (603-bp) and rpoB (711-bp) sequences from 65 M. massiliense Korean isolates. We found that hsp65 sequence analysis could clearly differentiate them into two distinct genotypes, Type I and Type II, which were isolated from 35 (53.8%) and 30 patients (46.2%), respectively. The rpoB sequence analysis revealed a total of four genotypes (R-I to R-IV) within M. massiliense strains, three of which (R-I, R-II and R-III) correlated with hsp65 Type I, and other (R-IV), which correlated with Type II. Interestingly, genotyping by the hsp65 method agreed well with colony morphology. Despite some exceptions, Type I and II correlated with smooth and rough colonies, respectively. Also, both types were completely different from one another in terms of MALDI-TOF mass spectrometry profiles of whole lipid. In addition, we developed PCR-restriction analysis (PRA) based on the Hinf I digestion of 644-bp hsp65 PCR amplicons, which enables the two genotypes within M. massiliense to be easily and reliably separated. In conclusion, two distinct hsp65 genotypes exist within M. massiliense strains, which differ from one another in terms of both morphology and lipid profile. Furthermore, our data indicates that Type II is a novel M. massiliense genotype being herein presented for the first time. The disparity in clinical traits between these two hsp65 genotypes needs to be exploited in the future study. PMID:22693637

Kim, Byoung-Jun; Yi, Su-Yeon; Shim, Tae-Sun; Do, Seung Yeon; Yu, Hee-Kyung; Park, Young-Gil; Kook, Yoon-Hoh; Kim, Bum-Joon

2012-06-05

 
 
 
 
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Improve protective efficacy of a TB DNA-HSP65 vaccine by BCG priming  

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Full Text Available Abstract Vaccines are considered by many to be one of the most successful medical interventions against infectious diseases. But many significant obstacles remain, such as optimizing DNA vaccines for use in humans or large animals. The amount of doses, route and easiness of administration are also important points to consider in the design of new DNA vaccines. Heterologous prime-boost regimens probably represent the best hope for an improved DNA vaccine strategy. In this study, we have shown that heterologous prime-boost vaccination against tuberculosis (TB) using intranasal BCG priming/DNA-HSP65 boosting (BCGin/DNA) provided significantly greater protection than that afforded by a single subcutaneous or intranasal dose of BCG. In addition, BCGin/DNA immunization was also more efficient in controlling bacterial loads than were the other prime-boost schedules evaluated or three doses of DNA-HSP65 as a naked DNA. The single dose of DNA-HSP65 booster enhanced the immunogenicity of a single subcutaneous BCG vaccination, as evidenced by the significantly higher serum levels of anti-Hsp65 IgG2a Th1-induced antibodies, as well as by the significantly greater production of IFN-? by antigen-specific spleen cells. The BCG prime/DNA-HSP65 booster was also associated with better preservation of lung parenchyma. The improvement of the protective effect of BCG vaccine mediated by a DNA-HSP65 booster suggests that our strategy may hold promise as a safe and effective vaccine against TB.

Gonçalves Eduardo DC; Bonato Vânia; da Fonseca Denise M; Soares Edson G; Brandão Izaíra T; Soares Ana; Silva Célio L

2007-01-01

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Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strate (more) gy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-? but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.

Rocha, C.D.; Trombone, A.P.F.; Lorenzi, J.C.C.; Almeida, L.P.; Gembre, A.F.; Padilha, E.; Ramos, S.G.; Silva, C.L.; Coelho-Castelo, A.A.M.

2012-12-01

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Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis  

Directory of Open Access Journals (Sweden)

Full Text Available In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-? but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.

C.D. Rocha; A.P.F. Trombone; J.C.C. Lorenzi; L.P. Almeida; A.F. Gembre; E. Padilha; S.G. Ramos; C.L. Silva; A.A.M. Coelho-Castelo

2012-01-01

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Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes  

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Full Text Available Abstract Background The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally. Results We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 ?g of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-? and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 ?g). Conclusion Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease.

Rosada Rogério S; Torre Lucimara; Frantz Fabiani G; Trombone Ana PF; Zárate-Bladés Carlos R; Fonseca Denise M; Souza Patrícia RM; Brandão Izaíra T; Masson Ana P; Soares Édson G; Ramos Simone G; Faccioli Lúcia H; Silva Célio L; Santana Maria HA; Coelho-Castelo Arlete AM

2008-01-01

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Differentiation of Mycobacterial Species by hsp65 Duplex PCR Followed by Duplex-PCR-Based Restriction Analysis and Direct Sequencing?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Here we describe a novel duplex PCR method which can differentiate Mycobacterium tuberculosis and nontuberculosis mycobacteria (NTM) strains by amplifying hsp65 DNAs of different sizes (195 and 515 bp, respectively). The devised technique was applied to 54 reference and 170 clinical isolates and dif...

Kim, Hyun-Ju; Mun, Ho-Suk; Kim, Hong; Oh, Eun-Ju; Ha, Youngju; Bai, Gill-Han; Park, Young-Gil; Cha, Chang-Yong; Kook, Yoon-Hoh

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Immunization with a HSP65-HER2 fusion peptide selectively eliminates HER2(+) B16 melanoma cells in a xenograft tumor mouse model.  

UK PubMed Central (United Kingdom)

HER2/neu peptide-based vaccines can eliminate human tumors overexpressing the human epidermal growth factor receptor 2 (HER2/neu), but the efficacy of this therapeutic strategy is suboptimal. Heat shock proteins (HSPs) are capable of eliciting efficient cytotoxic T lymphocyte (CTL) responses by cross-presentation. To evaluate whether immunization with a HSP65-HER2 fusion peptide could selectively eliminate HER2(+) B16 melanoma cells in a xenograft tumor mouse model, a HSP65-HER2 fusion peptide was incubated with immature dendritic cells (iDCs) in vitro to determine whether loading of iDCs with HSP65-HER2 could induce the expression of the immunomodulatory cell surface molecule, CD86. In vivo mouse immunizations with HSP65-HER2 or PBS (control) were performed to determine the antitumor effects by longitudinally monitoring changes in tumor volume, weight, and incidence. The effects on percentages of HER2(+) B16 cells in tumors were assessed by confocal microscopy and flow cytometry. The results indicated that loading of iDCs with HSP65-HER2 induced the expression of CD86 in vitro, suggesting that the hybrid antigen was able to stimulate an immune response. Immunization with HSP65-HER2 had no significant influence on tumor weight or volume but significantly reduced tumor incidence (62.5 % in mice injected with 25 ?g of HSP65-HER2 vs. 100 % in PBS-injected controls; P?HSP65-HER2 immunization significantly reduced the percentages of HER2(+) B16 cells in xenografted tumors (1.86 % vs. 30.56 % in PBS-injected controls; P?=?0.01). Our findings suggest that immunization with the HSP65-HER2 fusion peptide selectively eliminates HER2(+) B16 melanoma cells in a xenograft tumor mouse model and may represent a novel and efficacious targeted therapy of HER2/neu(+) tumors.

Wang J; Wang X; Chen Y; Wan M; Xiang Z; Wu X; Wei H; Wang L; Zhang P; Wang L; Yu Y

2013-02-01

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A subunit vaccine based on biodegradable microspheres carrying rHsp65 protein and KLK protects BALB/c mice against tuberculosis infection.  

UK PubMed Central (United Kingdom)

Of the hundreds of new tuberculosis (TB) vaccine candidates, some have therapeutic value in addition to their prophylactic properties. This is the case for the DNA vaccine encoding heat-shock protein 65 (DNAhsp65) from Mycobacterium leprae. However, there are concerns about the use of DNA vaccines in certain populations such as newborns and pregnant women. Thus, the optimization of vaccination strategies that circumvent this limitation is a priority. This study evaluated the efficacy of a single dose subunit vaccine based on recombinant Hsp65 protein against infection with M. tuberculosis H37Rv. The Hsp65 protein in this study was either associated or not with immunostimulants, and was encapsulated in biodegradable PLGA microspheres. Our results demonstrate that the protein was entrapped in microspheres of adequate diameter to be engulfed by phagocytes. Mice vaccinated with a single dose of Hsp65-microspheres or Hsp65+CpG-microspheres developed both humoral and cellular-specific immune responses. However, they did not protect mice against challenge with M. tuberculosis. By contrast, Hsp65+KLK-microspheres induced specific immune responses that reduced bacilli loads and minimized lung parenchyma damage. These data suggest that a subunit vaccine based on recombinant protein Hsp65 is feasible.

dos Santos SA; Zárate-Bladés CR; de Sá Galetti FC; Brandão IT; Masson AP; Soares EG; Araújo AP; Silva CL

2010-12-01

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Combined rpoB duplex PCR and hsp65 PCR restriction fragment length polymorphism with capillary electrophoresis as an effective algorithm for identification of Mycobacterial species from clinical isolates  

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Full Text Available Abstract Background Mycobacteria can be quickly and simply identified by PCR restriction-enzyme analysis (PRA), but misidentification can occur because of similarities in band sizes that are critical for discriminating among species. Capillary electrophoresis can provide computer-aided band discrimination. The aim of this research was to develop an algorithm for identifying mycobacteria by combined rpoB duplex PRA (DPRA) and hsp65 PRA with capillary electrophoresis. Results Three hundred and seventy-six acid-fast bacillus smear-positive BACTEC cultures, including 200 Mycobacterium tuberculosis complexes (MTC) and 176 non-tuberculous mycobacteria (NTM) were analyzed. With combined hsp65 and rpoB DPRA, the accuracy rate was 100% (200 isolates) for the MTC and 91.4% (161 isolates) for the NTM. Among the discordant results (8.6%) for the NTM, one isolate of Mycobacterial species and an isolate of M. flavescens were found as new sub-types in hsp65 PRA. Conclusions This effective and novel identification algorithm using combined rpoB DPRA and hsp65 PRA with capillary electrophoresis can rapidly identify mycobacteria and find new sub-types in hsp65 PRA. In addition, it is complementary to 16 S rDNA sequencing.

Huang Chen-Cheng; Chen Jiann-Hwa; Hu Shiau-Ting; Chiou Chien-Shun; Huang Wei-Chang; Hsu Jeng-Yuan; Lu Jang-Jih; Shen Gwan-Han

2012-01-01

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Combined rpoB duplex PCR and hsp65 PCR restriction fragment length polymorphism with capillary electrophoresis as an effective algorithm for identification of mycobacterial species from clinical isolates.  

UK PubMed Central (United Kingdom)

BACKGROUND: Mycobacteria can be quickly and simply identified by PCR restriction-enzyme analysis (PRA), but misidentification can occur because of similarities in band sizes that are critical for discriminating among species. Capillary electrophoresis can provide computer-aided band discrimination. The aim of this research was to develop an algorithm for identifying mycobacteria by combined rpoB duplex PRA (DPRA) and hsp65 PRA with capillary electrophoresis. RESULTS: Three hundred and seventy-six acid-fast bacillus smear-positive BACTEC cultures, including 200 Mycobacterium tuberculosis complexes (MTC) and 176 non-tuberculous mycobacteria (NTM) were analyzed. With combined hsp65 and rpoB DPRA, the accuracy rate was 100% (200 isolates) for the MTC and 91.4% (161 isolates) for the NTM. Among the discordant results (8.6%) for the NTM, one isolate of Mycobacterial species and an isolate of M. flavescens were found as new sub-types in hsp65 PRA. CONCLUSIONS: This effective and novel identification algorithm using combined rpoB DPRA and hsp65 PRA with capillary electrophoresis can rapidly identify mycobacteria and find new sub-types in hsp65 PRA. In addition, it is complementary to 16 S rDNA sequencing.

Huang CC; Chen JH; Hu ST; Chiou CS; Huang WC; Hsu JY; Lu JJ; Shen GH

2012-01-01

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Methods for preventing formation of inhibitory antibodies in the setting of gene therapy  

UK PubMed Central (United Kingdom)

The invention provides a method of preventing the formation of inhibitory antibodies in a mammal undergoing gene therapy. The method comprises administering to the mammal an immunosuppressive agent in conjunction with the gene therapy.

HIGH KATHERINE A; FIELDS PAUL A; ARRUDA VALDER R; HERZOG ROLAND W

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Gene Variants That Prevent African Sleeping Sickness Increase Kidney Disease Risk  

Science.gov (United States)

... Winter 2011 Kidney Disease Research Updates Winter 2011 Gene Variants That Prevent African Sleeping Sickness Increase Kidney Disease Risk A gene that evolved to protect against trypanosomes—microscopic parasites ...

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FHIT: from gene discovery to cancer treatment and prevention.  

Science.gov (United States)

Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity, are among the most common features of human tumours. The short arm of human chromosome 3, particularly the region 3p14.2, is a major site of such rearrangements. The 3p14.2 region spans the most active common fragile site of the human genome, encompassing a familial-kidney-cancer-associated breakpoint and a papilloma virus integration site. 6 years ago, the FHIT gene was identified in this region. Subsequent studies have shown that FHIT is commonly the target of chromosomal aberrations involving the long arm of human chromosome 3 and is thereby inactivated in most of the common human malignant diseases, including cancers of the lung, oesophagus, stomach, breast, and kidney. During the past 5 years, evidence has accumulated in support of a tumour-suppressor function for FHIT. In this review, we describe the recent findings in the molecular biology of FHIT with particular focus on the opportunities for treatment and prevention of cancer that have emerged. PMID:12473516

Pekarsky, Yuri; Zanesi, Nicola; Palamarchuk, Alexey; Huebner, Kay; Croce, Carlo M

2002-12-01

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FHIT: from gene discovery to cancer treatment and prevention.  

UK PubMed Central (United Kingdom)

Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity, are among the most common features of human tumours. The short arm of human chromosome 3, particularly the region 3p14.2, is a major site of such rearrangements. The 3p14.2 region spans the most active common fragile site of the human genome, encompassing a familial-kidney-cancer-associated breakpoint and a papilloma virus integration site. 6 years ago, the FHIT gene was identified in this region. Subsequent studies have shown that FHIT is commonly the target of chromosomal aberrations involving the long arm of human chromosome 3 and is thereby inactivated in most of the common human malignant diseases, including cancers of the lung, oesophagus, stomach, breast, and kidney. During the past 5 years, evidence has accumulated in support of a tumour-suppressor function for FHIT. In this review, we describe the recent findings in the molecular biology of FHIT with particular focus on the opportunities for treatment and prevention of cancer that have emerged.

Pekarsky Y; Zanesi N; Palamarchuk A; Huebner K; Croce CM

2002-12-01

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Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis  

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Full Text Available Abstract Background mRNAs are highly versatile, non-toxic molecules that are easy to produce and store, which can allow transient protein expression in all cell types. The safety aspects of mRNA-based treatments in gene therapy make this molecule one of the most promising active components of therapeutic or prophylactic methods. The use of mRNA as strategy for the stimulation of the immune system has been used mainly in current strategies for the cancer treatment but until now no one tested this molecule as vaccine for infectious disease. Results We produce messenger RNA of Hsp65 protein from Mycobacterium leprae and show that vaccination of mice with a single dose of 10 ?g of naked mRNA-Hsp65 through intranasal route was able to induce protection against subsequent challenge with virulent strain of Mycobacterium tuberculosis. Moreover it was shown that this immunization was associated with specific production of IL-10 and TNF-alpha in spleen. In order to determine if antigen presenting cells (APCs) present in the lung are capable of capture the mRNA, labeled mRNA-Hsp65 was administered by intranasal route and lung APCs were analyzed by flow cytometry. These experiments showed that after 30 minutes until 8 hours the populations of CD11c+, CD11b+ and CD19+ cells were able to capture the mRNA. We also demonstrated in vitro that mRNA-Hsp65 leads nitric oxide (NO) production through Toll-like receptor 7 (TLR7). Conclusions Taken together, our results showed a novel and efficient strategy to control experimental tuberculosis, besides opening novel perspectives for the use of mRNA in vaccines against infectious diseases and clarifying the mechanisms involved in the disease protection we noticed as well.

Lorenzi Julio CC; Trombone Ana PF; Rocha Carolina D; Almeida Luciana P; Lousada Ricardo L; Malardo Thiago; Fontoura Isabela C; Rossetti Renata AM; Gembre Ana F; Silva Aristóbolo M; Silva Celio L; Coelho-Castelo Arlete AM

2010-01-01

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From gene engineering to gene modulation and manipulation: can we prevent or detect gene doping in sports?  

Science.gov (United States)

During the last 2 decades, progress in deciphering the human gene map as well as the discovery of specific defective genes encoding particular proteins in some serious human diseases have resulted in attempts to treat sick patients with gene therapy. There has been considerable focus on human recombinant proteins which were gene-engineered and produced in vitro (insulin, growth hormone, insulin-like growth factor-1, erythropoietin). Unfortunately, these substances and methods also became improper tools for unscrupulous athletes. Biomedical research has focused on the possible direct insertion of gene material into the body, in order to replace some defective genes in vivo and/or to promote long-lasting endogenous synthesis of deficient proteins. Theoretically, diabetes, anaemia, muscular dystrophies, immune deficiency, cardiovascular diseases and numerous other illnesses could benefit from such innovative biomedical research, though much work remains to be done. Considering recent findings linking specific genotypes and physical performance, it is tempting to submit the young athletic population to genetic screening or, alternatively, to artificial gene expression modulation. Much research is already being conducted in order to achieve a safe transfer of genetic material to humans. This is of critical importance since uncontrolled production of the specifically coded protein, with serious secondary adverse effects (polycythaemia, acute cardiovascular problems, cancer, etc.), could occur. Other unpredictable reactions (immunogenicity of vectors or DNA-vector complex, autoimmune anaemia, production of wild genetic material) also remain possible at the individual level. Some new substances (myostatin blockers or anti-myostatin antibodies), although not gene material, might represent a useful and well-tolerated treatment to prevent progression of muscular dystrophies. Similarly, other molecules, in the roles of gene or metabolic activators [5-aminoimidazole-4-carboxamide 1-?-D-ribofuranoside (AICAR), GW1516], might concomitantly improve endurance exercise capacity in ischaemic conditions but also in normal conditions. Undoubtedly, some athletes will attempt to take advantage of these new molecules to increase strength or endurance. Antidoping laboratories are improving detection methods. These are based both on direct identification of new substances or their metabolites and on indirect evaluation of changes in gene, protein or metabolite patterns (genomics, proteomics or metabolomics). PMID:23832852

Fischetto, Giuseppe; Bermon, Stéphane

2013-10-01

36

From Gene Engineering to Gene Modulation and Manipulation: Can We Prevent or Detect Gene Doping in Sports?  

UK PubMed Central (United Kingdom)

During the last 2 decades, progress in deciphering the human gene map as well as the discovery of specific defective genes encoding particular proteins in some serious human diseases have resulted in attempts to treat sick patients with gene therapy. There has been considerable focus on human recombinant proteins which were gene-engineered and produced in vitro (insulin, growth hormone, insulin-like growth factor-1, erythropoietin). Unfortunately, these substances and methods also became improper tools for unscrupulous athletes. Biomedical research has focused on the possible direct insertion of gene material into the body, in order to replace some defective genes in vivo and/or to promote long-lasting endogenous synthesis of deficient proteins. Theoretically, diabetes, anaemia, muscular dystrophies, immune deficiency, cardiovascular diseases and numerous other illnesses could benefit from such innovative biomedical research, though much work remains to be done. Considering recent findings linking specific genotypes and physical performance, it is tempting to submit the young athletic population to genetic screening or, alternatively, to artificial gene expression modulation. Much research is already being conducted in order to achieve a safe transfer of genetic material to humans. This is of critical importance since uncontrolled production of the specifically coded protein, with serious secondary adverse effects (polycythaemia, acute cardiovascular problems, cancer, etc.), could occur. Other unpredictable reactions (immunogenicity of vectors or DNA-vector complex, autoimmune anaemia, production of wild genetic material) also remain possible at the individual level. Some new substances (myostatin blockers or anti-myostatin antibodies), although not gene material, might represent a useful and well-tolerated treatment to prevent progression of muscular dystrophies. Similarly, other molecules, in the roles of gene or metabolic activators [5-aminoimidazole-4-carboxamide 1-?-D-ribofuranoside (AICAR), GW1516], might concomitantly improve endurance exercise capacity in ischaemic conditions but also in normal conditions. Undoubtedly, some athletes will attempt to take advantage of these new molecules to increase strength or endurance. Antidoping laboratories are improving detection methods. These are based both on direct identification of new substances or their metabolites and on indirect evaluation of changes in gene, protein or metabolite patterns (genomics, proteomics or metabolomics).

Fischetto G; Bermon S

2013-07-01

37

Novel diagnostic algorithm using tuf gene amplification and restriction fragment length polymorphism is promising tool for identification of nontuberculous mycobacteria.  

Science.gov (United States)

Nontuberculous mycobacteria (NTM) are a major cause of opportunistic infections in immunocompromised patients, making the reliable and rapid identification of NTM to the species level very important for the treatment of such patients. Therefore, this study evaluated the usefulness of the novel target genes tuf and tmRNA for the identification of NTM to the species level, using a PCRrestriction fragment length polymorphism analysis (PRA). A total of 44 reference strains and 17 clinical isolates of the genus Mycobacterium were used. The 741 bp or 744 bp tuf genes were amplified, restricted with two restriction enzymes (HaeIII/MboI), and sequenced. The tuf gene-PRA patterns were compared with those for the tmRNA (AvaII), hsp65 (HaeIII/HphI), rpoB (MspI/HaeIII), and 16S rRNA (HaeIII) genes. For the reference strains, the tuf gene-PRA yielded 43 HaeIII patterns, of which 35 (81.4%) showed unique patterns on the species level, whereas the tmRNA, hsp65, rpoB, and 16S rRNA-PRAs only showed 10 (23.3%), 32 (74.4%), 19 (44.2%), and 3 (7%) unique patterns after single digestion, respectively. The tuf gene-PRA produced a clear distinction between closely related NTM species, such as M. abscessus (557-84- 58) and M. chelonae (477-84-80-58), and M. kansasii (141- 136-80-63-58-54-51) and M. gastri (141-136-117-80-58-51). No difference was observed between the tuf-PRA patterns for the reference strains and clinical isolates. Thus, a diagnostic algorithm using a tuf gene-targeting PRA is a promising tool with more advantages than the previously used hsp65, rpoB, and 16S rRNA genes for the identification of NTM to the species level. PMID:19349759

Shin, Ji-Hyun; Cho, Eun-Jin; Lee, Jung-Yeon; Yu, Jae-Yon; Kang, Yeon-Ho

2009-03-01

38

Novel diagnostic algorithm using tuf gene amplification and restriction fragment length polymorphism is promising tool for identification of nontuberculous mycobacteria.  

UK PubMed Central (United Kingdom)

Nontuberculous mycobacteria (NTM) are a major cause of opportunistic infections in immunocompromised patients, making the reliable and rapid identification of NTM to the species level very important for the treatment of such patients. Therefore, this study evaluated the usefulness of the novel target genes tuf and tmRNA for the identification of NTM to the species level, using a PCRrestriction fragment length polymorphism analysis (PRA). A total of 44 reference strains and 17 clinical isolates of the genus Mycobacterium were used. The 741 bp or 744 bp tuf genes were amplified, restricted with two restriction enzymes (HaeIII/MboI), and sequenced. The tuf gene-PRA patterns were compared with those for the tmRNA (AvaII), hsp65 (HaeIII/HphI), rpoB (MspI/HaeIII), and 16S rRNA (HaeIII) genes. For the reference strains, the tuf gene-PRA yielded 43 HaeIII patterns, of which 35 (81.4%) showed unique patterns on the species level, whereas the tmRNA, hsp65, rpoB, and 16S rRNA-PRAs only showed 10 (23.3%), 32 (74.4%), 19 (44.2%), and 3 (7%) unique patterns after single digestion, respectively. The tuf gene-PRA produced a clear distinction between closely related NTM species, such as M. abscessus (557-84- 58) and M. chelonae (477-84-80-58), and M. kansasii (141- 136-80-63-58-54-51) and M. gastri (141-136-117-80-58-51). No difference was observed between the tuf-PRA patterns for the reference strains and clinical isolates. Thus, a diagnostic algorithm using a tuf gene-targeting PRA is a promising tool with more advantages than the previously used hsp65, rpoB, and 16S rRNA genes for the identification of NTM to the species level.

Shin JH; Cho EJ; Lee JY; Yu JY; Kang YH

2009-03-01

39

Sucrose prevents up-regulation of senescence-associated genes in carnation petals.  

Science.gov (United States)

cDNA microarrays were used to characterize senescence-associated gene expression in petals of cut carnation (Dianthus caryophyllus) flowers, sampled from anthesis to the first senescence symptoms. The population of PCR fragments spotted on these microarrays was enriched for flower-specific and senescence-specific genes, using subtractive hybridization. About 90% of the transcripts showed a large increase in quantity, approximately 25% transiently, and about 65% throughout the 7 d experiment. Treatment with silver thiosulphate (STS), which blocks the ethylene receptor and prevented the normal senescence symptoms, prevented the up-regulation of almost all of these genes. Sucrose treatment also considerably delayed visible senescence. Its effect on gene expression was very similar to that of STS, suggesting that soluble sugars act as a repressor of ethylene signal transduction. Two fragments that encoded a carnation EIN3-like (EIL) protein were isolated, some of which are key transcription factors that control ethylene response genes. One of these (Dc-EIL3) was up-regulated during senescence. Its up-regulation was delayed by STS and prevented by sucrose. Sucrose, therefore, seems to repress ethylene signalling, in part, by preventing up-regulation of Dc-EIL3. Some other transcription factors displayed an early increase in transcript abundance: a MYB-like DNA binding protein, a MYC protein, a MADS-box factor, and a zinc finger protein. Genes suggesting a role in senescence of hormones other than ethylene encoded an Aux/IAA protein, which regulate transcription of auxin-induced genes, and a cytokinin oxidase/dehydrogenase, which degrades cytokinin. Taken together, the results suggest a master switch during senescence, controlling the co-ordinated up-regulation of numerous ethylene response genes. Dc-EIL3 might be (part of) this master switch. PMID:17630294

Hoeberichts, Frank A; van Doorn, Wouter G; Vorst, Oscar; Hall, Robert D; van Wordragen, Monique F

2007-07-13

40

Gene therapy approaches to prevent corneal graft rejection: where do we stand?  

UK PubMed Central (United Kingdom)

Cornea transplantation (penetrating keratoplasty) is the most frequently performed transplant procedure in humans. Despite advances in microsurgery and immunosuppressive treatment protocols, a significant number of corneal grafts still undergo immune-mediated allograft rejection. Topical treatment with corticosteroids is currently the gold standard and while this treatment is effective in many corneal transplant patients, it is much less effective in 'high-risk' patients with previous episodes of neovascularisation or graft rejection. Therefore, alternative approaches such as genetic modification of donor corneas are needed to prevent corneal transplant rejection. Cornea transplantation holds the unique advantage in that gene therapy can be used to modify allografts ex vivo prior to transplantation. Many preclinical studies using local (and systemic) gene transfer have been performed to date and many different gene transfer vehicles (gene therapy vectors) and therapeutic strategies (immunomodulatory or graft-protective) have been investigated to prevent corneal allograft rejection. The most recent gene therapy applications to prevent corneal allograft rejection will be reviewed in this article. Moreover, it will be discussed why the development of clinical trials for the genetic modification of corneal grafts prior to transplantation is lagging behind of those for the treatment of inherited retinal diseases.

Ritter T; Wilk M; Nosov M

2013-01-01

 
 
 
 
41

Molecular genetic, diagnosis, prevention and gene therapy in prostatic cancer: review article  

Directory of Open Access Journals (Sweden)

Full Text Available "nThe prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer), and also the second leading cause of cancer death (after lung cancer) among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.

Noori Daloii MR; Ebrahimzadeh Vesal E

2009-01-01

42

Suppression of the vacuolar invertase gene prevents cold-induced sweetening in potato.  

UK PubMed Central (United Kingdom)

Potato (Solanum tuberosum) is the third most important food crop in the world. Potato tubers must be stored at cold temperatures to prevent sprouting, minimize disease losses, and supply consumers and the processing industry with high-quality tubers throughout the year. Unfortunately, cold storage triggers an accumulation of reducing sugars in tubers. High-temperature processing of these tubers results in dark-colored, bitter-tasting products. Such products also have elevated amounts of acrylamide, a neurotoxin and potential carcinogen. We demonstrate that silencing the potato vacuolar acid invertase gene VInv prevents reducing sugar accumulation in cold-stored tubers. Potato chips processed from VInv silencing lines showed a 15-fold acrylamide reduction and were light in color even when tubers were stored at 4°C. Comparable, low levels of VInv gene expression were observed in cold-stored tubers from wild potato germplasm stocks that are resistant to cold-induced sweetening. Thus, both processing quality and acrylamide problems in potato can be controlled effectively by suppression of the VInv gene through biotechnology or targeted breeding.

Bhaskar PB; Wu L; Busse JS; Whitty BR; Hamernik AJ; Jansky SH; Buell CR; Bethke PC; Jiang J

2010-10-01

43

Disruption of the MacMARCKS gene prevents cranial neural tube closure and results in anencephaly.  

UK PubMed Central (United Kingdom)

MacMARCKS is a member of the MARCKS family of protein kinase C (PKC) substrates. Biochemical evidence demonstrates that these proteins integrate calcium and PKC-dependent signals to regulate actin structure at the membrane. We report here that deletion of the MacMARCKS gene prevents cranial neural tube closure in the developing brain, resulting in anencephaly. This suggests a central role for MacMARCKS and the PKC signal transduction pathway in the folding of the anterior neural plate during the early phases of brain formation, and supports the hypothesis that actin-based motility directs cranial neural tube closure.

Chen J; Chang S; Duncan SA; Okano HJ; Fishell G; Aderem A

1996-06-01

44

HDAC inhibitors prevent the induction of the immediate-early gene FOSL1, but do not alter the nucleosome response.  

UK PubMed Central (United Kingdom)

Dynamic histone acetylation, catalyzed by lysine acetyltransferases and HDACs, is critical to IEG expression. Expression of IEGs, such as FOSL1, is induced by several signal transduction pathways resulting in activation of the protein kinase MSK and phosphorylation of histone H3 at serine 10 of nucleosomes (the nucleosome response) at the upstream promoter and regulatory region of target genes. HDAC inhibitors prevent FOSL1 gene induction and the association of HDAC1, 2 and 3 with the gene body. However, HDAC inhibitors did not prevent the nucleosome response. Thus HDAC inhibitors perturb events downstream of the nucleosome response required for FOSL1 transcription initiation.

Khan DH; Davie JR

2013-05-01

45

HDAC inhibitors prevent the induction of the immediate-early gene FOSL1, but do not alter the nucleosome response.  

Science.gov (United States)

Dynamic histone acetylation, catalyzed by lysine acetyltransferases and HDACs, is critical to IEG expression. Expression of IEGs, such as FOSL1, is induced by several signal transduction pathways resulting in activation of the protein kinase MSK and phosphorylation of histone H3 at serine 10 of nucleosomes (the nucleosome response) at the upstream promoter and regulatory region of target genes. HDAC inhibitors prevent FOSL1 gene induction and the association of HDAC1, 2 and 3 with the gene body. However, HDAC inhibitors did not prevent the nucleosome response. Thus HDAC inhibitors perturb events downstream of the nucleosome response required for FOSL1 transcription initiation. PMID:23542037

Khan, Dilshad H; Davie, James R

2013-03-29

46

Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes.  

UK PubMed Central (United Kingdom)

In eukaryotic cells, transgene expression levels may be limited by an unfavourable chromatin structure at the integration site. Epigenetic regulators are DNA sequences which may protect transgenes from such position effect. We evaluated different epigenetic regulators for their ability to protect transgene expression at telomeres, which are commonly associated to low or inconsistent expression because of their repressive chromatin environment. Although to variable extents, matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE) and the chicken cHS4 insulator acted as barrier elements, protecting a telomeric-distal transgene from silencing. MARs also increased the probability of silent gene reactivation in time-course experiments. Additionally, all MARs improved the level of expression in non-silenced cells, unlike other elements. MARs were associated to histone marks usually linked to actively expressed genes, especially acetylation of histone H3 and H4, suggesting that they may prevent the spread of silencing chromatin by imposing acetylation marks on nearby nucleosomes. Alternatively, an UCOE was found to act by preventing deposition of repressive chromatin marks. We conclude that epigenetic DNA elements used to enhance and stabilize transgene expression all have specific epigenetic signature that might be at the basis of their mode of action.

Majocchi S; Aritonovska E; Mermod N

2013-09-01

47

Maize x Teosinte Hybrid Cobs Do Not Prevent Crop Gene Introgression.  

UK PubMed Central (United Kingdom)

Maize x Teosinte Hybrid Cobs Do Not Prevent Crop Gene Introgression. Whether introgression from crops to wild relatives can occur is an important component of transgene risk assessment. In the case of maize, which co-occurs with its wild relative teosinte in Mexico, the possibility of introgression has been controversial. Maize is cross-compatible with teosinte, and spontaneous hybridization is known to occur. Some scientists have hypothesized that the maize x teosinte cob infructescence will prevent progeny dispersal, thus preventing introgression. Motivated by a prior study where we found maize x teosinte hybrid fruits naturally dispersed under field conditions, we tested whether hybrid cobs hold their fruits as tightly as maize cobs. We found the force required to detach hybrid fruits was substantially and significantly less than that for maize. Consequently, we expect that introgression of transgenes from maize into teosinte in Mexico should occur largely unimpeded by the hybrid cob.La mazorca o elote híbrido de maíz x teocintle no impide la introgresión de genes transgénicos provenientes del cultivo. La introgresión entre el maíz cultivado y el maíz silvestre, o teocintle, es un componente importante en la evaluación ambiental relacionada con los riesgos de la introducción de genes transgénicos. La posibilidad de introgresión entre el maíz domesticado y el teocintle ha sido un tema controversial, en particular en México, donde maíz y teocintle coexisten. El maíz es compatible con el teocintle y la hibridización espontánea ocurre entre ellos. Algunos científicos han planteado como hipótesis que al cruzar el maíz con teocintle, la estructura interna de la infrutescencia que sujeta los frutos conocida como la mazorca de maíz o el elote, impide la dispersión de la progenie evitando que la introgresión ocurra. Los resultados de un estudio previo evidencian la dispersión de los frutos híbridos del maíz x teocintle en condiciones naturales. Motivados por estos resultados, hemos decidido investigar si la mazorca o el elote de las infrutescencias del híbrido sujetan los frutos con una fuerza comparable o mayor a la del maíz. Nuestras mediciones implican que la fuerza necesaria para liberar los frutos híbridos son substancial y significativamente menores que aquellas necesarias para desprender los frutos del maíz. Como conclusión sugerimos que en México, la mazorca o el elote no representan una barrera que impida la introgresión de los genes transgénicos del maíz al teocintle.

Chavez NB; Flores JJ; Martin J; Ellstrand NC; Guadagnuolo R; Heredia S; Welles SR

2012-06-01

48

Maize x Teosinte Hybrid Cobs Do Not Prevent Crop Gene Introgression.  

Science.gov (United States)

Maize x Teosinte Hybrid Cobs Do Not Prevent Crop Gene Introgression. Whether introgression from crops to wild relatives can occur is an important component of transgene risk assessment. In the case of maize, which co-occurs with its wild relative teosinte in Mexico, the possibility of introgression has been controversial. Maize is cross-compatible with teosinte, and spontaneous hybridization is known to occur. Some scientists have hypothesized that the maize x teosinte cob infructescence will prevent progeny dispersal, thus preventing introgression. Motivated by a prior study where we found maize x teosinte hybrid fruits naturally dispersed under field conditions, we tested whether hybrid cobs hold their fruits as tightly as maize cobs. We found the force required to detach hybrid fruits was substantially and significantly less than that for maize. Consequently, we expect that introgression of transgenes from maize into teosinte in Mexico should occur largely unimpeded by the hybrid cob.La mazorca o elote híbrido de maíz x teocintle no impide la introgresión de genes transgénicos provenientes del cultivo. La introgresión entre el maíz cultivado y el maíz silvestre, o teocintle, es un componente importante en la evaluación ambiental relacionada con los riesgos de la introducción de genes transgénicos. La posibilidad de introgresión entre el maíz domesticado y el teocintle ha sido un tema controversial, en particular en México, donde maíz y teocintle coexisten. El maíz es compatible con el teocintle y la hibridización espontánea ocurre entre ellos. Algunos científicos han planteado como hipótesis que al cruzar el maíz con teocintle, la estructura interna de la infrutescencia que sujeta los frutos conocida como la mazorca de maíz o el elote, impide la dispersión de la progenie evitando que la introgresión ocurra. Los resultados de un estudio previo evidencian la dispersión de los frutos híbridos del maíz x teocintle en condiciones naturales. Motivados por estos resultados, hemos decidido investigar si la mazorca o el elote de las infrutescencias del híbrido sujetan los frutos con una fuerza comparable o mayor a la del maíz. Nuestras mediciones implican que la fuerza necesaria para liberar los frutos híbridos son substancial y significativamente menores que aquellas necesarias para desprender los frutos del maíz. Como conclusión sugerimos que en México, la mazorca o el elote no representan una barrera que impida la introgresión de los genes transgénicos del maíz al teocintle. PMID:22707759

Chavez, Nancy B; Flores, Jose J; Martin, Joseph; Ellstrand, Norman C; Guadagnuolo, Roberto; Heredia, Sylvia; Welles, Shana R

2012-04-26

49

Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Apoptosis is an early event involved in cardiomyopathy associated with diabetes mellitus. Toll-like receptor (TLR) signaling triggers cell apoptosis through multiple mechanisms. Up-regulation of TLR4 expression has been shown in diabetic mice. This study aimed to delineate the role of TLR4 in myocardial apoptosis, and to block this process through gene silencing of TLR4 in the myocardia of diabetic mice. Methods Diabetes was induced in C57/BL6 mice by the injection of streptozotocin. Diabetic mice were treated with 50 ?g of TLR4 siRNA or scrambled siRNA as control. Myocardial apoptosis was determined by TUNEL assay. Results After 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated. Treatment of TLR4 siRNA knocked down gene expression as well as diminished its elevation in diabetic mice. Apoptosis was evident in cardiac tissues of diabetic mice as detected by a TUNEL assay. In contrast, treatment with TLR4 siRNA minimized apoptosis in myocardial tissues. Mechanistically, caspase-3 activation was significantly inhibited in mice that were treated with TLR4 siRNA, but not in mice treated with control siRNA. Additionally, gene silencing of TLR4 resulted in suppression of apoptotic cascades, such as Fas and caspase-3 gene expression. TLR4 deficiency resulted in inhibition of reactive oxygen species (ROS) production and NADPH oxidase activity, suggesting suppression of hyperglycemia-induced apoptosis by TLR4 is associated with attenuation of oxidative stress to the cardiomyocytes. Conclusions In summary, we present novel evidence that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.

Zhang Yuwei; Peng Tianqing; Zhu Huaqing; Zheng Xiufen; Zhang Xusheng; Jiang Nan; Cheng Xiaoshu; Lai Xiaoyan; Shunnar Aminah; Singh Manpreet; Riordan Neil; Bogin Vladimir; Tong Nanwei; Min Wei-Ping

2010-01-01

50

Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice.  

UK PubMed Central (United Kingdom)

Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis.

Reggiani PC; Barbeito CG; Zuccolilli GO; Cónsole GM; Flamini AM; Dardenne M; Goya RG

2012-08-01

51

Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation.  

UK PubMed Central (United Kingdom)

Necrotizing enterocolitis (NEC), an extensive intestinal inflammatory disease of premature infants, is caused, in part, by an excessive inflammatory response to initial bacterial colonization due to the immature expression of innate immune response genes. In a randomized placebo-controlled clinical trial, supplementation of very low birth weight infants with probiotics significantly reduced the incidence of NEC. The primary goal of this study was to determine whether secreted products of these two clinically effective probiotic strains, Bifidobacterium infantis and Lactobacillus acidophilus, prevented NEC by accelerating the maturation of intestinal innate immune response genes and whether both strains are required for this effect. After exposure to probiotic conditioned media (PCM), immature human enterocytes, immature human intestinal xenografts, and primary enterocyte cultures of NEC tissue (NEC-IEC) were assayed for an IL-8 and IL-6 response to inflammatory stimuli. The latter two models were also assayed for innate immune response gene expression. In the immature xenograft, PCM exposure significantly attenuated LPS and IL-1?-induced IL-8 and IL-6 expression, decreased TLR2 mRNA and TLR4 mRNA, and increased mRNA levels of specific negative regulators of inflammation, SIGIRR and Tollip. In NEC-IEC, PCM decreased TLR2-dependent IL-8 and IL-6 induction and increased SIGIRR and Tollip expression. The attenuated inflammatory response with PCM was reversed with Tollip siRNA-mediated knockdown. The anti-inflammatory secreted factor is a 5- to 10-kDa molecule resistant to DNase, RNase, protease, heat stress, and acid exposure. B. infantis-conditioned media showed superior anti-inflammatory properties to that of L. acidophilus in immature human enterocytes, suggesting a strain specificity to this effect. We conclude that PCM promotes maturation of innate immune response gene expression, potentially explaining the protective effects of probiotics in clinical NEC.

Ganguli K; Meng D; Rautava S; Lu L; Walker WA; Nanthakumar N

2013-01-01

52

Immunomodulatory gene therapy prevents antibody formation and lethal hypersensitivity reactions in murine pompe disease.  

UK PubMed Central (United Kingdom)

Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 x 10(10) particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, and IgE antibodies to GAA in Pompe disease mice, when compared with mock-treated mice (P < 0.05). AAV-LSPhGAApA had the same effect on GAA-antibody production whether it was given prior to, following, or simultaneously with the initial GAA injection. Mice given AAV-LSPhGAApA had significantly less decrease in body temperature (P < 0.001) and lower anaphylactic scores (P < 0.01) following the GAA challenge. Mouse mast cell protease-1 (MMCP-1) followed the pattern associated with hypersensitivity reactions (P < 0.05). Regulatory T cells (Treg) were demonstrated to play a role in the tolerance induced by gene therapy as depletion of Treg led to an increase in GAA-specific IgG (P < 0.001). Treg depleted mice were challenged with GAA and had significantly stronger allergic reactions than mice given gene therapy without subsequent Treg depletion (temperature: P < 0.01; symptoms: P < 0.05). Ubiquitous GAA expression failed to prevent antibody formation. Thus, immunomodulatory gene therapy could provide adjunctive therapy in lysosomal storage disorders treated by enzyme replacement.

Sun B; Kulis MD; Young SP; Hobeika AC; Li S; Bird A; Zhang H; Li Y; Clay TM; Burks W; Kishnani PS; Koeberl DD

2010-02-01

53

The bcl-2 gene product prevents programmed cell death of ventricular myocytes.  

UK PubMed Central (United Kingdom)

BACKGROUND: To formally test whether the antiapoptotic protein bcl-2 would prevent programmed cell death in cardiac muscle cells provoked by p53, a known trigger of apoptosis in a variety of different cell types, we used replication defective adenovirus encoding either the bcl-2 and p53 genes to deliver bcl-2 and p53 to ventricular myocytes with high efficiency and uniformity. METHODS AND RESULTS: Vital staining of ventricular myocytes revealed a significant (7-fold, P<.05) increase in myocyte cell death in the presence of p53 in contrast to uninfected cells or those infected with a control virus. In addition, in the presence of p53, nucleosomal DNA fragmentation observed by Hoescht 33258 staining and terminal transferase deoxynucleotide end labeling indicated a significant increase in apoptotic cardiac nuclei compared with control cells, confirming the hypothesis that p53 alone is sufficient to trigger apoptosis of ventricular myocytes. Moreover, a significant increase in transcription of the bax promoter was seen in the presence but not in the absence of p53 compared with control cells. Expression of the antiapoptotic gene bcl-2 in ventricular myocytes was sufficient to prevent ventricular myocyte death and apoptosis provoked by p53. Importantly, the antiapoptotic effects of bcl-2 were independent of altered p53 expression or localization of p53 to cardiac nuclei. However, p53 dependent transcription of bax was repressed 4-fold (P<.05) by bcl-2, suggesting a tentative link between p53-mediated apoptosis and the protective properties conferred by bcl-2 in ventricular myocytes. CONCLUSIONS: To our knowledge, the data provide the first indication for the operation of bcl-2 in ventricular myocytes as an antiapoptotic factor.

Kirshenbaum LA; de Moissac D

1997-09-01

54

PHARMACEUTICAL COMPOSITION FOR PREVENTING AND/OR TREATING OF CORNEAL DYSTROPHY ASSOCIATED WITH TGFBI GENE MUTATION AND ITS SCREENING METHOD  

UK PubMed Central (United Kingdom)

PURPOSE: A pharmaceutical composition containing lithium for preventing or treating corneal dystrophy associated with TGFBI gene mutation is provided. CONSTITUTION: A pharmaceutical composition for preventing or treating corneal dystrophy associated with TGFBI gene mutation contains lithium. The lithium is contained in the composition in the form of a lithium ion, pharmaceutically acceptable lithium salt, or solvate or hydrate thereof. The pharmaceutically acceptable litium salt is lithium carbonate(Li_2CO_3), litium citrate, lithium sulfate(Li_2SO_4), litium aspartate, litium orotate, lithium chloride(LiCl), or lithium acetate.

KIM EUNG KWEON; CHOI SEUNG IL

55

Essential Gene Pathways for Glioblastoma Stem Cells: Clinical Implications for Prevention of Tumor Recurrence  

Directory of Open Access Journals (Sweden)

Full Text Available Glioblastoma (World Health Organization/WHO grade IV) is the most common and most aggressive adult glial tumor. Patients with glioblastoma, despite being treated with gross total resection and post-operative radiation/chemotherapy, will almost always develop tumor recurrence. Glioblastoma stem cells (GSC), a minor subpopulation within the tumor mass, have been recently characterized as tumor-initiating cells and hypothesized to be responsible for post-treatment recurrence because of their enhanced radio-/chemo-resistant phenotype and ability to reconstitute tumors in mouse brains. Genome-wide expression profile analysis uncovered molecular properties of GSC distinct from their differentiated, proliferative progeny that comprise the majority of the tumor mass. In contrast to the hyperproliferative and hyperangiogenic phenotype of glioblastoma tumors, GSC possess neuroectodermal properties and express genes associated with neural stem cells, radial glial cells, and neural crest cells, as well as portray a migratory, quiescent, and undifferentiated phenotype. Thus, cell cycle-targeted radio-chemotherapy, which aims to kill fast-growing tumor cells, may not completely eliminate glioblastoma tumors. To prevent tumor recurrence, a strategy targeting essential gene pathways of GSC must be identified and incorporated into the standard treatment regimen. Identifying intrinsic and extrinsic cues by which GSC maintain stemness properties and sustain both tumorigenesis and anti-apoptotic features may provide new insights into potentially curative strategies for treating brain cancers.

Kazunari Yamada; Jonathan Tso; Fei Ye; Jinny Choe; Yue Liu; Linda M. Liau; Cho-Lea Tso

2011-01-01

56

Physical training prevents body weight gain but does not modify adipose tissue gene expression  

Directory of Open Access Journals (Sweden)

Full Text Available The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.

T.S. Higa; F.C. Bergamo; F. Mazzucatto; M.H. Fonseca-Alaniz; F.S. Evangelista

2012-01-01

57

Sutherlandia frutescens prevents changes in diabetes-related gene expression in a fructose-induced insulin resistant cell model.  

UK PubMed Central (United Kingdom)

ETHNOPHARMACOLOGICAL RELEVANCE: The African medicinal plant Sutherlandia frutescens (L.) R.Br. (Fabaceae) is traditionally used to treat diabetes and has been shown to have anti-diabetic properties in animal models. The present study investigated the capacity of an aqueous extract of Sutherlandia frutescens to prevent insulin resistance (a precursor of type 2 diabetes) in a human liver cell culture and to identify genes regulated by Sutherlandia frutescens treatment. MATERIALS AND METHODS: A combination of insulin and fructose was used to generate an in vitro model of insulin resistance in human liver cells to compare untreated control, insulin resistant and Sutherlandia frutescens treated insulin resistant cultures. Insulin resistance and its prevention by Sutherlandia frutescens were measured by glucose uptake, gluconeogenesis and lipid accumulation in the cell cultures. Changes in gene expression were quantified using the RT(2)Profiler(TM) PCR Array of 84 diabetes-related genes. RESULTS: The insulin resistant Chang liver cells took up significantly less 2-[(3)H]-deoxyglucose (p<0.05) than controls, released more glucose into the culture medium (p<0.05) and accumulated more intracellular lipid (p<0.05). Simultaneous treatment with Sutherlandia frutescens prevented development of these insulin resistance parameters (p<0.05). A total of 27 potential gene targets of Sutherlandia frutescens were significantly up or down regulated in the Sutherlandia frutescens treated insulin resistant cells. The gene VAMP3, which plays a role in vesicle transport, was down-regulated by insulin resistance, and up-regulated by Sutherlandia frutescens. Twenty six other genes encoding vesicle transporters, receptors, signalling molecules, transcription factors, and metabolic enzymes were significantly regulated by Sutherlandia frutescens. CONCLUSION: These results confirm that Sutherlandia frutescens can prevent insulin resistance in hepatocytes. The identified changes in gene expression indicate several potential mechanisms of anti-diabetic action for Sutherlandia frutescens, reflecting the multiple bioactive compounds previously identified in aqueous extracts of Sutherlandia frutescens.

Williams S; Roux S; Koekemoer T; van de Venter M; Dealtry G

2013-03-01

58

Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-?B-dependent genes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Induction of NF-?B-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease (ALD). Curcumin, a phenolic antioxidant, inhibits the activation of NF-?B. We determined whether treatment with curcumin would prevent experimental ALD and elucidated the underlying mechani...

Nanji, AA; Jokelainen, K; Tipoe, GL; Rahemtulla, A; Thomas, P; Dannenberg, AJ

59

Improve protective efficacy of a TB DNA-HSP65 vaccine by BCG priming  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Vaccines are considered by many to be one of the most successful medical interventions against infectious diseases. But many significant obstacles remain, such as optimizing DNA vaccines for use in humans or large animals. The amount of doses, route and easiness of administration are also important ...

Gonçalves, Eduardo DC; Bonato, Vânia Luiza D; da Fonseca, Denise M; Soares, Edson G; Brandão, Izaíra T; Soares, Ana Paula M

60

RB gene expression prevents apoptosis in an RB-negative cancer cell line  

Energy Technology Data Exchange (ETDEWEB)

To examine the RB gene function in vivo, we established an RB-positive cell line, H-CL2, by transfecting the RB-negative human bladder carcinoma cell line, HTB9, with an RB expression vector. RB-positive H-CL2 cells grow in a serum-dependent manner and lack tumorigenicity in nude mice. At confluency, H-CL2 cells showed contact inhibition, whereas HTB9 cells continued to undergo cell division and detached from the plate within several hours. These detached cells were dye exclusive and fragmentation of nuclei was observed. In addition, DNA extracted from those cells showed ladder formation characteristic of apoptotic cells. In contrast, none of these phenomena was observed with H-CL2 following confluency. However, both H-CL2 and HTB9 cells expressed equally high levels of Fas antigen and had negative sensitivity to TNF. Serum stimulation of HTB9 resulted in increased c-myc expression followed by DNA synthesis, whereas no such increase in c-myc and DNA levels was observed in H-CL2 cells. These results suggest that RB protein expression prevents apoptosis of HTB9 cells through down-regulation of c-myc and suppression of DNA synthesis.

Hashimoto, T.; Furuyama, J.; Kaji, M. [Hyogo College of Medicine, Nishnomiya (Japan)] [and others

1994-09-01

 
 
 
 
61

Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes  

Directory of Open Access Journals (Sweden)

Full Text Available DNA damage is a pre-requisite for the initiation of cancer and agents that reduce this damage are useful in cancer prevention. In this study, we evaluated the ability of whole berries and berry phytochemical, ellagic acid to reduce endogenous oxidative DNA damage. Ellagic acid was selected based on > 95% inhibition of 8-oxodeoxyguosine (8-oxodG) and other unidentified oxidative DNA adducts induced by 4-hydroxy-17B;-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 u(micro)M) than that for 8-oxodG (100 u(micro)M). In the in vivo study, female CD-1 mice (n=6) were fed either a control diet or diet supplemented with ellagic acid (400 ppm) and dehydrated berries (5% w/w) with varying ellagic acid contents -- blueberry (low), strawberry (medium) and red raspberry (high), for 3 weeks. Blueberry and strawberry diets showed moderate reductions in endogenous DNA adducts (25%). However, both red raspberry and ellagic acid diets showed a significant reduction of 59% (p < 0.001) and 48% (p < 0.01), respectively. Both diets also resulted in a 3-8 fold over-expression of genes involved in DNA repair such as xeroderma pigmentosum group A complementing protein (XPA), DNA excision repair protein (ERCC5) and DNA ligase III (DNL3). These results suggest that red raspberry and ellagic acid reduce endogenous oxidative DNA damage by mechanisms which may involve increase in DNA repair.

Harini S. Aiyer; Manicka V. Vadhanam; Radka Stoyanova; Gerard D. Caprio; Margie L. Clapper; Ramesh C. Gupta

2008-01-01

62

Heart failure-inducible gene therapy targeting protein phosphatase 1 prevents progressive left ventricular remodeling.  

UK PubMed Central (United Kingdom)

BACKGROUND: The targeting of Ca(2+) cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR) Ca(2+) ATPase, or ablation of phospholamban (PLN) and associated protein phosphatase 1 (PP1) protein complexes. We previously reported that PP1?, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+) uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+) downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1?-inhibition by adeno-associated viral-9 (AAV9) vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice. METHODS: We created an adeno-associated virus 9 (AAV9) vector encoding PP1? short-hairpin RNA (shRNA) or negative control (NC) shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP) promoter conjugated to emerald-green fluorescence protein (EmGFP) and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1?shRNA and AAV9-BNP-EmGFP-NCshRNA) were injected into the tail vein (2×10(11) GC/mouse) of muscle LIM protein deficient mice (MLPKO), followed by serial analysis of echocardiography, hemodynamic measurement, biochemical and histological analysis at 3 months. RESULTS: In the MLPKO mice, BNP promoter activity was shown to be increased by detecting both EmGFP expression and the induced reduction of PP1? by 25% in the myocardium. Inducible PP1?shRNA delivery preferentially ameliorated left ventricular diastolic function and mitigated adverse ventricular remodeling. PLN phosphorylation was significantly augmented in the AAV9-BNP-EmGFP-PP1?shRNA injected hearts compared with the AAV9-BNP-EmGFP-NCshRNA group. Furthermore, BNP production was reduced, and cardiac interstitial fibrosis was abrogated at 3 months. CONCLUSION: Heart failure-inducible molecular targeting of PP1? has potential as a novel therapeutic strategy for heart failure.

Miyazaki Y; Ikeda Y; Shiraishi K; Fujimoto SN; Aoyama H; Yoshimura K; Inui M; Hoshijima M; Kasahara H; Aoki H; Matsuzaki M

2012-01-01

63

SERCA2a gene transfer prevents intimal proliferation in an organ culture of human internal mammary artery.  

UK PubMed Central (United Kingdom)

Coronary restenosis, a major complication of percutaneous balloon angioplasty, results from neointimal proliferation of vascular smooth muscle cells (VSMCs). The sarco/endoplasmic reticulum calcium ATPase 2a isoform (SERCA2a), specific to contractile VSMCs, has been reported previously to be involved in the control of the Ca(2+)-signaling pathways governing proliferation and migration. Moreover, SERCA2a gene transfer was reported to inhibit in vitro VSMC proliferation and to prevent neointimal thickening in a rat carotid injury model. The aim of this study was to evaluate the potential therapeutic interest of SERCA2a gene transfer for prevention of in-stent restenosis using a ex vivo model of human left internal mammary artery (hIMA) intimal thickening. Left hIMAs, obtained at the time of aorto-coronary bypass surgeries, were subjected to balloon dilatation followed by infection for 30 min with adenoviruses encoding either human SERCA2 and green fluorescence protein (GFP) or control gene (?-galactosidase, ?-gal) and GFP. Proliferation of subendothelial VSMCs and neointimal thickening were observed in balloon-injured hIMA maintained 14 days in organ culture under constant pressure and perfusion. SERCA2a gene transfer prevented vascular remodeling and significantly (P<0.01, n=5) reduced neointimal thickening in injured arteries (intima/media ratio was 0.07±0.01 vs 0.40±0.03 in ?-gal-infected arteries). These findings could have potential implications for treatment of pathological in-stent restenosis.

Lipskaia L; Hadri L; Le Prince P; Esposito B; Atassi F; Liang L; Glorian M; Limon I; Lompre AM; Lehoux S; Hajjar RJ

2013-04-01

64

Taurine prevented cell cycle arrest and restored neurotrophic gene expression in arsenite-treated SH-SY5Y cells.  

Science.gov (United States)

The study investigated the effect of taurine on cell viability and neurotrophic gene expression in arsenite-treated human neuroblastoma SH-SY5Y cells. Arsenite-induced intracellular reactive oxygen species (ROS) and interrupted cell cycle in SH-SY5Y cells. In addition, arsenite reduced mitochondria membrane potential (MMP) and decreased neurotrophic gene expressions such as n-myc downstream-regulated gene 4 (NDRG-4), brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT-1) in SH-SY5Y cells. In parallel, taurine prevented cell cycle, restored MMP and reduced the intracellular ROS level, and taurine recovered NDRG-4, BDNF and SIRT-1 gene expressions in arsenite-treated SH-SY5Y cells while taurine alone has no effect on these parameters. PMID:23744399

Chou, Chien-Te; Lin, Wen-Feng; Kong, Zwe-Ling; Chen, Shiow-Yi; Hwang, Deng-Fwu

2013-06-07

65

Taurine prevented cell cycle arrest and restored neurotrophic gene expression in arsenite-treated SH-SY5Y cells.  

UK PubMed Central (United Kingdom)

The study investigated the effect of taurine on cell viability and neurotrophic gene expression in arsenite-treated human neuroblastoma SH-SY5Y cells. Arsenite-induced intracellular reactive oxygen species (ROS) and interrupted cell cycle in SH-SY5Y cells. In addition, arsenite reduced mitochondria membrane potential (MMP) and decreased neurotrophic gene expressions such as n-myc downstream-regulated gene 4 (NDRG-4), brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT-1) in SH-SY5Y cells. In parallel, taurine prevented cell cycle, restored MMP and reduced the intracellular ROS level, and taurine recovered NDRG-4, BDNF and SIRT-1 gene expressions in arsenite-treated SH-SY5Y cells while taurine alone has no effect on these parameters.

Chou CT; Lin WF; Kong ZL; Chen SY; Hwang DF

2013-10-01

66

Gene-activation mechanisms in the regression of atherosclerosis, elimination of diabetes type 2, and prevention of dementia.  

UK PubMed Central (United Kingdom)

Atherosclerotic vascular disease, diabetes mellitus (DM) and dementia are major global health problems. Both endogenous and exogenous factors activate genes functioning in biological processes. This review article focuses on gene-activation mechanisms that regress atherosclerosis, eliminate DM type 2 (DM2), and prevent cognitive decline and dementia. Gene-activating compounds upregulating functions of liver endoplasmic reticulum (ER) and affecting lipid and protein metabolism, increase ER size through membrane synthesis, and produce an antiatherogenic plasma lipoprotein profile. Numerous gene-activators regress atherosclerosis and reduce the occurrence of atherosclerotic disease. The gene-activators increase glucose disposal rate and insulin sensitivity and, by restoring normal glucose and insulin levels, remove metabolic syndrome and DM2. Patients with DM2 show an improvement of plasma lipoprotein profile and glucose tolerance together with increase in liver phospholipid (PL) and cytochrome (CYP) P450. The gene-activating compounds induce hepatic protein and PL synthesis, and upregulate enzymes including CYPs and glucokinase, nuclear receptors, apolipoproteins and ABC (ATP-binding cassette) transporters. They induce reparation of ER structures and eliminate consequences of ER stress. Healthy living habits activate mechanisms that maintain high levels of HDL and apolipoprotein AI, promote health, and prevent cognitive decline and dementia. Agonists of liver X receptor (LXR) reduce amyloid in brain plaques and improve cognitive performance in mouse models of Alzheimer's disease. The gene activation increases the capacity to withstand cellular stress and to repair cellular damage and increases life span. Life free of major health problems and in good cognitive health promotes well-being and living a long and active life.

Luoma PV

2011-07-01

67

Two Gene Variants May Predict Who Will Benefit from Breast Cancer Prevention Drugs  

Science.gov (United States)

... June 13, 2013, 10 a.m. EDT Two gene variants may predict who will benefit from breast ... National Institutes of Health have now identified two gene variants that may predict which women are most ...

68

Error prevention and mitigation as forces in the evolution of genes and genomes.  

UK PubMed Central (United Kingdom)

Why are short introns rarely a multiple of three nucleotides long? Why do essential genes cluster? Why are genes in operons often lined up in the order in which they are needed in the encoded pathway? In this Opinion article, we argue that these and many other - ostensibly disparate - observations are all pieces of an emerging picture in which multiple aspects of gene anatomy and genome architecture have evolved in response to error-prone gene expression.

Warnecke T; Hurst LD

2011-12-01

69

Nerve growth factor gene therapy using adeno-associated viral vectors prevents cardiomyopathy in type 1 diabetic mice.  

Science.gov (United States)

Diabetes is a cause of cardiac dysfunction, reduced myocardial perfusion, and ultimately heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system. This study investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice. We worked with mice with streptozotocin-induced type 1 diabetes and with nondiabetic control mice. After having established that diabetes reduces cardiac NGF mRNA expression, we tested NGF gene therapies with adeno-associated viral vectors (AAVs) for the capacity to protect the diabetic mouse heart. To this aim, after 2 weeks of diabetes, cardiac expression of human NGF or ?-Gal (control) genes was induced by either intramyocardial injection of AAV serotype 2 (AAV2) or systemic delivery of AAV serotype 9 (AAV9). Nondiabetic mice were given AAV2-?-Gal or AAV9-?-Gal. We found that the diabetic mice receiving NGF gene transfer via either AAV2 or AAV9 were spared the progressive deterioration of cardiac function and left ventricular chamber dilatation observed in ?-Gal-injected diabetic mice. Moreover, they were additionally protected from myocardial microvascular rarefaction, hypoperfusion, increased deposition of interstitial fibrosis, and increased apoptosis of endothelial cells and cardiomyocytes, which afflicted the ?-Gal-injected diabetic control mice. Our data suggest therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects. PMID:22187379

Meloni, Marco; Descamps, Betty; Caporali, Andrea; Zentilin, Lorena; Floris, Ilaria; Giacca, Mauro; Emanueli, Costanza

2012-01-01

70

Nerve growth factor gene therapy using adeno-associated viral vectors prevents cardiomyopathy in type 1 diabetic mice.  

UK PubMed Central (United Kingdom)

Diabetes is a cause of cardiac dysfunction, reduced myocardial perfusion, and ultimately heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system. This study investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice. We worked with mice with streptozotocin-induced type 1 diabetes and with nondiabetic control mice. After having established that diabetes reduces cardiac NGF mRNA expression, we tested NGF gene therapies with adeno-associated viral vectors (AAVs) for the capacity to protect the diabetic mouse heart. To this aim, after 2 weeks of diabetes, cardiac expression of human NGF or ?-Gal (control) genes was induced by either intramyocardial injection of AAV serotype 2 (AAV2) or systemic delivery of AAV serotype 9 (AAV9). Nondiabetic mice were given AAV2-?-Gal or AAV9-?-Gal. We found that the diabetic mice receiving NGF gene transfer via either AAV2 or AAV9 were spared the progressive deterioration of cardiac function and left ventricular chamber dilatation observed in ?-Gal-injected diabetic mice. Moreover, they were additionally protected from myocardial microvascular rarefaction, hypoperfusion, increased deposition of interstitial fibrosis, and increased apoptosis of endothelial cells and cardiomyocytes, which afflicted the ?-Gal-injected diabetic control mice. Our data suggest therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects.

Meloni M; Descamps B; Caporali A; Zentilin L; Floris I; Giacca M; Emanueli C

2012-01-01

71

Human placental ectonucleoside triphosphate diphosphohydrolase gene transfer via gelatin-coated stents prevents in-stent thrombosis.  

UK PubMed Central (United Kingdom)

BACKGROUND: In-stent thrombosis is mainly triggered by adenosine diphosphate (ADP)-dependent platelet aggregation after percutaneous coronary stent implantation. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) rapidly hydrolyzes ADP to adenosine monophosphate, inhibiting platelet aggregation. We tested the hypothesis that local delivery of human placental E-NTPDase (pE-NTPDase) gene into injured arteries via gene-eluting stent could prevent subacute in-stent thrombosis. METHODS AND RESULTS: We generated gene-eluting stents by coating bare metal stents with cationic gelatin hydrogel containing pE-NTPDase cDNA (pE-NTPDase stent), and implanted the stents into rabbit femoral arteries (FA) prone to production of platelet-rich thrombi due to repeated balloon injury at 4-week intervals. After the second injury, E-NTPDase gene expression was severely decreased; however, the implantation of pE-NTPDase stent increased E-NTPDase mRNA levels and NTPDase activity to higher level than normal FA. The FAs with pE-NTPDase stents maintained patency in all rabbits (P<0.01), whereas the stent-implanted FAs without pE-NTPDase gene showed low patency rates (17% to 25%). The occlusive platelet-rich thrombi, excessive neointimal growth, and infiltration of macrophages were inhibited in stent implanted FA with pE-NTPDase gene, but not without pE-NTPDase gene. CONCLUSIONS: Human pE-NTPDase gene transfer via cationic gelatin-coated stents inhibited subacute in-stent thrombosis and suppressed neointimal hyperplasia and inflammation without antiplatelet drugs.

Takemoto Y; Kawata H; Soeda T; Imagawa K; Somekawa S; Takeda Y; Uemura S; Matsumoto M; Fujimura Y; Jo J; Kimura Y; Tabata Y; Saito Y

2009-06-01

72

Antidigoxin antiserum prevents endogenous digitalis-like compound-mediated reperfusion injury via modulating sodium pump isoform gene expression.  

UK PubMed Central (United Kingdom)

Endogenous digitalis-like compound (EDLC) is an endogenous ligand of the digitalis receptor and can remarkably inhibit Na+/K+-ATPase activity. Antidigoxin antiserum (ADA), a selective EDLC antagonist, may lessen myocardial reperfusion injury; however, the molecular mechanisms underlying the effect remain unclear. Therefore, this study investigated whether ADA may prevent myocardial reperfusion injury and modulate gene expression of sodium pump alpha isoforms. Cardiac function was examined in isolated rat hearts subjected to ischemia and reperfusion (I/R). The infarct size, EDLC level, Na+/K+-ATPase activity, and the levels of mRNA for sodium pump alpha isoforms were measured in vivo I/R rat hearts in the presence or absence of ADA. It was found that ADA significantly improved the recovery of cardiac function, decreased infarct size, decreased EDLC level, and recovered Na+/K+-ATPase activity in I/R hearts. Further studies showed that sodium pump alpha1, alpha2, and alpha3 isoform mRNA levels were significantly reduced in I/R hearts, and pretreatment with ADA induced a large increase in the mRNA levels. These results indicate that EDLC may participate in depressing Na+/K+-ATPase activity and sodium pump alpha isoform gene expression in I/R heart. It is suggested that treatment with ADA may prevent EDLC-mediated reperfusion injury via modulating sodium pump isoform gene expression.

Wang HG; Chu YF; Zou JG; Ke YS

2010-01-01

73

[Effect of folic acid in preventing aberrant methylation of fetal endometriosis susceptibility gene HOXA10].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To detect aberrant methylation in the promoter region of fetal endometriosis susceptibility gene homeobox-10 (HOXA10) in women with and without folic acid supplementation and explore the effect of folic acid in optimizing intrauterine environment. METHODS: Thirty-six cord blood specimens were collected between January, 2010 and December, 2012 from pregnant women with endometriosis, including 22 with folic acid treatment and 15 without. Methylation-specific polymerase chain reaction (MSP) and bisulfite salt modified sequencing (BSP) were employed to detect aberrant methylation of HOXA10 gene in these specimens. RESULTS: The methylation rate of HOXA10 gene differed significantly between pregnant women with endometriosis taking folic acid and those who did (P<0.05). CONCLUSION: Folic acid treatment can significantly reduce the methylation rate of fetal endometriosis susceptibility gene HOXA10.

Liu M; Huang X; Xu S; Li L

2013-06-01

74

Suppression of the vacuolar invertase gene prevents cold-induced sweetening in potato  

Science.gov (United States)

Storing potato (Solanum tuberosum) tubers at cold temperatures prevents sprouting and minimizes losses due to disease. Unfortunately, cold storage triggers an accumulation of reducing sugars, a phenomenon referred to as cold-induced sweetening (CIS). High-temperature processing of potato tubers wit...

75

Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression.  

Science.gov (United States)

Many lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA Pol(II) is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts. PMID:20876850

Mazzarella, Luca; Jørgensen, Helle F; Soza-Ried, Jorge; Terry, Anna V; Pearson, Stella; Lacaud, Georges; Kouskoff, Valerie; Merkenschlager, Matthias; Fisher, Amanda G

2010-09-28

76

The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The molecular mechanism responsible for a decline of stem cell functioning after replicative stress remains unknown. We used mouse embryonic fibroblasts (MEFs) and hematopoietic stem cells (HSCs) to identify genes involved in the process of cellular aging. In proliferating and senescent MEFs one of ...

Kamminga, Leonie M.; Bystrykh, Leonid V.; de Boer, Aletta; Houwer, Sita; Douma, José; Weersing, Ellen; Dontje, Bert

77

Molecular Evidence of Lateral Gene Transfer in rpoB Gene of Mycobacterium yongonense Strains via Multilocus Sequence Analysis  

Science.gov (United States)

Recently, a novel species, Mycobacterium yongonense (DSM 45126T), was introduced and while it is phylogenetically related to Mycobacterium intracellulare, it has a distinct RNA polymerase ?-subunit gene (rpoB) sequence that is identical to that of Mycobacterium parascrofulaceum, which is a distantly related scotochromogen, which suggests the acquisition of the rpoB gene via a potential lateral gene transfer (LGT) event. The aims of this study are to prove the presence of the LGT event in the rpoB gene of the M. yongonense strains via multilocus sequence analysis (MLSA). In order to determine the potential of an LGT event in the rpoB gene of the M. yongonense, the MLSA based on full rpoB sequences (3447 or 3450 bp) and on partial sequences of five other targets [16S rRNA (1383 or 1395 bp), hsp65 (603 bp), dnaJ (192 bp), recA (1053 bp), and sodA (501 bp)] were conducted. Incongruences between the phylogenetic analysis of the full rpoB and the five other genes in a total of three M. yongonense strains [two clinical strains (MOTT-12 and MOTT-27) and one type strain (DSM 45126T)] were observed, suggesting that rpoB gene of three M. yongonense strains may have been acquired very recently via an LGT event from M. parascrofulaceum, which is a distantly related scotochromogen.

Kim, Byoung-Jun; Hong, Seok-Hyun; Kook, Yoon-Hoh; Kim, Bum-Joon

2013-01-01

78

Molecular evidence of lateral gene transfer in rpoB gene of Mycobacterium yongonense strains via multilocus sequence analysis.  

UK PubMed Central (United Kingdom)

Recently, a novel species, Mycobacterium yongonense (DSM 45126(T)), was introduced and while it is phylogenetically related to Mycobacterium intracellulare, it has a distinct RNA polymerase ?-subunit gene (rpoB) sequence that is identical to that of Mycobacterium parascrofulaceum, which is a distantly related scotochromogen, which suggests the acquisition of the rpoB gene via a potential lateral gene transfer (LGT) event. The aims of this study are to prove the presence of the LGT event in the rpoB gene of the M. yongonense strains via multilocus sequence analysis (MLSA). In order to determine the potential of an LGT event in the rpoB gene of the M. yongonense, the MLSA based on full rpoB sequences (3447 or 3450 bp) and on partial sequences of five other targets [16S rRNA (1383 or 1395 bp), hsp65 (603 bp), dnaJ (192 bp), recA (1053 bp), and sodA (501 bp)] were conducted. Incongruences between the phylogenetic analysis of the full rpoB and the five other genes in a total of three M. yongonense strains [two clinical strains (MOTT-12 and MOTT-27) and one type strain (DSM 45126(T))] were observed, suggesting that rpoB gene of three M. yongonense strains may have been acquired very recently via an LGT event from M. parascrofulaceum, which is a distantly related scotochromogen.

Kim BJ; Hong SH; Kook YH; Kim BJ

2013-01-01

79

Rtt109 prevents hyper-amplification of ribosomal RNA genes through histone modification in budding yeast.  

UK PubMed Central (United Kingdom)

The genes encoding ribosomal RNA are the most abundant in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure, ribosomal RNA genes (rDNA) are easily lost by recombination events within the repeated cluster. We previously identified a unique gene amplification system driven by unequal sister-chromatid recombination during DNA replication. The system compensates for such copy number losses, thus maintaining proper copy number. Here, through a genome-wide screen for genes regulating rDNA copy number, we found that the rtt109 mutant exhibited a hyper-amplification phenotype (?3 times greater than the wild-type level). RTT109 encodes an acetyl transferase that acetylates lysine 56 of histone H3 and which functions in replication-coupled nucleosome assembly. Relative to unequal sister-chromatid recombination-based amplification (?1 copy/cell division), the rate of the hyper-amplification in the rtt109 mutant was extremely high (>100 copies/cell division). Cohesin dissociation that promotes unequal sister-chromatid recombination was not observed in this mutant. During hyper-amplification, production level of extra-chromosomal rDNA circles (ERC) by intra-chromosomal recombination in the rDNA was reduced. Interestingly, during amplification, a plasmid containing an rDNA unit integrated into the rDNA as a tandem array. These results support the idea that tandem DNA arrays are produced and incorporated through rolling-circle-type replication. We propose that, in the rtt109 mutant, rDNA hyper-amplification is caused by uncontrolled rolling-circle-type replication.

Ide S; Saka K; Kobayashi T

2013-04-01

80

Physical training prevents body weight gain but does not modify adipose tissue gene expression  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P (more) 0.28 g, P

Higa, T.S.; Bergamo, F.C.; Mazzucatto, F.; Fonseca-Alaniz, M.H.; Evangelista, F.S.

2012-10-01

 
 
 
 
81

Targeting activation of specific NF-?B subunits prevents stress-dependent atherothrombotic gene expression.  

Science.gov (United States)

Psychosocial stress has been shown to be a contributing factor in the development of atherosclerosis. Although the underlying mechanisms have not been elucidated entirely, it has been shown previously that the transcription factor nuclear factor-?B (NF-?B) is an important component of stress-activated signaling pathway. In this study, we aimed to decipher the mechanisms of stress-induced NF-?B-mediated gene expression, using an in vitro and in vivo model of psychosocial stress. Induction of stress led to NF-?B-dependent expression of proinflammatory (tissue factor, intracellular adhesive molecule 1 [ICAM-1]) and protective genes (manganese superoxide dismutase [MnSOD]) via p50, p65 or cRel. Selective inhibition of the different subunits and the respective kinases showed that inhibition of cRel leads to the reduction of atherosclerotic lesions in apolipoprotein(-/-) (ApoE(-/-)) mice via suppression of proinflammatory gene expression. This observation may therefore provide a possible explanation for ineffectiveness of antioxidant therapies and suggests that selective targeting of cRel activation may provide a novel approach for the treatment of stress-related inflammatory vascular disease. PMID:23114885

Djuric, Zdenka; Kashif, Muhammed; Fleming, Thomas; Muhammad, Sajjad; Piel, David; von Bauer, Rüdiger; Bea, Florian; Herzig, Stephan; Zeier, Martin; Pizzi, Marina; Isermann, Berend; Hecker, Markus; Schwaninger, Markus; Bierhaus, Angelika; Nawroth, Peter P

2012-12-20

82

Optimization of Streptomyces bacteriophage phi C31 integrase system to prevent post integrative gene silencing in pulmonary type II cells.  

Science.gov (United States)

phi C31 integrase has emerged as a potent tool for achieving long-term gene expression in different tissues. The present study aimed at optimizing elements of phi C31 integrase system for alveolar type II cells. Luciferase and beta-galactosidase activities were measured at different time points post transfection. 5-Aza-2'deoxycytidine (AZA) and trichostatin A (TSA) were used to inhibit DNA methyltransferase and histone deacetylase complex (HDAC) respectively. In A549 cells, expression of the integrase using a CMV promoter resulted in highest integrase activity, whereas in MLE12 cells, both CAG and CMV promoter were equally effective. Effect of polyA site was observed only in A549 cells, where replacement of SV40 polyA by bovine growth hormone (BGH) polyA site resulted in an enhancement of integrase activity. Addition of a C-terminal SV40 nuclear localization signal (NLS) did not result in any significant increase in integrase activity. Long-term expression studies with AZA and TSA, provided evidence for post-integrative gene silencing. In MLE12 cells, both DNA methylases and HDACs played a significant role in silencing, whereas in A549 cells, it could be attributed majorly to HDAC activity. Donor plasmids comprising cellular promoters ubiquitin B (UBB), ubiquitin C (UCC) and elongation factor 1 alpha (EF1 alpha) in an improved backbone prevented post-integrative gene silencing. In contrast to A549 and MLE12 cells, no silencing could be observed in human bronchial epithelial cells, BEAS-2B. Donor plasmid coding for murine erythropoietin under the EF1 alpha promoter when combined with phi C31 integrase resulted in higher long-term erythropoietin expression and subsequently higher hematocrit levels in mice after intravenous delivery to the lungs. These results provide evidence for cell specific post integrative gene silencing with C31 integrase and demonstrate the pivotal role of donor plasmid in long-term expression attained with this system. PMID:19745601

Aneja, Manish Kumar; Geiger, Johannes; Imker, Rabea; Uzgun, Senta; Kormann, Michael; Hasenpusch, Guenther; Maucksch, Christof; Rudolph, Carsten

2009-12-31

83

Optimization of Streptomyces bacteriophage phi C31 integrase system to prevent post integrative gene silencing in pulmonary type II cells.  

UK PubMed Central (United Kingdom)

phi C31 integrase has emerged as a potent tool for achieving long-term gene expression in different tissues. The present study aimed at optimizing elements of phi C31 integrase system for alveolar type II cells. Luciferase and beta-galactosidase activities were measured at different time points post transfection. 5-Aza-2'deoxycytidine (AZA) and trichostatin A (TSA) were used to inhibit DNA methyltransferase and histone deacetylase complex (HDAC) respectively. In A549 cells, expression of the integrase using a CMV promoter resulted in highest integrase activity, whereas in MLE12 cells, both CAG and CMV promoter were equally effective. Effect of polyA site was observed only in A549 cells, where replacement of SV40 polyA by bovine growth hormone (BGH) polyA site resulted in an enhancement of integrase activity. Addition of a C-terminal SV40 nuclear localization signal (NLS) did not result in any significant increase in integrase activity. Long-term expression studies with AZA and TSA, provided evidence for post-integrative gene silencing. In MLE12 cells, both DNA methylases and HDACs played a significant role in silencing, whereas in A549 cells, it could be attributed majorly to HDAC activity. Donor plasmids comprising cellular promoters ubiquitin B (UBB), ubiquitin C (UCC) and elongation factor 1 alpha (EF1 alpha) in an improved backbone prevented post-integrative gene silencing. In contrast to A549 and MLE12 cells, no silencing could be observed in human bronchial epithelial cells, BEAS-2B. Donor plasmid coding for murine erythropoietin under the EF1 alpha promoter when combined with phi C31 integrase resulted in higher long-term erythropoietin expression and subsequently higher hematocrit levels in mice after intravenous delivery to the lungs. These results provide evidence for cell specific post integrative gene silencing with C31 integrase and demonstrate the pivotal role of donor plasmid in long-term expression attained with this system.

Aneja MK; Geiger J; Imker R; Uzgun S; Kormann M; Hasenpusch G; Maucksch C; Rudolph C

2009-12-01

84

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions.  

UK PubMed Central (United Kingdom)

There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to preterm birth. To address this experimentally, we generated a mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth due to premature decidual senescence with increased mTORC1 activity and COX2 signaling. Here we provide evidence that this predisposition provoked preterm birth in 100% of females exposed to a mild inflammatory insult with LPS, revealing the high significance of gene-environment interactions in preterm birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53-deficient mice when they were treated with a combination of rapamycin (mTORC1 inhibitor) and progesterone (P4), without adverse effects on maternal or fetal health. These results provide evidence for the cooperative contributions of two sites of action (decidua and ovary) toward preterm birth. Moreover, a similar signature of decidual senescence with increased mTORC1 and COX2 signaling was observed in women undergoing preterm birth. Collectively, our findings show that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and suggest that combined treatment with low doses of rapamycin and P4 may help reduce the incidence of preterm birth in high-risk women.

Cha J; Bartos A; Egashira M; Haraguchi H; Saito-Fujita T; Leishman E; Bradshaw H; Dey SK; Hirota Y

2013-09-01

85

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions  

Science.gov (United States)

There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to preterm birth. To address this experimentally, we generated a mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth due to premature decidual senescence with increased mTORC1 activity and COX2 signaling. Here we provide evidence that this predisposition provoked preterm birth in 100% of females exposed to a mild inflammatory insult with LPS, revealing the high significance of gene-environment interactions in preterm birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53-deficient mice when they were treated with a combination of rapamycin (mTORC1 inhibitor) and progesterone (P4), without adverse effects on maternal or fetal health. These results provide evidence for the cooperative contributions of two sites of action (decidua and ovary) toward preterm birth. Moreover, a similar signature of decidual senescence with increased mTORC1 and COX2 signaling was observed in women undergoing preterm birth. Collectively, our findings show that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and suggest that combined treatment with low doses of rapamycin and P4 may help reduce the incidence of preterm birth in high-risk women.

Cha, Jeeyeon; Bartos, Amanda; Egashira, Mahiro; Haraguchi, Hirofumi; Saito-Fujita, Tomoko; Leishman, Emma; Bradshaw, Heather; Dey, Sudhansu K.; Hirota, Yasushi

2013-01-01

86

Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Adiponectin, secreted mainly by mature adipocytes, is a protein with insulin-sensitising and anti-atherogenic effects. Human adiponectin is encoded by the ADIPOQ gene on the chromosomal locus 3q27. Variations in ADIPOQ are associated with obesity, type 2 diabetes (T2DM) and related phenotypes in several populations. Our aim was to study the association of the ADIPOQ variations with body weight, serum adiponectin concentrations and conversion to T2DM in overweight subjects with impaired glucose tolerance. Moreover, we investigated whether ADIPOQ gene variants modify the effect of lifestyle changes on these traits. Methods Participants in the Finnish Diabetes Prevention Study were randomly assigned to a lifestyle intervention group or a control group. Those whose DNA was available (n = 507) were genotyped for ten ADIPOQ single nucleotide polymorphisms (SNPs). Associations between SNPs and baseline body weight and serum adiponectin concentrations were analysed using the univariate analysis of variance. The 4-year longitudinal weight data were analysed using linear mixed models analysis and the change in serum adiponectin from baseline to year four was analysed using Kruskal-Wallis test. In addition, the association of SNPs with the risk of developing T2DM during the follow-up of 0-11 (mean 6.34) years was analysed by Cox regression analysis. Results rs266729, rs16861205, rs1501299, rs3821799 and rs6773957 associated significantly (p Conclusions These results from the Finnish Diabetes Prevention Study support the concept that genetic variation in ADIPOQ locus contributes to variation in body size and serum adiponectin concentrations and may also modify the risk of developing T2DM. Trial registration number ClinicalTrials.gov NCT00518167

Siitonen Niina; Pulkkinen Leena; Lindström Jaana; Kolehmainen Marjukka; Eriksson Johan G; Venojärvi Mika; Ilanne-Parikka Pirjo; Keinänen-Kiukaanniemi Sirkka; Tuomilehto Jaakko; Uusitupa Matti

2011-01-01

87

Prevention of PDT-induced esophageal stricture by MnSOD-PL gene therapy  

International Nuclear Information System (INIS)

Photodynamic Therapy (PDT) is currently being used to treat esophageal cancer and Barrett's esophagus. PDT is very promising except that it results in a high rate of esophageal stricture. The clinical protocol involves the injection of Photofrin into the patient followed 48 hours later with a laser treatment of 630 nm of light. At this wavelength Photofrin reacts with the light and results in production of reactive oxygen species (ROS) in the mitochondria. To determine if MnSOD-PL prevents esophageal stricture we developed a pig model. Pigs (20 kg outbred female) were injected intravenously with Photofrin (2 mg/kg) and an endoscope was placed into the esophagus where MnSOD-PL (10 mg plasmid DNA) was administered at the site of PDT treatment. Control pigs received Photofrin only. Twenty-four hours later an endoscope was placed into the esophagus and the laser inserted through the endoscope to 10 cm above the GE junction where 400 Joules of light were administered to the esophagus. A second PDT treatment of 400 Joules was given 48 hours later. The pigs were followed for development of esophageal stricture as determined by a 10% weight loss, an endoscopic exam demonstrating esophageal stricture, and an x-ray following barium swallow. Upon detection of esophageal stricture, the pigs were sacrificed. The esophagus was removed and pathological examination performed. By 14-21 days all control pigs developed esophageal stricture while pigs receiving MnSOD-PL had a prolonged survival for at least 6 weeks after injection of MnSOD-PL. At this time, the MnSOD-PL-injected pigs were sacrificed. The esophagus was removed from each animal and examined for the development of esophageal stricture. No esophageal stricture was detected by x-ray following barium swallow, endoscopic exam or pathological examination in esophagus samples from MnSOD-PL treated pigs. Results of these experiments demonstrate that MnSOD-PL may be effective in preventing normal esophageal tissue damage by PDT

2003-01-01

88

Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans.  

UK PubMed Central (United Kingdom)

Abstract? Twelve weeks of daily l-carnitine and carbohydrate feeding in humans increases skeletal muscle total carnitine content, and prevents body mass accrual associated with carbohydrate feeding alone. Here we determined the influence of l-carnitine and carbohydrate feeding on energy metabolism, body fat mass and muscle expression of fuel metabolism genes. Twelve males exercised at 50% maximal oxygen consumption for 30 min once before and once after 12 weeks of twice daily feeding of 80 g carbohydrate (Control, n = 6) or 1.36 g l-carnitine + 80 g carbohydrate (Carnitine, n = 6). Maximal carnitine palmitolytransferase 1 (CPT1) activity remained similar in both groups over 12 weeks. However, whereas muscle total carnitine, long-chain acyl-CoA and whole-body energy expenditure did not change over 12 weeks in Control, they increased in Carnitine by 20%, 200% and 6%, respectively (P < 0.05). Moreover, body mass and whole-body fat mass (dual-energy X-ray absorptiometry) increased over 12 weeks in Control by 1.9 and 1.8 kg, respectively (P < 0.05), but did not change in Carnitine. Seventy-three of 187 genes relating to fuel metabolism were upregulated in Carnitine vs. Control after 12 weeks, with 'insulin signalling', 'peroxisome proliferator-activated receptor signalling' and 'fatty acid metabolism' as the three most enriched pathways in gene functional analysis. In conclusion, increasing muscle total carnitine in healthy humans can modulate muscle metabolism, energy expenditure and body composition over a prolonged period, which is entirely consistent with a carnitine-mediated increase in muscle long-chain acyl-group translocation via CPT1. Implications to health warrant further investigation, particularly in obese individuals who have a reduced reliance on muscle fat oxidation during low-intensity exercise.

Stephens FB; Wall BT; Marimuthu K; Shannon CE; Constantin-Teodosiu D; Macdonald IA; Greenhaff PL

2013-09-01

89

Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans.  

Science.gov (United States)

Abstract? Twelve weeks of daily l-carnitine and carbohydrate feeding in humans increases skeletal muscle total carnitine content, and prevents body mass accrual associated with carbohydrate feeding alone. Here we determined the influence of l-carnitine and carbohydrate feeding on energy metabolism, body fat mass and muscle expression of fuel metabolism genes. Twelve males exercised at 50% maximal oxygen consumption for 30 min once before and once after 12 weeks of twice daily feeding of 80 g carbohydrate (Control, n = 6) or 1.36 g l-carnitine + 80 g carbohydrate (Carnitine, n = 6). Maximal carnitine palmitolytransferase 1 (CPT1) activity remained similar in both groups over 12 weeks. However, whereas muscle total carnitine, long-chain acyl-CoA and whole-body energy expenditure did not change over 12 weeks in Control, they increased in Carnitine by 20%, 200% and 6%, respectively (P Carnitine. Seventy-three of 187 genes relating to fuel metabolism were upregulated in Carnitine vs. Control after 12 weeks, with 'insulin signalling', 'peroxisome proliferator-activated receptor signalling' and 'fatty acid metabolism' as the three most enriched pathways in gene functional analysis. In conclusion, increasing muscle total carnitine in healthy humans can modulate muscle metabolism, energy expenditure and body composition over a prolonged period, which is entirely consistent with a carnitine-mediated increase in muscle long-chain acyl-group translocation via CPT1. Implications to health warrant further investigation, particularly in obese individuals who have a reduced reliance on muscle fat oxidation during low-intensity exercise. PMID:23818692

Stephens, Francis B; Wall, Benjamin T; Marimuthu, Kanagaraj; Shannon, Chris E; Constantin-Teodosiu, Dumitru; Macdonald, Ian A; Greenhaff, Paul L

2013-07-01

90

Gene Therapy for the Prevention of in- Stent Restenosis Post Coronary Angioplasty  

Directory of Open Access Journals (Sweden)

Full Text Available Around the world, Coronary Artery Disease (CAD) is quickly becoming the most common cause of morbidity and mortality. Percutaneous coronary interventions- angioplasty and stent insertion- have proved effective and reliable treatments for CAD but their long-term efficacy is limited by the high rate of restenosis. This occurs in 30 – 50% of patients undergoing angioplasty and results in symptoms requiring repeat intervention in up to 75% of them. Stent insertion has been shown to reduce this rate but in-stent restenosis still occurs in 20-40% of cases. The high incidence of restenosis represents a large economic burden on health resources. As a consequence of the resistance of restenosis to traditional therapeutic approaches, gene therapy has emerged an attractive potential therapy for this problem. Excessive extracellular matrix (ECM) deposition in the neointima is the main mechanism leading to luminal loss after coronary stenting. Transforming growth factor-? (TGF-?) is a major regulator of ECM deposition and there is substantial evidence to suggest its role in restenosis. TGF-?1 is the predominant isoform in vascular tissues and its production is observed to be upregulated in human restenotic lesions and in the intima of injured animal vessels. The aim of this study is to develop, investigate and compare the effects of two potentially therapeutic recombinant, replication-deficient adenoviruses, which will give rise to the expression of transgenic proteins which antagonise the fibrogenic effects of TGF-?1 in coronary arteries post stent insertion. The cDNA for these proteins have each been inserted into replication deficient adenovirus vectors under the control of the Major Immediate/Early Murine Cytomegalovirus (MIEmCMV) promoter. Virus identity and the presence of transgenes have been confirmed by restriction analysis and Southern blotting respectively. Efficient transgene expression has been confirmed in cultured porcine coronary vascular smooth muscle cells (VSMC) by a series of immunocytochemistry. The work is currently underway to evaluate biological activity of transgenes in cultured VSMC and the transgenes expression and their effects on luminal loss in stented porcine coronary artery model in vivo.

P Ranjzad; PA Kingston

2005-01-01

91

Tea polyphenols prevent lung from preneoplastic lesions and effect p53 and bcl-2 gene expression in rat lung tissues.  

UK PubMed Central (United Kingdom)

Lung cancer is one of the cancers that have the highest incidence and the highest mortality rate, and it is of great interest to identify ways to prevent its occurrence. We had established an animal model by using 3,4-benzopyrene intra-pulmonary injection in our previous study, and had observed that the rats lung carcinoma incidence and multiplicity were significantly reduced by green tea administration. This study further investigated the effect of tea polyphenols on rat lung preneoplastic lesions using the lung carcinoma model established by 3,4-benzopyrene intra-pulmonary injection. Sprague-Dawley rats of the same age were randomly divided into 10 groups and treated with 3,4-benzopyrene by intra-pulmonary injection. Five groups were given 0.3% solution of tea polyphenols (equivalent to 1.2% of green tea) in drinking water, while the other 5 groups were given pure drinking water. The rats were sacrificed at 0, 1, 4, 8 and 16 weeks after carcinogen treatment. In the control groups of rats, local bronchial inflammation were observed at 1 week after 3,4-benzopyrene treatment. From 4 weeks to 16 weeks after carcinogen treatment, hyperplasia, cell hyperproliferation, heterogeneity were observed in the bronchial epithelium. Meanwhile, the expression of p53 mRNA and protein, as well as the level of bcl-2, increased in the bronchial epithelial lesion. Tea polyphenols treatment significantly alleviated the bronchial epithelial lesions. At the same time, tea polyphenols treatment enhanced p53 expression, but reduced bcl-2 expression. These results indicated that tea polyphenols may have preventive effect against lung preneoplasm lesions, possibly through regulating the expression of some critical genes such as p53 and bcl-2.

Gu Q; Hu C; Chen Q; Xia Y

2013-01-01

92

Tea polyphenols prevent lung from preneoplastic lesions and effect p53 and bcl-2 gene expression in rat lung tissues  

Science.gov (United States)

Lung cancer is one of the cancers that have the highest incidence and the highest mortality rate, and it is of great interest to identify ways to prevent its occurrence. We had established an animal model by using 3,4-benzopyrene intra-pulmonary injection in our previous study, and had observed that the rats lung carcinoma incidence and multiplicity were significantly reduced by green tea administration. This study further investigated the effect of tea polyphenols on rat lung preneoplastic lesions using the lung carcinoma model established by 3,4-benzopyrene intra-pulmonary injection. Sprague–Dawley rats of the same age were randomly divided into 10 groups and treated with 3,4-benzopyrene by intra-pulmonary injection. Five groups were given 0.3% solution of tea polyphenols (equivalent to 1.2% of green tea) in drinking water, while the other 5 groups were given pure drinking water. The rats were sacrificed at 0, 1, 4, 8 and 16 weeks after carcinogen treatment. In the control groups of rats, local bronchial inflammation were observed at 1 week after 3,4-benzopyrene treatment. From 4 weeks to 16 weeks after carcinogen treatment, hyperplasia, cell hyperproliferation, heterogeneity were observed in the bronchial epithelium. Meanwhile, the expression of p53 mRNA and protein, as well as the level of bcl-2, increased in the bronchial epithelial lesion. Tea polyphenols treatment significantly alleviated the bronchial epithelial lesions. At the same time, tea polyphenols treatment enhanced p53 expression, but reduced bcl-2 expression. These results indicated that tea polyphenols may have preventive effect against lung preneoplasm lesions, possibly through regulating the expression of some critical genes such as p53 and bcl-2.

Gu, Qihua; Hu, Chengping; Chen, Qiong; Xia, Ying

2013-01-01

93

Identification of Multipath Genes Differentially Expressed in Pathway-Targeted Microarrays in Zebrafish Infected and Surviving Spring Viremia Carp Virus (SVCV) Suggest Preventive Drug Candidates  

Science.gov (United States)

Spring viremia carp virus (SVCV) is a rhabdovirus seasonally affecting warm-water cyprinid fish farming causing high impacts in worldwide economy. Because of the lack of effective preventive treatments, the identification of multipath genes involved in SVCV infection might be an alternative to explore the possibilities of using drugs for seasonal prevention of this fish disease. Because the zebrafish (Danio rerio) is a cyprinid susceptible to SVCV and their genetics and genome sequence are well advanced, it has been chosen as a model for SVCV infections. We have used newly designed pathway-targeted microarrays 3-4-fold enriched for immune/infection functional-relevant probes by using zebrafish orthologous to human genes from selected pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG). The comparative analysis of differential expression of genes through 20 pathways in 2-day exposed or 30-day survivors of SVCV infection allowed the identification of 16 multipath genes common to more than 6 pathways. In addition, receptors (Toll-like, B-cell, T-cell, RIG1-like) as well as viral RNA infection pathways were identified as the most important human-like pathways targeted by SVCV infection. Furthermore, by using bioinformatic tools to compare the promoter sequences corresponding to up and downregulated multipath gene groups, we identified putative common transcription factors which might be controlling such responses in a coordinated manner. Possible drug candidates to be tested in fish, can be identified now through search of data bases among those associated with the human orthologous to the zebrafish multipath genes. With the use of pathway-targeted microarrays, we identified some of the most important genes and transcription factors which might be implicated in viral shutoff and/or host survival responses after SVCV infection. These results could contribute to develop novel drug-based prevention methods and consolidate the zebrafish/SVCV as a model for vertebrate viral diseases.

Encinas, Paloma; Garcia-Valtanen, Pablo; Chinchilla, Blanca; Gomez-Casado, Eduardo; Estepa, Amparo; Coll, Julio

2013-01-01

94

Identification of Multipath Genes Differentially Expressed in Pathway-Targeted Microarrays in Zebrafish Infected and Surviving Spring Viremia Carp Virus (SVCV) Suggest Preventive Drug Candidates.  

UK PubMed Central (United Kingdom)

Spring viremia carp virus (SVCV) is a rhabdovirus seasonally affecting warm-water cyprinid fish farming causing high impacts in worldwide economy. Because of the lack of effective preventive treatments, the identification of multipath genes involved in SVCV infection might be an alternative to explore the possibilities of using drugs for seasonal prevention of this fish disease. Because the zebrafish (Danio rerio) is a cyprinid susceptible to SVCV and their genetics and genome sequence are well advanced, it has been chosen as a model for SVCV infections. We have used newly designed pathway-targeted microarrays 3-4-fold enriched for immune/infection functional-relevant probes by using zebrafish orthologous to human genes from selected pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG). The comparative analysis of differential expression of genes through 20 pathways in 2-day exposed or 30-day survivors of SVCV infection allowed the identification of 16 multipath genes common to more than 6 pathways. In addition, receptors (Toll-like, B-cell, T-cell, RIG1-like) as well as viral RNA infection pathways were identified as the most important human-like pathways targeted by SVCV infection. Furthermore, by using bioinformatic tools to compare the promoter sequences corresponding to up and downregulated multipath gene groups, we identified putative common transcription factors which might be controlling such responses in a coordinated manner. Possible drug candidates to be tested in fish, can be identified now through search of data bases among those associated with the human orthologous to the zebrafish multipath genes. With the use of pathway-targeted microarrays, we identified some of the most important genes and transcription factors which might be implicated in viral shutoff and/or host survival responses after SVCV infection. These results could contribute to develop novel drug-based prevention methods and consolidate the zebrafish/SVCV as a model for vertebrate viral diseases.

Encinas P; Garcia-Valtanen P; Chinchilla B; Gomez-Casado E; Estepa A; Coll J

2013-01-01

95

Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice  

Science.gov (United States)

Castleman's disease is a lymphoproliferative disorder thought to be related to deregulated production of IL-6. We have previously shown that mice lacking the trans-acting factor C/EBP beta, a transcriptional regulator of IL-6 and a mediator of IL-6 intracellular signaling, develop a pathology nearly identical to multicentric Castleman's disease, together with increasingly high levels of circulating IL-6. We describe here how the simultaneous inactivation of both IL-6 and C/EBP beta genes prevents the development of pathological traits of Castleman's disease observed in C/EBP beta-deficient mice. Histological and phenotypic analysis of lymph nodes and spleen of double mutant mice did not show either the lymphoadenopathy and splenomegaly or the abnormal expansion of myeloid, B and plasma cell compartments observed in C/EBP beta-/- mice, while B cell development, although delayed, was normal. Our data demonstrate that IL-6 is essential for the development of multicentric Castleman's disease in C/EBP beta-/- mice.

1996-01-01

96

Prevention of experimental autoimmune myocarditis by hydrodynamics-based naked plasmid DNA encoding CTLA4-Ig gene delivery.  

UK PubMed Central (United Kingdom)

BACKGROUND: Rat experimental autoimmune myocarditis (EAM) is a T cell-mediated disease that resembled the giant cell myocarditis seen in humans. Soluble CTLA4 improves some autoimmune diseases by blocking costimulatory signals on T cell. We investigated the effect of hydrodynamics-based naked plasmid DNA encoding CTLA4-immunoglobulin (Ig) gene delivery. METHODS AND RESULTS: Lewis rats were immunized with cardiac myosin and treated with hydrodynamic-based transfection, namely a rapid tail vein injection of a large volume of pCAGGS encoding CTLA4-Ig chimera solution on Day 0. The vector-derived CTLA4-Ig mRNA expressions were mainly detected in the liver and plasma CTLA4-Ig protein levels were maintained at about 2 mug/mL during the experiment period. On Day 17, the ratio of heart to body weight, the amount of mRNA of atrial natriuretic peptide, and the inflammatory areas in CTLA4 group were significantly lower than in the control group treated with empty plasmid. Maximum rate of intraventricular pressure rise and decline (dP/dT), minimum dP/dT, left ventricular end-diastolic pressure, and central venous pressure improved significantly after treatment with CTLA4-Ig. On Day 14, expressions of IL-2 in popliteal lymph nodes in the CTLA4-Ig group were significantly lower than in the control group. CONCLUSION: Hydrodynamics-based transfection of plasmid encoding CTLA4-Ig chimera dramatically prevented EAM.

Abe S; Hanawa H; Hayashi M; Yoshida T; Komura S; Watanabe R; Lie H; Chang H; Kato K; Kodama M; Maruyama H; Nakazawa M; Miyazaki J; Aizawa Y

2005-09-01

97

Challenges and opportunities for controlling and preventing animal diseases in developing countries through gene-based technologies  

International Nuclear Information System (INIS)

[en] The livestock revolution so robustly and frequently described in the past five years, is argued to provide a real opportunity for the rural livestock keeper in developing countries to escape the poverty trap, move away from subsistence farming and enter the more rewarding areas of farm enterprise and income generation. To do so though, will require more than merely acknowledging this marketing opportunity. It will be essential to address the many constraints and critical risks that constantly face rural farming in developing countries. Of these, livestock disease rates as one of the most challenging. However, for effective participation in the livestock revolution it will be essential that livestock disease is either controlled or prevented. For the livestock producer in developing countries, many of the life threatening diseases that have been eradicated from the developed world area are ever present and the extent and range of production-limiting diseases are considerable. The situation is further compounded since in many cases veterinary services and other animal health delivery systems are either nonexistent or ineffective. For some time donor organisations have been driving countries in transition to privatise services such as animal health delivery. The current situation is the virtual elimination of functioning State veterinary services without replacement by a private system and certainly not in rural areas. The elimination of the major killer diseases of livestock in the developed world was achieved, for the most part, through considerable State investment, extensive veterinary input and a large share of public money. Such resources are certainly not available today in most developing countries. No wonder therefore that diseases such as Contagious Bovine Pleuropneumonia, African Swine Fever ad Foot and Mouth Disease continue to exist endemically in most poorer regions of Africa and elsewhere. In terms of the production limiting diseases, control of these in most developed countries is through a mixture of management and therapy. The former requires knowledge and considerable local understanding and the latter resources and supplies. Both of these are limited in the developing country situation, particularly in a rural setting. Given this complex of challenges, can gene-based technologies really make a difference to the management of livestock disease for the producer in developing countries? To be effective in the developing country situation, any intervention must be relatively simple, cost effective, sustainable and convincing. Can this be delivered? Perhaps an insight can be gained from an appreciation of the fundamental nature of gene-based technologies. Inherent in the approach is the recognition that the gene is the basic building block of biology. Management and manipulation of the gene therefore enables us to design and direct an endless array of precise solutions, whether this be designer livestock, genetically engineered biological products or genetically altered organisms. Without doubt, the availability of livestock resistant to disease, or at least one or two of the major diseases affecting livestock in a particular region, is a simple and applicable solution to the developing country situation. Attempts to understand the genetic basis of trypanotolerence are still on-going but if successful would enable livestock production in large areas of Africa currently restricted by the presence of trypanosomosis. Another example would be the demonstration of resistance to internal parasites by certain breeds of sheep. Locating the genetic basis of this could be revolutionary in the management of this particular disease risk. As work starts on sequencing both the bovine and the ovine genome, the future opportunities for designing livestock resistant or tolerant to a range of diseases looks highly promising. Looking at the causative agents of livestock disease, the ability to exquisitely alter these to better understand the way they cause disease is providing a fast track to developing ways of contro

2003-01-01

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Prevention of beta cell dysfunction and apoptosis by adenoviral gene transfer of rat insulin-like growth factor 1.  

UK PubMed Central (United Kingdom)

BACKGROUND: Islet beta-cells are almost completely destroyed when patients with type 1 diabete are diagnosed. To date, insulin substitute therapy is still one of the main treatments. The cure of type 1 diabetes requires beta-cell regeneration from islet cell precursors and prevention of recurring autoimmunity. Therefore, beta-cell regeneration and proliferation emerge as a new research focus on therapy for type 1 diabetes. Islet beta-cell regeneration and development are controlled by many growth factors, especially insulin-like growth factor-1 (IGF-1). METHODS: Recombinant adenovirus encoding rat IGF-1 (rIGF-1) was constructed and transduced into rat beta-cells, RINm5F cells. Western blotting analysis and ELISA were used to detect rIGF-1 protein. Streptozotocin (STZ) was used to induce RINm5F cell destruction. The level of nitric oxide (NO) was detected in cell culture supernatants by the Griess reaction. Islet cell function was evaluated by glucose-stimulated insulin production. Flow cytometry analysis was further used to investigate the apoptosis of RINm5F cells. Thiaoollyl blue viability assay was applied to determine cell viability. RESULTS: The recombined adenovirus-rIGF-1 was successfully constructed and the titer was 4.0 x 10(8) pfu/ml. The rIGF-1 protein was effectively expressed in the RINm5F cells and cell culture supernatants. rIGF-1 expression remarkably inhibited STZ-induced islet cell apoptosis and significantly decreased the level of NO. Furthermore, IGF-1 expression also significantly protected insulin secretion and cell proliferation in a time-dependent manner. CONCLUSIONS: Our study suggests that locally produced rIGF-I from RINm5F cells may be beneficial in maintaining beta-cell function, protecting beta-cells from the destruction of apoptosis factors and promoting beta-cell survival and proliferation. IGF-I might be considered as a candidate gene in gene therapy for type 1 diabetes. In addition, it appears that the apoptosis induced by STZ may be NO-dependent.

Chen ZH; Li T; Chen ZB; Luo B; Sun RP

2009-09-01

99

Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study.  

Science.gov (United States)

Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999-2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy. PMID:23132673

Lupo, Philip J; Canfield, Mark A; Chapa, Claudia; Lu, Wei; Agopian, A J; Mitchell, Laura E; Shaw, Gary M; Waller, D Kim; Olshan, Andrew F; Finnell, Richard H; Zhu, Huiping

2012-11-06

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Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene.  

UK PubMed Central (United Kingdom)

Diabetes leads to a decompensated myopathy, but the etiology of the cardiac disease is poorly understood. Oxidative stress is enhanced with diabetes and oxygen toxicity may alter cardiac progenitor cell (CPC) function resulting in defects in CPC growth and myocyte formation, which may favor premature myocardial aging and heart failure. We report that in a model of insulin-dependent diabetes mellitus, the generation of reactive oxygen species (ROS) leads to telomeric shortening, expression of the senescent associated proteins p53 and p16INK4a, and apoptosis of CPCs, impairing the growth reserve of the heart. However, ablation of the p66shc gene prevents these negative adaptations of the CPC compartment, interfering with the acquisition of the heart senescent phenotype and the development of heart failure with diabetes. ROS elicit 3 cellular reactions: low levels activate cell growth, intermediate quantities trigger cell apoptosis, and high amounts initiate cell necrosis. CPC replication predominates in diabetic p66shc-/-, whereas CPC apoptosis and myocyte apoptosis and necrosis prevail in diabetic wild type. Expansion of CPCs and developing myocytes preserves cardiac function in diabetic p66shc-/-, suggesting that intact CPCs can effectively counteract the impact of uncontrolled diabetes on the heart. The recognition that p66shc conditions the destiny of CPCs raises the possibility that diabetic cardiomyopathy is a stem cell disease in which abnormalities in CPCs define the life and death of the heart. Together, these data point to a genetic link between diabetes and ROS, on the one hand, and CPC survival and growth, on the other.

Rota M; LeCapitaine N; Hosoda T; Boni A; De Angelis A; Padin-Iruegas ME; Esposito G; Vitale S; Urbanek K; Casarsa C; Giorgio M; Lüscher TF; Pelicci PG; Anversa P; Leri A; Kajstura J

2006-07-01

 
 
 
 
101

Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice.  

Science.gov (United States)

Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer's disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury. PMID:23059457

Tweedie, David; Rachmany, Lital; Rubovitch, Vardit; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Perez, Evelyn; Miller, Jonathan; Hoffer, Barry J; Greig, Nigel H; Pick, Chaim G

2012-10-08

102

Prevention of HIF-1 activation and iNOS gene targeting by low-dose cadmium results in loss of myocardial hypoxic preconditioning in the rat.  

UK PubMed Central (United Kingdom)

This study aimed to underline the interaction between hypoxia-inducible factor-1 (HIF-1) and the inducible nitric oxide synthase (iNOS) gene in vivo and their contribution to the delayed myocardial preconditioning induced by acute intermittent hypoxia (IH) in the rat using chromatin immunoprecipitation and pharmacological inhibition by low-dose cadmium. Langendorff-perfused hearts of Wistar rats exposed to normoxia or IH 24 h earlier were submitted to global ischemia and reperfusion. Effects of iNOS inhibition by aminoguanidine (100 microM) before ischemia or of low-dose injection of cadmium chloride (1 mg/kg) before normoxia or IH were tested. Myocardial HIF-1 and iNOS quantification and in vivo chromatin immunoprecipitation of HIF-1 bound to the iNOS gene promoter were performed. IH-induced delayed cardioprotection resulted in an improvement in coronary flow and functional recovery at reperfusion and a decrease in infarct size. Myocardial HIF-1 activity was increased with resulting targeting of the iNOS gene. Aminoguanidine abolished the cardioprotective effects of IH. Cadmium chloride treatment before IH prevented myocardial HIF-1 activation (72.3 +/- 4.0 vs. 42.1 +/- 9.7 arbitrary units after cadmium chloride; P < 0.05), targeting of the iNOS gene, iNOS expression, and preconditioning (infarct size: 15.9 +/- 5.6 vs. 30.1 +/- 5.4% after cadmium chloride; P < 0.05). This study is the first to demonstrate the interaction of HIF-1 with the myocardial iNOS gene in situ after hypoxic preconditioning. Prevention of HIF-1 activation and iNOS gene targeting by a single low dose of cadmium abolished the delayed cardioprotective effects, bringing insight into the cardiovascular consequences of cadmium exposure.

Belaidi E; Beguin PC; Levy P; Ribuot C; Godin-Ribuot D

2008-02-01

103

Prevention of HIF-1 activation and iNOS gene targeting by low-dose cadmium results in loss of myocardial hypoxic preconditioning in the rat.  

Science.gov (United States)

This study aimed to underline the interaction between hypoxia-inducible factor-1 (HIF-1) and the inducible nitric oxide synthase (iNOS) gene in vivo and their contribution to the delayed myocardial preconditioning induced by acute intermittent hypoxia (IH) in the rat using chromatin immunoprecipitation and pharmacological inhibition by low-dose cadmium. Langendorff-perfused hearts of Wistar rats exposed to normoxia or IH 24 h earlier were submitted to global ischemia and reperfusion. Effects of iNOS inhibition by aminoguanidine (100 microM) before ischemia or of low-dose injection of cadmium chloride (1 mg/kg) before normoxia or IH were tested. Myocardial HIF-1 and iNOS quantification and in vivo chromatin immunoprecipitation of HIF-1 bound to the iNOS gene promoter were performed. IH-induced delayed cardioprotection resulted in an improvement in coronary flow and functional recovery at reperfusion and a decrease in infarct size. Myocardial HIF-1 activity was increased with resulting targeting of the iNOS gene. Aminoguanidine abolished the cardioprotective effects of IH. Cadmium chloride treatment before IH prevented myocardial HIF-1 activation (72.3 +/- 4.0 vs. 42.1 +/- 9.7 arbitrary units after cadmium chloride; P < 0.05), targeting of the iNOS gene, iNOS expression, and preconditioning (infarct size: 15.9 +/- 5.6 vs. 30.1 +/- 5.4% after cadmium chloride; P < 0.05). This study is the first to demonstrate the interaction of HIF-1 with the myocardial iNOS gene in situ after hypoxic preconditioning. Prevention of HIF-1 activation and iNOS gene targeting by a single low dose of cadmium abolished the delayed cardioprotective effects, bringing insight into the cardiovascular consequences of cadmium exposure. PMID:18083903

Belaidi, Elise; Beguin, Pauline C; Levy, Patrick; Ribuot, Christophe; Godin-Ribuot, Diane

2007-12-14

104

Effective prevention of thrombocytopenia in mice using adenovirus-mediated transfer of HST-1 (FGF-4) gene.  

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HST-1 (FGF-4) gene product is a member of the fibroblast growth factor family with a signal peptide and plays a crucial role in limb development. We showed previously that an intraperitoneal injection of replication-deficient adenovirus containing the HST-1 gene (Adex1HST-1) into normal mice caused ...

Konishi, H; Ochiya, T; Sakamoto, H; Tsukamoto, M; Saito, I; Muto, T; Sugimura, T; Terada, M

105

Downregulation of apoptosis-inducing factor in Harlequin mice induces progressive and severe optic atrophy which is durably prevented by AAV2-AIF1 gene therapy.  

UK PubMed Central (United Kingdom)

The Harlequin mutant mouse, characterized by loss of function of apoptosis-inducing factor, represents a reliable genetic model that resembles pathologies caused by human mitochondrial complex I deficiency. Therefore, we extensively characterized the retinal morphology and function of Harlequin mice during the course of neuronal cell death leading to blindness, with the aim of preventing optic atrophy. Retinas and optic nerves from these mice showed an isolated respiratory chain complex I defect correlated with retinal ganglion cell loss, optic atrophy, glial and microglial cell activation. All of these changes led to irreversible vision loss. In control mice, retinas AIF1 messenger RNA was 2.3-fold more abundant than AIF2, both messenger RNAs being sorted to the mitochondrial surface. In Harlequin mouse retinas, there was a 96% decrease of both AIF1 and AIF2 messenger RNA steady-state levels. We attained substantial and long-lasting protection of retinal ganglion cell and optic nerve integrity, the preservation of complex I function in optic nerves, as well as the prevention of glial and microglial responses after intravitreal administration of an AAV2 vector containing the full-length open reading frame and the 3' untranslated region of the AIF1 gene. Therefore, we demonstrate that gene therapy for mitochondrial diseases due to mutations in nuclear DNA can be achieved, so long as the 'therapeutic gene' permits the accurate cellular localization of the corresponding messenger RNA.

Bouaita A; Augustin S; Lechauve C; Cwerman-Thibault H; Bénit P; Simonutti M; Paques M; Rustin P; Sahel JA; Corral-Debrinski M

2012-01-01

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SAMe treatment prevents the ethanol-induced epigenetic alterations of genes in the Toll-like receptor pathway.  

UK PubMed Central (United Kingdom)

Prior studies showed that Toll-like receptor (TLR) signaling pathway genes were upregulated in the liver of rats fed ethanol, but not in rats fed ethanol plus S-adenosylmethionine (SAMe). These results were obtained using a PCR microplate array analysis for TLRs and associated proteins such as proinflammatory cytokines and chemokine mRNA levels. A large number of genes were upregulated by the ethanol diet, but not the ethanol plus SAMe diet. In the present study, using the same experimental rat livers, DNA methylation analysis was done by using an Epitect Methyl DNA Restriction Kit (Qiagen, 335451) (24 genes). The results of all the genes combined show a highly significant increase in methylation in the ethanol-fed group of rats, but not in the dextrose-fed, SAMe-fed or ethanol plus SAMe-fed groups of rats. There was also an increase in DNA methylation in rats with high blood alcohol levels compared to a rat with a low blood alcohol level. The individual genes that were upregulated as indicated by the increased mRNA measured by qPCR correlated positively with the increased methylation of the DNA of the corresponding genes as follows: Cd14, Hspa1a, Irf1, Irak1, Irak2, Map3k7, Myd88, Ppar?, Ripk2, Tollip and Traf6.

Khachatoorian R; Dawson D; Maloney EM; Wang J; French BA; French SW; French SW

2013-02-01

107

Pseudomonas aeruginosa pvdQ gene prevents Caco-2 cells from obstruction of quorum-sensing signal.  

UK PubMed Central (United Kingdom)

Quorum sensing (QS) system plays an important role in bacterial pathopoiesis of incurable Pseudomonas aeruginosa infection, which strongly warrants new strategies for absence of curative treatment to date. Latest investigations show that pvdQ gene of P. aeruginosa can attenuate the pathopoiesis of the bacteria by encoding acylase enzyme and hydrolyze N-(3-oxododecanoyl)-Homoserine Lactone (3O-oxo-C(12)-HSL), the key signal molecule of QS system. This study tries to resist the pathogenicity of P. aeruginosa by transfecting human intestinal epithelial Caco-2 cells with pvdQ gene. We found that 3O-oxo-C(12)-HSL was decreased in the supernatant of cells transfected with pvdQ gene. Moreover, the result of flow cytometry showed that the 3O-oxo-C(12)-HSL evoked apoptosis rate of Caco-2 cells was inhibited when the cells were transfected with pvdQ gene. In contrast, the control result displayed increased Caco-2 cells' apoptosis rate after stimulation of 3O-oxo-C(12)-HSL without protection of pvdQ gene. In conclusion, we successfully protect mammalian cells Caco-2 from injure of QS signal molecule 3O-oxo-C(12)-HSL through imputing pvdQ gene, which may suggest a new therapeutic strategy for P. aeruginosa infection.

Ye L; Li G; Li H; Wang L; Mao Y; Xie X; Xia C; Chen J; Song J

2011-01-01

108

Dietary fish oil did not prevent sleep deprived rats from a reduction in adipose tissue adiponectin gene expression  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Sleep deprivation in humans has been related to weight gain and consequently, increased risk for insulin resistance. In contrast, there is a significant loss of weight in sleep deprived rats suggesting a state of insulin resistance without obesity interference. Thus, we aimed to assess the effects of a rich fish oil dietetic intervention on glucose tolerance, serum insulin and adiponectin, and adipose tissue gene expression of adiponectin and TNF-? of paradoxically sleep deprived (PSD) rats. The study was performed in thirty day-old male Wistar randomly assigned into two groups: rats fed with control diet (soybean oil as source of fat) and rats fed with a fish oil rich diet. After 45 days of treatment, the animals were submitted to PSD or maintained as home cage control group for 96 h. Body weight and food intake were carefully monitored in all groups. At the end of PSD period, a glucose tolerance test was performed and the total blood and adipose tissues were collected. Serum insulin and adiponectin were analyzed. Adipose tissues were used for RT-PCR to estimate the gene expression of adiponectin and TNF-?. Results showed that although fish oil diet did not exert any effect upon these measurements, PSD induced a reduction in adiponectin gene expression of retroperitoneal adipose tissues, with no change in serum adiponectin concentration or in adiponectin and TNF-? gene expression of epididymal adipose tissue. Thus, the stress induced by sleep deprivation lead to a desbalance of adiponectin gene expression.

de Mattos Ana; Pinto Mônica; Oliveira Cristiane; Biz Carolina; Ribeiro Eliane; do Nascimento Claudia; Andersen Monica; Tufik Sergio; Oyama Lila

2008-01-01

109

Electroporation-enhanced nonviral gene transfer for the prevention or treatment of immunological, endocrine and neoplastic diseases.  

Science.gov (United States)

Nonviral gene transfer is markedly enhanced by the application of in vivo electroporation (also denoted electro-gene transfer or electrokinetic enhancement). This approach is safe and can be used to deliver nucleic acid fragments, oligonucleotides, siRNA, and plasmids to a wide variety of tissues, such as skeletal muscle, skin and liver. In this review, we address the principles of electroporation and demonstrate its effectiveness in disease models. Electroporation has been shown to be equally applicable to small and large animals (rodents, dogs, pigs, other farm animals and primates), and this addresses one of the major problems in gene therapy, that of scalability to humans. Gene transfer can be optimized and tissue injury minimized by the selection of appropriate electrical parameters. We and others have applied this approach in preclinical autoimmune and/or inflammatory diseases to deliver either cytokines, anti-inflammatory agents or immunoregulatory molecules. Electroporation is also effective for the intratumoral delivery of therapeutic vectors. It strongly boost DNA vaccination against infectious agents (e.g., hepatitis B virus, human immunodeficiency virus-1) or tumor antigens (e.g., HER-2/neu, carcinoembryonic antigen). In addition, we found that electroporation-enhanced DNA vaccination against islet-cell antigens ameliorated autoimmune diabetes. One of the most likely future applications, however, may be in intramuscular gene transfer for systemic delivery of either endocrine hormones (e.g., growth hormone releasing hormone and leptin), hematopoietic factors (e.g., erythropoietin, GM-CSF), antibodies, enzymes, or numerous other protein drugs. In vivo electroporation has been performed in humans, and it seems likely it could be applied clinically for nonviral gene therapy. PMID:16611045

Prud'homme, Gérald J; Glinka, Yelena; Khan, Amir S; Draghia-Akli, Ruxandra

2006-04-01

110

Two B3 domain transcriptional repressors prevent sugar-inducible expression of seed maturation genes in Arabidopsis seedlings  

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During development of plant seeds, embryos import nutrients and store massive amounts of reserves. Seed reserves are rapidly degraded and mobilized to support seedling development after germination. HIGH-LEVEL EXPRESSION OF SUGAR-INDUCIBLE GENE 2 (HSI2) of Arabidopsis thaliana is a B3 DNA-binding do...

Tsukagoshi, Hironaka; Morikami, Atsushi; Nakamura, Kenzo

111

Insights into the biology and prevention of tumor metastasis provided by the Nm23 metastasis suppressor gene.  

Science.gov (United States)

Metastatic disease is the major cause of death among cancer patients. A class of genes, named metastasis suppressors, has been described to specifically regulate the metastatic process. The metastasis suppressor genes are downregulated in the metastatic lesion compared to the primary tumor. In this review, we describe the body of research surrounding the first metastasis suppressor identified, Nm23. Nm23 overexpression in aggressive cancer cell lines reduced their metastatic potential in vivo with no significant reduction in primary tumor size. A complex mechanism of anti-metastatic action is unfolding involving several known Nm23 enzymatic activities (nucleotide diphosphate kinase, histidine kinase, and 3'-5' exonuclease), protein-protein interactions, and downstream gene regulation properties. Translational approaches involving Nm23 have progressed to the clinic. The upregulation of Nm23 expression by medroxyprogesterone acetate has been tested in a phase II trial. Other approaches with significant preclinical success include gene therapy using traditional or nanoparticle delivery, and cell permeable Nm23 protein. Recently, based on the inverse correlation of Nm23 and LPA1 expression, a LPA1 inhibitor has been shown to both inhibit metastasis and induce metastatic dormancy. PMID:22706779

Marino, Natascia; Nakayama, Joji; Collins, Joshua W; Steeg, Patricia S

2012-12-01

112

Insights into the biology and prevention of tumor metastasis provided by the Nm23 metastasis suppressor gene.  

UK PubMed Central (United Kingdom)

Metastatic disease is the major cause of death among cancer patients. A class of genes, named metastasis suppressors, has been described to specifically regulate the metastatic process. The metastasis suppressor genes are downregulated in the metastatic lesion compared to the primary tumor. In this review, we describe the body of research surrounding the first metastasis suppressor identified, Nm23. Nm23 overexpression in aggressive cancer cell lines reduced their metastatic potential in vivo with no significant reduction in primary tumor size. A complex mechanism of anti-metastatic action is unfolding involving several known Nm23 enzymatic activities (nucleotide diphosphate kinase, histidine kinase, and 3'-5' exonuclease), protein-protein interactions, and downstream gene regulation properties. Translational approaches involving Nm23 have progressed to the clinic. The upregulation of Nm23 expression by medroxyprogesterone acetate has been tested in a phase II trial. Other approaches with significant preclinical success include gene therapy using traditional or nanoparticle delivery, and cell permeable Nm23 protein. Recently, based on the inverse correlation of Nm23 and LPA1 expression, a LPA1 inhibitor has been shown to both inhibit metastasis and induce metastatic dormancy.

Marino N; Nakayama J; Collins JW; Steeg PS

2012-12-01

113

NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145.  

UK PubMed Central (United Kingdom)

The NK cell-activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described NKG2D ligand. We show that MCMV infection strongly induces MULT-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus. Screening a panel of MCMV deletion mutants defined the gene m145 as the viral regulator of MULT-1. The MCMV m145-encoded glycoprotein turned out to be necessary and sufficient to regulate MULT-1 by preventing plasma membrane residence of MULT-1. The importance of MULT-1 in NK cell regulation in vivo was confirmed by the attenuating effect of the m145 deletion that was lifted after NK cell depletion. Our findings underline the significance of escaping MULT-1/NKG2D signaling for viral survival and maintenance.

Krmpotic A; Hasan M; Loewendorf A; Saulig T; Halenius A; Lenac T; Polic B; Bubic I; Kriegeskorte A; Pernjak-Pugel E; Messerle M; Hengel H; Busch DH; Koszinowski UH; Jonjic S

2005-01-01

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The rs1800629 polymorphism in the TNF gene interacts with physical activity on the changes in C-reactive protein levels in the Finnish Diabetes Prevention Study  

DEFF Research Database (Denmark)

Physical activity exerts anti-inflammatory effects, but genetic variation may modify its influence. In particular, the rs1800629 single-nucleotide polymorphism (SNP) in the tumor necrosis factor ( TNF) gene and the rs1800795 SNP in the interleukin-6 ( IL6) gene have been found to modify the effect of exercise training on circulating levels of C-reactive protein (CRP) and IL-6, respectively. We assessed whether rs1800629 and rs1800795 modified the effect of moderate-to-vigorous physical activity on changes in serum levels of high-sensitivity CRP and IL-6 in the Finnish Diabetes Prevention Study (DPS). Genotype and 1-year data on changes in physical activity, serum CRP and IL-6 were available for 390 overweight subjects with impaired glucose tolerance. The rs1800629 SNP in TNF interacted with the 1-year change in moderate-to-vigorous physical activity on changes in CRP among those who had high (?3 mg/L) baseline CRP levels ( P = 0.034 for interaction). Carriers of the GG genotype showed a greater decrease in CRP with increasing physical activity than the individuals with the A allele. No interaction between the rs1800795 SNP in IL6 and changes in moderate-to-vigorous physical activity on the 1-year change in serum IL-6 was found. In conclusion, the rs1800629 SNP in the TNF gene may modify the effect of moderate-to-vigorous physical activity on serum levels of CRP.

Oskari Kilpeläinen, Tuomas; Laaksonen, D E

2010-01-01

115

Regulations of Gene Expression in Medullary Thymic Epithelial Cells Required for Preventing the Onset of Autoimmune Diseases  

Science.gov (United States)

Elimination of potential self-reactive T cells in the thymus is crucial for preventing the onset of autoimmune diseases. Epithelial cell subsets localized in thymic medulla [medullary thymic epithelial cells (mTECs)] contribute to this process by supplying a wide range of self-antigens that are otherwise expressed in a tissue-specific manner (TSAs). Expression of some TSAs in mTECs is controlled by the autoimmune regulator (AIRE) protein, of which dysfunctional mutations are the causative factor of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). In addition to the elimination of self-reactive T cells, recent studies indicated roles of mTECs in the development of Foxp3-positive regulatory T cells, which suppress autoimmunity and excess immune reactions in peripheral tissues. The TNF family cytokines, RANK ligand, CD40 ligand, and lymphotoxin were found to promote the differentiation of AIRE- and TSA-expressing mTECs. Furthermore, activation of NF-?B is essential for mTEC differentiation. In this mini-review, we focus on molecular mechanisms that regulate induction of AIRE and TSA expression and discuss possible contributions of these mechanisms to prevent the onset of autoimmune diseases.

Akiyama, Taishin; Shinzawa, Miho; Qin, Junwen; Akiyama, Nobuko

2013-01-01

116

HPV Prevention  

Science.gov (United States)

... Digg Google Bookmarks Prevention How can people prevent HPV? There are several ways that people can lower ... way to avoid HPV. How can people prevent HPV-related diseases? There are ways to prevent the ...

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Thrombophilia screening in young patients with cryptogenic stroke. Prevalence of gene polymorphisms compared to healthy blood donors and impact on secondary stroke prevention.  

UK PubMed Central (United Kingdom)

UNLABELLED: The clinical relevance of thrombophilia screening in stroke patients is still a matter of debate, and descriptions of larger patterns of genetic variability are rare. We assessed the frequency of hereditary hypercoagulability in young patients with cryptogenic stroke (n = 44) and in healthy blood donors (n = 282) without prior cardiovascular event. Furthermore, we focused on the impact of thrombophilia screening on secondary stroke prevention. RESULTS: Compared to the control group (19-67 years; median 38.5 years; 64% women), there was a lower prevalence of the FVII-R353Q mutation (p = 0.033) in stroke patients (17-52 years; median 36 years; 59.1% women). Of note, the FVII-R353Q mutation lowers FVII plasma levels, probably reducing the risk of cardiovascular events. The prevalence of the remaining 13 gene polymorphisms did not differ significantly. However, the prevalence of FV Leiden mutation tended to be higher among stroke patients. CONCLUSION: Overall, extended screening for inherited thrombophilia had an impact on medical stroke prevention in every sixth patient with cryptogenic stroke.

Haeusler KG; Herm J; Hoppe B; Kasabov R; Malzahn U; Endres M; Koscielny J; Jungehulsing GJ

2012-01-01

118

Variations in Helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention.  

UK PubMed Central (United Kingdom)

Helicobacter pylori (HP) is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes) pathogenicity island (cagPAI), a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS). This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma) using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche) methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous) showed statistically significant differences (P<0.05), and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value?=?2.07×10??), and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations.

Rizzato C; Torres J; Plummer M; Muñoz N; Franceschi S; Camorlinga-Ponce M; Fuentes-Pananá EM; Canzian F; Kato I

2012-01-01

119

Variations in Helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention.  

Science.gov (United States)

Helicobacter pylori (HP) is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes) pathogenicity island (cagPAI), a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS). This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma) using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche) methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous) showed statistically significant differences (P<0.05), and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value?=?2.07×10??), and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations. PMID:22235308

Rizzato, Cosmeri; Torres, Javier; Plummer, Martyn; Muñoz, Nubia; Franceschi, Silvia; Camorlinga-Ponce, Margarita; Fuentes-Pananá, Ezequiel M; Canzian, Federico; Kato, Ikuko

2012-01-03

120

AAV-based gene therapy prevents neuropathology and results in normal cognitive development in the hyperargininemic mouse.  

Science.gov (United States)

Complete arginase I deficiency is the least severe urea cycle disorder, characterized by hyperargininemia and infrequent episodes of hyperammonemia. Patients suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation and seizures, and is associated with intellectual disability. In mice, onset is heralded by weight loss beginning around day 15; gait instability follows progressing to inability to stand and development of tail tremor with seizure-like activity and death. Here we report that hyperargininemic mice treated neonatally with an adeno-associated virus (AAV)-expressing arginase and followed long-term lack any presentation consistent with brain dysfunction. Behavioral and histopathological evaluation demonstrated that treated mice are indistinguishable from littermates, and that putative compounds associated with neurotoxicity are diminished. In addition, treatment results in near complete resolution of metabolic abnormalities early in life; however, there is the development of some derangement later with decline in transgene expression. Ammonium challenging revealed that treated mice are affected by exogenous loading much greater than littermates. These results demonstrate that AAV-based therapy for hyperargininemia is effective and prevents development of neurological abnormalities and cognitive dysfunction in a mouse model of hyperargininemia; however, nitrogen challenging reveals that these mice remain impaired in the handling of waste nitrogen. PMID:23388701

Lee, E K; Hu, C; Bhargava, R; Ponnusamy, R; Park, H; Novicoff, S; Rozengurt, N; Marescau, B; De Deyn, P; Stout, D; Schlichting, L; Grody, W W; Cederbaum, S D; Lipshutz, G S

2013-02-07

 
 
 
 
121

Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To assess associations and genotype × treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits. DESIGN AND METHODS: Diabetes Prevention Program (DPP) participants (N=3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n=909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment. RESULTS: The rs1943218 minor allele was nominally associated with short-term (6 month; P=0.032) and long-term (2 year; P=0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all Pinteraction <0.05). CONCLUSION: This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions.

Pan Q; Delahanty LM; Jablonski KA; Knowler WC; Kahn SE; Florez JC; Franks PW

2013-03-01

122

MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation.  

UK PubMed Central (United Kingdom)

Mitochondrial transcription termination factor 1, MTERF1, has been reported to couple rRNA gene transcription initiation with termination and is therefore thought to be a key regulator of mammalian mitochondrial ribosome biogenesis. The prevailing model is based on a series of observations published over the last two decades, but no in vivo evidence exists to show that MTERF1 regulates transcription of the heavy-strand region of mtDNA containing the rRNA genes. Here, we demonstrate that knockout of Mterf1 in mice has no effect on mitochondrial rRNA levels or mitochondrial translation. Instead, loss of Mterf1 influences transcription initiation at the light-strand promoter, resulting in a decrease of de novo transcription manifested as reduced 7S RNA levels. Based on these observations, we suggest that MTERF1 does not regulate heavy-strand transcription, but rather acts to block transcription on the opposite strand of mtDNA to prevent transcription interference at the light-strand promoter.

Terzioglu M; Ruzzenente B; Harmel J; Mourier A; Jemt E; López MD; Kukat C; Stewart JB; Wibom R; Meharg C; Habermann B; Falkenberg M; Gustafsson CM; Park CB; Larsson NG

2013-04-01

123

Variation in the UCP2 and UCP3 genes associates with abdominal obesity and serum lipids: The Finnish Diabetes Prevention Study  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background We explored the associations of three variants in the uncoupling protein 2 (UCP2) gene, one variant in the UCP2-UCP3 intergenic region and five variants in the uncoupling protein 3 (UCP3) gene with obesity and diabetes related traits in subjects with impaired glucose tolerance participating in Finnish Diabetes Prevention Study. Altogether 507 overweight individuals (body mass index: 31.2 ± 4.5 kg/m2, age: 55 ± 7 years) for whom DNA was available were randomized to either an intensified diet and physical activity group or to a conventional care control group. Methods We analysed the data from the baseline and annual follow-up visits from years 1, 2 and 3. Measurements of anthropometry, plasma glucose and serum insulin in oral glucose tolerance test, serum total cholesterol, HDL-cholesterol and triglycerides were included. The median follow-up time for type 2 diabetes incidence was 7 years. Genetic variants were screened by restriction fragment length polymorphism or Illumina method. Results UCP3 gene variant rs3781907 was associated with increased serum total and LDL-cholesterol levels, at baseline and during the follow-up period. The same variant was associated with a higher risk of type 2 diabetes. Variants rs1726745, rs11235972 and rs1800849 in the UCP3 gene associated with serum total and LDL-cholesterol at baseline. Haploblock including variants rs659366, rs653529, rs15763, and rs1726745 was associated with measures of abdominal obesity at baseline and in the longitudinal analysis. The haplotype comprising alleles rs659366-G, rs653529-A, rs15763-G and rs1726745-A was associated with higher waist-to-hip ratio, and haplotype comprising alleles rs3781907-G, rs11235972-A, and rs1800849-T was associated with increased serum total and LDL-cholesterol concentrations. Conclusion Genetic variation in the UCP2-UCP3 gene cluster may act as a modifier increasing serum lipid levels and indices of abdominal obesity, and may thereby also contribute to the metabolic aberrations observed in obesity and type 2 diabetes.

Salopuro Titta; Pulkkinen Leena; Lindström Jaana; Kolehmainen Marjukka; Tolppanen Anna-Maija; Eriksson Johan G; Valle Timo T; Aunola Sirkka; Ilanne-Parikka Pirjo; Keinänen-Kiukaanniemi Sirkka; Tuomilehto Jaakko; Laakso Markku; Uusitupa Matti

2009-01-01

124

Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes  

DEFF Research Database (Denmark)

Many of the virulence factors produced by the opportunistic human pathogen Pseudomonas aeruginosa are quorum-sensing (QS) regulated. Among these are rhamnolipids, which have been shown to cause lysis of several cellular components of the human immune system, e.g. monocyte-derived macrophages and polymorphonuclear leukocytes (PMNs). We have previously shown that rhamnolipids produced by P. aeruginosa cause necrotic death of PMNs in vitro. This raises the possibility that rhamnolipids may function as a 'biofilm shield' in vivo, which contributes significantly to the increased tolerance of P. aeruginosa biofilms to PMNs. In the present study, we demonstrate the importance of the production of rhamnolipids in the establishment and persistence of P. aeruginosa infections, using an in vitro biofilm system, an intraperitoneal foreign-body model and a pulmonary model of P. aeruginosa infections in mice. Our experimental data showed that a P. aeruginosa strain, unable to produce any detectable rhamnolipids due to an inactivating mutation in the single QS-controlled rhlA gene, did not induce necrosis of PMNs in vitro and exhibited increased clearance compared with its wild-type counterpart in vivo. Conclusively, the results support our model that rhamnolipids are key protective agents of P. aeruginosa against PMNs.

van Gennip, Maria; Christensen, Louise Dahl

2009-01-01

125

?-1-antitrypsin gene delivery reduces inflammation, increases T-regulatory cell population size and prevents islet allograft rejection.  

Science.gov (United States)

Antiinflammatory clinical-grade, plasma-derived human ?-1 antitrypsin (hAAT) protects islets from allorejection as well as from autoimmune destruction. hAAT also interferes with disease progression in experimental autoimmune encephalomyelitis (EAE) and in collagen-induced arthritis (CIA) mouse models. hAAT increases IL-1 receptor antagonist expression in human mononuclear cells and T-regulatory (Treg) cell population size in animal models. Clinical-grade hAAT contains plasma impurities, multiple hAAT isoforms and various states of inactive hAAT. We thus wished to establish islet-protective activities and effect on Treg cells of plasmid-derived circulating hAAT in whole animals. Islet function was assessed in mice that received allogeneic islet transplants after mice were given hydrodynamic tail-vein injection with pEF-hAAT, a previously described Epstein-Barr virus (EBV) plasmid construct containing the EBV nuclear antigen 1 (EBNA1) and the family of repeat EBNA1 binding site components (designated "EF") alongside the hAAT gene. Sera collected from hAAT-expressing mice were added to lipopolysaccharide (LPS)-stimulated macrophages to assess macrophage responsiveness. Also, maturation of peritoneal cells from hAAT-expressing mice was evaluated. hAAT-expressing mice accepted islet allografts (n = 11), whereas phosphate-buffered saline-injected animals (n = 11), as well as mice treated with truncated-hAAT-plasmid (n = 6) and untreated animals (n = 20) rapidly rejected islet allografts. In hAAT-expressing animals, local Treg cells were abundant at graft sites, and the IL-1 receptor antagonist was elevated in grafts and circulation. Sera from hAAT-expressing mice, but not control mice, inhibited macrophage responses. Finally, peritoneal cells from hAAT-expressing mice exhibited a semimature phenotype. We conclude that plasmid-derived circulating hAAT protects islet allografts from acute rejection, and human plasma impurities are unrelated to islet protection. Future studies may use this in vivo approach to examine the structure-function characteristics of the protective activities of AAT by manipulation of the hAAT plasmid. PMID:21670848

Shahaf, Galit; Moser, Hadas; Ozeri, Eyal; Mizrahi, Mark; Abecassis, Avishag; Lewis, Eli C

2011-06-09

126

?-1-antitrypsin gene delivery reduces inflammation, increases T-regulatory cell population size and prevents islet allograft rejection.  

UK PubMed Central (United Kingdom)

Antiinflammatory clinical-grade, plasma-derived human ?-1 antitrypsin (hAAT) protects islets from allorejection as well as from autoimmune destruction. hAAT also interferes with disease progression in experimental autoimmune encephalomyelitis (EAE) and in collagen-induced arthritis (CIA) mouse models. hAAT increases IL-1 receptor antagonist expression in human mononuclear cells and T-regulatory (Treg) cell population size in animal models. Clinical-grade hAAT contains plasma impurities, multiple hAAT isoforms and various states of inactive hAAT. We thus wished to establish islet-protective activities and effect on Treg cells of plasmid-derived circulating hAAT in whole animals. Islet function was assessed in mice that received allogeneic islet transplants after mice were given hydrodynamic tail-vein injection with pEF-hAAT, a previously described Epstein-Barr virus (EBV) plasmid construct containing the EBV nuclear antigen 1 (EBNA1) and the family of repeat EBNA1 binding site components (designated "EF") alongside the hAAT gene. Sera collected from hAAT-expressing mice were added to lipopolysaccharide (LPS)-stimulated macrophages to assess macrophage responsiveness. Also, maturation of peritoneal cells from hAAT-expressing mice was evaluated. hAAT-expressing mice accepted islet allografts (n = 11), whereas phosphate-buffered saline-injected animals (n = 11), as well as mice treated with truncated-hAAT-plasmid (n = 6) and untreated animals (n = 20) rapidly rejected islet allografts. In hAAT-expressing animals, local Treg cells were abundant at graft sites, and the IL-1 receptor antagonist was elevated in grafts and circulation. Sera from hAAT-expressing mice, but not control mice, inhibited macrophage responses. Finally, peritoneal cells from hAAT-expressing mice exhibited a semimature phenotype. We conclude that plasmid-derived circulating hAAT protects islet allografts from acute rejection, and human plasma impurities are unrelated to islet protection. Future studies may use this in vivo approach to examine the structure-function characteristics of the protective activities of AAT by manipulation of the hAAT plasmid.

Shahaf G; Moser H; Ozeri E; Mizrahi M; Abecassis A; Lewis EC

2011-09-01

127

Challenges and opportunities for controlling and preventing animal diseases in developing countries through gene-based technologies  

International Nuclear Information System (INIS)

Polymerase Chain Reaction (PCR) technology allows scientist to amplify, copy, identify, characterize and manipulate genes in a relatively simple way. Exploitation of the technology to devise new products and translate these to the commercial sector has been remarkable. Molecular technologies are not difficult to establish and use, and can appear to offer developing countries many opportunities. However, developing countries should look in a different way at the apparent advantages offered. Whilst molecular biological science appears to offer solutions to many problems, there are a number of drawbacks. This desire to adopt the latest technology often overrides any considerations of the use of more conventional technologies to address needs. The conventional, and often more practical, methods already provide many specific tools in the disease control area. Changing the technology can also deflect critical resources into the molecular field in terms of laboratory funding and training. This may cause redundancy of staff, limit further development in conventional techniques, and polarize scientists into the older (less glossy) and newer (molecular) camps. Animal disease diagnosis still primarily utilizes conventional techniques such as Enzyme Linked Immunosorbent Assay (ELISA). This will not change drastically in developing countries, but developments will combine such methods with more discriminatory molecular techniques, and a balanced and parallel development is needed. An understanding of the use and possible advantages of the various technologies is required by both scientists and policy-makers in developing nations. Vaccines based on molecular science could have a real impact in developing countries, but 'vaccinology' needs to examine both the animal (immunology of target species) and the disease agent itself. This is a research-based science and, as such, is expensive, with no surety of success. Developing countries should exploit links with developed countries to provide the 'field' genetic resource (endemic disease situation) in order to devise and test vaccines developed through molecular studies. Development of technologies cannot be divorced from an understanding of the epidemiology of the diseases found in developing countries. This is frequently not undertaken due to the many competing demands on the scarce resources available. However, increased livestock trade possibilities may provide the focus and catalyst needed to ensure that animal health science is applied appropriately and usefully for the benefit of developing countries. (author)

2005-01-01

128

The use of a two-gene sequencing approach to accurately distinguish between the species within the Mycobacterium abscessus complex and Mycobacterium chelonae.  

UK PubMed Central (United Kingdom)

Mycobacterium abscessus [M. abscessus (sensu lato) or M. abscessus complex] comprises three closely related species: M. abscessus (sensu stricto), hereafter referred to as M. abscessus, M. bolletii and M. massiliense. We describe here an accurate and robust method for distinguishing M. chelonae from M. abscessus, M. bolletii and M. massiliense, using polymerase chain reaction (PCR) and the sequencing of house-keeping gene targets (hsp65 and rpoB). Sequencing of the sodA gene is of little additional value in discriminating between species, but M. massiliense can be rapidly identified by amplification of the truncated erm(41) gene without the need for amplicon sequencing. We have applied the method to 81 isolates from 40 patients from two hospitals, the majority of whom were cystic fibrosis (CF) patients. Of these patients, 21 had previously been identified as M. chelonae and 59 as M. abscessus complex using commercial line probe assays. We identified these as 46 M. abscessus isolates, 20 M. massiliense isolates, five M. bolletii isolates and nine M. chelonae isolates and confirmed the one M. fortuitum isolate. This is the first study that has identified the individual members of the M. abscessus complex in a UK cohort of mainly CF patients.

Blauwendraat C; Dixon GL; Hartley JC; Foweraker J; Harris KA

2012-08-01

129

Polymerase chain reaction-restriction fragment length polymorphism of the rpoB gene for identification of Mycobacterium avium subsp. paratuberculosis and differentiation of Mycobacterium avium subspecies.  

UK PubMed Central (United Kingdom)

Mycobacterial speciation by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis (PRA) of the rpoB gene was evaluated for identification of Mycobacterium avium subsp. paratuberculosis (MAP) and other Mycobacterium avium complex (MAC) members to the species or subspecies level by comparison with conventional methods including hsp65 sequencing, high-performance liquid chromatography, and PCR for accepted species- or subspecies-specific genomic targets. A total of 185 type and clinical mycobacterial strains from humans, animals, and environments were tested. A 360-bp PCR product was subsequently digested with MspI, HaeIII, and SmaI restriction enzymes. The PRA using SmaI restriction showed a unique digestion pattern for MAP distinguishing it from other MAC members and other Mycobacterium spp. Moreover, HaeIII and MspI restriction of the rpoB gene enabled MAC-species and -subspecies discrimination. The rpoB-PRA using SmaI or MspI and HaeIII restriction of the rpoB gene is a simple, convenient, and reliable confirmatory assay for simultaneous identification of MAP and other MAC members.

Whang J; Lee BS; Choi GE; Cho SN; Kil PY; Collins MT; Shin SJ

2011-05-01

130

Polymerase chain reaction-restriction fragment length polymorphism of the rpoB gene for identification of Mycobacterium avium subsp. paratuberculosis and differentiation of Mycobacterium avium subspecies.  

Science.gov (United States)

Mycobacterial speciation by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis (PRA) of the rpoB gene was evaluated for identification of Mycobacterium avium subsp. paratuberculosis (MAP) and other Mycobacterium avium complex (MAC) members to the species or subspecies level by comparison with conventional methods including hsp65 sequencing, high-performance liquid chromatography, and PCR for accepted species- or subspecies-specific genomic targets. A total of 185 type and clinical mycobacterial strains from humans, animals, and environments were tested. A 360-bp PCR product was subsequently digested with MspI, HaeIII, and SmaI restriction enzymes. The PRA using SmaI restriction showed a unique digestion pattern for MAP distinguishing it from other MAC members and other Mycobacterium spp. Moreover, HaeIII and MspI restriction of the rpoB gene enabled MAC-species and -subspecies discrimination. The rpoB-PRA using SmaI or MspI and HaeIII restriction of the rpoB gene is a simple, convenient, and reliable confirmatory assay for simultaneous identification of MAP and other MAC members. PMID:21429694

Whang, Jake; Lee, Byung Soo; Choi, Go-Eun; Cho, Sang-Nae; Kil, Park Young; Collins, Michael T; Shin, Sung Jae

2011-03-22

131

Tonic activation of A(2A) adenosine receptors unmasks, and of A(1) receptors prevents, a facilitatory action of calcitonin gene-related peptide in the rat hippocampus.  

UK PubMed Central (United Kingdom)

1. We investigated how manipulations of the degree of activation of adenosine A(1) and A(2A) receptors influences the action of the neuropeptide, calcitonin gene-related peptide (CGRP) on synaptic transmission in hippocampal slices. Field excitatory post-synaptic potentials (EPSPs) from the CA1 area were recorded. 2. When applied alone, CGRP (1 - 30 nM) was without effect on field EPSPs. However, CGRP (10 - 30 nM) significantly increased the field EPSP slope when applied to hippocampal slices in the presence of the A(1) receptor antagonist, 1,3-dipropyl-8-cyclopenthyl xanthine (DPCPX, 10 nM), or in the presence of the A(2A) adenosine receptor agonist CGS 21680 (10 nM). 3. The A(2A) receptor antagonist, ZM 241385 (10 nM) as well as adenosine deaminase (ADA, 2 U ml(-1)), prevented the enhancement of field EPSP slope caused by CGRP (30 nM) in the presence of DPCPX (10 nM), suggesting that this effect of CGRP requires the concomitant activation of A(2A) adenosine receptors by endogenous adenosine. 4. The protein kinase-A inhibitors, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004, 10 microM) and adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS, 50 microM), as well as the inhibitor of ATP-sensitive potassium (K(ATP)) channels, glibenclamide (30 microM), prevented the facilitation of synaptic transmission caused by CGRP (30 nM) in the presence of DPCPX (10 nM), suggesting that this effect of CGRP involves both K(ATP) channels and protein kinase-A. 5. It is concluded that the ability of CGRP to facilitate synaptic transmission in the CA1 area of the hippocampus is under tight control by adenosine, with tonic A(1) receptor activation by endogenous adenosine 'braking' the action of CGRP, and the A(2A) receptors triggering this action.

Sebastião AM; Macedo MP; Ribeiro JA

2000-01-01

132

Expression of a GALACTINOL SYNTHASE gene in tomato seeds is up-regulated before maturation desiccation and again after imbibition whenever radicle protrusion is prevented.  

Science.gov (United States)

Raffinose family oligosaccharides (RFOs) have been implicated in mitigating the effects of environmental stresses on plants. In seeds, proposed roles for RFOs include protecting cellular integrity during desiccation and/or imbibition, extending longevity in the dehydrated state, and providing substrates for energy generation during germination. A gene encoding galactinol synthase (GOLS), the first committed enzyme in the biosynthesis of RFOs, was cloned from tomato (Lycopersicon esculentum Mill. cv Moneymaker) seeds, and its expression was characterized in tomato seeds and seedlings. GOLS (LeGOLS-1) mRNA accumulated in developing tomato seeds concomitant with maximum dry weight deposition and the acquisition of desiccation tolerance. LeGOLS-1 mRNA was present in mature, desiccated seeds but declined within 8 h of imbibition in wild-type seeds. However, LeGOLS-1 mRNA accumulated again in imbibed seeds prevented from completing germination by dormancy or water deficit. Gibberellin-deficient (gib-1) seeds maintained LeGOLS-1 mRNA amounts after imbibition unless supplied with gibberellin, whereas abscisic acid (ABA) did not prevent the loss of LeGOLS-1 mRNA from wild-type seeds. The presence of LeGOLS-1 mRNA in ABA-deficient (sitiens) tomato seeds indicated that wild-type amounts of ABA are not necessary for its accumulation during seed development. In all cases, LeGOLS-1 mRNA was most prevalent in the radicle tip. LeGOLS-1 mRNA accumulation was induced by dehydration but not by cold in germinating seeds, whereas both stresses induced LeGOLS-1 mRNA accumulation in seedling leaves. The physiological implications of LeGOLS-1 expression patterns in seeds and leaves are discussed in light of the hypothesized role of RFOs in plant stress tolerance. PMID:12644684

Downie, Bruce; Gurusinghe, Sunitha; Dahal, Petambar; Thacker, Richard R; Snyder, John C; Nonogaki, Hiroyuki; Yim, Kyuock; Fukanaga, Keith; Alvarado, Veria; Bradford, Kent J

2003-03-01

133

Expression of a GALACTINOL SYNTHASE gene in tomato seeds is up-regulated before maturation desiccation and again after imbibition whenever radicle protrusion is prevented.  

UK PubMed Central (United Kingdom)

Raffinose family oligosaccharides (RFOs) have been implicated in mitigating the effects of environmental stresses on plants. In seeds, proposed roles for RFOs include protecting cellular integrity during desiccation and/or imbibition, extending longevity in the dehydrated state, and providing substrates for energy generation during germination. A gene encoding galactinol synthase (GOLS), the first committed enzyme in the biosynthesis of RFOs, was cloned from tomato (Lycopersicon esculentum Mill. cv Moneymaker) seeds, and its expression was characterized in tomato seeds and seedlings. GOLS (LeGOLS-1) mRNA accumulated in developing tomato seeds concomitant with maximum dry weight deposition and the acquisition of desiccation tolerance. LeGOLS-1 mRNA was present in mature, desiccated seeds but declined within 8 h of imbibition in wild-type seeds. However, LeGOLS-1 mRNA accumulated again in imbibed seeds prevented from completing germination by dormancy or water deficit. Gibberellin-deficient (gib-1) seeds maintained LeGOLS-1 mRNA amounts after imbibition unless supplied with gibberellin, whereas abscisic acid (ABA) did not prevent the loss of LeGOLS-1 mRNA from wild-type seeds. The presence of LeGOLS-1 mRNA in ABA-deficient (sitiens) tomato seeds indicated that wild-type amounts of ABA are not necessary for its accumulation during seed development. In all cases, LeGOLS-1 mRNA was most prevalent in the radicle tip. LeGOLS-1 mRNA accumulation was induced by dehydration but not by cold in germinating seeds, whereas both stresses induced LeGOLS-1 mRNA accumulation in seedling leaves. The physiological implications of LeGOLS-1 expression patterns in seeds and leaves are discussed in light of the hypothesized role of RFOs in plant stress tolerance.

Downie B; Gurusinghe S; Dahal P; Thacker RR; Snyder JC; Nonogaki H; Yim K; Fukanaga K; Alvarado V; Bradford KJ

2003-03-01

134

Preventing Suicide  

Science.gov (United States)

... Añadir en... Favorites Delicious Digg Google Bookmarks Preventing Suicide Each year, more than 36,000 Americans take ... for self-inflicted injuries. September 10th is World Suicide Prevention Day. Help prevent suicide in your community. ...

135

Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns.  

Science.gov (United States)

This study was conducted to determine the mechanisms implicated in the beneficial effects of apple polyphenols (APs) against diet-induced obesity in Wistar rats, described in a previous study from our group. Supplementation of high-fat sucrose diet with AP prevented adiposity increase by inhibition of adipocyte hypertrophy. Rats supplemented with AP exhibited improved glucose tolerance while adipocytes isolated from these rats showed an enhanced lipolytic response to isoproterenol. AP intake led to reduced Lep, Plin, and sterol regulatory element binding transcription factor 1 (Srebf1) mRNA levels and increased aquaporin 7 (Aqp7), adipocyte enhancer binding protein 1 (Aebp1), and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (Ppargc1a) mRNA levels in epididymal adipocytes. In addition, we found different methylation patterns of Aqp7, Lep, Ppargc1a, and Srebf1 promoters in adipocytes from apple-supplemented rats compared to high-fat sucrose fed rats. The administration of AP protects against body weight gain and fat deposition and improves glucose tolerance in rats. We propose that AP exerts the antiobesity effects through the regulation of genes involved in adipogenesis, lipolysis, and fatty acid oxidation, in a process that could be mediated in part by epigenetic mechanisms. PMID:23529981

Boqué, Noemi; de la Iglesia, Rocío; de la Garza, Ana L; Milagro, Fermín I; Olivares, Mónica; Bañuelos, Oscar; Soria, Ana Cristina; Rodríguez-Sánchez, Sonia; Martínez, José Alfredo; Campión, Javier

2013-03-25

136

Prevention of baculovirus-induced apoptosis of BTI-Tn-5B1-4 (Hi5) cells by the p35 gene of Trichoplusia ni multicapsid nucleopolyhedrovirus.  

UK PubMed Central (United Kingdom)

A typical apoptosis of BTI-Tn-5B1-4 (Hi5) cells induced by Heliothis armigera single capsid nucleopolyhedrovirus (HaSNPV) infection was completely suppressed by coinfection with Trichoplusia ni multicapsid nucleopolyhedrovirus polyhedron-negative recombinant (TnMNPV-SVI- G) (OCC-) at a low multiplicity of infection (6.5 x 10(-2)). To determine whether TnMNPV p35 alone was sufficient to inhibit the apoptosis, two recombinant plasmids containing the early promoter of p35, or the very late promoter of TnMNPV polh were constructed to study p35 function by transient expression assay. It was shown that expression of p35 alone could partially prevent HaSNPV-induced apoptosis but did not facilitate HaSNPV replication in Hi5 cells. The data suggests that both P35 of TnMNPV and other unknown gene products are required for the suppression of apoptosis and facilitation of HaSNPV replication in Hi5 cells.

Dai X; Shi X; Pang Y; Su D

1999-07-01

137

Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.  

Science.gov (United States)

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene. PMID:12829659

Kubaszek, Agata; Pihlajamäki, Jussi; Komarovski, Vladislav; Lindi, Virpi; Lindström, Jaana; Eriksson, Johan; Valle, Timo T; Hämäläinen, Helena; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Tuomilehto, Jaakko; Uusitupa, Matti; Laakso, Markku

2003-07-01

138

Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.  

UK PubMed Central (United Kingdom)

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.

Kubaszek A; Pihlajamäki J; Komarovski V; Lindi V; Lindström J; Eriksson J; Valle TT; Hämäläinen H; Ilanne-Parikka P; Keinänen-Kiukaanniemi S; Tuomilehto J; Uusitupa M; Laakso M

2003-07-01

139

Energy restriction prevents the development of type 2 diabetes in Zucker diabetic fatty rats : coordinated patterns of gene expression for energy metabolism in insulin-sensitive tissues and pancreatic islets determined by oligonucleotide microarray analysis  

DEFF Research Database (Denmark)

Energy restriction (ER) causes metabolic improvement in the prediabetic and diabetic state. Little information exists on the mechanism of action of ER, for example, on the changes at the transcriptional gene level in insulin-sensitive tissues. To gain further insight, we have investigated changes in gene expressions in skeletal muscle, liver, fat, and pancreatic islets after ER in male Zucker diabetic fatty rats. Eighteen Zucker diabetic fatty rats were divided at the age of 7 weeks into a control group (ad libitum diet) and an ER group (30% ER compared with the control group). Blood glucose, weight, and food intake were measured weekly. After 5 weeks, blood samples, and skeletal muscle, liver, visceral fat (epididymal fat pads), and islets tissue were collected. Gene expression was quantified with high-density oligonucleotide, microarray GeneChip technology. ER ameliorated the development of hyperglycemia, increased the levels of plasma insulin, and reduced plasma total cholesterol and the glucagon-insulin ratio (P <.05). In skeletal muscle, the expression of 55 genes increased and 245 decreased involving genes related to glucose metabolism (eg, phosphorylase kinase, pyruvate dehydrogenase kinase 4), lipid metabolism (eg, carnitine palmitoyltransferase 1, fatty acid transporter), and signaling pathways (eg, mitogen-activated protein kinases, protein kinase C). In the liver, the expression of 123 genes increased and 103 decreased involving genes related primarily to lipid metabolism. In pancreatic islets, the expression of 110 genes increased and that of 127 decreased, whereas in visceral fat, the expression of 279 genes increased and that of 528 decreased. ER counteracts the development of diabetes and causes changes in the expression of multiple genes involved in glucose and lipid metabolism in skeletal muscle, liver, and pancreatic islets, which may play an important role for the prevention of diabetes.

Colombo, Michele; Kruhoeffer, Mogens

2006-01-01

140

Preventing encopresis.  

UK PubMed Central (United Kingdom)

Pediatric nurses can play a major role in preventing encopresis through anticipatory guidance and education. An understanding of contributing factors that may lead to constipation and encopresis will assist pediatric nurses in their efforts to help prevent this condition.

Stadtler AC

1989-05-01

 
 
 
 
141

Cutaneous manifestations of Nocardia brasiliensis infection in Taiwan during 2002-2012-clinical studies and molecular typing of pathogen by gyrB and 16S gene sequencing.  

UK PubMed Central (United Kingdom)

To observe the clinicopathologic and resistance profiles of the Nocardia brasiliensis causing cutaneous nocardiosis in Taiwan, 12 N. brasiliensis isolates were prospectively collected from patients with cutaneous nocardiosis in a hospital during 2002-2012. Clinicopathologic data were obtained, and isolates were identified by biochemical methods and 16S rRNA sequencing. Susceptibilities to 14 antimicrobial compounds were tested. Isolates were further genotyped by sequencing of 16S rRNA, secA1, hsp65, and gyrB genes. The nodulopustular pyoderma associated with sporotrichoid spreading was the most common skin presentations caused by N. brasiliensis. All of the isolates were susceptible to amikacin, gentamicin, tobramycin, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole and resistant to kanamycin, erythromycin, and oxacillin, while susceptibilities to imipenem, vancomycin, penicillin-G, tetracycline, clindamycin, and ciprofloxacin varied among the 12 isolates. GyrB genotyping delineated the 12 isolates into 2 major groups, which was coincident with different single nucleotide substitutions at position 160 (G versus T) of 16S rRNA, different levels of imipenem minimum inhibition concentration (4-32 versus 0.25-0.75 mg/L), and prevalence of lymphadenitis (66.7 versus 16.7%). We have noted that tiny pustular lesions can be the first sign of cutaneous nocardiosis, which we believe has not been previously emphasized. No resistance to trimethoprim and sulfamethoxazole was found; therefore, sulphonamide drugs remain effective for treatment of cutaneous nocardiosis in Taiwan.

Chen KW; Lu CW; Huang TC; Lu CF; Liau YL; Lin JF; Li SY

2013-09-01

142

Cutaneous manifestations of Nocardia brasiliensis infection in Taiwan during 2002-2012-clinical studies and molecular typing of pathogen by gyrB and 16S gene sequencing.  

Science.gov (United States)

To observe the clinicopathologic and resistance profiles of the Nocardia brasiliensis causing cutaneous nocardiosis in Taiwan, 12 N. brasiliensis isolates were prospectively collected from patients with cutaneous nocardiosis in a hospital during 2002-2012. Clinicopathologic data were obtained, and isolates were identified by biochemical methods and 16S rRNA sequencing. Susceptibilities to 14 antimicrobial compounds were tested. Isolates were further genotyped by sequencing of 16S rRNA, secA1, hsp65, and gyrB genes. The nodulopustular pyoderma associated with sporotrichoid spreading was the most common skin presentations caused by N. brasiliensis. All of the isolates were susceptible to amikacin, gentamicin, tobramycin, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole and resistant to kanamycin, erythromycin, and oxacillin, while susceptibilities to imipenem, vancomycin, penicillin-G, tetracycline, clindamycin, and ciprofloxacin varied among the 12 isolates. GyrB genotyping delineated the 12 isolates into 2 major groups, which was coincident with different single nucleotide substitutions at position 160 (G versus T) of 16S rRNA, different levels of imipenem minimum inhibition concentration (4-32 versus 0.25-0.75 mg/L), and prevalence of lymphadenitis (66.7 versus 16.7%). We have noted that tiny pustular lesions can be the first sign of cutaneous nocardiosis, which we believe has not been previously emphasized. No resistance to trimethoprim and sulfamethoxazole was found; therefore, sulphonamide drugs remain effective for treatment of cutaneous nocardiosis in Taiwan. PMID:23791388

Chen, Kuo-Wei; Lu, Chun-Wei; Huang, Ting-Chi; Lu, Chin-Fang; Liau, Yea-Ling; Lin, Jeng-Fong; Li, Shu-Ying

2013-06-19

143

HIV Prevention  

Centers for Disease Control (CDC) Podcasts

Dr. Kevin Fenton, Director of CDCâ??s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

2012-02-01

144

Poly(A) Signals Located near the 5? End of Genes Are Silenced by a General Mechanism That Prevents Premature 3?-End Processing ? † ‡  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Poly(A) signals located at the 3? end of eukaryotic genes drive cleavage and polyadenylation at the same end of pre-mRNA. Although these sequences are expected only at the 3? end of genes, we found that strong poly(A) signals are also predicted within the 5? untranslated regions (UTRs) of many Droso...

Guo, Jiannan; Garrett, Matthew; Micklem, Gos; Brogna, Saverio

145

Molecular identification of nontuberculous mycobacteria isolates in a Brazilian mycobacteria reference laboratory.  

UK PubMed Central (United Kingdom)

This study utilized the hsp65 polymerase chain reaction restriction analysis (PRA) method in the identification of nontuberculous mycobacteria (NTMs) isolated in a Brazilian mycobacteria laboratory. NTM isolates from clinical specimens collected from 192 patients were characterized using the hsp65 PRA method and analyzed using both 16S rRNA and hsp65 gene sequencing. Only 30% of the NTM strains were correctly identified through PRA, though the suggested inclusion of an additional restriction enzyme could increase the resolution to roughly 90%. A total of 17 NTM strains were not identified to species level and may represent a new taxonomic entity classified as belonging to the Mycobacterium simiae complex. This study demonstrates the applicability of hsp65 PRA in the identification of several NTM strains in a reference laboratory, though the results suggest that some modifications to the original PRA method could increase its resolution substantially.

da Costa AR; Lopes ML; Furlaneto IP; de Sousa MS; Lima KV

2010-12-01

146

Tuberculosis Prevention  

Science.gov (United States)

... JavaScript on. Read more information on enabling JavaScript. Tuberculosis (TB) Skip Content Marketing Share this: Prevention TB ... patients. Many people who are infected with Mycobacterium tuberculosis ( Mtb ) do not get sick or spread the ...

147

Transcriptome analysis of epigenetically modulated genome indicates signature genes in manifestation of type 1 diabetes and its prevention in NOD mice.  

UK PubMed Central (United Kingdom)

Classic genetic studies implicated several genes including immune response genes in the risk of developing type 1 diabetes in humans. However, recent evidence including discordant diabetes incidence among monozygotic twins suggested a role for epigenetics in disease manifestation. NOD mice spontaneously develop type 1 diabetes like humans and serve as an excellent model system to study the mechanisms of type 1 diabetes as well as the efficacy of maneuvers to manipulate the disease. Using this preclinical model, we have recently demonstrated that pharmacological inhibition of histone deacetylases can lead to histone hyperacetylation, selective up-regulation of interferon-? and its transactivator Tbx21/Tbet, and amelioration of autoimmune diabetes. In the current study, we show that chromatin remodeling can render splenocytes incapable of transferring diabetes into immunodeficient NOD.scid mice. To elucidate the underlying mechanisms of drug-mediated protection against type 1 diabetes, we performed global gene expression profiling of splenocytes using high throughput microarray technology. This unbiased transcriptome analysis unraveled the exaggerated expression of a novel set of closely related inflammatory genes in splenocytes of acutely diabetic mice and their repression in mice cured of diabetes by chromatin remodeling. Analysis of gene expression by qRT-PCR using RNA derived from spleens and pancreata of cured mice validated the suppression of most of these genes, indicating an inverse correlation between the high levels of these inflammatory genes and protection against diabetes in NOD mice. In addition, higher-level expression of genes involved in insulin sensitivity, erythropoiesis, hemangioblast generation, and cellular redox control was evident in spleens of cured mice, indicating their possible contribution to protection against type 1 diabetes. Taken together, these results are consistent with the involvement of epistatic mechanisms in the manifestation of autoimmune diabetes and further indicate the utility of chromatin remodeling in curing this complex autoimmune disorder.

Jayaraman S; Patel A; Jayaraman A; Patel V; Holterman M; Prabhakar B

2013-01-01

148

Identification of non-tuberculous mycobacteria from the Central Public Health Laboratory from Mato Grosso do Sul and analysis of clinical relevance/ Identificação de micobactérias não-tuberculosas do Laboratório Central de Saúde Pública de Mato Grosso de Sul e análise de dados clínicos dos pacientes  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese Micobactérias não-tuberculosas isoladas no Laboratório Central de Saúde Pública de Mato Grosso do Sul em 2003 e 2004 foram identificadas usando métodos fenotípicos convencionais (TI) e PCR-Restriction Enzyme Analysis (PRA) tendo o gene hsp65 como alvo (PRA-hsp65). Em 15 dos 32 isolados analisados os resultados obtidos com ambos métodos foram concordantes, sendo 8 Mycobacterium avium, 3 M. fortutium, 1 M. kansasii, 1 M. flavescens, 1 M. peregrinum e 1 Nocardia bras (more) iliensis. TI de 12 isolados não foi conclusiva. Perfis não descritos de PRA-hsp65 foram observados com 11 isolados. Dados dos prontuários médicos foram avaliados para inferir a relevância clínica dos isolados. Abstract in english Non-tuberculous mycobacteria isolated at the Central Public Health Laboratory from Mato Grosso do Sul in 2003 and 2004 were identified by conventional phenotypic methods (TI) and by PCR-Restriction Enzyme Analysis (PRA) using the hsp65 gene as target (PRA-hsp65). With 15 of the 32 analysed isolates, results of both methods were concordant, being 8 Mycobacterium avium, 3 M. fortutium, 1 M. kansasii, 1 M. flavescens, 1 M. peregrinum and 1 Nocardia brasiliensis. TI of 12 iso (more) lates was inconclusive. Novel PRA-hsp65 patterns were observed with 11 isolates. Medical data were evaluated for inference of clinical relevance of these isolates.

Moraes, Paulo Ricardo de Souza; Chimara, Erica; Telles, Maria Alice da Silva; Ueki, Suely Yoko Misuka; Cunha, Eunice Atsuko Totumi; Honer, Michael Robin; Leão, Sylvia Cardoso

2008-06-01

149

Fenretinide treatment prevents diet-induced obesity in association with major alterations in retinoid homeostatic gene expression in adipose, liver, and hypothalamus.  

UK PubMed Central (United Kingdom)

The synthetic retinoid, Fenretinide (FEN), inhibits obesity and insulin resistance in mice and is in early clinical trials for treatment of insulin resistance in obese humans. We aimed to determine whether alterations in retinoic acid (RA)-responsive genes contribute to the beneficial effects of FEN. We examined the effect of FEN on 3T3-L1 adipocyte differentiation and alterations in gene expression in C57Bl/6 and retinaldehyde dehydrogenase (RALDH) 1 knockout (KO) mice fed a high-fat (HF) diet. FEN completely inhibited adipocyte differentiation by blocking CCAAT/enhancer-binding protein (C/EBP) ?/peroxisome proliferator-activated receptor (PPAR) ?-mediated induction of downstream genes and upregulating RA-responsive genes like cellular retinol-binding protein-1. In mice fed an HF diet, RA-responsive genes were markedly increased in adipose, liver, and hypothalamus, with short-term and long-term FEN treatment. In adipose, FEN inhibited the downregulation of PPAR? and improved insulin sensitivity and the levels of adiponectin, resistin, and serum RBP (RBP4). FEN inhibited hyperleptinemia in vivo and leptin expression in adipocytes. Surprisingly, hypothalamic neuropeptide Y expression was completely suppressed, suggesting a central effect of FEN to normalize hyperglycemia. Moreover, FEN induced RA-responsive genes in RALDH1 KO mice, demonstrating that FEN can augment RA signaling when RA synthesis is impaired. We show that FEN-mediated beneficial effects are through alterations in retinoid homeostasis genes, and these are strong candidates as therapeutic targets for the treatment of obesity and insulin resistance.

Mcilroy GD; Delibegovic M; Owen C; Stoney PN; Shearer KD; McCaffery PJ; Mody N

2013-03-01

150

Lysine Represses Transcription of the Escherichia coli dapB Gene by Preventing Its Activation by the ArgP Activator? †  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The Escherichia coli dapB gene encodes one of the enzymes of the biosynthetic pathway leading to lysine and its immediate precursor, diaminopimelate. Expression of dapB is repressed by lysine, but no trans-acting regulator has been identified so far. Our analysis of the dapB regulatory region shows ...

Bouvier, Jean; Stragier, Patrick; Morales, Violette; Rémy, Elisabeth; Gutierrez, Claude

151

Plagiarism Prevention  

Science.gov (United States)

Plagiarism does exist at universities today. In some cases, students are naive with respect to understanding what plagiarism is and how to avoid it. In other cases, students blatantly disregard and disrespect the written work of others, claiming it as their own. Regardless, educators must be vigilant in their efforts to discourage and prevent

Probett, Christine

2011-01-01

152

Suicide Prevention  

Science.gov (United States)

Suicide Prevention If you or someone you know has ongoing thoughts of death or suicide—or if a suicide attempt has been made—contact a doctor go ... can also include thoughts of self-harm or suicide. Whether we have suicidal thoughts ourselves, or know ...

153

The genome-defence gene Tex19.1 suppresses LINE-1 retrotransposons in the placenta and prevents intra-uterine growth retardation in mice.  

UK PubMed Central (United Kingdom)

DNA methylation plays an important role in suppressing retrotransposon activity in mammalian genomes, yet there are stages of mammalian development where global hypomethylation puts the genome at risk of retrotransposition-mediated genetic instability. Hypomethylated primordial germ cells appear to limit this risk by expressing a cohort of retrotransposon-suppressing genome-defence genes whose silencing depends on promoter DNA methylation. Here, we investigate whether similar mechanisms operate in hypomethylated trophectoderm-derived components of the mammalian placenta to couple expression of genome-defence genes to the potential for retrotransposon activity. We show that the hypomethylated state of the mouse placenta results in activation of only one of the hypomethylation-sensitive germline genome-defence genes: Tex19.1. Tex19.1 appears to play an important role in placenta function as Tex19.1(-/-) mouse embryos exhibit intra-uterine growth retardation and have small placentas due to a reduction in the number of spongiotrophoblast, glycogen trophoblast and sinusoidal trophoblast giant cells. Furthermore, we show that retrotransposon mRNAs are derepressed in Tex19.1(-/-) placentas and that protein encoded by the LINE-1 retrotransposon is upregulated in hypomethylated trophectoderm-derived cells that normally express Tex19.1. This study suggests that post-transcriptional genome-defence mechanisms are operating in the placenta to protect the hypomethylated cells in this tissue from retrotransposons and suggests that imbalances between retrotransposon activity and genome-defence mechanisms could contribute to placenta dysfunction and disease.

Reichmann J; Reddington JP; Best D; Read D; Ollinger R; Meehan RR; Adams IR

2013-05-01

154

[Preventive immunotherapy].  

Science.gov (United States)

Allergen specific immunotherapy has been shown to be effective in rigorous double-blind placebo-controlled clinical trials in both children and adults A recent WHO position paper stated that immunotherapy is an effective treatment for patients with allergic rhinitis/conjunctivitis, allergic asthma and allergic reactions from stinging insects and is thought to be more effective in children than in adults. When speaking about children there are several questions that are important regarding the natural course of the disease. One of the most important is whether immunotherapy can prevent asthma, either by preventing sensitisation to allergens related to the development of asthma or by preventing the inflammation in the lungs caused by allergen exposure. Another point could be to establish the differences in the long term outcome of those patients treated with immunotherapy and medication during childhood, compared to the long term outcome of those with comparable asthma features who received only antiasthmatic medication The PAT study is a European multi-center study. The end-point is to show in what capacity allergen specific subcutaneous immunotherapy can prevent the development of asthma in children who only have rhinoconjunctivitis secondary to grass or birch pollen sensitisation. Two hundred and ten children aged from 5 to 13 years were included in the study. Children were randomised to the active treatment group receiving allergen specific immunotherapy with birch and/or timothy pollen allergen extract or to the control group receiving only pharmacotherapy. It is important to highlight that the main criteria to be included was that the children should never have had any asthmatic symptom. Immunotherapy has been effective in terms of decreasing significantly the amount of symptoms in the active group compared to the control one. It was safe with no serious adverse reactions and reduced the risk of the onset of asthma. After two years of treatment more children in the control group developed clinical asthma than in the active group: p = 0.004. Des Roches et al reported the results of a prospective non randomised trial of immunotherapy with Dermatophagoides pteronyssinus in 44 asthmatic children younger than six years of age who were sensitive only to dust mites. The purpose of the study was to assess whether immunotherapy could reduce the development of new sensitisation during a period of three years of follow up. Specific immunotherapy was given with only D. Pteronyssinus extract. All 22 children in the control group developed new sensitivities as determined by skin testing and in vitro tests, while 10 (45%) of 22 children who received mite immunotherapy did not develop additional sensitivities. The findings of this study suggests that immunotherapy may alter the natural course of the allergic sensitisation reducing the risk of developing new sensitisation in mono sensitive children. A limited number of studies have examined the long terms effects of immunotherapy on the clinical presentation of asthma and rhinoconjunctivitis, and have shown a long lasting efficacy decreasing the amount of symptoms 6-10 years after termination. In a retrospective study of children treated with immunotherapy during childhood for at least three years, that were re-evaluated in early adulthood, the control patients who were treated with medication and no immunotherapy suffered almost 3.5 times more symptoms than the active group treated with immunotherapy. The current findings suggest that immunotherapy should be considered earlier in the course of allergic disease to prevent progression or to prevent the development of new sensitisation. Further studies with long term follow up particularly in children could address this possibility. PMID:10867376

Boquete, M; Carballada, F; Expósito, F; González, A

155

Allergy prevention.  

UK PubMed Central (United Kingdom)

BACKGROUND: Evidence-based primary prevention of allergic conditions is important in view of their increasing prevalence in Western industrialized countries. METHODS: The Cochrane and Medline databases were searched for relevant scientific publications that appeared from February 2003 to May 2008. Articles in the reference lists of recent reviews were also considered, and experts were directly asked for their opinions. The retrieved publications were screened for relevance by evaluation of the title and abstract, and then by evaluation of the entire text. Each study chosen for inclusion was assigned an evidence grade as well as a grade for study quality relating to its potential for bias (low or high). The revised recommendations were then formally accepted by a consensus of representatives of medical specialist societies and other organizations, including a patient self-help group. RESULTS: The search initially yielded 4556 results out of which 217 articles (4 Cochrane reviews, 14 meta-analyses, 19 randomized clinical trials, 135 cohort studies, and 45 case-control studies) were chosen for inclusion and critical appraisal. No major changes ensued in the existing recommendations to avoid exposure to tobacco smoke, breast-feed for 4 months (or use hypoallergenic formulas), avoid a mould-promoting indoor climate, avoid exposure to furry pets (particularly cats), and vaccinate according to the current recommendations of the Standing Committee on Vaccination of the Robert Koch Institute (Ständige Impfkommission, STIKO). Neither the delayed introduction of solid food nor the avoidance of potent dietary allergens is recommended as a means of primary prevention. New recommendations were issued regarding fish consumption (by the mother while breastfeeding and nursing, and by the infant as solid food), avoidance of overweight, and reduction of exposure to air pollutants. CONCLUSIONS: This updated guideline serves as an aid in giving patients current, evidence-based recommendations for allergy prevention.

Muche-Borowski C; Kopp M; Reese I; Sitter H; Werfel T; Schäfer T

2009-09-01

156

[Use of different PCR-based techniques integrated into a non-tuberculous identification algorithm].  

UK PubMed Central (United Kingdom)

INTRODUCTION: The aim of the present work was to demonstrate the utility of a non-tuberculous mycobacteria (NTM) identification algorithm, which integrates different PCR-based techniques and basic phenotypic features. Moreover, the algorithm for pattern restriction analysis of hsp65 (hsp65 PRA) interpretation has been updated. METHODS: The workflow chosen consisted of the identification by a DNA hybridization probe method, followed by PCR-restriction enzyme analysis of hsp65 (hsp65 PRA) in those isolates that cannot be identified by hybridization probes. If necessary, 16S rRNA gene and hsp65 gene sequencing were used for speciation. RESULTS: A total of 236 NTM were collected, in which 102 (43.2%) isolates were identified by DNA specific probes and 76 (32.2%) isolates were identified with hsp65 PRA. Partial sequencing of the 16S rRNA gene was used for species identification of the remaining 58 (24.5%) isolates. Fifty-three (22.4%) were identified using this method. Five isolates (2.1%) were submitted for partial sequencing of hsp65 gene and one isolate was identified with this method. Four strains (1.7%) could not be identified at species level. Three new PRA patterns were found. Seven isolates tested positive with the AccuProbe Mycobacterium avium complex identification test but did not test positive with the M. avium or Mycobacterium intracellulare specific probes. Five and two of these isolates were identified as M. intracellulare and Mycobacterium colombiense, respectively. CONCLUSION: This approach allowed us to identify almost all NTM isolates found in this study, including some recently described species.

Esparcia Ó; Español M; Garrigó M; Moreno C; Montemayor M; Navarro F; Coll P

2012-01-01

157

Z-360, a novel therapeutic agent for pancreatic cancer, prevents up-regulation of ephrin B1 gene expression and phosphorylation of NR2B via suppression of interleukin-1 ? production in a cancer-induced pain model in mice  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Z-360 is an orally active cholecystokinin-2 (CCK2)/gastrin receptor antagonist currently under development as a therapeutic drug for pancreatic cancer. It was previously reported that Z-360 treatment in combination with gemcitabine prolonged the survival period in a lethal pancreatic cancer xenograft model in mice. In a phase Ib/IIa clinical study, Z-360 treatment displayed a trend of reduced pain in patients with advanced pancreatic cancer in combination with gemcitabine including analgesics such as opioids. Here, we investigated the mechanism of analgesic action of Z-360 in a severe cancer-induced pain model in mice, which is considered to be opioid-resistant, by examining ephrin B1 gene expression, N-methyl-D-aspartate receptor NR2B subunit phosphorylation, and interleukin-1? (IL-1?) production. Results In a mouse model of cancer-induced pain, ephrin B1 gene expression in dorsal root ganglia (DRGs) and the phosphorylation of NR2B in the spinal cord were induced. Z-360 treatment inhibited both ephrin B1 gene expression and the phosphorylation of NR2B. In addition, IL-1? production increased in the cancer-inoculated hind paw of mice, but could be suppressed by treatment with Z-360. Moreover, we observed that the CCK1 receptor antagonist devazepide similarly suppressed up-regulation of ephrin B1 gene expression and IL-1? production, and that the intraperitoneal injection of sulfated CCK-8 induced the production of IL-1? in the cancer-inoculated region. Conclusions We have identified a novel pain cascade, in which IL-1? production in cancer-inoculated regions induces ephrin B1 gene expression in DRGs and then ephrin B1 enhances the tyrosine phosphorylation of NR2B via Eph B receptor in the spinal cord. Notably, Z-360 relieves cancer-induced pain by preventing this pain cascade through the suppression of IL-1? production, likely via the blockade of CCK1 receptor. The pre-clinical results presented here support the analgesic action of Z-360 in pancreatic cancer patients with severe, opioid-resistant pain. Pre-clinical and clinical results have demonstrated that Z-360 combined with gemcitabine represents a promising pancreatic cancer therapy approach with characteristic analgesic effects in addition to the prolongation of survival.

Orikawa Yuki; Kato Hiroki; Seto Koichi; Kobayashi Nobuyoshi; Yoshinaga Koji; Hamano Hiroki; Hori Yuko; Meyer Tim; Takei Mineo

2010-01-01

158

Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase.  

UK PubMed Central (United Kingdom)

Choroideremia (CHM), an X-linked degeneration of the retinal pigmented epithelium (RPE), photoreceptors, and choroid, ultimately leads to blindness. It is caused by loss-of-function of the CHM gene product, the Rab escort protein 1 (REP1) that is involved, together with its homologue REP2, in prenylation of Rab GTPases, key regulators of intracellular vesicular traffic. Here, we report the molecular characterization of 20 unrelated Italian families affected by CHM. We identified 19 different mutations, nine of which are new. In most cases, we analyzed the effect of the mutations at the mRNA level. Furthermore, we demonstrated, by in vitro trancription/translation assays, that the mutated mRNAs produced truncated proteins in all cases but one. In fact, we also identified a novel REP1 missense variant (c.1520A>G; p.H507R) associated to CHM. Thus far, only two other CHM-associated missense mutations have been identified, one of which was a splicing alteration. We investigated the impact of the p.H507R amino acid change on REP1 structure and function, thus providing the first experimental demonstration that correlates a missense mutation in CHM with a functional impairment of REP1. Overall, our results indicate that the REP1-Rab geranyl-geranyl transferase interaction and consequently REP1-mediated Rab prenylation is essential for RPE and photoreceptor function.

Esposito G; De Falco F; Tinto N; Testa F; Vitagliano L; Tandurella IC; Iannone L; Rossi S; Rinaldi E; Simonelli F; Zagari A; Salvatore F

2011-12-01

159

Rotating preventers  

International Nuclear Information System (INIS)

[en] This paper reports that recent changes in the oil and gas industry and ongoing developments in horizontal and underbalanced drilling necessitated development of a better rotating head. A new device called the rotating blowout preventer (RBOP) was developed by Seal-Tech. It is designed to replace the conventional rotating control head on top of BOP stacks and allows drilling operations to continue even on live (underbalanced) wells. Its low wear characteristics and high working pressure (1,500 psi) allow drilling rig crews to drill safely in slightly underbalanced conditions or handle severe well control problems during the time required to actuate other BOPs in the stack. Drilling with a RBOP allows wellbores to be completely closed in tat the drill floor rather than open as with conventional BOPs

1992-01-01

160

Association of ADIPOR2 gene variants with cardiovascular disease and type 2 diabetes risk in individuals with impaired glucose tolerance: the Finnish Diabetes Prevention Study  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic effects. Two receptors for adiponectin, ADIPOR1 and ADIPOR2, have been characterized that mediate effects of adiponectin in various tissues. We examined whether genetic variation in ADIPOR2 predicts the development of cardiovascular disease (CVD) and/or Type 2 Diabetes (T2DM) in individuals with impaired glucose tolerance (IGT) participating the Finnish Diabetes Prevention Study (DPS). Methods CVD morbidity and mortality data were collected during a median follow-up of 10.2 years (range 1-13 years) and conversion from IGT to T2DM was assessed during a median follow-up of 7 years (range 1-11 years). Altogether eight SNPs in the ADIPOR2 locus were genotyped in 484 participants of the DPS. Moreover, the same SNPs were genotyped and the mRNA expression levels of ADIPOR2 were determined in peripheral blood mononuclear cells and subcutaneous adipose tissue samples derived from 56 individuals participating in the Genobin study. Results In the DPS population, four SNPs (rs10848554, rs11061937, rs1058322, rs16928751) were associated with CVD risk, and two remained significant (p = 0.014 for rs11061937 and p = 0.020 for rs1058322) when all four were included in the same multi-SNP model. Furthermore, the individuals homozygous for the rare minor alleles of rs11061946 and rs11061973 had increased risk of converting from IGT to T2DM. Allele-specific differences in the mRNA expression levels for the rs1058322 variant were seen in peripheral blood mononuclear cells derived from participants of the Genobin study. Conclusions Our results suggest that SNPs in the ADIPOR2 may modify the risk of CVD in individuals with IGT, possibly through alterations in the mRNA expression levels. In addition an independent genetic signal in ADIPOR2 locus may have an impact on the risk of developing T2DM in individuals with IGT. Trial registration number ClinicalTrials.gov NCT00518167

Siitonen Niina; Pulkkinen Leena; Lindström Jaana; Kolehmainen Marjukka; Schwab Ursula; Eriksson Johan G; Ilanne-Parikka Pirjo; Keinänen-Kiukaanniemi Sirkka; Tuomilehto Jaakko; Uusitupa Matti

2011-01-01

 
 
 
 
161

Prostate cancer gene 3 score predicts prostate biopsy outcome in men receiving dutasteride for prevention of prostate cancer: results from the REDUCE trial.  

UK PubMed Central (United Kingdom)

OBJECTIVES: To examine the ability of the urinary prostate cancer gene 3 (PCA3) assay to predict biopsy-detected cancers in men receiving dutasteride in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study cohort. METHODS: Urine and serum samples from 930 men in the active arm were acquired at years 2 and 4 of the biopsy visits. In addition to univariate logistic regression and receiver operating characteristic analysis, multivariate analysis for association with biopsy outcome was performed for PCA3 score in the presence of serum prostate-specific antigen (PSA), age, prostate volume, and family history of prostate cancer. RESULTS: At year 2, the univariate PCA3 score area under the receiver operating characteristic curve (AUC) was 0.668 versus 0.603 for PSA. At year 4, the PCA3 assay significantly predicted the biopsy outcome (AUC 0.628, 95% confidence interval 0.556-0.700), and the PSA level was not predictive (AUC 0.556, 95% confidence interval 0.469-0.642). The year 2 multivariate model yielded an AUC of 0.712. Removing the PCA3 score decreased the AUC to 0.660 (P = .0166 vs the full model). The median PCA3 scores in the dutasteride arm were not different from those in the 1072 men in the placebo arm (16.2 and 17.2 at year 2, P = .1755; and 18.8 and 18.1 at year 4, P = .2340, respectively). However, the PSA values were reduced >50% in the dutasteride arm at both visits (both P < .0001 vs placebo). At a PCA3 score cutoff of 35, the sensitivity and specificity were equivalent between the 2 arms. CONCLUSIONS: In the present study, the PCA3 assay outperformed PSA for cancer detection in men undergoing dutasteride treatment and improved the diagnostic accuracy when combined with the PSA level and other clinical variables. In addition, no adjustment in PCA3 score was needed to yield equivalent clinical performance between the dutasteride and placebo arms. These findings are particularly important in light of the potential role of dutasteride for prostate cancer chemoprevention.

Aubin SM; Reid J; Sarno MJ; Blase A; Aussie J; Rittenhouse H; Rittmaster RS; Andriole GL; Groskopf J

2011-08-01

162

Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin.  

UK PubMed Central (United Kingdom)

UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR-mediated photodamage and induce the DNA-base-oxidized, intermediate 8-hydroxy-2'-deoxyguanosine (8-OHdG). Herein, we report the protective action of melatonin against UVR-induced 8-OHdG formation and depletion of antioxidative enzymes using ex vivo human full-thickness skin exposed to UVR in a dose (0, 100, 300 mJ/cm(2))- and time-dependent manner (0, 24, 48 hr post-UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8-OHdG formation were studied by real-time PCR and immunofluorescence/immunohistochemical staining. UVR-treated skin revealed significant and immediate (0 hr 300 mJ/cm(2)) reduction of gene expression, and this effect intensified within 24 hr post-UVR. Simultaneous increase in 8-OHdG-positive keratinocytes occurred already after 0 hr post-UVR reaching 71% and 99% up-regulation at 100 and 300 mJ/cm(2), respectively (P < 0.001). Preincubation with melatonin (10(-3) M) led to 32% and 29% significant reductions in 8-OHdG-positive cells and the prevention of antioxidative enzyme gene and protein suppression. Thus, melatonin was shown to play a crucial role as a potent antioxidant and DNA protectant against UVR-induced oxidative damage in human skin.

Fischer TW; Kleszczy?ski K; Hardkop LH; Kruse N; Zillikens D

2013-04-01

163

Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin.  

Science.gov (United States)

UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR-mediated photodamage and induce the DNA-base-oxidized, intermediate 8-hydroxy-2'-deoxyguanosine (8-OHdG). Herein, we report the protective action of melatonin against UVR-induced 8-OHdG formation and depletion of antioxidative enzymes using ex vivo human full-thickness skin exposed to UVR in a dose (0, 100, 300 mJ/cm(2))- and time-dependent manner (0, 24, 48 hr post-UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8-OHdG formation were studied by real-time PCR and immunofluorescence/immunohistochemical staining. UVR-treated skin revealed significant and immediate (0 hr 300 mJ/cm(2)) reduction of gene expression, and this effect intensified within 24 hr post-UVR. Simultaneous increase in 8-OHdG-positive keratinocytes occurred already after 0 hr post-UVR reaching 71% and 99% up-regulation at 100 and 300 mJ/cm(2), respectively (P < 0.001). Preincubation with melatonin (10(-3) M) led to 32% and 29% significant reductions in 8-OHdG-positive cells and the prevention of antioxidative enzyme gene and protein suppression. Thus, melatonin was shown to play a crucial role as a potent antioxidant and DNA protectant against UVR-induced oxidative damage in human skin. PMID:23110400

Fischer, Tobias W; Kleszczy?ski, Konrad; Hardkop, Lena H; Kruse, Nathalie; Zillikens, Detlef

2012-10-30

164

Tetra-O-methyl nordihydroguaiaretic acid (Terameprocol) inhibits the NF-?B-dependent transcription of TNF-? and MCP-1/CCL2 genes by preventing RelA from binding its cognate sites on DNA.  

UK PubMed Central (United Kingdom)

BACKGROUND: Tetra-O-methyl nordihydroguaiaretic acid, also known as terameprocol (TMP), is a naturally occurring phenolic compound found in the resin of the creosote bush. We have shown previously that TMP will suppress production of certain inflammatory cytokines, chemokines and lipids from macrophages following stimulation with LPS or infection with H1N1 influenza virus. In this study our goal was to elucidate the mechanism underlying TMP-mediated suppression of cytokine and chemokine production. We focused our investigations on the response to LPS and the NF-?B protein RelA, a transcription factor whose activity is critical to LPS-responsiveness. METHODS: Reporter assays were performed with HEK293 cells overexpressing either TLR-3, -4, or -8 and a plasmid containing the luciferase gene under control of an NF-?B response element. Cells were then treated with LPS, poly(I:C), or resiquimod, and/or TMP, and lysates measured for luciferase activity.RAW 264.7 cells treated with LPS and/or TMP were used in ChIP and EMSA assays. For ChIP assays, chromatin was prepared and complexes precipitated with anti-NF-?B RelA Ab. Cross-links were reversed, DNA purified, and sequence abundance determined by Q-PCR. For EMSA assays, nuclear extracts were incubated with radiolabeled probes, analyzed by non-denaturing PAGE and visualized by autoradiography.RAW 264.7 cells treated with LPS and/or TMP were also used in fluorescence microscopy and western blot experiments. Translocation experiments were performed using a primary Ab to NF-?B RelA and a fluorescein-conjugated secondary Ab. Western blots were performed using Abs to I?B-? and phospho-I?B-?. Bands were visualized by chemiluminescence. RESULTS: In reporter assays with TLR-3, -4, and -8 over-expressing cells, TMP caused strong inhibition of NF-?B-dependent transcription.ChIP assays showed TMP caused virtually complete inhibition of RelA binding in vivo to promoters for the genes for TNF-?, MCP-1/CCL2, and RANTES/CCL5 although the LPS-dependent synthesis of I?B-? was not inhibited. EMSA assays did not reveal an effect of TMP on the binding of RelA to naked DNA templates in vitro.TMP did not inhibit the nuclear translocation of NF-?B RelA nor the phosphorylation of I?B-?. CONCLUSION: TMP acts indirectly as an inhibitor of NF-?B-dependent transcription by preventing RelA from binding the promoters of certain key cytokine and chemokine genes.

Oyegunwa AO; Sikes ML; Wilson JR; Scholle F; Laster SM

2010-01-01

165

Tetra-O-methyl nordihydroguaiaretic acid (Terameprocol) inhibits the NF-?B-dependent transcription of TNF-? and MCP-1/CCL2 genes by preventing RelA from binding its cognate sites on DNA  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Tetra-O-methyl nordihydroguaiaretic acid, also known as terameprocol (TMP), is a naturally occurring phenolic compound found in the resin of the creosote bush. We have shown previously that TMP will suppress production of certain inflammatory cytokines, chemokines and lipids from macrophages following stimulation with LPS or infection with H1N1 influenza virus. In this study our goal was to elucidate the mechanism underlying TMP-mediated suppression of cytokine and chemokine production. We focused our investigations on the response to LPS and the NF-?B protein RelA, a transcription factor whose activity is critical to LPS-responsiveness. Methods Reporter assays were performed with HEK293 cells overexpressing either TLR-3, -4, or -8 and a plasmid containing the luciferase gene under control of an NF-?B response element. Cells were then treated with LPS, poly(I:C), or resiquimod, and/or TMP, and lysates measured for luciferase activity. RAW 264.7 cells treated with LPS and/or TMP were used in ChIP and EMSA assays. For ChIP assays, chromatin was prepared and complexes precipitated with anti-NF-?B RelA Ab. Cross-links were reversed, DNA purified, and sequence abundance determined by Q-PCR. For EMSA assays, nuclear extracts were incubated with radiolabeled probes, analyzed by non-denaturing PAGE and visualized by autoradiography. RAW 264.7 cells treated with LPS and/or TMP were also used in fluorescence microscopy and western blot experiments. Translocation experiments were performed using a primary Ab to NF-?B RelA and a fluorescein-conjugated secondary Ab. Western blots were performed using Abs to I?B-? and phospho-I?B-?. Bands were visualized by chemiluminescence. Results In reporter assays with TLR-3, -4, and -8 over-expressing cells, TMP caused strong inhibition of NF-?B-dependent transcription. ChIP assays showed TMP caused virtually complete inhibition of RelA binding in vivo to promoters for the genes for TNF-?, MCP-1/CCL2, and RANTES/CCL5 although the LPS-dependent synthesis of I?B-? was not inhibited. EMSA assays did not reveal an effect of TMP on the binding of RelA to naked DNA templates in vitro. TMP did not inhibit the nuclear translocation of NF-?B RelA nor the phosphorylation of I?B-?. Conclusion TMP acts indirectly as an inhibitor of NF-?B-dependent transcription by preventing RelA from binding the promoters of certain key cytokine and chemokine genes.

Oyegunwa Akinbolade O; Sikes Michael L; Wilson Jason R; Scholle Frank; Laster Scott M

2010-01-01

166

Molecular Characterization of Environmental Non-Tuberculous Mycobacteria Using PCR- RFLP Analysis of 441 Bp Heat Shock Protein 65 Fragments.  

UK PubMed Central (United Kingdom)

BACKGROUND: Non- Tuberculous Mycobacteria are environmental opportunistic pathogens that can be found in various terrestrial and aquatic habitats. There are an epidemiological links between species isolated in tap water and those isolated from patients. hsp65 gene has more variability in its sequences, compared to the some more conserved genes in NTM, for identification of mycobacteria to species level. In this study, the prevalence of NTM in Isfahan City water samples was determined using culture, biochemical tests and PCR-RFLP analyses of hsp65 gene. METHODS: Eighty-five water samples were collected and cultured. The mycobacterial isolates were identified by conventional biochemical tests. A 441 bp fragment of hsp65 genes was amplified and digested by two restriction enzymes, BstEII and HaeII. Digested products were analyzed using polyacrilamid gel electrophoresis (PAGE). RESULTS: 25.9% of the water samples contained different species of NTM. Dominant isolates were M. fortuitum (26.7%), M. chelonae like organism (13.3%) and M. mucogenicum (13.3%). Nineteen isolates of Mycobacteria were differentiated using hsp65 genes PCR-RFLP. Three isolates could not be identified at the species level because their RFLP patterns were different from other known PCR-RFLP profiles. There were different hsp65 gene PCR-RFLP profiles produced by digestion with BstEII and HaeIII. CONCLUSION: This study showed that PCR-RFLP of hsp65 gene in mycobacteria is more reliable method for identification of NTM at the specie level than conventional phenotypic methods (P<0.05). In comparing of RFLP patterns of this study to other investigation, some minor differences were negligible.

Nasr-Esfahani B; Sarikhani E; Moghim S; Faghri J; Fazeli H; Hoseini N; Rezaei-Yazdi H

2012-01-01

167

Molecular Characterization of Environmental Non-Tuberculous Mycobacteria Using PCR- RFLP Analysis of 441 Bp Heat Shock Protein 65 Fragments  

Directory of Open Access Journals (Sweden)

Full Text Available Background: Non- Tuberculous Mycobacteria are environmental opportunistic pathogens that can be found in various terrestrial and aquatic habitats. There are an epidemiological links between species isolated in tap water and those isolated from patients. hsp65 gene has more variability in its sequences, compared to the some more conserved genes in NTM, for identification of mycobacteria to species level. In this study, the prevalence of NTM in Isfahan City water samples was determined using culture, biochemical tests and PCR-RFLP analyses of hsp65 gene.Methods: Eighty-five water samples were collected and cultured. The mycobacterial isolates were identified by conventional biochemical tests. A 441 bp fragment of hsp65 genes was amplified and digested by two restriction enzymes, BstEII and HaeII. Digested products were analyzed using polyacrilamid gel electrophoresis (PAGE).Results: 25.9% of the water samples contained different species of NTM. Dominant isolates were M. fortuitum (26.7%), M. chelonae like organism (13.3%) and M. mucogenicum (13.3%). Nineteen isolates of Mycobacteria were differentiated using hsp65 genes PCR-RFLP. Three isolates could not be identified at the species level because their RFLP patterns were different from other known PCR-RFLP profiles. There were different hsp65 gene PCR-RFLP profiles produced by digestion with BstEII and HaeIII. Conclusion: This study showed that PCR-RFLP of hsp65 gene in mycobacteria is more reliable method for identification of NTM at the specie level than conventional phenotypic methods (P<0.05). In comparing of RFLP patterns of this study to other investigation, some minor differences were negligible.

B Nasr-Esfahani; E Sarikhani; S Moghim; J Faghri; H Fazeli; N Hoseini; H Rezaei-Yazdi

2012-01-01

168

Gene doping: gene delivery for olympic victory.  

UK PubMed Central (United Kingdom)

With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place.

Gould D

2013-08-01

169

PREVENT Governance Structure  

Science.gov (United States)

With the governance structure and unified PREVENT program mission, NCI will make data-driven decisions following PREVENT Decision Gate guidelines to maximize potential for success at each consecutive stage. As such, the PREVENT Program is envisioned to streamline the development and testing of promising new cancer preventative agents and expedite their delivery to bedside.

170

The price of prevention.  

UK PubMed Central (United Kingdom)

Supporters of the health system reform law hope a whole lot of prevention - and free prevention, at that - will significantly reduce Americans' mortality and morbidity from cancer, smoking, obesity, vaccine-preventable illnesses, and other diseases. A provision of the Affordable Care Act (ACA) requires health plans to cover a wide array of preventive care services without charging patients copayments, coinsurance, or deductibles.

Ortolon K

2011-03-01

171

Detection of Mycobacterium bovis and Mycobacterium tuberculosis from Cattle: Possible Public Health Relevance  

DEFF Research Database (Denmark)

Mycobacterium bovis and Mycobacterium tuberculosis infect both animals and humans. The disease epidemiology by these agents differs in developed and developing countries due to the differences in the implementation of the prevention and control strategies. The present study describes the detection of M. bovis and M. tuberculosis from specimens of lungs and pulmonary lymph nodes of four cattle died in an organized herd of 183 cattle in the state of Himachal Pradesh, India, with inconclusive skin test results. Identification and distinction of these closely related mycobacterial species was done by PCR-RFLP targeting hsp65 gene followed by spacer oligonucleotide typing. Mixed infection of M. bovis and M. tuberculosis was detected in one cattle.

Thakur, Aneesh; Sharma, Mandeep

2012-01-01

172

Mycobacterium thermoresistibile: Case report of a rarely isolated mycobacterium from Europe and review of literature  

Directory of Open Access Journals (Sweden)

Full Text Available Mycobacterium thermoresistibile is a non-tuberculous mycobacterium strongly associated with human infections. Since 1966, there have only been six reports of its isolation from clinical samples. We report on the first case from Europe and review all the previous cases. Identification was achieved with sequencing of the 16S rRNA and hsp65 genes. This study presents its phenotypic and biochemical profile, susceptibilities to selected antibiotics and hsp65 polymerase chain reaction-restriction fragment length polymorphism profile with BsteII and Hae III .

Neonakis I; Gitti Z; Kontos F; Baritaki S; Petinaki E; Baritaki M; Zerva L; Spandidos D

2009-01-01

173

Mycobacterium thermoresistibile: case report of a rarely isolated mycobacterium from Europe and review of literature.  

Science.gov (United States)

Mycobacterium thermoresistibile is a non-tuberculous mycobacterium strongly associated with human infections. Since 1966, there have only been six reports of its isolation from clinical samples. We report on the first case from Europe and review all the previous cases. Identification was achieved with sequencing of the 16S rRNA and hsp65 genes. This study presents its phenotypic and biochemical profile, susceptibilities to selected antibiotics and hsp65 polymerase chain reaction-restriction fragment length polymorphism profile with BsteII and Hae III . PMID:19584513

Neonakis, I K; Gitti, Z; Kontos, F; Baritaki, S; Petinaki, E; Baritaki, M; Zerva, L; Spandidos, D A

174

Mycobacterium thermoresistibile: case report of a rarely isolated mycobacterium from Europe and review of literature.  

UK PubMed Central (United Kingdom)

Mycobacterium thermoresistibile is a non-tuberculous mycobacterium strongly associated with human infections. Since 1966, there have only been six reports of its isolation from clinical samples. We report on the first case from Europe and review all the previous cases. Identification was achieved with sequencing of the 16S rRNA and hsp65 genes. This study presents its phenotypic and biochemical profile, susceptibilities to selected antibiotics and hsp65 polymerase chain reaction-restriction fragment length polymorphism profile with BsteII and Hae III .

Neonakis IK; Gitti Z; Kontos F; Baritaki S; Petinaki E; Baritaki M; Zerva L; Spandidos DA

2009-07-01

175

Mycobacterium arupense pulmonary infection: antibiotic resistance and restriction fragment length polymorphism analysis.  

UK PubMed Central (United Kingdom)

Mycobacterium arupense is a novel mycobacterium species. It was first identified from clinical specimens in 2006 and since then there have been only two reports of its recovery from clinical samples. In the present case M. arupense was isolated from the sputum of a 62-year-old man with a malignant mass in his left kidney, who presented with a one-month history of recurrent fever, dyspnea and haemoptysis. M. arupense was identified with sequencing of hsp65 and 16S rRNA genes. In the present study, its biochemical profile along with its resistance status and hsp65 RFLP analysis is presented.

Neonakis IK; Gitti Z; Kontos F; Baritaki S; Petinaki E; Baritaki M; Liakou V; Zerva L; Spandidos DA

2010-04-01

176

Mycobacterium arupense pulmonary infection: antibiotic resistance and restriction fragment length polymorphism analysis.  

Science.gov (United States)

Mycobacterium arupense is a novel mycobacterium species. It was first identified from clinical specimens in 2006 and since then there have been only two reports of its recovery from clinical samples. In the present case M. arupense was isolated from the sputum of a 62-year-old man with a malignant mass in his left kidney, who presented with a one-month history of recurrent fever, dyspnea and haemoptysis. M. arupense was identified with sequencing of hsp65 and 16S rRNA genes. In the present study, its biochemical profile along with its resistance status and hsp65 RFLP analysis is presented. PMID:20404471

Neonakis, I K; Gitti, Z; Kontos, F; Baritaki, S; Petinaki, E; Baritaki, M; Liakou, V; Zerva, L; Spandidos, D A

177

Mycobacterium arupense pulmonary infection: Antibiotic resistance and restriction fragment length polymorphism analysis  

Directory of Open Access Journals (Sweden)

Full Text Available Mycobacterium arupense is a novel mycobacterium species. It was first identified from clinical specimens in 2006 and since then there have been only two reports of its recovery from clinical samples. In the present case M. arupense was isolated from the sputum of a 62-year-old man with a malignant mass in his left kidney, who presented with a one-month history of recurrent fever, dyspnea and haemoptysis. M. arupense was identified with sequencing of hsp65 and 16S rRNA genes. In the present study, its biochemical profile along with its resistance status and hsp65 RFLP analysis is presented.

Neonakis I; Gitti Z; Kontos F; Baritaki S; Petinaki E; Baritaki M; Liakou V; Zerva L; Spandidos D

2010-01-01

178

Suicide Prevention and Research  

Medline Plus

Full Text Available ... these numbers. More Information about: Suicide Prevention More Video and Audio about: Suicide Prevention Subscribe to RSS Feeds NIMH Video NIMH Audio Director’s Blog Recent Updates Bookmark & Share ...

179

Preventing Construction Falls  

Science.gov (United States)

... Añadir en... Favorites Delicious Digg Google Bookmarks Preventing Construction Falls In April 2008, a series of episodes ... at work and how to prevent them. Why construction falls? The focus of the storyline was determined ...

180

Suicide Prevention and Research  

Medline Plus

Full Text Available ... More Information about: Suicide Prevention More Video and Audio about: Suicide Prevention Subscribe to RSS Feeds NIMH Video NIMH Audio Director’s Blog Recent Updates Bookmark & Share External Link: ...

 
 
 
 
181

National Suicide Prevention Lifeline  

Science.gov (United States)

... main content Skip to our phone number National Suicide Prevention Lifeline Home Get Help Help for Yourself ... Bingo Strong Networks Active Listening Strong Support Network Suicide Prevention Week 2013 Learn More Mental Health Therapy ...

182

Suicide Prevention for Children  

Science.gov (United States)

... Problems > Suicide Prevention For Children Health Issues Listen Suicide Prevention For Children Article Body Occasionally, during times ... the six-to-twelve age range rarely commit suicide, but there is an increasing trend for them ...

183

Suicide Prevention and Research  

Medline Plus

Full Text Available August 22, 2011 Suicide Prevention and Research NIMH researcher Dr. Jane Pearson talks about warning signs as well as progress in suicide prevention. Download this video. Watch on YouTube. Transcript ...

184

Suicide Prevention and Research  

Science.gov (United States)

August 22, 2011 Suicide Prevention and Research NIMH researcher Dr. Jane Pearson talks about warning signs as well as progress in suicide prevention. Download this video. Watch on YouTube. Transcript ...

185

Preventing Weight Gain  

Science.gov (United States)

... Añadir en... Favorites Delicious Digg Google Bookmarks Preventing Weight Gain If you're currently at a healthy weight, ... of cancer. Choosing an Eating Plan to Prevent Weight Gain So, how do you choose a healthful eating ...

186

Suicide Prevention and Research  

Medline Plus

Full Text Available August 22, 2011 Suicide Prevention and Research NIMH researcher Dr. Jane Pearson talks about warning signs as well as progress in suicide prevention. Download this video. Watch on YouTube. ...

187

Preventing HIV with Medicine  

Science.gov (United States)

... information in Spanish ( en español ) Preventing HIV with medicine Get medicine right after you are exposed to ... to top More information on Preventing HIV with medicine Explore other publications and websites National HIV and ...

188

Treating and Preventing Burns  

Science.gov (United States)

... Preventing Burns Health Issues Listen Treating and Preventing Burns Article Body Burns are divided into three categories , according to their severity. First-degree burns are the mildest and cause redness and perhaps ...

189

Preventing Pressure Sores  

Medline Plus

Full Text Available Experts \\ Preventing Pressure Sores Topics Adult Injuries Spinal Cord Injury 101 The Basics of SCI Rehabilitation Preventing Pressure Sores Transition from Hospital to Home Spasticity, Physical ...

190

Molecular epidemiology and cancer prevention  

Energy Technology Data Exchange (ETDEWEB)

A review of recent studies of biologic markers in populations with model exposures to carcinogens (cigarette smoke and polycyclic aromatic hydrocarbons) illustrates their potential role in cancer prevention. Data on macromolecular adducts and oncogene activation from cross-sectional, serial sampling and case-control studies demonstrate the usefulness of biologic markers in signalling a potential carcinogenic risk and in estimating the magnitude of interindividual variation within exposed groups. Recommendations for future research include nested case-control studies to establish the relationship between markers of biologic dose and effect (e.g., adducts, gene mutation, oncogene activation) and cancer risk. 31 references.

Perera, F.P.; Jeffrey, A.M.; Brandt-Rauf, P.W.; Brenner, D.; Mayer, J.L.; Smith, S.J.; Latriano, L.; Hemminki, K.; Santella, R.M. (Columbia Univ. School of Public Health, New York, NY (USA))

1990-01-01

191

NOVEL PREVENTIVE FOR INFECTIONS  

UK PubMed Central (United Kingdom)

Effective preventive agent for infectious diseases, an enhancer of an infectious disease-preventive action of cysteine and food and feed effective for infectious diseases are provided. An agent for preventing infectious diseases wherein cystine and the like and theanine are combined, an enhancer of an infectious disease-preventive action of cystine and the like, which contains theanine, and food and feed wherein cystine and the like and theanine are combined.

SHIBAHARA Susumu AJINOMOTO CO. INC.

192

Wildfire Prevention Strategies.  

Science.gov (United States)

|This document provides information and guidance on wildfire prevention strategies. Chapters include: (1) "Introduction"; (2) "How to Use this Guide"; (3) "Fire Cause Classification"; (4) "Relative Effectiveness"; (5) "Degree of Difficulty"; (6) "Intervention Techniques"; (7) "Prevention Activities"; (8) "Sample Prevention Strategies"; and (9)…

National Wildlife Coordinating Group, Boise, ID.

193

Characterization of mycobacteria from a major Brazilian outbreak suggests that revision of the taxonomic status of members of the Mycobacterium chelonae-M. abscessus group is needed.  

Science.gov (United States)

An outbreak of postsurgical infections caused by rapidly growing mycobacteria has been ongoing in Brazil since 2004. The degrees of similarity of the rpoB and hsp65 sequences from the clinical isolates and the corresponding sequences from both the Mycobacterium massiliense and the M. bolletii type strains were above the accepted limit for interspecies variability, leading to conflicting identification results. Therefore, an extensive characterization of members of the M. chelonae-M. abscessus group was carried out. The M. abscessus, M. chelonae, M. immunogenum, M. massiliense, and M. bolletii type strains and a subset of clinical isolates were analyzed by biochemical tests, high-performance liquid chromatography, drug susceptibility testing, PCR-restriction enzyme analysis of hsp65 (PRA-hsp65), rpoB, and hsp65 gene sequencing and analysis of phylogenetic trees, DNA-DNA hybridization (DDH), and restriction fragment length polymorphism (RFLP) analysis of the 16S rRNA gene (RFLP-16S rRNA). The clinical isolates and the M. abscessus, M. massiliense, and M. bolletii type strains could not be separated by phenotypic tests and were grouped in the phylogenetic trees obtained. The results of DDH also confirmed the >70% relatedness of the clinical isolates and the M. abscessus, M. massiliense, and M. bolletii type strains; and indistinguishable RFLP-16S rRNA patterns were obtained. On the contrary, the separation of clinical isolates and the M. abscessus, M. massiliense, and M. bolletii type strains from M. chelonae and M. immunogenum was supported by the results of PRA-hsp65, DDH, and RFLP-16S rRNA and by the rpoB and hsp65 phylogenetic trees. Taken together, these results led to the proposition that M. abscessus, M. massiliense, and M. bolletii represent a single species, that of M. abscessus. Two subspecies are also proposed, M. abscessus subsp. abscessus and M. abscessus subsp. massiliense, and these two subspecies can be distinguished by two different PRA-hsp65 patterns, which differ by a single HaeIII band, and by differences in their rpoB (3.4%) and hsp65 (1.3%) sequences. PMID:19571015

Leao, Sylvia Cardoso; Tortoli, Enrico; Viana-Niero, Cristina; Ueki, Suely Yoko Mizuka; Lima, Karla Valeria Batista; Lopes, Maria Luiza; Yubero, Jesus; Menendez, Maria Carmen; Garcia, Maria Jesus

2009-07-01

194

Skin cancer prevention.  

UK PubMed Central (United Kingdom)

Prevention signifies the avoidance of diseases. It also includes the early detection of diseases and taking measures to avoid worsening of an existing disease. Prevention is divided into primary, secondary and tertiary prevention. The prevention of skin cancer is particularly important due to the rising incidence of skin cancer in recent years. In Germany, 195.000 new cases of skin cancer, including non melanoma skin cancer and melanoma are occurring. Therefore, skin cancer is among the most common cancer diseases. Primary prevention comprises the reduction of skin cancer risk behavior, including education about the danger of UV exposure and the right way of dealing with natural and artificial UV radiation. The implementation of a systematic skin cancer screening in Germany contributes to secondary prevention. First data from the initial project in Schleswig-Holstein, Germany's most northern state, indicate for the first time that the incidence and mortality of melanoma can be reduced by secondary prevention. For tertiary prevention, the national associations recommend a risk-adapted, evidence-based follow-up for all types of skin cancer. From the perspectives of the payers and from the patients, prevention is assessed positively. Prevention can contribute to a reduction of disease burden.

Kornek T; Augustin M

2013-04-01

195

Discovering genes underlying QTL  

Energy Technology Data Exchange (ETDEWEB)

A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

2002-02-01

196

Prevention in liver disease.  

UK PubMed Central (United Kingdom)

Prevention has become an important component of medical therapy for a variety of diseases. Preventive strategies in liver disease are relatively underdeveloped and have focused mainly on specific complications of chronic liver disease and vaccination for viral hepatitis. Although public health initiatives designed to prevent certain forms of liver disease are in place, they seem to be underutilized and their utility has not been evaluated. The development of a comprehensive approach using public health initiatives in conjunction with strategies by health care providers is important because of the potential for decreasing the human and health care costs associated with hepatic dysfunction. This article reviews the available literature regarding prevention for health care providers, includes a summary of ongoing public health initiatives, and suggests an approach to prevention in liver disease. It is intended to raise awareness and encourage implementation of preventive strategies in hepatology.

Arguedas MR; Fallon MB

2001-02-01

197

Facility pollution prevention planning  

Energy Technology Data Exchange (ETDEWEB)

Pollution prevention planning is a comprehensive and continual evaluation of business operations. The results pollution prevention program affects many functional areas within a company, such as the production line, accounting practices, and management. It has much in common with the planning already conducted for other aspects of business operations, but it looks at the facility as an integrated whole instead of as a series of disjoint parts or operations. A flowchart is presented illustrating the major elements in the pollution prevention program. This section describes the elements of pollution prevention program planning and design. These elements include building support for pollution prevention throughout the company, organizing the program, setting goals and objectives, performing a preliminary assessment of pollution prevention opportunities, and identifying potential problems and their solutions.

Evers, D.P. [Battelle Memorial Inst., Columbus, OH (United States)

1995-09-01

198

Prevention of Prosthetic Dentistry  

Directory of Open Access Journals (Sweden)

Full Text Available Prevention in prosthetic dentistry is not just a regular oral hygiene and the prevention of caries in the early stages of its development. The initial goal of orthopedic and dental should be the ability to convey to the patient's sense of pros-thetics that proteziruya one saved more. An example is included prosthetic dental arch defects with bridges or single artificial crowns on implants that will prevent movement of teeth and the continuity of the dentition

Takhtarov M.V.; Eremin O.V.

2011-01-01

199

[Primary prevention of osteopenia  

UK PubMed Central (United Kingdom)

In industrialized countries the clinical and socioeconomic importance of osteoporosis has been well recognized in recent years. Various treatments have been introduced for secondary prevention in established osteoporosis. There is, however, a deficit in the primary prevention of osteopenia. In every age group physical exercise stimulates mineralization of the bone. With regular training adolescents can achieve a higher peak bone mass. In old age the physiologic decrease of bone mass can be retarded by physical exercise. A diet rich in calcium has positive effects on mineralization of the bone. Estrogens have proved efficacious in the prevention of osteoporosis in postmenopausal women. Abstinence from nicotine and alcohol contributes to the prevention of osteopenia.

Falkenbach A

1992-11-01

200

Preventative Medicine today  

Directory of Open Access Journals (Sweden)

Full Text Available The great majority of chronic diseases can be prevented byreducing risks, understood as factors that increase the probabilityof a specific disease or condition, such as hypertension,hypercholesterolemia, inadequate diet, smoking habit, obesity andsedentarism. These aspects are evaluated in this article as wellas prevention and screening methods.

José Antonio Maluf de Carvalho

2005-01-01

 
 
 
 
201

DIABETES PREVENTION PROGRAM  

Science.gov (United States)

The Diabetes Prevention Program (DPP) was a major clinical trial, or research study, aimed at discovering whether either diet and exercise or the oral diabetes drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in people with impaired glucose toleranc...

202

Skin Cancer Prevention Study  

Science.gov (United States)

Actinic keratoses (AKs) are precancerous skin growths that are usually caused by sun exposure. This study seeks to determine if the drug celecoxib prevents new AKs from developing, causes existing AKs to go away, and prevents AKs from progressing to squamous cell cancer.

203

Suicide is preventable, sometimes.  

UK PubMed Central (United Kingdom)

OBJECTIVE: The objective was to examine the assumption that suicide is inevitably preventable. CONCLUSIONS: Suicide may not always be avoidable. This does not mean that every effort should not be made to prevent it or vigorously treat illnesses that are often contributory. The assumption, however, may give rise to undue optimism, and unjustified blame when suicides do occur.

Walter G; Pridmore S

2012-08-01

204

Measuring waste prevention.  

UK PubMed Central (United Kingdom)

The Waste Framework Directive (WFD-2008/98/EC) has set clear waste prevention procedures, including reporting, reviewing, monitoring and evaluating. Based on the WFD, the European Commission and will offer support to Member States on how to develop waste prevention programmes through guidelines and information sharing on best practices. Monitoring and evaluating waste prevention activities are critical, as they constitute the main tools to enable policy makers, at the national and local level, to build their strategic plans and ensure that waste prevention initiatives are effective and deliver behaviour change. However, how one can measure something that is not there, remains an important and unresolved research question. The paper reviews and attempts to evaluate the methods that are being used for measuring waste prevention and the impact of relevant implemented activities at the household level, as the available data is still limited.

Zorpas AA; Lasaridi K

2013-05-01

205

Prevention of preterm birth.  

UK PubMed Central (United Kingdom)

Preterm birth (delivery before 37 completed weeks of gestation) is common and rates are increasing. In the past, medical efforts focused on ameliorating the consequences of prematurity rather than preventing its occurrence. This approach resulted in improved neonatal outcomes, but it remains costly in terms of both the suffering of infants and their families and the economic burden on society. Increased understanding of the pathophysiology of preterm labor has altered the approach to this problem, with increased focus on preventive strategies. Primary prevention is a limited strategy which involves public education, smoking cessation, improved nutritional status and avoidance of late preterm births. Secondary prevention focuses on recurrent preterm birth which is the most recognisable risk factor. Widely accepted strategies include cervical cerclage, progesterone and dedicated clinics. However, more research is needed to explore the role of antibiotics and anti-inflammatory treatments in the prevention of this complex problem.

Flood K; Malone FD

2012-02-01

206

Geographically targeting pollution prevention  

Energy Technology Data Exchange (ETDEWEB)

In an effort to promote greater environmental protection and reduce pollution in California in 1993, the Department of Toxic Substances Control (Department) began experimenting with a new marketing technique, geographic pollution prevention targeting. The program was designed to test the effectiveness of this type of educational outreach. The general goal of the project was to elevate community awareness to pollution prevention opportunities by demonstrating that low cost alternatives exist to reduce the amount of pollutants being discharged to air, land, and water. The first State sponsored geographically targeted pollution prevention project took place in Stockton, a community located in the heart of the San Joaquin Valley in central California. The pilot project, called Targeted Opportunities to Prevent Pollution in Stockton (TOPPS), began in December of 1992. The types of activities implemented under TOPPS included: pollution prevention training workshops and seminars; technical assistance to businesses that generate hazardous pollutant; information distribution to businesses, schools, community organizations, and neighborhoods; and household hazardous waste collection events.

Wright, D.A.; Hogg, L.D. [California Environmental Protection Agency, Sacramento, CA (United States). Dept. of Toxic Substances Control

1994-12-31

207

[The natural triterpenoid miliacin prevents methotrexate-induced oxidative stress and normalizes the expression of genes encoding the cytochrome P-450 2E1 isoform and glutathione reductase in the liver].  

UK PubMed Central (United Kingdom)

We studied the role of the natural triterpenoid miliacin (3-3-methoxy-Al8-oleanene) in the regulation of oxidative stress in the liver of (CBAxC57B1(6))F1 mice exposed to methotrexate. Miliacin attenuated methotrexate-induced lipid peroxidation as determined by an attenuation of thiobarbituric acid-reacting products in the liver. Furthermore, miliacin normalized the expression of genes encoding the 2e1 isoform of cytochrome P-450 and glutathione reductase that were dramatically dysregulated by methotrexate. These results established the role of miliacin in modulation of redox genes, thereby providing evidence for a new mechanism of organ protection by this triterpenoid.

Kalinina OV; Kolotova ES; Panfilova TV; Shtil AA; Frolov BA

2013-01-01

208

Condensin Loaded onto the Replication Fork Barrier Site in the rRNA Gene Repeats during S Phase in a FOB1-Dependent Fashion To Prevent Contraction of a Long Repetitive Array in Saccharomyces cerevisiae†  

Digital Repository Infrastructure Vision for European Research (DRIVER)

An average of 200 copies of the rRNA gene (rDNA) is clustered in a long tandem array in Saccharomyces cerevisiae. FOB1 is known to be required for expansion/contraction of the repeats by stimulating recombination, thereby contributing to the maintenance of the average copy number. In ?fob1 cells, th...

Johzuka, Katsuki; Terasawa, Masahiro; Ogawa, Hideyuki; Ogawa, Tomoko; Horiuchi, Takashi

209

Effect of long term selenium yeast intervention on activity and gene expression of antioxidant and xenbiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study  

DEFF Research Database (Denmark)

Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in different blood compartments, and expression of selected phase 1 and phase 2 genes in leucocytes (GPX1, gamma-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription factor Fos-related antigen I (Fral), NAD(P)H:quinone oxidoreductase (NQO1), and aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age 71.3 (SD 4.26) years; 36% reporting use of multivitamin/mineral supplements) participated and were supplemented daily for 5 years with placebo, 100 mu g, 200 mu g or 300 mu g Se as Se-enriched yeast (SelenoPrecise (R)). Blood samples were collected after 5 years of intervention. When all four groups were compared we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX, GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX activity at the two highest dosage levels in women only, but not in men. No effects on GPX1, NQOI or AhRR gene expression were found. When all Se-supplemented groups were pooled we found significant down regulation of the expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR gene expression with smoking was found but was independent of Se supplementation. Down regulation of phase 2 genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues.

Ravn-Haren, Gitte; Krath, Britta

2008-01-01

210

Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study  

DEFF Research Database (Denmark)

Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in different blood compartments, and expression of selected phase 1 and phase 2 genes in leucocytes (GPX1, gamma-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription factor Fos-related antigen 1 (Fra1), NAD(P)H:quinone oxidoreductase (NQO1), and aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age 71.3 (sd 4.26) years; 36 % reporting use of multivitamin/mineral supplements) participated and were supplemented daily for 5 years with placebo, 100 mug, 200 mug or 300 mug Se as Se-enriched yeast (SelenoPrecise(R)). Blood samples were collected after 5 years of intervention. When all four groups were compared we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX, GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX activity at the two highest dosage levels in women only, but not in men. No effects on GPX1, NQO1 or AhRR gene expression were found. When all Se-supplemented groups were pooled we found significant down regulation of the expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR gene expression with smoking was found but was independent of Se supplementation. Down regulation of phase 2 genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues.

Ravn-Haren, Lejla Gitte; Krath, Britta Naimi

2007-01-01

211

Wellness and prevention.  

UK PubMed Central (United Kingdom)

BACKGROUND AND OBJECTIVES: The importance of wellness and prevention in medical education is well documented. This report discusses the educational innovations in wellness and prevention that were implemented as part of the Undergraduate Medical Education for the 21st Century (UME-21) project. METHODS: Eight partner schools and four of the 10 associate partner schools provided specific information about learning objectives, content, and methods used in incorporating wellness and prevention into the curriculum. Based on these reports, common learning objectives and core content were identified. RESULTS: Many schools emphasized that integration of content across courses and throughout the preclinical and clinical years was important in incorporating wellness and prevention content into existing curricula. A variety of instructional methods were used, including didactic lectures, workshops, smallgroup sessions, case studies, computer-based instructional modules, patient simulators, and standardized patient encounters. Based on partner reports, after completing the UME-21 project, students demonstrated gains in knowledge, clinical skills, and positive attitudes toward preventive care and wellness. The project outcome data indicated that student instruction in and exposure to preventive care was increased during the project. However, these increases were not significant when compared to their peers from non-UME-21 schools. CONCLUSIONS: Although partner schools used different methods to incorporate wellness and prevention, the UME-21 project was an effective project in improving the educational experience in this content area for students from institutions that included this area in their educational innovations.

Grigsby DG; McClanahan KG; Garr DR

2004-01-01

212

National Crime Prevention Council  

Science.gov (United States)

Growing out of the National Citizens' Crime Prevention Campaign in the late 1970s, the organization gained great publicity through its use of the popular spokesperson McGruff the Crime Dog, and later became the National Crime Prevention Council. Today the Council is perhaps the best known nonprofit educational organization dedicated to crime prevention, and its website is an important place for the web-surfing public citizens to gather materials about working towards the prevention of crime in their own communities. Many of these resources are brought together in the section called Topics in Crime Prevention, accessible through the top right-hand side of the homepage. Here visitors can browse for materials by subject (such as bullying, civil rights organizations, and cybercrime), or by an extensive list of subjects, including funding opportunities, crime prevention, and violence prevention. Of course, visitors would be remiss not to examine the section that tells about the genesis of McGruff the Crime Dog, who has been one of the most enduring public service announcement characters of the past few decades.

213

Aging: gene silencing or gene activation?  

Science.gov (United States)

According to the author's theory of gene silencing, the key process in aging involves reduced expression of a number of genes. Silencing of genes has a complex mechanism, which involves methylation of DNA, histone modification and chromatin remodeling. In addition to deacetylation of the histones and methylation of DNA, recently described RNAi mechanism could initiate formation of silenced chromatin. Hypermethylation of the promoter will silence the gene. Genome-wide hypomethylation will induce genomic instability, amplification of oncogenes and also silencing of the genes through RNAi mechanism. Studies by different groups, conducted in yeast, worms, flies and mice, confirmed substantial changes in gene expression in aging. Among them, the most important was silencing of tumor suppressors and other genes involved in the control of cell cycle, apoptosis, detoxification, and cholesterol metabolism. There was also increased expression of the smaller group of oncogenes and other genes which are associated with typical diseases of old age. Caloric restriction normalizes expression of a substantial percentage of these genes. Animal studies confirmed importance of caloric restriction, which decreases signaling through the IGF-1/AKT pathway and expression of gene p53. These studies, however, cannot be directly applied to human aging. It is proposed that age management therapy should attempt to normalize gene expression in the older population to the level typical for young adults. This would require activation of silenced genes and normalization of overexpressed genes. Caloric restriction and exercise are helpful in decreasing the activity of important oncogenes and activation of silenced tumor suppressors, and may have a positive impact, not only on aging, but also on prevention of cancer. Dietary supplements containing phytochemicals should normalize increased expression of oncogenes. Examples are: genistein and EGCG, which effect signaling through the IGF-1/AKT pathway and resveratrol and limonen, which do so through the RAS pathway. A group of amino acid derivatives and organic acids of animal and human origin should activate silenced tumor suppressor genes (Aminocare A10, Aminocare Extra). Among them 3-phenylacetylamino-2, 6-piperidinedione intercalates specifically with DNA and protects sequences of tumor suppressor genes, which are vulnerable to the effects of carcinogens. Phenylacetate activates p53 and p21 through inhibition of methyltransferase and farnesylation of the RAS protein. Phenylbutyrate activates tumor suppressor genes through inhibition of histone deacetylation. Phenylacetylglutamine decreases genomic instability and expression of oncogenes and promotes apoptosis. The application of DNA microarray techniques to human studies should provide more information about differences in gene expression in different age groups and help design more effective age management regimens. PMID:15533642

Burzynski, Stanislaw R

2005-01-01

214

Virus-mediated gene delivery for human gene therapy.  

Science.gov (United States)

After over 20 years from the first application of gene transfer in humans, gene therapy is now a mature discipline, which has progressively overcome several of the hurdles that prevented clinical success in the early stages of application. So far, the vast majority of gene therapy clinical trials have exploited viral vectors as very efficient nucleic acid delivery vehicles both in vivo and ex vivo. Here we summarize the current status of viral gene transfer for clinical applications, with special emphasis on the molecular properties of the major classes of viral vectors and the information so far obtained from gene therapy clinical trials. PMID:22516095

Giacca, Mauro; Zacchigna, Serena

2012-04-10

215

Virus-mediated gene delivery for human gene therapy.  

UK PubMed Central (United Kingdom)

After over 20 years from the first application of gene transfer in humans, gene therapy is now a mature discipline, which has progressively overcome several of the hurdles that prevented clinical success in the early stages of application. So far, the vast majority of gene therapy clinical trials have exploited viral vectors as very efficient nucleic acid delivery vehicles both in vivo and ex vivo. Here we summarize the current status of viral gene transfer for clinical applications, with special emphasis on the molecular properties of the major classes of viral vectors and the information so far obtained from gene therapy clinical trials.

Giacca M; Zacchigna S

2012-07-01

216

Preventable childhood injuries.  

UK PubMed Central (United Kingdom)

BACKGROUND: This is a literature review generated from The Committee on Trauma and Prevention of Pediatric Orthopaedic Society of North America to bring to the forefront 4 main areas of preventable injuries in children. METHODS: Literature review of pertinent published studies or available information of 4 areas of childhood injury: trampoline and moonbouncers, skateboards, all-terrain vehicles, and lawn mowers. RESULTS: Much literature exists on these injuries. CONCLUSIONS: Preventable injuries occur at alarming rates in children. By arming the orthopaedist with a concise account of these injuries, patient education and child safety may be promoted. LEVEL OF EVIDENCE: 3.

Lovejoy S; Weiss JM; Epps HR; Zionts LE; Gaffney J

2012-10-01

217

Biotechnology for pollution prevention  

Energy Technology Data Exchange (ETDEWEB)

Biotechnology uses natural processes; therefore, pollution prevention is almost always incorporated. Using microorganisms, microbial enzymes as catalysts, and natural feedstocks reduces or eliminates the need for pollution control. Many biotechnology processes could be substituted for existing production processes to create environmentally incorporated manufacturing or ecological bioprocessing. Rapid changes and new technical developments characterize the biotechnology field; therefore, only selected aspects and developments can be discussed in a single chapter such as this one. This chapter focuses on the accepted tabulation of pollution prevention techniques and gives examples of biotechnology applications for these pollution prevention categories.

Bordacs-Irwin, K.

1995-09-01

218

Suicide Prevention and Research  

Medline Plus

Full Text Available ... 2011 Suicide Prevention and Research NIMH researcher Dr. Jane Pearson talks about warning signs as well as ... Download this video. Watch on YouTube. Transcript Dr. Jane Pearson: Suicide is a major public health problem ...

219

High Blood Cholesterol Prevention  

Science.gov (United States)

... en... Favorites Delicious Digg Google Bookmarks High Blood Cholesterol Prevention What You Can Do Guidelines and Recommendations ... 800-CDC-INFO Fax: 770-488–8151 Email Cholesterol Home About Cholesterol LDL and HDL Signs and ...

220

Preventing Pressure Sores  

Medline Plus

Full Text Available ... Spinal Cord Injury 101 The Basics of SCI Rehabilitation Preventing Pressure Sores Transition from Hospital to Home ... Cord Injury 101 The Basics of Pediatric SCI Rehabilitation Transitions for Children with SCI What is a ...

 
 
 
 
221

Suicide Prevention and Research  

Medline Plus

Full Text Available ... prevention research team at the National Institute of Mental Health in Bethesda. The tragedy of suicide touches large ... FOIA Accessibility Topic Finder The National Institute of Mental Health (NIMH) is part of the National Institutes of ...

222

Preventing West Nile Virus  

Science.gov (United States)

... Nile Virus Health Issues Listen Preventing West Nile Virus Article Body The West Nile virus has received plenty of attention in recent years. ... children have become ill when infected with the virus, in most cases the symptoms are mild. Mosquitoes ...

223

Work hazard prevention plans  

International Nuclear Information System (INIS)

[en] The prevention of industrial risks is a constantly evolving discipline that has changed considerable in the last 25 years. The Cofrentes Nuclear Power Plants has always been operated with a clear policy favoring prevention by supporting the principle of its integration, i. e., that the hierarchical functional organization of the company make sure that industrial risk prevention is effective and that health and safety standards are met. The historical evolution of occupational safety in the Cofrentes Nuclear Power Plant shows a a clear trend towards improvement and is the results of many years of hard work and effort by the plants own and contractor personnel in the field of industrial risk prevention. (Author)

2009-01-01

224

Preventing Pressure Sores  

Medline Plus

Full Text Available ... Pressure Sores Topics Adult Injuries Spinal Cord Injury 101 The Basics of SCI Rehabilitation Preventing Pressure Sores ... After SCI Pediatric Injuries Pediatric Spinal Cord Injury 101 The Basics of Pediatric SCI Rehabilitation Transitions for ...

225

Primary prevention of cancer  

Energy Technology Data Exchange (ETDEWEB)

This book is organized under the following headings: Cancer registration in Europe; Coordination and role in cancer control, Chemoprevention of cancer, Smokeless tobacco and cancer, Occupational risks from radiation, Stochholm cancer prevention program.

Eylenbosch, W.J. (Univ. Instelling Antwerpen, Epidemiologie en Sociale Geneeskunde, 2610 Antwerpen (BE)); Depoorter, A.M. (Vrije Univ. Brussel, School voor Maatschappelijke, Gezondheidszorg, 1090 Brussel (BE)); Van Larebeke, N. (Lab. voor Histologie, 9000 Gent (BE))

1988-01-01

226

Household Safety: Preventing Drowning  

Science.gov (United States)

KidsHealth > Parents > First Aid & Safety > Home Sweet Home > Household Safety: Preventing Drowning Print A A A Text ... Parents MORE ON THIS TOPIC Backyard and Pool: Household Safety Checklist Summer Safety Household Safety Checklists Childproofing ...

227

Disaster prevention surveillance system  

International Nuclear Information System (INIS)

Fuji Electric Co., Ltd. has supplied many management systems to nuclear reactor institution. 'The nuclear countermeasures-against-calamities special-measures' was enforced. A nuclear entrepreneur has devised the measure about expansion prevention and restoration of a calamity while it endeavors after prevention of generating of a nuclear calamity. Our company have supplied the 'disaster prevention surveillance system' to the Japan Atomic Energy Research Institute Tokai Research Establishment aiming at strengthening of the monitoring function at the time (after the accident) of the accident used as one of the above-mentioned measures. A 'disaster prevention surveillance system' can share the information on the accident spot in an on-site command place, an activity headquarters, and support organizations, when the serious accident happens. This system is composed of various sensors (temperature, pressure and radiation), cameras, computers and network. (author)

2001-01-01

228

Disaster prevention surveillance system  

Energy Technology Data Exchange (ETDEWEB)

Fuji Electric Co., Ltd. has supplied many management systems to nuclear reactor institution. 'The nuclear countermeasures-against-calamities special-measures' was enforced. A nuclear entrepreneur has devised the measure about expansion prevention and restoration of a calamity while it endeavors after prevention of generating of a nuclear calamity. Our company have supplied the 'disaster prevention surveillance system' to the Japan Atomic Energy Research Institute Tokai Research Establishment aiming at strengthening of the monitoring function at the time (after the accident) of the accident used as one of the above-mentioned measures. A 'disaster prevention surveillance system' can share the information on the accident spot in an on-site command place, an activity headquarters, and support organizations, when the serious accident happens. This system is composed of various sensors (temperature, pressure and radiation), cameras, computers and network. (author)

Nara, Satoru [FFC, Tokyo (Japan); Kamiya, Eisei [Fuji Electric Co. Ltd., Tokyo (Japan)

2001-07-01

229

[Primary prevention of osteopenia].  

Science.gov (United States)

In industrialized countries the clinical and socioeconomic importance of osteoporosis has been well recognized in recent years. Various treatments have been introduced for secondary prevention in established osteoporosis. There is, however, a deficit in the primary prevention of osteopenia. In every age group physical exercise stimulates mineralization of the bone. With regular training adolescents can achieve a higher peak bone mass. In old age the physiologic decrease of bone mass can be retarded by physical exercise. A diet rich in calcium has positive effects on mineralization of the bone. Estrogens have proved efficacious in the prevention of osteoporosis in postmenopausal women. Abstinence from nicotine and alcohol contributes to the prevention of osteopenia. PMID:1439691

Falkenbach, A

1992-11-01

230

Preventing Frostbite and Hypothermia  

Science.gov (United States)

Preventing Frostbite and Hypothermia Prolonged exposure to low temperatures, wind or moisture—whether it be on a ski slope ... can result in cold-related illnesses such as frostbite and hypothermia. The National Safety Council offers these ...

231

Scabies: Prevention and Control  

Science.gov (United States)

... please visit this page: About CDC.gov . Parasites - Scabies Parasites Home Share Compartir Add this to... Añadir ... Prevention & Control When a person is infested with scabies mites the first time, symptoms may not appear ...

232

Bullying Prevention for Kids  

Centers for Disease Control (CDC) Podcasts

This podcast discusses what victims of bullying may experience and provides recommendations for coping with it.  Created: 1/19/2012 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 1/19/2012.

2012-01-19

233

Preventing Pressure Sores  

Medline Plus

Full Text Available ... Topics Adult Injuries Spinal Cord Injury 101 The Basics of SCI Rehabilitation Preventing Pressure Sores Transition from ... Pediatric Injuries Pediatric Spinal Cord Injury 101 The Basics of Pediatric SCI Rehabilitation Transitions for Children with ...

234

Golf Injury Prevention  

Science.gov (United States)

Copyright 2011 American Academy of Orthopaedic Surgeons Golf Injury Prevention Many people consider golf a low-level physical activity without much risk for injury. Many injuries can be caused by playing ...

235

[Preventing pressure ulcers].  

UK PubMed Central (United Kingdom)

Preventing the occurrence of pressure ulcers requires multi-disciplinary care of the patient. Firstly, it is necessary to identify patients predisposed to developing pressure ulcers thanks to awareness of the risk factors and using where necessary adapted assessment scales. Preventative measures then comprise the suitable positioning of the patient, regularly changing their position, the use of special support equipment, nursing care and the treatment of undernutrition.

Néouze A

2013-05-01

236

Prevention of water hammer  

Energy Technology Data Exchange (ETDEWEB)

Rapid shutoff of a fast-flowing liquid causes water hammer upstream and downstream of the valve. To prevent or minimize this cavitation, which may be quite pronounced downstream of the valve in dependence of velocity, the difference of levels friction etc., Czech engineers have developed an inlet valve to be installed downstream of the barrage. Air enters the pipeline through this inlet valve so that the cavitation phenomenon is prevented. The recoil is taken up by an air pad.

Slechta, A.M.

1981-05-01

237

Compliance through pollution prevention  

Energy Technology Data Exchange (ETDEWEB)

Decreased budgetary resources have caused the Air Force Materiel Command to look for a better way to target pollution prevention investments. The new paradigm, Compliance through Pollution Prevention (CTP2), is based upon the Code of Environmental Management Principles (CEMP) for federal facilities. It provides a procedure to assure that all future AFMC P2 investments result in the greatest reduction in environmental compliance burden possible. This paper describes the evolution of this new environmental management system, both past and future.

McCarty, B.D.; Coyle, S.; Kachel, W.M.

1999-07-01

238

Preventing parasites in cats.  

Science.gov (United States)

The monthly administration of broad-spectrum heartworm medications can effectively prevent a variety of internal and external parasitic diseases in cats. Although not every parasite can be stopped, many of the common feline parasites are susceptible to these agents. This article discusses the epidemiology and prevention strategies for those parasites that can be controlled by the administration of ivermectin, milbemycin oxime, or selamectin, either alone or in conjunction with an external parasiticide. PMID:16299672

Dryden, Michael W; Payne, Patricia A

2005-01-01

239

Pancreatic cancer: Pathogenesis, prevention and treatment  

International Nuclear Information System (INIS)

Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-?B pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-?B, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer

2007-11-01

240

Prevention of Football Injuries  

Directory of Open Access Journals (Sweden)

Full Text Available Purpose: Every sport has a unique profile of injury and risk of injury.In recent years, there have been numerous attempts at conducting injury prevention trials for specific injuries or for injuries within specific sports to provide evidence useful to the sports medicine and sport community. Football has been a focus of a number of randomized injury prevention trials. Methods: MEDLINE was searched with the first order keywords of “injury prevention” and “sport”. This list was restricted to “clinical trial” or “randomized controlled trial” which had been conducted on children and adults whose goal was preventing common football injuries. Our objective was to find studies with an exercise-based training program, thus projects that used mechanical interventions were excluded. Results: A structured, generalized warm-up has been shown to be effective at preventing common injuries in football, reducing injuries by about one-third. Conclusion: The huge participation numbers in the worldwide family of football would suggest that any reduction in injury should have a public health impact. Professionals in sports medicine need to promote injury prevention programs that have been shown to be effective.

Donald T. Kirkendall; Astrid Junge; Jiri Dvorak

2010-01-01

 
 
 
 
241

Genes and gene regulation  

Energy Technology Data Exchange (ETDEWEB)

Genetics has long been a central topic for biologists, and recent progress has captured the public imagination as well. This book addresses questions that are at the leading edge of this continually advancing discipline. In tune with the increasing emphasis on molecular biology and genetic engineering, this text emphasizes the molecular aspects of gene expression, and the evolution of gene sequence organization and control. It reviews the genetic material of viruses, bacteria, and of higher organisms. Cells and organisms are compared in terms of gene numbers, their arrangements within a cell, and the control mechanisms which regulate the activity of genes.

MacLean, N.

1988-01-01

242

Pneumocystis pneumonia Risk and Prevention  

Science.gov (United States)

... Digg Google Bookmarks Risk & Prevention Who gets pneumocystis pneumonia (PCP)? PCP is extremely rare in healthy people. ... chronic lung diseases How can I prevent pneumocystis pneumonia (PCP)? There is no vaccine to prevent PCP. ...

243

Differential susceptibility to prevention: GABAergic, dopaminergic, and multilocus effects.  

UK PubMed Central (United Kingdom)

Background:? Randomized prevention trials provide a unique opportunity to test hypotheses about the interaction of genetic predispositions with contextual processes to create variations in phenotypes over time. Methods:? Using two longitudinal, randomized prevention trials, molecular genetic and alcohol use outcome data were gathered from more than 900 youths to determine whether prevention program participation would, across 2?years, moderate genetic risk for increased alcohol use conferred by the dopaminergic and GABAergic systems. Results:? We found that (a) variance in dopaminergic (DRD2, DRD4, ANKK1) and GABAergic (GABRG1, GABRA2) genes forecast increases in alcohol use across 2?years, and (b) youths at genetic risk who were assigned to the control condition displayed greater increases in alcohol use across 2?years than did youths at genetic risk who were assigned to the prevention condition or youths without genetic risk who were assigned to either condition. Conclusions:? This study is unique in combining data from two large prevention trials to test hypotheses regarding genetic main effects and gene?×?prevention interactions. Focusing on gene systems purported to confer risk for alcohol use and abuse, the study demonstrated that participation in efficacious prevention programs can moderate genetic risk. The results also support the differential susceptibility hypothesis that some youths, for genetic reasons, are more susceptible than others to both positive and negative contextual influences.

Brody GH; Chen YF; Beach SR

2013-08-01

244

[Prevention of bipolar disorders.  

UK PubMed Central (United Kingdom)

In the past, preventive measures for psychoses have focused mainly on schizophrenic disorders. Bipolar disorders are often diagnosed and treated with a significant delay. The expansion of preventive measures for bipolar disorders aims at minimizing the substantial negative consequences associated with the disease. Some of the shared aspects of prevention in psychoses and bipolar disorders are that the first symptoms commonly appear during adolescence and early adulthood and that there is a symptomatic overlap between the disorders. To improve efforts to seek early help, public information about mental illness, low threshold services as well as cooperation between adult, child and adolescent psychiatry are needed for this target group. One differences is that psychotic symptoms play a minor role in bipolar disorders. Specific biological markers, such as disturbances of sleep and circadian rhythm and clinical characteristics, such as substance use and behavioral problems in childhood and youth supplement (subsyndromal) clinical symptoms in a multifactorial risk model. Besides severity and frequency of symptoms, specific periodic course patterns are crucial. Strategies of early intervention require a careful consideration of risks and benefits. Two aims should be distinguished: the improvement of current symptomatology and the prevention of conversion to bipolar disorder. Currently, studies evaluating risks and benefits of such interventions are first conducted. Expertise and resources for early recognition of psychoses and bipolar disorders should be pooled. Common standards are the basis for advancement and implementation of preventive strategies for bipolar disorders.

Leopold K; Pfennig A; Severus E; Bauer M

2013-10-01

245

[Prevention of osteoporosis].  

UK PubMed Central (United Kingdom)

Of all interventions for osteoporosis as an overt lifestyle-related disease, primary prevention is given first priority, where gaining beneficial lifestyle habits during younger years leads to acquisition of maximum bone mass. Clear increases in bone mass are seen before the age of 18 years, with the increases being most conspicuous from 10 to 14 years of age, the time of onset of menarche, during which, for individuals in adequate nutritional status, vertical load exercises are the most efficient of all approaches in ensuring acquisition of maximum bone mass. After the young adult mean (YAM) has been attained between 20 and 44 years, the focus in primary prevention is shifted to prevention of bone mass decreases, in which high bone mass acquired through beneficial diet and exercise habits during younger years helps to delay the onset of osteoporosis even in advanced age.

Ohta H

2012-06-01

246

Preventing employee burnout.  

UK PubMed Central (United Kingdom)

Burnout, a condition that is affecting an increasing number of employees in industry today, can transform top-performing employees into indifferent, frequently absent, ineffective workers. What can human resources managers do to help prevent burnout among employees? Authors Susan E. Jackson, assistant professor of organizational psychology in the psychology department at the University of Maryland, and Randall S. Schuler, associate professor of personnel and human resources management in the department of management at New York University, suggest three specific approaches to preventing burnout. One of these, anticipatory socialization programs, is a way of preventing "reality shock" from sending idealistic new employees with unrealistic expectations about a job into burnout. The philosophy underlying anticipatory socialization programs holds that reality shock should be experienced before the individual begins his or her first full-time job- and, further, that it should be experienced in a context that permits and encourages the development of constructive strategies for coping with the unexpected reality.

Jackson SE; Schuler RS

1983-03-01

247

Statins and cancer prevention.  

UK PubMed Central (United Kingdom)

Randomized controlled trials for preventing cardiovascular disease indicated that statins had provocative and unexpected benefits for reducing colorectal cancer and melanoma. These findings have led to the intensive study of statins in cancer prevention, including recent, large population-based studies showing statin-associated reductions in overall, colorectal and prostate cancer. Understanding the complex cellular effects (for example, on angiogenesis and inflammation) and the underlying molecular mechanisms of statins (for example, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase-dependent processes that involve geranylgeranylation of Rho proteins, and HMG-CoA-independent processes that involve lymphocyte-function-associated antigen 1) will advance the development of molecularly targeted agents for preventing cancer. This understanding might also help the development of drugs for other ageing-related diseases with interrelated molecular pathways.

Demierre MF; Higgins PD; Gruber SB; Hawk E; Lippman SM

2005-12-01

248

Synmastia: prevention and correction.  

UK PubMed Central (United Kingdom)

Synmastia is a condition of aberrant communication of the breasts. Apart from the rare congenital cases, this is usually a result of technical complications during breast augmentation surgery caused by an overdissection at the medial side of the pocket, over the sternum, in the subglandular plane; or overdivision of the major pectoralis muscle insertion along the sternum, in the submuscular plane. A multidatabase search about synmastia has been performed. Between November 2004 and April 2009, the senior author (G.S.) has performed 924 breast augmentations and his experience in preventing synmastia is discussed and compared with the literature. Accurate surgical plan, correct choice of implants' size, and correct surgical technique are the most important rules to prevent synmastia. It is difficult to correct synmastia: additional reoperations expose patient to risks, cost, and dissatisfaction. On the basis of the recent literature and personal experience, we propose some classifications and guidelines to prevent synmastia.

Selvaggi G; Giordano S; Ishak L

2010-11-01

249

Medicament for preventing encephalitis  

UK PubMed Central (United Kingdom)

The invention discloses a medicament for preventing encephalitis. A formulation for the medicament comprises the following components: 4 to 6 grams of raw lotus leaf, 40 to 60 grams of folium isatidis, 400 to 600 grams of white gourd, 130 to 170 grams of lalang rhizome, and 80 to 120 grams of dandelion. The medicament is prepared from pure Chinese medicinal herbs, is a Chinese medicament for oral administration, has good taste, has the functions of eliminating summer heat, promoting diuresis, discharging body toxin and strengthening human body resistivity, and has good effect on preventing the encephalitis.

XIANLIANG ZHOU

250

Adolescent preventive services.  

UK PubMed Central (United Kingdom)

Today, there are significant risks to the health of teenagers. Drugs (tobacco, alcohol, steroids and others), sex (pregnancy, STDs, date rape), nutrition (obesity and eating disorders), and violence (abuse, fighting) are unfortunately a part of many teens' lives. These risks increase throughout the teen years. Since each risk has a strong behavioral component, we hope to modify the behavior and minimize the risk. Prevention and health promotion are an important part of health care for teens. Primary care providers, such as family physicians, are in an excellent position to provide teen preventative care that is comprehensive and specific to the needs of each teen.

Reif CJ; Elster AB

1998-03-01

251

Preventable neurological diseases worldwide.  

UK PubMed Central (United Kingdom)

Neuropsychiatric disorders make up a large proportion of medical conditions causing disability and death worldwide. This paper reviews the most significant neurological disorders, emphasizing the preventability of most of them. The worldwide impact of cerebrovascular disease, protein-energy malnutrition causing cognitive impairment, tetanus, dementia, meningitis, and epilepsy is summarized. The burden of neurological dysfunction as a complication of tuberculosis, measles, road accidents, congenital anomalies, malaria, falls, war, violence, alcohol, HIV, diabetes, syphilis, and rheumatic heart disease might also be lessened by preventive measures. As in other health problems, major risk factors are poverty, poor access to health care, and social instability.

Bergen DC

1998-01-01

252

Prevention of skin contamination  

International Nuclear Information System (INIS)

Under consideration of the physiological and anatomical properties of human skin and the reactions which take place during contamination of the skin's surface, preventive measures can be successfully drawn up for practical application in the nuclear field. It is essential that the use of appropriate decontamination and cleansing agents does not damage or affect the cuticle or epidermis in any way. The obligatory use of a suitable body lotion prior to work begin is an additional decisive preventive measure. The author describes the appropriate substances and the corresponding measures. (orig.)

1985-01-01

253

[Prevention, why resist it?  

UK PubMed Central (United Kingdom)

Prevention, why resist it? Based on a 1988 speech the author gave to infection control professionals in Montréal, this article draws a parallel between individuals' resistance to change and their reaction to infection control programs. Gladly, many of the same well-honed techniques that help change along can be applied to infection control efforts, he says. Analyzing the implementation of an infection control program for AIDS in a health center, the author emphasizes do's and don'ts and explores appropriate and inappropriate approaches to leadership, conflict prevention and problem solving. To sell your program, he says, you must also sell yourself; you must be convincing and credible.

Laurin JC

1989-01-01

254

[Prevention, why resist it?].  

Science.gov (United States)

Prevention, why resist it? Based on a 1988 speech the author gave to infection control professionals in Montréal, this article draws a parallel between individuals' resistance to change and their reaction to infection control programs. Gladly, many of the same well-honed techniques that help change along can be applied to infection control efforts, he says. Analyzing the implementation of an infection control program for AIDS in a health center, the author emphasizes do's and don'ts and explores appropriate and inappropriate approaches to leadership, conflict prevention and problem solving. To sell your program, he says, you must also sell yourself; you must be convincing and credible. PMID:2912544

Laurin, J C

1989-01-01

255

Preventing Deep Vein Thrombosis  

Science.gov (United States)

What is deep vein thrombosis (DVT)? Deep vein thrombosis is a condition in which blood clots (or thrombi) form in deep veins in the legs or other ... to prevent PE. Who is at risk of DVT? DVT can occur in anyone, but some factors ...

256

Injury Prevention Research  

Centers for Disease Control (CDC) Podcasts

Research provides the knowledge that we need to understand what is possible, what is not, and the best way to proceed in our intervention efforts.  Created: 9/1/2009 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 9/1/2009.

2009-09-01

257

Corrosion prevention additive  

Energy Technology Data Exchange (ETDEWEB)

Corrosion is prevented in a non-aqueous cell, having iron containing components kept at cathode potentials above 2.5 volts, by the inclusion within said cell of an additive comprised of a lewis base tertiary amine particularly heterocyclic imides such as 1,3-dimethylimidazolidinone and 3,5 dimethylisoxazole wherein all the nitrogens thereof contain no acidic protons.

Kearney, S. D.; Moses, P. R.

1985-07-02

258

Prevention of relapsing backache  

Directory of Open Access Journals (Sweden)

Full Text Available Background: The condition of non-specific back pain is characterized by high prevalence, non satisfactory therapeutic options and severe socioeconomic consequences. Therefore prevention seems an attractive option to downsize the problem. However, the construction of effective preventive measures is complicated by the obscure aetiology of the condition, the multidimensionality of risk and prognostic factors (bio psychosocial model!) and the variability of its natural as well as clinical course. This led to the development of a wide variety of preventive measures: e. g. exercise programs, educational measures (including back school), ergonomic modification of the work environment, mechanical supports (e. g. back belts) as well as multidisciplinary interventions. For two reasons the workplace seems to be a suitable setting for prevention. First, because a number of strong risk factors are associated with working conditions and second, because it allows addressing a large proportion of the adult population. Against this background the assessment at hand sets out to answer the following questions: What is the amount and methodological quality of the available scientific literature on the effectiveness of back pain prevention in the workplace environment? What are effective measures for the prevention of back pain and its consequences in the workplace environment and how effective are they? Is back pain prevention in the workplace environment cost-effective? Is there a need for more research? As primary outcomes for effectiveness the assessment will focus on time lost from work and the frequency and duration of episodes with back pain. The preventive measures assessed belong to the following categories: exercise programs, educational and information measures, multidimensional interventions, back belts, lifting teams and ergonomic interventions. Methods: The assessment is based on a systematic review of the published literature according to the methodological requirements of DAHTA. Proceedings of the electronic literature searches are documented in the appendix. In addition references of review articles were searched. Methodological quality of publications (systematic reviews, HTA reports) was assessed using the checklists developed by the German Scientific Working Group for Technology Assessment in Health Care (GSWGTAHC) or with the Jadad-Score (controlled trials) respectively. Due to the large number of relevant publications the assessment is mainly based on data reported by systematic reviews and supplemented by the results of newer trials. A separate economic assessment was not performed because of the low amount of available data. An assessment of ethical, legal and social impact was omitted due to resource constraints.ResultsFor preventive interventions based on exercise programs most of the analysed trials demonstrate some effectiveness. Due to the heterogeneity of the programs it is not possible to conclude whether positive effects are associated with a special type, duration or intensity of exercise. For purely educational measures or information strategies applied in a workplace setting the available trials were not able to demonstrate effectiveness. Back school programs, which in addition to theoretical instructions offer intensive exercising may in the short term, be successful in reducing the incidence of new episodes of back pain. Some trials in high risk groups demonstrate effectiveness of multidimensional interventions on time lost from work. These programs include education and exercise as well as cognitive behavioural interventions to change pain perception. The assessment of the benefits of back belts for the prevention of back pain is based on results of high quality efficacy as well as effectiveness trials. Their results imply for the otherwise healthy working population no protective effect of back belts on time lost from work due to back pain, on the incidence of painful episodes or on days with impairment by back pain. So far there are no data from controlled trials that demonstrate t

Lühmann, Dagmar; Stoll, Susanne; Burkhardt-Hammer, Tatjana; Raspe, Heiner

2006-01-01

259

Prevention of nuclear war  

International Nuclear Information System (INIS)

Removing the threat of a nuclear war-as the General Assembly formally stated in the Final Document of its first special session devoted to disarmament, in 1978-is considered to be the task of the present day. In that Document, the General Assembly sought to establish principles, guidelines and procedures for preventing nuclear war. It declared that to that end, it was imperative to remove the threat of nuclear weapons, to halt and reverse the nuclear-arms race until the total elimination of nuclear weapons and their delivery systems had been achieved (see chapter iv), and to prevent the proliferation of nuclear weapons (see chapter VII). At the same time, it called for other measures designed to prevent the outbreak of nuclear war and to lessen the danger of the treat or use of nuclear weapons. The Assembly's clear call for action was dictated by the awareness that there was no insuperable barrier dividing peace from war and that, unless nations brought the spiralling nuclear-arms race to an end, the day might come when nuclear weapons would actually be used, with catastrophic consequences. In adopting the Final Document, the international community achieved, for the first time, a consensus on an international disarmament strategy having as its immediate goal the elimination of the danger of a nuclear war and the implementation of measures to halt and reverse the arms race. The General Assembly, at its second special session on disarmament, in 1982, reaffirmed the validity of the 1978 Final Document. This paper reports that nuclear issues and in particular the prevention of nuclear war remain, however, major concerns of all States. Undoubtedly, all nations have a vital interest in the negotiation of effective measures for her prevention of nuclear war, since nuclear weapons pose a unique threat to human survival. If nuclear war were to occur, its consequences would be global, not simple regional

1990-01-01

260

Emerging target-based paradigms to prevent and treat migraine.  

UK PubMed Central (United Kingdom)

Migraine is a primary brain disorder resulting from altered modulation of normal sensory stimuli and trigeminal nerve dysfunction. The second edition of the International Classification of Headache Disorders (ICHD-2) defines seven subtypes of migraine. Migraine treatment can be acute or preventive. New targeted therapies include 5-HT(1F) receptor agonists, calcitonin gene-related peptide (CGRP) antagonists, nitric oxide synthetase inhibitors, and ion channel antagonists. A recent development is the creation of antibodies to CGRP and its receptor for migraine prevention.

Silberstein SD

2013-01-01

 
 
 
 
261

Interventions for cardiovascular disease prevention.  

UK PubMed Central (United Kingdom)

Cardiovascular disease prevention is a continuum that encompasses the life-course. This article discusses preventive strategies focusing on policy and clinical initiatives including primordial prevention (lifestyle changes involving smoking, diet and exercise), primary prevention (risk factor control), and secondary prevention (acute and chronic disease management). Combined use of all the three strategies can have an immediate and large impact on reducing CVD morbidity and mortality.

Gupta R; Deedwania P

2011-02-01

262

Pacific Craniofacial Team and Cleft Prevention Program.  

UK PubMed Central (United Kingdom)

There is no doubt modern genetics have greatly influenced our professional and personal lives during the last decade. Uncovering genetic causes of many medical and dental pathologies is helping to narrow the diagnosis and select a treatment plan that would provide the best outcome. Importantly, having an understanding of multifactorial etiology helps direct our attention toward prevention. We now understand much better our own health problems. In some cases, we can modify our lifestyle and diet in order to prevent "environmental factors" from triggering the mutated genes inherited from our parents. Good examples are diabetes and cardiovascular diseases. If we realize we might have inherited genes for cardiovascular problems from several ancestors who had heart attacks, we already know that these genes will make us only "susceptible" for disease. Those who exercise, watch one's weight, diet, and carefully monitor one's lifestyle will very likely--though possessing "susceptibility genes"--stay healthier and, maybe, will never experience any cardiovascular problems. In principle, the same applies for craniofacial anomalies, especially for nonsyndromic cleft lip and palate. One needs to understand genetic and environmental causes of nonsyndromic orofacial clefts in order to prevent them. With all this in mind, the Pacific Craniofacial Team and Cleft Prevention Program have been established at the Department of Orthodontics, University of the Pacific Arthur A. Dugoni School of Dentistry in San Francisco. A partnership with Rotaplast International, Inc., has made it possible for the faculty, orthodontic residents, and students to participate in 27 multidisciplinary cleft medical missions in underdeveloped and developing countries by donating professional and educational services, and, last but not least, by collecting valuable data and specimens to further research. A significant number of research studies, including 15 master of science theses, have been accomplished in UOP's Craniofacial Genetics Laboratory, with contributions by faculty, undergraduate and graduate students. It has been leading to a better understanding of etiology of nonsyndromic orofacial clefts. It has been learned that genetic factors and environmental factors are ethnicity-specific and, in many places throughout the world, location-specific. Thus, a specific protocol for cleft prevention has to be worked out based on genetic and nutritional studies of each specific population group in order to be effective. This is our ultimate goal.

Tolarová MM; Poulton D; Aubert MM; Oh H; Ellerhorst T; Mosby T; Tolar M; Boyd RL

2006-10-01

263

Ficus deltoidea (Mas cotek) extract exerted anti-melanogenic activity by preventing tyrosinase activity in vitro and by suppressing tyrosinase gene expression in B16F1 melanoma cells.  

Science.gov (United States)

Ficus deltoidea (Mas cotek) water extract has been widely used for woman health in Malaysia. Our investigation focused to identify anti-melanogenic efficacy of F. deltoidea since it has been known to have strong anti-oxidant activities. Anti-melanogenic effect of F. deltoidea extract was analyzed using cultured B16F1 melanoma cells. Cytotoxicity of the extract was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and determined the highest concentration of the extract that did not affect cell viability as 0.1% (w/v). ?-MSH-induced melanin synthesis was significantly inhibited with dose-dependent manner by treatment of F. deltoidea leave extract, which was comparable to that of kojic acid. The extract directly inhibited mushroom tyrosinase activity and intracellular tyrosinase activity of B16F1 as well. The inhibition of intracellular tyrosinase activity was found to be exerted at the protein expression level when analyzed by immunoblot and tyrosinase zymography. The expression of microphthalmia-associated transcription factor (MITF) was also reduced by the F. deltoidea extract. In conclusion, F. deltoidea extract has strong anti-melanogenic activity that is exerted by direct inhibition of tyrosinase enzyme activity and by down-regulation of the expression of genes involved in the melanogenesis pathways. Collectively, data shown in this study strongly suggest that F. deltoidea extract has potential to be used as a novel depigmenting agent for cosmetics. PMID:20981431

Oh, Myoung-Jin; Hamid, Mariani Abdul; Ngadiran, Sulaiman; Seo, Young-Kwon; Sarmidi, Mohamad Roji; Park, Chang Seo

2010-10-28

264

Ficus deltoidea (Mas cotek) extract exerted anti-melanogenic activity by preventing tyrosinase activity in vitro and by suppressing tyrosinase gene expression in B16F1 melanoma cells.  

UK PubMed Central (United Kingdom)

Ficus deltoidea (Mas cotek) water extract has been widely used for woman health in Malaysia. Our investigation focused to identify anti-melanogenic efficacy of F. deltoidea since it has been known to have strong anti-oxidant activities. Anti-melanogenic effect of F. deltoidea extract was analyzed using cultured B16F1 melanoma cells. Cytotoxicity of the extract was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and determined the highest concentration of the extract that did not affect cell viability as 0.1% (w/v). ?-MSH-induced melanin synthesis was significantly inhibited with dose-dependent manner by treatment of F. deltoidea leave extract, which was comparable to that of kojic acid. The extract directly inhibited mushroom tyrosinase activity and intracellular tyrosinase activity of B16F1 as well. The inhibition of intracellular tyrosinase activity was found to be exerted at the protein expression level when analyzed by immunoblot and tyrosinase zymography. The expression of microphthalmia-associated transcription factor (MITF) was also reduced by the F. deltoidea extract. In conclusion, F. deltoidea extract has strong anti-melanogenic activity that is exerted by direct inhibition of tyrosinase enzyme activity and by down-regulation of the expression of genes involved in the melanogenesis pathways. Collectively, data shown in this study strongly suggest that F. deltoidea extract has potential to be used as a novel depigmenting agent for cosmetics.

Oh MJ; Hamid MA; Ngadiran S; Seo YK; Sarmidi MR; Park CS

2011-04-01

265

The Inhibition of Stat5 by a Peptide Aptamer Ligand Specific for the DNA Binding Domain Prevents Target Gene Transactivation and the Growth of Breast and Prostate Tumor Cells  

Directory of Open Access Journals (Sweden)

Full Text Available The signal transducer and activator of transcription Stat5 is transiently activated by growth factor and cytokine signals in normal cells, but its persistent activation has been observed in a wide range of human tumors. Aberrant Stat5 activity was initially observed in leukemias, but subsequently also found in carcinomas. We investigated the importance of Stat5 in human tumor cell lines. shRNA mediated downregulation of Stat5 revealed the dependence of prostate and breast cancer cells on the expression of this transcription factor. We extended these inhibition studies and derived a peptide aptamer (PA) ligand, which directly interacts with the DNA-binding domain of Stat5 in a yeast-two-hybrid screen. The Stat5 specific PA sequence is embedded in a thioredoxin (hTRX) scaffold protein. The resulting recombinant protein S5-DBD-PA was expressed in bacteria, purified and introduced into tumor cells by protein transduction. Alternatively, S5-DBD-PA was expressed in the tumor cells after infection with a S5-DBD-PA encoding gene transfer vector. Both strategies impaired the DNA-binding ability of Stat5, suppressed Stat5 dependent transactivation and caused its intracellular degradation. Our experiments describe a peptide based inhibitor of Stat5 protein activity which can serve as a lead for the development of a clinically useful compound for cancer treatment.

Axel Weber; Corina Borghouts; Christian Brendel; Richard Moriggl; Natalia Delis; Boris Brill; Vida Vafaizadeh; Bernd Groner

2013-01-01

266

Preventive Diplomacy and Conflict Prevention: Obstacles and Opportunities  

Directory of Open Access Journals (Sweden)

Full Text Available Preventive diplomacy, conflict prevention and other forms of preventive action intended to stop armed conflicts before they escalate to widespread violence are the subject of intense debate. And despite their elevation to a norm in the United Nations, where they have been debated in the General Assembly and addressed in prominent reports from the Secretary-General, preventive diplomacy and conflict prevention continue to face daunting obstacles. Drawing from recent high-level consultations on the topic, this piece considers some recurrent obstacles and emerging opportunities in relation to preventive action.

Steven A. Zyck; Robert Muggah

2012-01-01

267

Immunoglobulin genes  

Energy Technology Data Exchange (ETDEWEB)

This book reports on the structure, function, and expression of the genes encoding antibodies in normal and neoplastic cells. Topics covered are: B Cells; Organization and rearrangement of immunoglobin genes; Immunoglobin genes in disease; Immunoglobin gene expression; and Immunoglobin-related genes.

Honjo, T. (Kyoto Univ. (Japan)); Alt, F.W. (Columbia Univ., Dobbs Ferry, NY (USA). Hudson Labs.); Rabbitts, T.H. (Medical Research Council, Cambridge (UK))

1989-01-01

268

Gene Cloning  

Science.gov (United States)

This lesson covers the utilization of gene cloning to isolate and copy a specific gene of interest. The transformation of bacteria with plasmids containing antibiotic resistance genes to make gene libraries and the selection of bacteria colonies that contain the specific gene of interest are described.

269

[Prevention of dermatophytoses].  

UK PubMed Central (United Kingdom)

Preventive measures against tinea pedis were discussed based on our mycological studies using foot-press method and house dust cultures. 1) Untreated patients with tinea pedis frequently disseminate pathogenic fungi into the environment, but dissemination could be easily controlled by simple application of antifungal agents. 2) A high proportion of dermatophytes disseminated in house dust perished naturally within a month under dry conditions, while under moist conditions they survived several months or more. Therefore, humid areas such as the floor and carpet of a bathroom should be cleaned or washed regularly. 3) Adhesion of dermatophytes onto healthy feet usually happens in public spaces where people enter without shoes. Wearing socks cannot prevent dermatophyte adhesion. Cleaning the feet by wiping with a towel or washing with soap seemed to be an effective prophylactic measure after stepping into such spaces.

Maruyama R; Fukuyama K; Katoh T; Sugimoto R; Taniguchi H; Watanabe K; Nishioka K

2003-01-01

270

Prevention of recurrent nephrolithiasis.  

Science.gov (United States)

The first episode of nephrolithiasis provides an opportunity to advise patients about measures for preventing future stones. Low fluid intake and excessive intake of protein, salt and oxalate are important modifiable risk factors for kidney stones. Calcium restriction is not useful and may potentiate osteoporosis. Diseases such as hyperparathyroidism, sarcoidosis and renal tubular acidosis should be considered in patients with nephrolithiasis. A 24-hour urine collection with measurement of the important analytes is usually reserved for use in patients with recurrent stone formation. In these patients, the major urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Effective preventive and treatment measures include thiazide therapy to lower the urinary calcium level, citrate supplementation to increase the urinary citrate level and, sometimes, allopurinol therapy to lower uric acid excretion. Uric acid stones are most often treated with citrate supplementation. Data now support the cost-effectiveness of evaluation and treatment of patients with recurrent stones. PMID:10593318

Goldfarb, D S; Coe, F L

1999-11-15

271

Blowout preventer testing apparatus  

Energy Technology Data Exchange (ETDEWEB)

This patent describes a wellhead structure for pressure testing a blowout preventer secured to the upper portion of a wellhead housing which has an internal landing seat and an internal load supporting groove above the landing seat. It comprises a hanger having an external landing shoulder landed within the housing on the internal housing landing seat; seal means for sealing between the exterior of the hanger rim and the interior of the housing; a closure member having a tubular body; means for closing the flow through the interior of the tubular closure member body; a downwardly facing exterior load shoulder on the closure member body; a split support ring surrounding the closure member body; and a sleeve surrounding the closure member body. The movement of the sleeve within the split support ring being responsive to testing pressure between the blowout preventer and the closure member.

Garbett, K.

1989-09-05

272

The prevention of thalassemia.  

UK PubMed Central (United Kingdom)

The thalassemias are among the most common inherited diseases worldwide, affecting individuals originating from the Mediterranean area, Middle East, Transcaucasia, Central Asia, Indian subcontinent, and Southeast Asia. As the diseases require long-term care, prevention of the homozygous state constitutes a major armament in the management. This article discusses the major prevention programs that are set up in many countries in Europe, Asia, and Australia, often drawing from the experience in Sardinia. These comprehensive programs involve carrier detections, molecular diagnostics, genetic counseling, and prenatal diagnosis. Variability of clinical severity can be attributable to interactions with ?-thalassemia and mutations that increase fetal productions. Special methods that are currently quite expensive and not widely applicable are preimplantation and preconception diagnosis. The recent successful studies of fetal DNA in maternal plasma may allow future prenatal diagnosis that is noninvasive for the fetus.

Cao A; Kan YW

2013-02-01

273

Osteoradionecrosis: Causes and prevention  

International Nuclear Information System (INIS)

[en] Osteoradionecrosis (ORN) is one of the most serious complications arising from head and neck radiation therapy. Current research has shown that ORN represents nonhealing, dead bone and is not a state of infection. ORN is the result of functional and structural bony changes that may not be expressed for months or years. ORN may occur spontaneously or in response to wounding. Predisposing factors include absorbed radiation dose, fractionation, delivery modality, and dental status. Timing of dental extractions and other factors have also been shown to affect incidence. ORN may be reduced through early intraoral evaluation, treatment, and adequate healing time prior to beginning RT. Hyperbaric oxygen (HBO) therapy has been beneficial in the prevention and treatment of ORN. It is of paramount importance for the medical community to recognize the factors that may reduce ORN incidence, endorse oral care protocols, and acknowledge the value of HBO therapy in the prevention and treatment of this disease. 60 references

1990-01-01

274

Osteoradionecrosis: Causes and prevention  

Energy Technology Data Exchange (ETDEWEB)

Osteoradionecrosis (ORN) is one of the most serious complications arising from head and neck radiation therapy. Current research has shown that ORN represents nonhealing, dead bone and is not a state of infection. ORN is the result of functional and structural bony changes that may not be expressed for months or years. ORN may occur spontaneously or in response to wounding. Predisposing factors include absorbed radiation dose, fractionation, delivery modality, and dental status. Timing of dental extractions and other factors have also been shown to affect incidence. ORN may be reduced through early intraoral evaluation, treatment, and adequate healing time prior to beginning RT. Hyperbaric oxygen (HBO) therapy has been beneficial in the prevention and treatment of ORN. It is of paramount importance for the medical community to recognize the factors that may reduce ORN incidence, endorse oral care protocols, and acknowledge the value of HBO therapy in the prevention and treatment of this disease. 60 references.

Friedman, R.B. (Medical College of Virginia Hospitals, Richmond (USA))

1990-01-01

275

Measuring pollution prevention progress  

Energy Technology Data Exchange (ETDEWEB)

Corporations and organizations of all types are increasingly concerned about their environmental performance. Corporate management is pressured to prove the success of their environmental programs. The federal government, under the Pollution Prevention Act of 1990, is required to establish standard methods for measuring source reduction. The public is demanding more information on what organizations are doing to reduce the quantities and toxicities of harmful releases in their communities, and environmental groups in particular have an interest in tracking environmental performance. This chapter discusses the importance of measuring pollution prevention and describes various measurement techniques available. The intent is not to identify the best or worst of available techniques, but to provide an overview which may serve to broaden and promote an improved understanding of ways to measure progress.

Warren, J. [Research Triangle Inst., Research Triangle Park, NC (United States); Craig, J. [Environmental Protection Agency, Washington, DC (United States)

1995-09-01

276

Expression of the psbA gene during photoinhibition and recovery in Synechocystis PCC 6714: inhibition and damage of transcriptional and translational machinery prevent the restoration of photosystem II activity.  

Science.gov (United States)

The D1 reaction center protein of the photosystem II complex is very sensitive to light. It is continuously being damaged, degraded and resynthesized. Under high light, photosystem II inactivation is observed. This is because the rate of D1 damage is faster than that of its replacement. This process can be reversed if exposure to high light is not too long. In this work we study the changes that occur in the transcriptional and translational machinery that could lead to irreversible photoinhibition in Synechocystis PCC 6714. In the first minutes of photoinhibition, high light induced an accumulation of psbA mRNA due to an increase in psbA transcription initiation. Although the transcription rate of other photosynthetic genes (e.g. psaE and cpcB-cpcA) declined, the high turnover of the psbA transcript was maintained for a long time. When the light stress was too long, the stability of psbA mRNA increased and the psbA transcription rate appeared to decrease. A high level of psbA mRNA was maintained even though translation no longer occurred and the cells were unable to recover. Experiments to measure newly synthesized D1 incorporation into the thylakoid membranes during recovery in the presence of rifampicin showed that the initiation of transcription was not required for translation of psbA mRNA when photoinhibition was still reversible. Since psbA translation did not depend on the level of psbA transcript or on the initiation of psbA transcription, we propose that damage to the translational machinery also occurred during light stress, leading to the inhibition of D1 synthesis and to irreversible photoinhibition. PMID:9177308

Constant, S; Perewoska, I; Alfonso, M; Kirilovsky, D

1997-05-01

277

Expression of the psbA gene during photoinhibition and recovery in Synechocystis PCC 6714: inhibition and damage of transcriptional and translational machinery prevent the restoration of photosystem II activity.  

UK PubMed Central (United Kingdom)

The D1 reaction center protein of the photosystem II complex is very sensitive to light. It is continuously being damaged, degraded and resynthesized. Under high light, photosystem II inactivation is observed. This is because the rate of D1 damage is faster than that of its replacement. This process can be reversed if exposure to high light is not too long. In this work we study the changes that occur in the transcriptional and translational machinery that could lead to irreversible photoinhibition in Synechocystis PCC 6714. In the first minutes of photoinhibition, high light induced an accumulation of psbA mRNA due to an increase in psbA transcription initiation. Although the transcription rate of other photosynthetic genes (e.g. psaE and cpcB-cpcA) declined, the high turnover of the psbA transcript was maintained for a long time. When the light stress was too long, the stability of psbA mRNA increased and the psbA transcription rate appeared to decrease. A high level of psbA mRNA was maintained even though translation no longer occurred and the cells were unable to recover. Experiments to measure newly synthesized D1 incorporation into the thylakoid membranes during recovery in the presence of rifampicin showed that the initiation of transcription was not required for translation of psbA mRNA when photoinhibition was still reversible. Since psbA translation did not depend on the level of psbA transcript or on the initiation of psbA transcription, we propose that damage to the translational machinery also occurred during light stress, leading to the inhibition of D1 synthesis and to irreversible photoinhibition.

Constant S; Perewoska I; Alfonso M; Kirilovsky D

1997-05-01

278

Gene therapy for hemophilia.  

UK PubMed Central (United Kingdom)

Hemophilia A and B are X-linked monogenic disorders resulting from deficiencies of factor VIII and FIX, respectively. Purified clotting factor concentrates are currently intravenously administered to treat hemophilia, but this treatment is non-curative. Therefore, gene-based therapies for hemophilia have been developed to achieve sustained high levels of clotting factor expression to correct the clinical phenotype. Over the past two decades, different types of viral and non-viral gene delivery systems have been explored for hemophilia gene therapy research with a variety of target cells, particularly hepatocytes, hematopoietic stem cells, skeletal muscle cells, and endothelial cells. Lentiviral and adeno-associated virus (AAV)-based vectors are among the most promising vectors for hemophilia gene therapy. In preclinical hemophilia A and B animal models, the bleeding phenotype was corrected with these vectors. Some of these promising preclinical results prompted clinical translation to patients suffering from a severe hemophilic phenotype. These patients receiving gene therapy with AAV vectors showed long-term expression of therapeutic FIX levels, which is a major step forwards in this field. Nevertheless, the levels were insufficient to prevent trauma or injury-induced bleeding episodes. Another challenge that remains is the possible immune destruction of gene-modified cells by effector T cells, which are directed against the AAV vector antigens. It is therefore important to continuously improve the current gene therapy approaches to ultimately establish a real cure for hemophilia.

Chuah MK; Evens H; VandenDriessche T

2013-06-01

279

Gene Switch  

Science.gov (United States)

Regulatory "switches" are found upstream from a gene. Regulatory molecules bind to the switches and recruit RNA polymerase to bind to the gene's promoter region, increasing the transcription of the gene into messenger RNA.

Howard Hughes Medical Institute (Howard Hughes Medical Institute;)

2008-04-09

280

Gene therapy and its implications in Periodontics  

Directory of Open Access Journals (Sweden)

Full Text Available Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense mechanism against infection by transfecting host cells with an antimicrobial peptide protein-encoding gene. -Periodontal vaccination. Gene therapy is one of the recent entrants and its applications in the field of periodontics are reviewed in general here.

Mahale Swapna; Dani Nitin; Ansari Shumaila; Kale Triveni

2009-01-01

 
 
 
 
281

Diet for Kidney Stone Prevention  

Science.gov (United States)

... Titles : Diet for Kidney Stone Prevention Diet for Kidney Stone Prevention On this page: How does diet affect ... How does diet affect the risk of developing kidney stones? Kidney stones can form when substances in the ...

282

Childproofing and Preventing Household Accidents  

Science.gov (United States)

... Media Pregnant? Your Baby's Growth Childproofing and Preventing Household Accidents KidsHealth > Parents > First Aid & Safety > Home Sweet ... detectors and carbon monoxide detectors. Check out these Household Safety articles for more information: Preventing Injuries From ...

283

Back Pain - How to Prevent  

Medline Plus

Full Text Available How to Prevent Back Pain Introduction Back pain is one of the most common medical problems that people have. ... of back pain, and measures you can take to prevent back pain. Anatomy The back has two ...

284

Periodontal Disease: Causes and Prevention  

Science.gov (United States)

Periodontal Disease: Causes and Prevention What Is Periodontal Disease? What Causes Periodontal Disease? Risks and Prevention What Is Periodontal Disease? If your hands bled when you washed them, you would be ...

285

Preventing cervical cancer globally.  

UK PubMed Central (United Kingdom)

Cervical cancer is one of the leading causes of cancer and cancer-related deaths among women worldwide. More than 85% of cases and deaths occur in the developing world where the availability of effective screening is limited. In this issue of the journal, Pierce and colleagues (beginning on page 1273) describe a novel technique using a high-resolution microendoscope (HRME) to diagnose cervical dysplasia. This perspective reviews the limitations of existing cervical cancer screening methods currently in use in low-resource settings and the potential for HRME imaging to contribute to cervical cancer prevention in the developing world.

Schmeler KM

2012-11-01

286

Accident prevention programme  

International Nuclear Information System (INIS)

This study by the Steel Industry Safety and Health Commission was made within the context of the application by undertakings of the principles of accident and disease prevention previously adopted by the said Commission. It puts forward recommendations for the effective and gradual implementation of a programme of action on occupational health and safety in the various departments of an undertaking and in the undertaking as a whole. The methods proposed in this study are likely to be of interest to all undertakings in the metallurgical industry and other industrial sectors

1978-01-01

287

[Medication errors: prevention strategies  

UK PubMed Central (United Kingdom)

Medication errors are an important aspect of health care. The American Institute of Medicine informs that 44,000 to 98,000 Americans die annually as a result of medication errors and that such errors affect 2 to 14% of hospitalized patients. The American Society of Hospital Pharmacists presents strategies that, if implemented, can prevent or reduce medication errors. This review discusses four strategies: electronic prescription, the pharmacist's role, the report of errors and the patient's role. A non-punitive culture that prioritizes patient's safety should be stimulated in institutions.

Cassiani SH

2000-07-01

288

[Medication errors: prevention strategies].  

Science.gov (United States)

Medication errors are an important aspect of health care. The American Institute of Medicine informs that 44,000 to 98,000 Americans die annually as a result of medication errors and that such errors affect 2 to 14% of hospitalized patients. The American Society of Hospital Pharmacists presents strategies that, if implemented, can prevent or reduce medication errors. This review discusses four strategies: electronic prescription, the pharmacist's role, the report of errors and the patient's role. A non-punitive culture that prioritizes patient's safety should be stimulated in institutions. PMID:12138424

Cassiani, S H

289

[Prevention of perioperative hypothermia].  

UK PubMed Central (United Kingdom)

Inadvertent perioperative hypothermia impairs postoperative outcome in surgical patients due to ischemic myocardial events, wound infections and coagulation disorders. Body core temperature should be assessed 1-2h preoperatively and continuously during surgery. To prevent hypothermia patients and nursing clinical staff should be teached and trained. Preoperatively surgical patients should always be prewarmed by using convective warming devices and active warming should be continued in surgeries longer than 1 hour. Warming of IV fluids is effective if infusion rates are above 1l/h. Core temperature should be measured in the recovery room and active warming should be started when patients are hypothermic or if they feel cold.

Horn EP; Torossian A

2010-03-01

290

FOODS FOR PREVENTING VOMITING  

UK PubMed Central (United Kingdom)

The present invention relates to an antiemetic food product comprising a solution containing one or more thickeners selected from low-methoxyl pectin, sodium alginate, alginic acid, kappa carrageenan, iota carrageenan, lambda carrageenan and gellan gum, to an antiemetic food product comprising, as one set, a solution containing any of these thickeners, and typically a calcium solution, and to a method for preventing a patient from suffering from emesis associated with the ingestion of liquid food, comprising feeding the antiemetic food product to the patient.

YAMAGATA Norimitsu 1301 Seiseki-sakuragaoka G-H; TANAKA Hiroshi; HAMACHIYO Yoshinori; ITO Hiroko; KANEDA Kazuhiko

291

Insect bite prevention.  

Science.gov (United States)

Protection from the bites of arthropod (insect and acarine) vectors of disease is the first line of defense against disease transmission and should be advised in all cases when traveling abroad. Details are described of the main approaches for the prevention of bites, including topical or skin repellents, impregnated clothing, bed nets, and spatial or aerial repellents and aerosols. The bionomics of the main arthropod vectors of disease are described along with photographic plates and tabulated advice to give the traveler. An in-depth treatment of the different protection methodologies provides an up-to-date overview of the technologies involved. PMID:22963776

Moore, Sarah J; Mordue Luntz, Anne Jennifer; Logan, James G

2012-09-01

292

Selenium for preventing cancer  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVE: Two research questions were addressed in this review: What is the evidence for: 1. an aetiological relationship between selenium exposure and cancer risk in women and men?; 2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched ele (more) ctronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio, OR, 0.69; 95% confidence interval, CI, 0.53 to 0.91) and mortality (OR 0.55, 95% CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics. The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification. The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.

Dennert, Gabriele; Zwahlen, Marcel; Brinkman, Maree; Vinceti, Marco; Zeegers, Maurice P. A.; Horneber, Markus

2012-01-01

293

Prevention of foodborne listeriosis  

Directory of Open Access Journals (Sweden)

Full Text Available Listeria monocytogenes is a foodborne pathogen that can cause serious invasive illness, mainly in certain well-defined high-risk groups, including elderly and immunocompromised patients, pregnant women, newborns and infants. L. monocytogenes primarily causes abortion, septicemia or meningitis. Contaminated meats (such as hot dogs, delicatessen meats and pat?), dairy products and seafood have all been implicated in outbreaks of listeriosis. The public health importance of listeriosis is not always recognized, particularly because listeriosis is a relatively rare disease compared with other common foodborne illnesses such as salmonellosis or botulism. However, because of its high case fatality rate, listeriosis ranks among the most frequent causes of death due to foodborne illness, ranking second after salmonellosis. L. monocytogenes emerged as an important foodborne pathogen in the latter part of the 20th century. Extensive work has been performed in many countries during the last decade to prevent outbreaks and decrease the incidence of listeriosis. An important reduction occurred in listeriosis incidence in some of these countries during the 90s, suggesting a relationship between preventive measures and incidence decrease of human listeriosis.

Rebagliati Victoria; Philippi Romina; Rossi Maria; Troncoso Alcides

2009-01-01

294

Cage flood prevention system  

UK PubMed Central (United Kingdom)

A flood prevention system for a ventilated cage includes a self-sealing drain valve that opens automatically to prevent the cage from flooding if a water supply valve or water bottle leaks. A preferred drain valve is mounted in the floor of the cage and includes a perforated drain cup, a perforated seal cup, and a drain seal, all held together by a connector such as a rivet. The perforated drain cup extends above the bottom surface of the cage a small amount, and the perforated seal cup extends downwardly from the drain cup to present a valve seat. The drain seal preferably comprises a diaphragm of a resiliently flexible material which normally abuts the valve seat. However, if the water supply valve or water bottle leaks sufficiently for water to accumulate in the perforated drain cup, the weight of the accumulated liquid forces the drain seal away from the valve seat to permit the water to drain away from the cage. The drain seal thereafter returns to its original position to preserve atmospheric integrity within the cage. A protective structure, such as a partition or tray, may also be provided in the cage to provide a dry area serving as a safe habitat for animals housed within the cage if bedding in the remainder of the cage becomes saturated.

EDSTROM SR WILLIAM E

295

Obesity prevention in children.  

UK PubMed Central (United Kingdom)

The prevalence of childhood overweight and obesity continues to be unacceptably high and of public health concern in Europe. During childhood and adolescence, environmental factors are the main drivers of obesity development. Obesity is caused by a chronic energy imbalance involving both dietary intake and physical activity patterns. Several risk factors are influencing obesity development, even starting in the prenatal period. From birth, along life, mainly diet and physical activity/inactivity are the most important drivers on top of genetic susceptibility. The first years of life can therefore be crucial to start preventive interventions that can have an impact on lifestyle and on later overweight and obesity. Schools are an attractive and popular setting for implementing interventions for children. Interventions including a community component are considered to be the most effective. Obesity control will require policy interventions to improve the environments that promote poor dietary intake and physical inactivity rather than individually focused interventions. More solid institutional and health policies are needed together with more effective interventions to obtain evident changes for the prevention of excess adiposity among children.

Moreno LA; Bel-Serrat S; Santaliestra-Pasías AM; Rodríguez G

2013-01-01

296

Antibody gene transfer for HIV immunoprophylaxis.  

UK PubMed Central (United Kingdom)

Antibody gene transfer, which involves the delivery of genes that encode potent, broadly neutralizing antibodies to human immunodeficiency virus (HIV), is a promising new strategy for preventing HIV infection. A satellite symposium at the AIDS Vaccine 2012 conference brought together many of the groups working in this field.

Balazs AB; West AP Jr

2013-01-01

297

Prevention of bacterial adhesion  

DEFF Research Database (Denmark)

Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation. As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become valuable weapons for preventing pathogen contamination and fighting infectious diseases in the future.

Klemm, Per; Vejborg, Rebecca Munk

2010-01-01

298

Preventive maintenance optimization  

Energy Technology Data Exchange (ETDEWEB)

Experiences gained with Reliability Centered Maintenance (RCM) by Ontario Hydro Service Company`s Transmission Division are discussed. An RCM pilot study was completed in 1997 after an exhaustive review of available Predictive Based Maintenance (PBM) techniques indicated that given the rapid evolution of new technology and relatively high installation costs, the PBM technology may not be economically justifiable for wide scale application, although it may be cost effective in a situation where equipment failure may have high consequences. Implementation of the RCM system commenced in 1998. Since then a Preventive Maintenance Optimization (PMO) process has been developed based on RCM principles. This paper provides an overview of the general principles underlying the PMO/RCM process, describes efforts to optimize the process by a computerized maintenance management system and provides a summary of key observations made during the PMO/RCM implementation during 1998 and operation to date. 3 figs.

Yung, C. [Ontario Hydro, Toronto, ON (Canada)

1999-09-01

299

Protective and preventative measures  

Directory of Open Access Journals (Sweden)

Full Text Available Health care workers who come in contact with blood and other body fluids in their working environment risk being exposed to bloodborne diseases such as human immunodefiency virus (HIV), hepatitis B and C. An anti-hepatitis B vaccine is available as well as hepatitis B immunoglobulin but no vaccine is available against hepatitis C and HIV. The best way to protect against exposure to blood and body fluids is to use "Universal Precautions" which encourage safe working methods. If an exposure does take place it should be regarded as an urgent medical problem and every facility should have a management policy to deal with this problem. The source patient's rights must also be protected. The preventative and protective measures available to health care workers as well as practical suggestions to carry out in the event of an exposure are discussed.

Freedman, P.N.

2002-01-01

300

[Cancer prevention and screening].  

UK PubMed Central (United Kingdom)

We show that cancer mortality is decreasing with time for most sites of cancer, the most notable exception being lung cancer in women. Cancer incidence is a misleading indicator because it can depend on diagnostic procedures, as observed with prostate cancer in men and breast or thyroid cancer in women. Overall these data contradict the alarming information that cancer is on the increase, which is widespread by the media and some health professionals. To be efficient in the prevention of cancer one needs to identify its causes and measure their relative importance. The major causes of cancer in France today are tobacco and alcohol. The variations of the price of tobacco and their effects on sales show the importance of the taxation policy. Cancer screening is practised in a way defying logic : a screening procedure with a demonstrated high efficacy is not part of a national programme whereas a useless and even potentially harmful procedure is very widely used.

Hill C

2013-06-01

 
 
 
 
301

Prevention of criticality accidents  

International Nuclear Information System (INIS)

[en] These notes used in the postgraduate course on Radiological Protection and Nuclear Safety discuss macro-and microscopic nuclear constants for fissile materials systems. Critical systems: their definition; criteria to analyze the critical state; determination of the critical size; analysis of practical problems about prevention of criticality. Safety of isolated units and of sets of units. Application of standards. Conception of facilities from the criticality control view point. (author)[es] Este apunte para el curso de postgrado de Proteccion Radiologica y Seguridad Nuclear abarca la consideracion de constantes nucleares macro y microscopicas de sistemas de materiales fisiles. Sistemas criticos; definicion de los mismos, criterio para el analisis de estados criticos; determinacion del tamano critico. Analisis de problemas practicos de prevencion de criticidad. Seguridad de unidades aisladas y de conjuntos de unidades. Aplicacion de normas. Concepcion de instalaciones desde el punto de vista del control de la criticidad. (autor)

1982-01-01

302

A preventive maintenance lubricant  

Energy Technology Data Exchange (ETDEWEB)

A method is disclosed to lower the adherence of materials by reducing the viscosity of a preventive maintenance lubricant against adhesion of moist, freeflowing materials, containing extract of selective cleaning of oil fractions and asphalt. Gas oil of catalytic cracking is added having a boiling point of 190-300 degrees, with the following ratio of components (%): selective cleaning extract, 43-50; asphalt, 14-16; and gas oil of catalytic cracking, the remainder, Treating a surface with the proposed lubricant lowers the specific resistance to shift of rock compared with the prototype (g/cm/sup 2/): sand (moisture content, 18%) from 3.82 to 1.55; and clay (moisture content 16%), from 5.41 to 3.51.

Chapaykina, S.A.; Ol' kov, P.L.; Pertsev, A.N.; Rodzevillo, I.T.; Rogacheva, O.I.; Zinov' yev, A.P.

1980-02-15

303

[Prevention of bacterial endocarditis  

UK PubMed Central (United Kingdom)

Prevention of bacterial endocarditis is aimed at limiting the frequency, size, and duration of transient bacteremia with subsequent bacterial implantation on valvular endothelium in patients with cardiopathy. Any procedure involving mucosa rich in normal flora or an infectious site can result in bacteremia, which can be minimized by selecting diagnostic and therapeutic procedures which are least traumatic. In addition, proper antibiotic prophylaxis should be administered according to the most frequently encountered bacteria: Streptococcus viridans during dental manipulations, enterococci during urogenital or intestinal procedures, and staphylococcal species from skin lacerations or cardiac surgery. The different antibiotic prophylactic regimens suggested at the present time vary according to the patient and the particular circumstances surrounding his illness. These regimens should be modified according to future epidemiologic findings in bacterial endocarditis.

Bouvet A; Acar JF

1985-01-01

304

Prevention of skateboard injuries.  

UK PubMed Central (United Kingdom)

Skateboarding has become extremely popular in the United Kingdom, and it is estimated that over two million skateboards have been sold. Previous surveys have shown the dangers of the sport, fractures of the limbs being a particularly common form of injury. Consequently the provision of skateboard parks and the wearing of adequate protective clothing were considered necessary to reduce to severity of the injuries sustained. Our survey does not support this view, and suggests that fractures are more likely to occur in people with full protective clothing and skating in a park. The reasons for this are discussed. It is also suggested that expert instruction in the use of the skateboard has been neglected as a means of accident prevention.

Morgan WJ; Galloway DJ; Patel AR

1980-01-01

305

Prevention of skateboard injuries.  

Science.gov (United States)

Skateboarding has become extremely popular in the United Kingdom, and it is estimated that over two million skateboards have been sold. Previous surveys have shown the dangers of the sport, fractures of the limbs being a particularly common form of injury. Consequently the provision of skateboard parks and the wearing of adequate protective clothing were considered necessary to reduce to severity of the injuries sustained. Our survey does not support this view, and suggests that fractures are more likely to occur in people with full protective clothing and skating in a park. The reasons for this are discussed. It is also suggested that expert instruction in the use of the skateboard has been neglected as a means of accident prevention. PMID:7209497

Morgan, W J; Galloway, D J; Patel, A R

1980-01-01

306

Scientific Methods for Prevention Intervention Research.  

Science.gov (United States)

Contents: Introduction: Scientific Methods for Prevention Intervention Research; Prevention Intervention Research: Focus and Perspective; Testing Theory through Developmental Epidemiologically Based Prevention Research; Hypothesis Formulation and Testing ...

A. Cazares L. A. Beatty

1994-01-01

307

PREVENTION OF HEPATITIS B  

Directory of Open Access Journals (Sweden)

Full Text Available Objective: To assess the knowledge and practice of first year MBBS students, for the prevention ofHepatitis B. Design: Descriptive study. Place and Duration of study: The study was conducted at Lahore Medical &Dental College, Lahore. The data was collected in two weeks in December, 2006. Methodology: A total of 50 studentswere recruited using a non probability random sampling technique, through the lottery method. A pre-tested structuredquestionnaire was administered to collect information about the knowledge and practice of students about theprevention of hepatitis B. Data was presented in the form of simple tables and graphs. Results: Out of 50 students,majority (96%) responded that it was a disease of liver. Regarding knowledge about the communicability of HepatitisB, 78% said it was communicable, 19% assumed that it was water borne. Other responses included spread via bloodtransfusion (28%), through use of injection (21%), close physical contact (8%) and un-hygienic conditions (18%). Forprevention of Hepatitis B, the more common responses were, provision of clean water (24%), improvement in hygiene(27%), restriction to single sex partner (6%), avoidance of sharing syringes and needles (19%), screening blood beforetransfusion (9%) and vaccination (15%). The high risk group was identified as the poor people living in unhygienicconditions (34%), surgeons (32%), barbers (12%), Intravenous drug users (8%), recipient of blood transfusion (6%)and uneducated people (6%). Only 1 respondent (2%) said that sex workers could be at risk of getting this disease.When inquired about their vaccination status, 66% of students admitted to have been vaccinated against Hepatitis B,while 34% of have not been vaccinated. Conclusion: The present study concludes that there is lack of awarenessamong the medical students entering into the profession about the hazards of Hepatitis B, its routes of spread and itsmodes of prevention. Similarly, all the students were not vaccinated against Hepatitis B, which made them veryvulnerable to this disease.

SEEMA DAUD

2007-01-01

308

Antiseptics for preventing omphalitis.  

UK PubMed Central (United Kingdom)

BACKGROUND: Omphalitis may cause serious complications and contribute to neonatal morbidity and mortality. From January 1997 to August 1998, the incidence of omphalitis in the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital had been increased from 0.9 to 17.4 per 1,000 live births. A prospective randomized trial using antiseptic applied directly to the umbilical stump was conducted aiming to reduce an epidemic outbreak of omphalitis in the newborn nursery. OBJECTIVE: To determine which antiseptic is appropriate for preventing omphalitis in the newborn infants. PATIENTS AND METHOD: Newborn infants delivered in the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital were randomized into group A (Triple dye) or group B (70% Alcohol). The infant with omphalitis was assessed by a pediatrician or a neonatology fellow. At home, the same antiseptic will be continually applied to the umbilical stump daily until a few days after cord detachment. Relative risk was calculated and statistical significance was tested by Chi-square test. RESULTS: Four hundred and twenty-seven infants were enrolled. Birth weight, gestational age and gender of the infants in both groups were not different. There were no known maternal risk factors for omphalitis. Omphalitis was observed in 9/213 (4.2%) infants in group A and 23/214 (10.7%) infants in group B. The relative incidence rate between each group was statistically significant (p<0.01). Triple dye group was 60 per cent less likely to develop omphalitis compared to 70 per cent Alcohol group (RR 0.39, 95% CI: 0.19-0.83). The mean duration for cord detachment were 13.6 and 11.5 days in group A and group B, respectively. CONCLUSION: During an epidemic outbreak of omphalitis, Triple dye was the most appropriate and effective antiseptic to prevent omphalitis but could delay cord separation.

Panyavudhikrai S; Danchaivijitr S; Vantanasiri C; Trakulsomboon S; Kolatat T; Dhiraputra C; Poomsuwan V; Srihapol N

2002-02-01

309

A Primary Preventive Medicine Implemantation: Prevention of Intraoperative Kidney Damage  

Directory of Open Access Journals (Sweden)

Full Text Available Post surgical acute renal failure (ARF) is a serious complication with high morbidity and mortality. The prevention of the development of ARF must be preferable approach rather than dealing with the complications for the patients undergoing surgery. Identifying and optimizing the patients in the risk group, making out an appropriate anesthetic plan, implementing specific monitoring and appropriate methods for following up the renal function and implementing effective methods when distortion comes out in renal function are basic principles for a successful prevention. In this article, the causes, risk factors, the incidence and preventive medicine implementations prevention of ARF. [TAF Prev Med Bull 2011; 10(6.000): 723-732

Gokhan Inangil; Murat Kuyumcu; Huseyin Sen; Sezai Ozkan; Guner Dagli

2011-01-01

310

Gene positioning.  

UK PubMed Central (United Kingdom)

Eukaryotic gene expression is an intricate multistep process, regulated within the cell nucleus through the activation or repression of RNA synthesis, processing, cytoplasmic export, and translation into protein. The major regulators of gene expression are chromatin remodeling and transcription machineries that are locally recruited to genes. However, enzymatic activities that act on genes are not ubiquitously distributed throughout the nucleoplasm, but limited to specific and spatially defined foci that promote preferred higher-order chromatin arrangements. The positioning of genes within the nuclear landscape relative to specific functional landmarks plays an important role in gene regulation and disease.

Ferrai C; de Castro IJ; Lavitas L; Chotalia M; Pombo A

2010-06-01

311

Paraoxonase gene mutations in amyotrophic lateral sclerosis.  

UK PubMed Central (United Kingdom)

Three clustered, homologous paraoxonase genes (PON1, PON2, and PON3) have roles in preventing lipid oxidation and detoxifying organophosphates. Recent reports describe a genetic association between the PON genes and sporadic amyotrophic lateral sclerosis (ALS). We now report that in genomic DNA from individuals with familial and sporadic ALS, we have identified at least 7 PON gene mutations that are predicted to alter PON function.

Ticozzi N; LeClerc AL; Keagle PJ; Glass JD; Wills AM; van Blitterswijk M; Bosco DA; Rodriguez-Leyva I; Gellera C; Ratti A; Taroni F; McKenna-Yasek D; Sapp PC; Silani V; Furlong CE; Brown RH Jr; Landers JE

2010-07-01

312

Paraoxonase gene mutations in amyotrophic lateral sclerosis.  

Science.gov (United States)

Three clustered, homologous paraoxonase genes (PON1, PON2, and PON3) have roles in preventing lipid oxidation and detoxifying organophosphates. Recent reports describe a genetic association between the PON genes and sporadic amyotrophic lateral sclerosis (ALS). We now report that in genomic DNA from individuals with familial and sporadic ALS, we have identified at least 7 PON gene mutations that are predicted to alter PON function. PMID:20582942

Ticozzi, Nicola; LeClerc, Ashley Lyn; Keagle, Pamela J; Glass, Jonathan D; Wills, Anne-Marie; van Blitterswijk, Marka; Bosco, Daryl A; Rodriguez-Leyva, Ildefonso; Gellera, Cinzia; Ratti, Antonia; Taroni, Franco; McKenna-Yasek, Diane; Sapp, Peter C; Silani, Vincenzo; Furlong, Clement E; Brown, Robert H; Landers, John E

2010-07-01

313

Challenges in pressure ulcer prevention.  

UK PubMed Central (United Kingdom)

Although this article is a stand-alone article, it sets the scene for later articles in this issue. Pressure ulcers are considered to be a largely preventable problem, and yet despite extensive training and the expenditure of a large amount of resources, they persist. This article reviews the current understanding of pressure ulcer aetiology: pressure, shear and microclimate. Individual risk factors for pressure ulceration also need to be understood in order to determine the level of risk of an individual. Such an assessment is essential to determine appropriate prevention strategies. The main prevention strategies in terms of reducing pressure and shear and managing microclimate are studied in this article. The problem of pressure ulceration related to medical devices is also considered as most of the standard prevention strategies are not effective in preventing this type of damage. Finally, the possibility of using dressings as an additional preventive strategy is raised along with the question: is there enough evidence to support their use?

Dealey C; Brindle CT; Black J; Alves P; Santamaria N; Call E; Clark M

2013-06-01

314

Imaging after vascular gene therapy  

Energy Technology Data Exchange (ETDEWEB)

Targets for cardiovascular gene therapy currently include limiting restenosis after balloon angioplasty and stent placement, inhibiting vein bypass graft intimal hyperplasia/stenosis, therapeutic angiogenesis for cardiac and lower-limb ischemia, and prevention of thrombus formation. While catheter angiography is still standard method to follow-up vascular gene transfer, other modern imaging techniques, especially intravascular ultrasound (IVUS), magnetic resonance (MR), and positron emission tomography (PET) imaging provide complementary information about the therapeutic effect of vascular gene transfer in humans. Although molecular imaging of therapeutic gene expression in the vasculatures is still in its technical development phase, it has already offered basic medical science an extremely useful in vivo evaluation tool for non- or minimally invasive imaging of vascular gene therapy.

Manninen, Hannu I. [Department of Clinical Radiology, Kuopio University Hospital, Puijonlaaksontie 2, FIN-70210 Kuopio (Finland)]. E-mail: Hannu.manninen@kuh.fi; Yang, Xiaoming [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore (United States)

2005-11-01

315

HIV treatment for prevention.  

UK PubMed Central (United Kingdom)

"No virus, no transmission." Studies have repeatedly shown that viral load (the quantity of virus present in blood and sexual secretions) is the strongest predictor of HIV transmission during unprotected sex or transmission from infected mother to child. Effective treatment lowers viral load to undetectable levels. If one could identify and treat all HIV-infected people immediately after infection, the HIV/AIDS epidemic would eventually disappear.Such a radical solution is currently unrealistic. In reality, not all people get tested, especially when they fear stigma and discrimination. Thus, not all HIV-infected individuals are known. Of those HIV-positive individuals for whom the diagnosis is known, not all of them have access to therapy, agree to be treated, or are taking therapy effectively. Some on effective treatment will stop, and in others, the development of resistance will lead to treatment failure. Furthermore, resources are limited: should we provide drugs to asymptomatic HIV-infected individuals without indication for treatment according to guidelines in order to prevent HIV transmission at the risk of diverting funding from sick patients in urgent need? In fact, the preventive potential of anti-HIV drugs is unknown. Modellers have tried to fill the gap, but models differ depending on assumptions that are strongly debated. Further, indications for antiretroviral treatments expand; in places like Vancouver and San Francisco, the majority of HIV-positive individuals are now under treatment, and the incidence of new HIV infections has recently fallen. However, correlation does not necessarily imply causation. Finally, studies in couples where one partner is HIV-infected also appear to show that treatment reduces the risk of transmission.More definite studies, where a number of communities are randomized to either receive the "test-and-treat" approach or continue as before, are now in evaluation by funding agencies. Repeated waves of testing would precisely measure the incidence of HIV infection. Such trials face formidable logistical, practical and ethical obstacles. However, without definitive data, the intuitive appeal of "test-and-treat" is unlikely to translate into action on a global scale. In the meantime, based on the available evidence, we must strive to provide treatment to all those in medical need under the current medical guidelines. This will lead to a decrease in HIV transmission while "test-and-treat" is fully explored in prospective clinical trials.

Ambrosioni J; Calmy A; Hirschel B

2011-01-01

316

Water Pollution Prevention and Conservation  

Science.gov (United States)

This lesson plan is designed to help students apply the pollution prevention (P2) concept to water. It contains the needed background information about water pollution and provides guidance and activities to help students describe water uses and sources, explain why water conservation is important, and explain how pollution prevention concepts can be used to conserve water and prevent water pollution. The preceding pages of the fact sheet contain background information and the definitions necessary to implement this lesson plan.

317

Gene Therapy  

Science.gov (United States)

... nih.gov/handbook/therapy. Accessed Nov. 12, 2012. Gene therapy for cancer: Questions and answers. National Cancer Institute. http://cancer.gov/cancertopics/factsheet/Therapy/gene. Accessed Nov. 12, 2012. Goldman L, et al. ...

318

Pollution prevention: A regulatory update  

International Nuclear Information System (INIS)

Pollution prevention is the emphasis of the 1990s environmental philosophy. This new environmental era was ushered in when President Bush signed the Pollution Prevention Act in October 1990. This law, with its accompanying philosophy, was in response to the realization that end-of-the-pipe treatment, which frequently changed the media in which a pollutant or waste was discharged, was inadequate to protect the environment and human health. Pollution prevention advocates source reduction, where material substitutions and engineering solutions are sought to reduce the volume and toxicity of waste and pollutants. This proactive approach reduces environmental impacts such as those of former waste sites which have produced environmental legacies that will cost billions of dollars and take decades to remediate. This paper describes pollution prevention philosophy and summarizes regulatory pollution prevention requirements. It describes current regulatory trends in the area of pollution prevention, including voluntary programs and enforcement actions. The Pollution Prevention Act of 1990 is described, and pollution prevention initiatives embodied in other laws, including the Clean Air Act, the Clean Water Act, the Emergency Planning and Community Right-To-Know Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, are discussed. A historical overview of waste minimization initiatives within the Department of Energy is given, and other pollution prevention initiatives that affect federal facilities, such as Executive Order 12780, which mandates recycling and the procurement of recycled materials, are also outlined.

1993-03-04

319

Municipal water pollution prevention program  

International Nuclear Information System (INIS)

EPA believes that the most effective and equitable means of assuring viability of this infrastructure is through environmentally preferred pollution prevention approaches especially through application of Municipal Water Pollution Prevention (MWPP). These approaches may enhance worker safety, improve the usability of sludge, increase the ability for local community expansion, and reduce operation and compliance costs. State-based municipal pollution prevention programs focus attention on a series of actions to prevent pollution in advance rather than taking more expensive corrective actions. MWPP encourages resource conservation to reduce water and energy use, appropriate pricing, toxicity reductions at the source, BOD reductions, recycling, proper treatment of wastes, and beneficial uses of sludge

1991-01-01

320

Gene transfer and gene therapy  

Energy Technology Data Exchange (ETDEWEB)

This book reports the progress in gene transfer that has been made in various species, from Drosophila to higher mammals, including illustrative examples of germline gene transfer and tissue-specific somatic gene regulation in the mouse. Important new information regarding developmental control of gene transcription includes the delineation of distal elements, both cis and trans, controlling specific gene regulation. The book also offers an overview of vectors for gene transfer, including retroviral vectors and new retroviral packaging cell lines designed to minimize production of replication-competent virus.

Beaudet, A.L.; Mulligan, R.; Verma, I.M.

1988-01-01

 
 
 
 
321

Osteoporosis prevention and nutrition.  

UK PubMed Central (United Kingdom)

Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, recent research has clarified the importance of several additional nutrients and food constituents. Further, results of calcium and vitamin D supplementation trials have been inconsistent, suggesting that reliance on this intervention may be inadequate. In addition to dairy, fruit and vegetable intake has emerged as an important modifiable protective factor for bone health. Several nutrients, including magnesium, potassium, vitamin C, vitamin K, several B vitamins, and carotenoids, have been shown to be more important than previously realized. Rather than having a negative effect on bone, protein intake appears to benefit bone status, particularly in older adults. Regular intake of cola beverages shows negative effects and moderate alcohol intake shows positive effects on bone, particularly in older women. Current research on diet and bone status supports encouragement of balanced diets with plenty of fruit and vegetables, adequate dairy and other protein foods, and limitation of foods with low nutrient density.

Tucker KL

2009-12-01

322

Osteoporosis prevention and nutrition.  

Science.gov (United States)

Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, recent research has clarified the importance of several additional nutrients and food constituents. Further, results of calcium and vitamin D supplementation trials have been inconsistent, suggesting that reliance on this intervention may be inadequate. In addition to dairy, fruit and vegetable intake has emerged as an important modifiable protective factor for bone health. Several nutrients, including magnesium, potassium, vitamin C, vitamin K, several B vitamins, and carotenoids, have been shown to be more important than previously realized. Rather than having a negative effect on bone, protein intake appears to benefit bone status, particularly in older adults. Regular intake of cola beverages shows negative effects and moderate alcohol intake shows positive effects on bone, particularly in older women. Current research on diet and bone status supports encouragement of balanced diets with plenty of fruit and vegetables, adequate dairy and other protein foods, and limitation of foods with low nutrient density. PMID:19968914

Tucker, Katherine L

2009-12-01

323

Optimizing preventive maintenance  

Energy Technology Data Exchange (ETDEWEB)

The traditional approach to preventive maintenance (PM) is based on adherence to manufacturers's requirements and recommended frequencies. When equipment fails, either new procedures are established or the frequency is increased. This leads to an increase in the number of PM activities, overloading not only maintenance resources, but support as well. There is no correlation between more PM and an increase in equipment reliability. More PM may actually induce failures. Reliability-centered maintenance, a new concept in utility maintenance, is based on identifying system/subsystem functions, failures, and dominant failure modes to develop or revise PM tasks. The activities described in this paper are based on actual implementation of this concept on an ongoing project to upgrade the PM program at one of the largest electric utilities in the country. Optimum PM activities are those that, when implemented, will minimize factors that c cause equipment to fail. One technique described illustrates how equipment performance, failure modes, and causes can be related to minimize the occurrence of failures. Operating history and service life of a component are key factors in determining the most effective PM activities, provided that the factors are related to failure modes and causes.

DiCola, F.E.

1988-01-01

324

Preventive self-governance  

Directory of Open Access Journals (Sweden)

Full Text Available No field of western society has remained untouched by the events of September 11. Lastly, science and science communication are also bearing the consequences. During the annual meeting of the American Association for the Advancement of Science in Denver, Colorado, on February 15, 2003, the major international scientific magazines, faced with the bioterrorism alarm and the fear of seeing important information fall in the wrong hands, announced their intention to resort to an unprecedented security measure: preventive self-governance.1 They consider the Statement on Scientific Publication and Security as a manifesto of the sense of responsibility that the scientific community feels about global terror. In part four, after recalling the 9/11tragedy, the 32 publishers, scientific associations and scientists who signed the Statement (among which also the directors of Nature and Science) stated that “On occasion an editor may conclude that the potential harm of publication outweighs the potential societal benefits. Under such circumstances, the paper should be modified, or not be published ”

Sturloni Giancarlo

2003-01-01

325

Fusion unit preventive maintenance  

Energy Technology Data Exchange (ETDEWEB)

The lack of preventive maintenance on any mechanical apparatus can lead to the death of that machine. Experience with fusion equipment, as well as other special purpose equipment manufactured has shown that improperly maintained equipment will require overhaul maintenance from 6 to 10 times earlier than a properly maintained one. This figure can probably be used for most pieces of equipment. The principle of heat fusion is to heat two opposing surfaces of a polyolefin material to a designated temperature, then fuse them together by application of a designated force. This causes flow of the melted materials that results in mixing of the molecular chains and thus fusion. Polyethylene consists of crystalline and amorphous materials, but for all practical purposes, at normal ambient temperatures, it is basically a crystalline structure. When the polyethylene is heated beyond melting temperature, the crystallinity disappears completely and the molecular structure becomes completely amorphous (has no definite shape). When fusion force is applied, the amorphous molecules from each pipe end or fitting mix. As the joint cools below the crystalline melting point, the molecular chain becomes crystalline again. When proper mixing occurs, crystals are formed from one pipe through the joining plane to the other pipe. The original interfaces are gone and the two pipes or fittings have become one homogenous material. The joint area becomes stronger than the pipe or fitting themselves.

Striplin, T.H.

1986-07-01

326

ACCIDENT PREVENTION EMERGENCY SPRAYHEAD  

UK PubMed Central (United Kingdom)

The present invention relates to an emergency sprayhead for accident prevention use, comprising a first conduit (7) connectable to water mains, a second conduit (10) in fluid connection with said first conduit and connectable to a terminal (5) wherefrom the dispensed water comes out and a valve (11 ) interposed between said first and said second conduit that regulates the water passage, said valve being able to be operated both through a manually actuable lever device (18), and exerting a pressure on said second conduit, or on the connected terminal, or concurrently in both modes. In the practice, the valve (11 ) may also be actuated by simply positioning the sprayhead at the eye or eyes to be washed, and pressing said terminal (5), for example an ocular cup, against the face in the zone surrounding the eye. The lever actuation device (18) is further arranged within a gripping body (2) and is controlled by an especially shaped button (26) for allowing the user to clench the hand around the grip for improving the sprayhead grip and handling.

MUCCI ANTONELLO

327

Prevention of nuclear war  

Energy Technology Data Exchange (ETDEWEB)

Physicians are exercising their responsibility as healers in their efforts to prevent nuclear war. Death for Hiroshima survivors was experienced in four stages: the immediate impact of destruction, the acute impact of radiation, delayed radiation effects, and later identification as an atomic bomb survivor. Each phase had its physical and psychological impacts and negates Hiroshima as a model for rational behavior despite those who claim survival is possible for those who are prepared. The psychic effects of modern nuclear, chemical, and germ warfare need to be challenged with a symbolization of life and immortality. Studies of psychological reactions to the terror children felt during practice air-raid drills indicate that the fears can be surpressed and re-emerge in adult life as a linking of death with collective annihilation. Other themes which emerge are feelings of impermanence, craziness, identification with the bomb, and a double existence. Psychic numbing and the religion of nuclearism cause dangerous conflicts with the anxieties caused by increasing awareness of death. (DCK)

Lifton, R.J.

1980-10-01

328

Prevention of nuclear war  

International Nuclear Information System (INIS)

Physicians are exercising their responsibility as healers in their efforts to prevent nuclear war. Death for Hiroshima survivors was experienced in four stages: the immediate impact of destruction, the acute impact of radiation, delayed radiation effects, and later identification as an atomic bomb survivor. Each phase had its physical and psychological impacts and negates Hiroshima as a model for rational behavior despite those who claim survival is possible for those who are prepared. The psychic effects of modern nuclear, chemical, and germ warfare need to be challenged with a symbolization of life and immortality. Studies of psychological reactions to the terror children felt during practice air-raid drills indicate that the fears can be surpressed and re-emerge in adult life as a linking of death with collective annihilation. Other themes which emerge are feelings of impermanence, craziness, identification with the bomb, and a double existence. Psychic numbing and the religion of nuclearism cause dangerous conflicts with the anxieties caused by increasing awareness of death

1980-01-01

329

PREVENTION OF OCCUPATIONAL ACCIDENTS  

Directory of Open Access Journals (Sweden)

Full Text Available Medical services, physicians and nurses play an essential role in the plant safety program through primary treatment of injured workers and by helping to identify workplace hazards. The physician and nurse should participate in the worksite investigations to identify specific hazard or stresses potentially causing the occupational accidents and injuries and in planning the subsequent hazard control program. Physicians and nurses must work closely and cooperatively with supervisors to ensure the prompt reporting and treatment of all work related health and safety problems. Occupational accidents, work related injuries and fatalities result from multiple causes, affect different segments of the working population, and occur in a myriad of occupations and industrial settings. Multiple factors and risks contribute to traumatic injuries, such as hazardous exposures, workplace and process design, work organization and environment, economics, and other social factors. With such a diversity of theories, it will not be difficult to understand that there does not exist one single theory that is considered right or correct and is universally accepted. These theories are nonetheless necessary, but not sufficient, for developing a frame of reference for understanding accident occurrences. Prevention strategies are also varied, and multiple strategies may be applicable to many settings, including engineering controls, protective equipment and technologies, management commitment to and investment in safety, regulatory controls, and education and training. Research needs are thus broad, and the development and application of interventions involve many disciplines and organizations.

Jovica Jovanovic

2004-01-01

330

Gene Regions  

Science.gov (United States)

This animation shows the three gene coding regions. This is the fourth of a series of seven animations that detail the process of crop genetic engineering. To begin at the beginning, see Overview of Crop Genetic Engineering. (To return to the animation previous to this, go to Gene Cloning. To go to the next animation, go to Gene Modification.)

331

May exercise prevent addiction?  

UK PubMed Central (United Kingdom)

Amphetamines exert their persistent addictive effects by activating brain's reward pathways, perhaps through the release of dopamine in the nucleus accumbens (and/or in other places). On the other hand, there is a relationship between dopamine and all behavioural aspects that involve motor activity and it has been demonstrated that exercise leads to an increase in the synthesis and release of dopamine, stimulates neuroplasticity and promotes feelings of well-being. Moreover, exercise and drugs of abuse activate overlapping neural systems. Thus, our aim was to study the influence of chronic exercise in the mechanism of addiction using an amphetamine-induced conditioned-place-preference in rats.Adult male Sprague-Dawley rats were randomly separated in groups with and without chronic exercise. Chronic exercise consisted in a 8 week treadmill running program, with increasing intensity. The conditioned place preference test was performed in both groups using a procedure and apparatus previously established. A 2 mg.kg(-1) amphetamine or saline solution was administered intraperitonially according to the schedule of the conditioned place preference. Before conditioning none of the animals showed preference for a specific compartment of the apparatus. The used amphetamine dose in the conditioning phase was able to produce a marked preference towards the drug-associated compartment in the group without exercise. In the animals with exercise a significant preference by the compartment associated with saline was observed. These results lead us to conclude that a previous practice of regular physical activity may help preventing amphetamine addiction in the conditions used in this test.

Fontes-Ribeiro CA; Marques E; Pereira FC; Silva AP; Macedo TR

2011-03-01

332

Terrorism prevention and electoral accountability  

Digital Repository Infrastructure Vision for European Research (DRIVER)

How does electoral accountability affect the effectiveness of terrorism prevention in a democ- racy? We analyze the connection between electoral accountability and policy effectiveness in the context of terrorism prevention. We develop a formal model of an interaction between a government, a minorit...

Dragu, Tiberiu; Polborn, Mattias

333

PREVENT IP and Data Access  

Science.gov (United States)

The following outlines the different patent and licensing mechanisms applicable to studies of third-party agents in the PREVENT Program. Please note that the NCI has a variety of agreement mechanisms by which these terms may be applied and will work with the NCI Technology Transfer Center to determine the appropriate agreement for the studies approved by the PREVENT Program.

334

[Quaternary prevention in the elderly].  

UK PubMed Central (United Kingdom)

Quaternary prevention is a group of measures taken to prevent, decrease and/or alleviate the harm caused by health activities. Health activities not only generally produce benefits, but also harm. That is to say, although medical intervention is mainly favourable, there is a dynamic balance that requires continuous assessment of the clinical situation as naturally only those health activities that achieve more benefit than harm at the end are justified. Quaternary prevention is the avoidance of unnecessary medical activity, such as "check-ups". In another example, quaternary prevention is the recommendation of preventive measures of proven efficacy. As regards diagnosis, quaternary prevention is, for example, the avoidance of screening without foundation, such as in prostate cancer. The appropriate use of antibiotics in upper respiratory tract infections serves as an example of quaternary prevention in the field of treatment. Another example is the application of the correct rehabilitation techniques in non-specific low back pain, such as swimming and maintaining an active life as much as possible. Not to forget other important "non-classic" aspects in the elderly, such as to limit the harm that can be caused by physical movement restriction devices. These and other examples in daily practice are considered in this article to encourage the continual assessment of quaternary prevention, the classic primum non nocere "first, do no harm".

Gérvas J

2012-11-01

335

DIABETES PREVENTION TRIAL TYPE 1  

Science.gov (United States)

The Diabetes Prevention Trial--Type 1 (DPT-1) is a nationwide study to see if we can prevent or delay type 1 diabetes, also known as insulin-dependent diabetes. Nine medical centers and more than 350 clinics in the United States and Canada are taking part in the study....

336

Develop multimedia pollution prevention strategies  

Energy Technology Data Exchange (ETDEWEB)

The economic, regulatory, and other benefits of preventing pollution at the source are well known to the chemical process industries (CPI). However, to avoid transferring chemicals from one environmental medium to another (for example, air to water, or water to soil), a multimedia pollution prevention approach is necessary that avoids single-medium, end-of-pipe control where feasible. Guidelines and requirements for setting up industrial pollution prevention programs, developing pollution prevention plans, and measuring and reporting progress are addressed elsewhere. This article presents a multimedia approach to conducting pollution prevention assessments and summarizes the practical lessons learned from its application. Examples from a synthetic rubber manufacturer, a specialty resin and paint manufacturer, and a circuit-board assembler demonstrate that the generic principles and approaches outlined here are applicable to most industrial facilities that use or manufacture chemicals. These examples also demonstrate that facility type and size are not necessarily limiting factors for successfully implementing pollution prevention projects. A pollution prevention assessment involves three main steps: (1) defining the problem; (2) developing conceptual pollution prevention strategies; and (3) performing a cost/benefit analysis to screen viable alternatives.

Chadha, N.

1994-11-01

337

Get Real about Diabetes Prevention  

Centers for Disease Control (CDC) Podcasts

This podcast delivers a diabetes prevention message promoting small steps that can lead to big rewards.  Created: 11/1/2007 by National Diabetes Education Program (NDEP), a joint program of the Centers for Disease Control and Prevention and the National Institutes of Health.   Date Released: 11/15/2007.

2007-11-01

338

Scooter-Related Injury Prevention  

Science.gov (United States)

... orthoinfo.aaos.org/topic.cfm?topic=A00425) Inline Skating Injury Prevention Inline Skating Injury Prevention (http://orthoinfo.aaos.org/topic.cfm? ... http://orthoinfo.aaos.org/topic.cfm?topic=A00042) Skateboarding Safety Skateboarding Safety (http://orthoinfo.aaos.org/topic. ...

339

Gene expression  

International Nuclear Information System (INIS)

[en] We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn2+ or Cd2+. We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

1983-01-01

340

Tamoxifen for breast cancer prevention  

Energy Technology Data Exchange (ETDEWEB)

The case for tamoxifen to be tested as a preventive for breast cancer has merit. Animal studies demonstrate that tamoxifen prevents mammary carcinogenesis and clinical studies now confirm that adjuvant tamoxifen therapy is the only systemic treatment that will prevent contralateral breast cancer. Developing clinical studies confirm the laboratory data that tamoxifen will maintain post-menopausal bone density in the lumbar spine and the neck of the femur; two important skeletal sites for the ultimate prevention of osteoporosis. However, a most important target site-specific effect of tamoxifen is the decrease in low-density lipoprotein cholesterol levels in postmenopausal women. This positive property of tamoxifen may be responsible for the recorded decreases in hospital visits for the treatment of cardiac conditions and the significant decrease in fatal myocardial infarction for women treated with 5 years of adjuvant tamoxifen. These data provide the scientific basis to undertake randomized, placebocontrolled clinical trials to test the worth of tamoxifen to prevent breast cancer.

Jordan, V.C. [Northwestern Univ. Medical School, Chicago, IL (United States)

1995-02-01

 
 
 
 
341

Maintenance operations and pollution prevention  

Energy Technology Data Exchange (ETDEWEB)

This chapter focuses on pollution prevention in industrial plant maintenance; continuing publicity surrounding environmental concerns suggests that the problems resulting from the generation of waste are approaching crisis proportions with the general public and have reached the highest levels of government. The initial reaction to these concerns has been the development of pollution prevention programs within most manufacturing plants. The long-term response must ben an emphasis on pollution prevention in all activities associated with manufacturing--from design and engineering through construction and operation. One area in which a pollution prevention orientation is crucial in maintenance, the vital link assuring that operation of the unit is able to achieve a performance level consistent with design and engineering. Many activities associated with maintenance, such as good housekeeping, tank cleaning, inventory control, and waste segregation, are among the first areas addressed in a pollution prevention program.

Berglund, R.L. [M.W. Kellogg Co., Houston, TX (United States)

1995-09-01

342

Gene therapy for deafness.  

UK PubMed Central (United Kingdom)

Hearing loss is the most common sensory deficit in humans and can result from genetic, environmental or combined etiologies that prevent normal function of the cochlea, the peripheral sensory organ. Recent advances in understanding the genetic pathways that are critical for the development and maintenance of cochlear function, as well as the molecular mechanisms that underlie cell trauma and death, have provided exciting opportunities for modulating these pathways to correct genetic mutations, to enhance the endogenous protective pathways for hearing preservation and to regenerate lost sensory cells with the possibility of ameliorating hearing loss. A number of recent animal studies have used gene-based therapies in innovative ways toward realizing these goals. With further refinement, some of the protective and regenerative approaches reviewed here may become clinically applicable.Gene Therapy advance online publication, 18 July 2013; doi:10.1038/gt.2013.39.

Kohrman DC; Raphael Y

2013-07-01

343

Breast Cancer Susceptibility Gene1 (BRCA1)  

Directory of Open Access Journals (Sweden)

Full Text Available Breast Cancer Susceptibility Gene1 (BRCA1) is a tumor suppressor gene for breast and ovarian cancers. The gene locates at chromosome 17q21 and encodes for 1863 amino acids protein. It is believed that BRCA1 protein is involved in many functions such as DNA repair, centrosome replication, cell cycle checkpoint and replication of other genes. More than 800 mutations have been found in the population with an increased risk of cancer incidence in their families. Germ-line mutation of BRCA1 accounts for 5-10 percent of all breast cancer cases. Epigenetic modifications also reduce the function of normal BRCA1 gene. Several methods are used for laboratory diagnosis of cancer-related mutations. The development of breast cancer in carriers at risk with BRCA1 mutations may be prevented by suitable prevention plans such as breast cancer screening, ovarian cancer screening, surgery and cancer chemotherapy.

Wasiksiri, S.; Ratanaphan, A.

2002-01-01

344

Pollution prevention: A new agenda  

Energy Technology Data Exchange (ETDEWEB)

Pollution prevention is a term used to describe production technologies and strategies that result in eliminating or reducing waste streams. The US Environmental Protection Agency (EPA) defines pollution prevention as the use of materials, processes, or practices that reduce or eliminate the creation of pollutants or wastes at the source. It includes practices that reduce the use of hazardous materials, energy, water, or other resources and practices that protect natural resources through conservation or more efficient use. The idea underlying the promotion of pollution prevention is that it makes far more sense for a generator not to produce waste than to develop extensive treatment schemes to ensure that the waste poses no threat to the quality of the environment.This chapter focuses on the following: benefits of pollution prevention; pollution prevention in other countries; and industrial programs which reflect both an interest in saving money and avoiding increasingly stringent end-of-the-pipe environmental regulations. This chapter focuses on the following: benefits of pollution prevention; pollution prevention in other countries; and industrial programs which reflect both an interest in saving money and avoiding increasingly stringent end-of-the-pipe environmental regulations.

Freeman, H.M. [Environmental Protection Agency, Cincinnati, OH (United States)

1995-09-01

345

Chinese medicament cold prevention toothpaste  

UK PubMed Central (United Kingdom)

The invention relates to Chinese medicament cold prevention toothpaste, which is characterized in that Chinese medicinal herb powder mixed in the substrate of the toothpaste is prepared form the following components in percentage by weight: 10 to 15 percent of radix bupleuri, 15 to 20 percent of raidx astragali, 5 to 10 percent of biond magnolia flower, 5 to 10 percent of liquoric root, 10 to 15 percent of divaricate saposhnikovia root, 5 to 10 percent of mint, 5 to 10 percent of wrinkled gianthyssop herb, 10 to 15 percent of indigowoad root and 15 to 20 percent of citrus root the nine Chinese medicinal herbs are put into a multifunctional extracting, separating, distilling and concentrating machine to be mixed pure water in an amount of 10 to 15 times of the weight of the Chinese medicinal herbs is added into the multifunctional extracting, separating, distilling and concentrating machine and the Chinese medicament cold prevention toothpaste is obtained by soaking, distillation, extraction, concentration and drying. Cold viruses enter a human body from mouth and noise to induce cold, so the Chinese medicament cold prevention toothpaste can prevent invasion by pathogenic factors, prevent cold easily and achieve a cold-preventing effect to ensure the health of a human body while preventing caries and decayed teeth and keeping the sanitation of the mouth.

HONGTAO WANG

346

Primary prevention of Down's syndrome  

Directory of Open Access Journals (Sweden)

Full Text Available Background: Antenatal screening has the capacity to detect more than 90% of Down's syndrome pregnancies leading to therapeutic abortion. Successes in recent years with such so-called 'secondary' prevention have not been matched with progress in primary prevention. Despite considerable research over many decades the principle cause of the disorder is unknown. Methods: This paper considers three potential primary prevention strategies, (1) avoiding reproduction at advanced maternal age, (2) pre-implantation genetic diagnosis for couples who are at high risk of Down's syndrome, and (3) folic acid supplementation. The principle aetiological hypotheses are also reviewed. Interpretation: A strategy of completing the family before a maternal age of 30 could more than halve the birth prevalence of this disorder. Women with a high a priori risk should have access to pre-implantation genetic diagnosis, which can lead to a reasonably high pregnancy rate with an extremely low risk of a Down's syndrome. The evidence suggesting an aetiological role for defective folate and methyl metabolism is not sufficient to justify an active preventative strategy of folic acid supplementation without performing a large clinical trial. Current supplementation policies designed to prevent neural tube defects may incidentally prevent Down's syndrome, provided a sufficiently high dose of folic acid is used. Further progress in primary prevention is hampered by limited aetiological knowledge and there is an urgent need to refocus research in that direction.

Cuckle Howard S

2005-01-01

347

The genomic applications in practice and prevention network.  

Science.gov (United States)

The authors describe the rationale and initial development of a new collaborative initiative, the Genomic Applications in Practice and Prevention Network. The network convened by the Centers for Disease Control and Prevention and the National Institutes of Health includes multiple stakeholders from academia, government, health care, public health, industry and consumers. The premise of Genomic Applications in Practice and Prevention Network is that there is an unaddressed chasm between gene discoveries and demonstration of their clinical validity and utility. This chasm is due to the lack of readily accessible information about the utility of most genomic applications and the lack of necessary knowledge by consumers and providers to implement what is known. The mission of Genomic Applications in Practice and Prevention Network is to accelerate and streamline the effective integration of validated genomic knowledge into the practice of medicine and public health, by empowering and sponsoring research, evaluating research findings, and disseminating high quality information on candidate genomic applications in practice and prevention. Genomic Applications in Practice and Prevention Network will develop a process that links ongoing collection of information on candidate genomic applications to four crucial domains: (1) knowledge synthesis and dissemination for new and existing technologies, and the identification of knowledge gaps, (2) a robust evidence-based recommendation development process, (3) translation research to evaluate validity, utility and impact in the real world and how to disseminate and implement recommended genomic applications, and (4) programs to enhance practice, education, and surveillance. PMID:19471162

Khoury, Muin J; Feero, W Gregory; Reyes, Michele; Citrin, Toby; Freedman, Andrew; Leonard, Debra; Burke, Wylie; Coates, Ralph; Croyle, Robert T; Edwards, Karen; Kardia, Sharon; McBride, Colleen; Manolio, Teri; Randhawa, Gurvaneet; Rasooly, Rebekah; St Pierre, Jeannette; Terry, Sharon

2009-07-01

348

The genomic applications in practice and prevention network.  

UK PubMed Central (United Kingdom)

The authors describe the rationale and initial development of a new collaborative initiative, the Genomic Applications in Practice and Prevention Network. The network convened by the Centers for Disease Control and Prevention and the National Institutes of Health includes multiple stakeholders from academia, government, health care, public health, industry and consumers. The premise of Genomic Applications in Practice and Prevention Network is that there is an unaddressed chasm between gene discoveries and demonstration of their clinical validity and utility. This chasm is due to the lack of readily accessible information about the utility of most genomic applications and the lack of necessary knowledge by consumers and providers to implement what is known. The mission of Genomic Applications in Practice and Prevention Network is to accelerate and streamline the effective integration of validated genomic knowledge into the practice of medicine and public health, by empowering and sponsoring research, evaluating research findings, and disseminating high quality information on candidate genomic applications in practice and prevention. Genomic Applications in Practice and Prevention Network will develop a process that links ongoing collection of information on candidate genomic applications to four crucial domains: (1) knowledge synthesis and dissemination for new and existing technologies, and the identification of knowledge gaps, (2) a robust evidence-based recommendation development process, (3) translation research to evaluate validity, utility and impact in the real world and how to disseminate and implement recommended genomic applications, and (4) programs to enhance practice, education, and surveillance.

Khoury MJ; Feero WG; Reyes M; Citrin T; Freedman A; Leonard D; Burke W; Coates R; Croyle RT; Edwards K; Kardia S; McBride C; Manolio T; Randhawa G; Rasooly R; St Pierre J; Terry S

2009-07-01

349

Pollution prevention and air quality  

International Nuclear Information System (INIS)

Pollution prevention (P2) results from the combined effect of the public opinion, a new environmental value system, government regulation, but above all, the search for an economic development within the context of environmental protection. The reasons for prevention are fundamental: profit from a new economic frontier; reduced potential for civil and criminal liability; and the effective and economic protection of the environment. This paper addresses, among other relevant issues, the following topics: justification and objective of pollution prevention; strategy and methodology for its implementation; examples of successes and tools; benefits and barriers and some recommendation

1997-01-01

350

AGENT FOR CHICKEN HEPATOSIS PREVENTION  

UK PubMed Central (United Kingdom)

FIELD: medicine, veterinary science. ^ SUBSTANCE: invention refers to veterinary science, namely to therapy of internal nontransmitting diseases, particularly to drugs for chicken hepatosis prevention. The agent for chicken hepatosis prevention contains the ingredients in the following relation: antihepatotoxic serum 0.9-1.15 titre units antisplenotoxic serum 0.9-1.15 titre units phenol 0.004-0.005 mg physiological solution up to 1 ml. The agent is introduced to chickens and chicks in dose 0.2 ml/kg of body weight subcutaneously or intramuscularly. ^ EFFECT: invention allows higher effectiveness of chicken hepatosis prevention. ^ 4 tbl

BURKOV PAVEL VALER EVICH; SHCHERBAKOV PAVEL NIKOLAEVICH; SHCHERBAKOVA TAT JANA BORISOVNA

351

Prevention of oncological diseases: primary and secondary prevention.  

UK PubMed Central (United Kingdom)

Cancer is the leading cause of death worldwide. Because there is presently no cure for cancer, the best strategy to combat oncological diseases is through early detection and prevention. The methods currently available are vaccines to target specific viruses (primary prevention), in combination with screening (secondary prevention), use of biomarkers, and administration of adjuvant therapy (tertiary prevention). Modifiable lifestyle-related risk factors are also important in cancer prevention. Vaccination has been proven to be highly effective against targeted diseases leading to the development of cancer, particularly if the vaccination is given in the early years of life. The need for regular screening (for breast cancer, cervical cancer, etc.) should not be neglected and should be followed to detect unusual changes or abnormalities in the body. With discoveries as targeted therapies, adjuvant treatment becomes a secure component of tertiary prevention in the betterment of disease management. The discovery of biomarkers and subsequent targeted therapies has led to personalized medicine as the current trend in cancer care.

Chow LW; Yip AY; Ng EL

2012-10-01

352

NITROXIDES FOR USE IN TREATING OR PREVENTING NEOPLASTIC DISEASE  

UK PubMed Central (United Kingdom)

Pharmaceutical compositions are provided that are useful in treating or preventing neoplastic disease, such as cancer. The compositions comprise a pharmaceutically acceptable carrier, and an effective therapeutic or prophylactic amount of a nitroxide antioxidant that alters the expression of one or more genes related to the cancer. Methods are also provided for the use of the pharmaceutical compositions in the treatment or prevention of cancer. In a preferred embodiment, the nitroxide antioxidant is Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), and the cancer is esophageal cancer, hepatocellular carcinoma, colon cancer, prostate cancer, lung cancer, gastric carcinoma, renal cell carcinoma, bone cancer, breast cancer, cervical cancer, brain cancer, or a cancer associated with the tumor suppressor gene p53.

HABASH LOUIS; JONES CLARENCE

353

Preventing cystic fibrosis in the RSA.  

UK PubMed Central (United Kingdom)

Prenatal diagnostic testing for cystic fibrosis (CF) in South Africa has been available by microvillar enzyme (MVE) assay since 1984 and by DNA investigation since 1987. The advantages and practical uses of these two procedures are reviewed. Over the period 1984-1989, 59 MVE assays and 13 DNA investigations (1 woman had both done; total number of pregnancies tested 71) were performed for the prenatal diagnosis of CF in high-risk families. Of the 71 pregnancies tested (65 white woman, 4 mixed race and 2 Indian), 18 fetuses were found to be affected: of these, 15 couples chose to have the pregnancies terminated. In 2 fetuses tested the MVE assays were 'equivocal' and the babies were born affected. By using population genetic and demographic data it is estimated that the present rate of prenatal diagnosis and prevention satisfies about one-quarter of the projected and practically achievable annual need. It is also tentatively shown that only about 60% of the projected number of high-risk families are at present on record. It is concluded that more systematic efforts should be directed at carefully guided information and awareness campaigns, in order to draw more CF families into the mainstream of voluntary genetic services. The identification and cloning of the CF gene (in 1989) has made it possible to extend considerably the present strategy of prevention and to include lower-risk and extended CF families in due time.

Hitzeroth HW; Petersen EM; Herbert J; Denter M

1991-07-01

354

NEW TYROSINASE GENE melB  

UK PubMed Central (United Kingdom)

PROBLEM TO BE SOLVED: To obtain a new tyrosinase gene (melB) which has characteristics of developing by solid culture, is useful for preventing browning of Sake koji and discoloration of brewed food, with which the tyrosinase is produced by culturing the transformant of the gene and the tyrosinase is not only useful as a reagent but also for screening its inhibitor and which can be expected to develop a color protection substance. SOLUTION: Cloning of the new tyrosinase gene (melB) is carried out and its base sequence is determined. The cloned new gene is inserted into a vector to transform a host (Aspergillus oryjae).

OBATA HIROSHI; ISHIDA HIROKI; HATA YOJI; KAWATO SHOJI; ABE YASUHISA; AKAO TAKESHI; AKITA OSAMU; ICHISHIMA EIJI

355

Body Lice Prevention and Control  

Science.gov (United States)

... please visit this page: About CDC.gov . Parasites - Lice - Body Lice Parasites Home Share Compartir Add this to... Añadir ... Favorites Delicious Digg Google Bookmarks Prevention & Control Body lice are spread most commonly by direct contact with ...

356

Head Lice: Tips for Preventing  

Science.gov (United States)

... and treatments E - H Head lice Tips Head lice: Tips for preventing Head lice: Most children get ... treatments for head lice. Learn more about head lice Head lice Head lice: Signs and symptoms Head ...

357

Preventing Falls in the Hospital  

Science.gov (United States)

English - Preventing Falls in the Hospital 2 min 45 sec To Listen to the Audio or Read/Print/Save the Handout, Click on a Picture Below To ... SAFE FROM FALLS Tool Kit by the Minnesota Hospital Association

358

Diet Choices to Prevent Cancer  

Science.gov (United States)

MENU Return to Web version Cancer Diet Choices to Prevent Cancer Can certain dietary choices reduce my risk of cancer? Ongoing studies are researching whether certain foods and nutrients can reduce ...

359

Medicine for preventing diabets mellitus  

UK PubMed Central (United Kingdom)

A Chinese medicine for preventing and treating diabetes is prepared from 4 raw materials including balsam pear, anemarrhena rhizome, chromium nicotinate, etc through extracting, proportional mixing, pulverizing, sieving and granulating. Its advantage is high curative effect.

ZHANG JINDUO; ZHANG YONG; WANG MEILING

360

Prevent the Spread of Norovirus  

Science.gov (United States)

... Delicious Digg Google Bookmarks Prevent the Spread of Norovirus Norovirus causes 19-21 million gastroenteritis cases each ... simple tips to stay healthy. New Strain of Norovirus In 2012, a new strain of norovirus was ...

 
 
 
 
361

Insurance and prevention: ethical aspects.  

Science.gov (United States)

In recent decades, prevention policies--i.e., insurance policies constructed to give incentives to investments in prevention and thereby reduce reliance on insurance--have been much discussed both with regard to different kinds of market insurance and, albeit primarily within a European context and in relation to an ongoing discussion about the need for a shift towards an "active" welfare state, with regard to social insurance. The present contribution identifies normative issues that deserve attention in relation to a general introduction of prevention policies in market insurance and social insurance. It is argued that the importance of these normative issues suggests that arguments and distinctions drawn from moral and political philosophy should play a more prominent role both in the debate on the shift towards an active welfare state and the use of prevention policies in market insurance. PMID:21274748

Dubois, Mikael

2011-02-01

362

Insurance and prevention: ethical aspects.  

UK PubMed Central (United Kingdom)

In recent decades, prevention policies--i.e., insurance policies constructed to give incentives to investments in prevention and thereby reduce reliance on insurance--have been much discussed both with regard to different kinds of market insurance and, albeit primarily within a European context and in relation to an ongoing discussion about the need for a shift towards an "active" welfare state, with regard to social insurance. The present contribution identifies normative issues that deserve attention in relation to a general introduction of prevention policies in market insurance and social insurance. It is argued that the importance of these normative issues suggests that arguments and distinctions drawn from moral and political philosophy should play a more prominent role both in the debate on the shift towards an active welfare state and the use of prevention policies in market insurance.

Dubois M

2011-02-01

363

Educational Stress: Sources, Reactions, Preventions.  

Science.gov (United States)

Effects of stress on educators and efforts to understand and cope with stress are discussed. Sources of stress, common reactions to stress, the effects of stress on educator performance, and suggested preventive methods are examined. (JN)

Kaiser, Jeffrey S.; Polczynski, James J.

1982-01-01

364

How to Prevent Medical Emergencies  

Medline Plus

Full Text Available ... a comprehensive list of poisonous house and garden plants, see the National Capital Poison Control Center’s Web site at www.poison.org/prevent/plants.asp . Avoid home and garden applications of pesticides ...

365

Can Liver Cancer Be Prevented?  

Science.gov (United States)

... Topic Can liver cancer be found early? Can liver cancer be prevented? Many liver cancers could be ... gets into drinking water. Treating diseases that increase liver cancer risk Certain inherited diseases can cause cirrhosis ...

366

Preventing tube degradation in Japan  

Energy Technology Data Exchange (ETDEWEB)

During the 1970s, Japanese PWRs were severely affected by steam generator tube degradation. In the past few years, however, a programme of preventive and corrective action has resulted in considerable improvements in performance.

1985-02-01

367

[Prevention of schizophrenia: a review].  

UK PubMed Central (United Kingdom)

Research over the years has introduced multiple interventions for schizophrenia. Notwithstanding the nature of intervention pharmacological or psychological a complete cure for the condition remains a much-desired, yet unachieved goal. What is required is an exploration of alternative intervention strategies for treating schizophrenia a preventive approach is such an option. The chronic nature of schizophrenia and its associated disabilities have a tremendously negative affect the quality of life of patients, their families, and communities. Among the preferred approaches to reducing the negative consequences associated with the disorder is the prevention of its emergence. This review aimed to present the available data on the prevention of schizophrenia data that suggest some pharmacological and non-pharmacological interventions have a potential role in the prevention of schizophrenia. Nonetheless, the findings are restricted to a few sites and are at best preliminary; as such, the findings must be replicated in new studies that include large samples and different settings.

Balhara YP

2013-01-01

368

Sports Injury Prevention Tip Sheet  

Science.gov (United States)

... a a a print email share Facebook Twitter Sports Injury Prevention Tip Sheet 4/9/2013 Article Body More American children are competing in sports than ever before. Sports help children and adolescents ...

369

Preventing fractures in the elderly.  

UK PubMed Central (United Kingdom)

Fractures in the elderly are devastating, causing premature death and compromised independence among survivors. With demographic changes, their occurrence is expected to double. Given their crippling consequences, the identification and treatment of osteoporosis and prevention of falls are priorities.

Walker-Bone K

2011-10-01

370

How to Prevent Medical Emergencies  

Medline Plus

Full Text Available ... phased out by the Environmental Protection Agency.) Buy medicines, vitamins and household products with child-resistant caps. ... same or similar medication, consider using color-coded medicine caps on the original container to prevent mixing ...

371

Can we prevent road rage?  

UK PubMed Central (United Kingdom)

Road rage has become a serious concern in many countries, and preventive efforts are required. This article reviews what can be done to prevent road rage by exploring potential prevention avenues in five areas. First, legal changes aimed at increasing the penalties for road rage behavior could be instituted, drawing on models from aggressive-driving or impaired-driving laws. A second approach would involve the adoption of court programs for convicted road ragers. Third, car redesign offers a means of reducing crime through environmental design. Fourth, mass media education could be implemented to inform drivers of the risk from road rage and how to avoid situations that facilitate road rage. Finally, prevention efforts could be directed to long-term societal changes that emphasize structural modifications, such as reducing congestion on the roads, reduced driver stress, or promoting public transportation. The strengths and weaknesses of these strategies are discussed.

Asbridge M; Smart RG; Mann RE

2006-04-01

372

How to Prevent Medical Emergencies  

Medline Plus

Full Text Available ... medicines, vitamins and household products with child-resistant caps. Store in their original containers and place out ... or similar medication, consider using color-coded medicine caps on the original container to prevent mixing up ...

373

Latex Allergy: A Prevention Guide  

Science.gov (United States)

... In this pamphlet, the term "latex" refers to natural rubber latex, the product manufactured from a milky fluid derived ... Alert No. 97-135, Preventing Allergic Reactions to Natural Rubber Latex in the Workplace , call 1-800-35-NIOSH ( ...

374

How to Prevent Medical Emergencies  

Medline Plus

Full Text Available ... degrees F to prevent scalding. Unplug curling irons, hair dryers and electric razors when not in use. Lock up any bottles of mouthwash, perfume, hair spray, or nail polish. Also any scissors, razor ...

375

Preventing the first or recurrent ulcers.  

UK PubMed Central (United Kingdom)

This article reviews the current evidence to prevent diabetic foot ulceration. Prevention is an ongoing process that requires a team approach including educators, physical therapists, physicians, podiatrists, nurses, pedorthists, and prothetists. Screening, risk stratification, education, regular foot care, and protective shoes and insoles are the mainstay of the prevention process. Diabetic foot prevention can prevent reulceration in high-risk patients by 50%.

Lavery LA; La Fontaine J; Kim PJ

2013-09-01

376

Preventive legal protection against plannings  

International Nuclear Information System (INIS)

The author investigates problems of preventive legal protection in special planning fields, e.g. in the atomic energy law. Further, he examines aspects of legal protection for communities, when their areas are affected by plannings of other executives. In his opinion there are no particularities for a preventive legal protection concerning preliminary determinations pursuant to sec. 7 a Atomic Energy Act and partial licences according to sec. 18 of the Nuclear Installations Ordinance. (WG).

1987-01-01

377

Skin contamination - prevention and decontaminating  

International Nuclear Information System (INIS)

[en] A detailed examination is made of the structure of human skin. Measures were drawn up to prevent skin contamination in nuclear installations as well as contaminated skin was decontaminated from the personnel. By systematically applying these measures a significant level of success was achieved in preventing contamination in nuclear installations. Cases where more far-reaching chemical methods had to be used were kept to a minimum. (R.P.)

2001-01-01

378

Blow out preventer handling system  

Energy Technology Data Exchange (ETDEWEB)

A system for testing and installing a blow out preventer on a floating vessel and offshore drilling rigs, although the system may be used on other rotary drilling rigs, is disclosed. Retractable rotary table supporting beams are disposed over the moon pool and the rotary table is releasably connected to them. Retractable sub-structure beams are provided below the rotary table so that means provided to move the assembled blow out preventer can move it through an opening in the derrick and over the moon pool when the rotary beams are retracted. Retractable moon pool skid beams are provided which support the blow out preventer when skidded through the moon pool opening in the substructure. In one aspect of the invention, the means connecting the rotary table to its support beams are self-aligning to that once the rotary table is aligned it can be removed and replaced without any further alignment. Also, support shoulders are provided on the main blow out preventer and lower riser section thereof which engage and are supported by the moon pool beams, so that the rotary support beams, rotary table and sub-structure support beams can be replaced and the blow out preventer hooked up to the riser, drill string or casing, the moon pool beams retracted and the blow out preventer lowered in the moon pool to the sea floor.

Guinn, D.C.; Haggard, A.K.; Thomas, J.P.

1980-10-28

379

Wildfire prevention : best management practices  

Energy Technology Data Exchange (ETDEWEB)

A proactive approach to wildfire prevention in the oil and gas industry is important to understand the corporate liabilities associated with the ignition of a fire, as well as the threat that a catastrophic fire poses to personnel, infrastructure and production. The basics of wildfire prevention include education and awareness, engineering vegetation to reduce flammability, and enforcement of fire prevention regulations. This document presented best management practices (BPM) to address fire prevention fundamentals across the industry. The purpose of this document was to assist the upstream oil and gas industry in the prevention of industry caused wildfires, and to mitigate the impact of catastrophic fires on industry infrastructure, operations, liability, personnel safety and the environment. The document included a best practices outline in appendix format as well as several case studies of industry-related wildfires. In addition to discussing best management practices for fire prevention, the document also discussed regulatory aspects such as legislation, codes, directives, guidelines and agreements; integrated land management; seasonal and daily fire danger; emergency response planning; and communications. Best management practices to mitigate the impact of wildland fires were also presented. refs., tabs., figs., appendices.

NONE

2008-01-15

380

Prevention of myelomeningocele: African perspectives.  

UK PubMed Central (United Kingdom)

BACKGROUND: The prevention of neural tube defects (NTDs) is now an issue of major public health concern. Myelomeningocele, the most common NTD, often results in severe disabilities and may be life threatening. In Africa, there is little awareness of the NTDs, and most African countries lag behind in the global efforts at preventing them. PURPOSE: Following a review of global literature, we discuss the burden of myelomeningocele on the society and the current state of its prevention with an emphasis on Africa within the global context. The realization that folate supplementation reduces the occurrence of NTDs by as much as 85 % offers an opportunity to promote global reduction in the incidence of NTDs through (1) effective folate supplementation strategies combined with (2) secondary prevention using prenatal detection and termination of NTD pregnancies within respective national legal frameworks. We call attention to the poor state of understanding of NTDs in Africa and the alarming rarity of policies to prevent the condition in the continent. CONCLUSIONS: The understanding of the contributions of folate deficiency to the causation of NTDs has enabled appropriate, though still inadequate, preventive measures to be taken in several countries. We call on African governments and the international community to rapidly promote policies aimed at making fortification of wheat (and or other substitute staple foods) with folic acid universally available.

Rabiu TB; Adeleye AO

2013-09-01

 
 
 
 
381

Trichoderma genes  

Energy Technology Data Exchange (ETDEWEB)

Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

Foreman, Pamela (Los Altos, CA); Goedegebuur, Frits (Vlaardingen, NL); Van Solingen, Pieter (Naaldwijk, NL); Ward, Michael (San Francisco, CA)

2012-06-19

382

Gene Gun  

Science.gov (United States)

How the gene gun works to transform cells with new DNA. This is thesixth of a series of seven animations that detail the process of cropgenetic engineering. To begin at the beginning, see Overview of Crop Genetic Engineering. (To return to the animation previous to this, go to Gene Modification. To go to the next animation, go to Backcross Breeding.)

383

Linear ubiquitination prevents inflammation and regulates immune signalling.  

UK PubMed Central (United Kingdom)

Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKK? or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1? was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.

Gerlach B; Cordier SM; Schmukle AC; Emmerich CH; Rieser E; Haas TL; Webb AI; Rickard JA; Anderton H; Wong WW; Nachbur U; Gangoda L; Warnken U; Purcell AW; Silke J; Walczak H

2011-03-01

384

Linear ubiquitination prevents inflammation and regulates immune signalling.  

Science.gov (United States)

Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKK? or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1? was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling. PMID:21455173

Gerlach, Björn; Cordier, Stefanie M; Schmukle, Anna C; Emmerich, Christoph H; Rieser, Eva; Haas, Tobias L; Webb, Andrew I; Rickard, James A; Anderton, Holly; Wong, Wendy W-L; Nachbur, Ueli; Gangoda, Lahiru; Warnken, Uwe; Purcell, Anthony W; Silke, John; Walczak, Henning

2011-03-31

385

Strategies for the prevention of autoimmune type 1 diabetes.  

UK PubMed Central (United Kingdom)

European experts on autoimmune Type 1 diabetes met for 2 days in October 2010 in Cambridge, to review the state-of-the-art and to discuss strategies for prevention of Type 1 diabetes (http://www-gene.cimr.cam.ac.uk/todd/sub_pages/T1D_prevention_Cambridge_workshop_20_21Oct2010.pdf). Meeting sessions examined the epidemiology of Type 1 diabetes; possible underlying causes of the continuing and rapid increase in Type 1 diabetes incidence at younger ages; and lessons learned from previous prevention trials. Consensus recommendations from the meeting were: 1. Resources such as national diabetes registries and natural history studies play an essential role in developing and refining assays to be used in screening for risk factors for Type 1 diabetes. 2. It is crucial to dissect out the earliest physiological events after birth, which are controlled by the susceptibility genes now identified in Type 1 diabetes, and the environmental factors that might affect these phenotypes, in order to bring forward a mechanistic approach to designing future prevention trials. 3. Current interventions at later stages of disease, such as in newly diagnosed Type 1 diabetes, have relied mainly on non-antigen-specific mechanisms. For primary prevention-preventing the onset of autoimmunity-interventions must be based on knowledge of the actual disease process such that: participants in a trial would be stratified according the disease-associated molecular phenotypes; the autoantigen(s) and immune responses to them; and the manipulation of the environment, as early as possible in life. Combinations of interventions should be considered as they may allow targeting different components of disease, thus lowering side effects while increasing efficacy.

Todd JA; Knip M; Mathieu C

2011-10-01

386

Heart Disease Prevention: Does Oral Health Matter?  

Science.gov (United States)

... use only. Heart disease prevention: Does oral health matter? By Mayo Clinic staff Original Article: http://www. ... up Question Heart disease prevention: Does oral health matter? Will taking care of my teeth help prevent ...

387

Take Steps to Prevent Type 2 Diabetes  

Science.gov (United States)

... Prevent Type 2 Diabetes Take Steps to Prevent Type 2 Diabetes The Basics Take Action! Ver en español Content ... do a lot to prevent or delay getting type 2 diabetes (“dy-ah-BEE-teez”), including: Watching your weight ...

388

76 FR 21652 - Oil Pollution Prevention; Spill Prevention, Control, and Countermeasure (SPCC) Rule-Amendments...  

Science.gov (United States)

...FRL-9297-3] RIN 2050-AG50 Oil Pollution Prevention; Spill Prevention, Control...see Comment and Response Document Oil Pollution Prevention; SPCC Plan Requirements...EPA will continue to enforce the Oil Pollution Prevention regulations for oil...

2011-04-18

389

Falls prevention for the elderly  

Directory of Open Access Journals (Sweden)

Full Text Available Background: An ageing population, a growing prevalence of chronic diseases and limited financial resources for health care underpin the importance of prevention of disabling health disorders and care dependency in the elderly. A wide variety of measures is generally available for the prevention of falls and fall-related injuries. The spectrum ranges from diagnostic procedures for identifying individuals at risk of falling to complex interventions for the removal or reduction of identified risk factors. However, the clinical and economic effectiveness of the majority of recommended strategies for fall prevention is unclear. Against this background, the literature analyses in this HTA report aim to support decision-making for effective and efficient fall prevention.Research questions: The pivotal research question addresses the effectiveness of single interventions and complex programmes for the prevention of falls and fall-related injuries. The target population are the elderly (> 60 years), living in their own housing or in long term care facilities. Further research questions refer to the cost-effectiveness of fall prevention measures, and their ethical, social and legal implications. Methods: Systematic literature searches were performed in 31 databases covering the publication period from January 2003 to January 2010. While the effectiveness of interventions is solely assessed on the basis of randomised controlled trials (RCT), the assessment of the effectiveness of diagnostic procedures also considers prospective accuracy studies. In order to clarify social, ethical and legal aspects all studies deemed relevant with regard to content were taken into consideration, irrespective of their study design. Study selection and critical appraisal were conducted by two independent assessors. Due to clinical heterogeneity of the studies no meta-analyses were performed.Results: Out of 12,000 references retrieved by literature searches, 184 meet the inclusion criteria. However, to a variable degree the validity of their results must be rated as compromised due to different biasing factors. In summary, it appears that the performance of tests or the application of parameters to identify individuals at risk of falling yields little or no clinically relevant information. Positive effects of exercise interventions may be expected in relatively young and healthy seniors, while studies indicate opposite effects in the fragile elderly. For this specific vulnerable population the modification of the housing environment shows protective effects. A low number of studies, low quality of studies or inconsistent results lead to the conclusion that the effectiveness of the following interventions has to be rated unclear yet: correction of vision disorders, modification of psychotropic medication, vitamin D supplementation, nutritional supplements, psychological interventions, education of nursing personnel, multiple and multifactorial programs as well as the application of hip protectors. For the context of the German health care system the economic evaluations of fall prevention retrieved by the literature searches yield very few useful results. Cost-effectiveness calculations of fall prevention are mostly based on weak effectiveness data as well as on epidemiological and cost data from foreign health care systems. Ethical analysis demonstrates ambivalent views of the target population concerning fall risk and the necessity of fall prevention. The willingness to take up preventive measures depends on a variety of personal factors, the quality of information, guidance and decision-making, the prevention program itself and social support. The analysis of papers regarding legal issues shows three main challenges: the uncertainty of which standard of care has to be expected with regard to fall prevention, the necessity to consider the specific conditions of every single case when measures for fall prevention are applied, and the difficulty to balance the rights to autonomous decision making and physical integrity. Discussion a

Katrin Balzer; Martina Bremer; Susanne Schramm; Dagmar Lühmann; Heiner Raspe

2012-01-01

390

Falls prevention for the elderly.  

UK PubMed Central (United Kingdom)

BACKGROUND: An ageing population, a growing prevalence of chronic diseases and limited financial resources for health care underpin the importance of prevention of disabling health disorders and care dependency in the elderly. A wide variety of measures is generally available for the prevention of falls and fall-related injuries. The spectrum ranges from diagnostic procedures for identifying individuals at risk of falling to complex interventions for the removal or reduction of identified risk factors. However, the clinical and economic effectiveness of the majority of recommended strategies for fall prevention is unclear. Against this background, the literature analyses in this HTA report aim to support decision-making for effective and efficient fall prevention. RESEARCH QUESTIONS: The pivotal research question addresses the effectiveness of single interventions and complex programmes for the prevention of falls and fall-related injuries. The target population are the elderly (> 60 years), living in their own housing or in long term care facilities. Further research questions refer to the cost-effectiveness of fall prevention measures, and their ethical, social and legal implications. METHODS: Systematic literature searches were performed in 31 databases covering the publication period from January 2003 to January 2010. While the effectiveness of interventions is solely assessed on the basis of randomised controlled trials (RCT), the assessment of the effectiveness of diagnostic procedures also considers prospective accuracy studies. In order to clarify social, ethical and legal aspects all studies deemed relevant with regard to content were taken into consideration, irrespective of their study design. Study selection and critical appraisal were conducted by two independent assessors. Due to clinical heterogeneity of the studies no meta-analyses were performed. RESULTS: Out of 12,000 references retrieved by literature searches, 184 meet the inclusion criteria. However, to a variable degree the validity of their results must be rated as compromised due to different biasing factors. In summary, it appears that the performance of tests or the application of parameters to identify individuals at risk of falling yields little or no clinically relevant information. Positive effects of exercise interventions may be expected in relatively young and healthy seniors, while studies indicate opposite effects in the fragile elderly. For this specific vulnerable population the modification of the housing environment shows protective effects. A low number of studies, low quality of studies or inconsistent results lead to the conclusion that the effectiveness of the following interventions has to be rated unclear yet: correction of vision disorders, modification of psychotropic medication, vitamin D supplementation, nutritional supplements, psychological interventions, education of nursing personnel, multiple and multifactorial programs as well as the application of hip protectors. For the context of the German health care system the economic evaluations of fall prevention retrieved by the literature searches yield very few useful results. Cost-effectiveness calculations of fall prevention are mostly based on weak effectiveness data as well as on epidemiological and cost data from foreign health care systems. Ethical analysis demonstrates ambivalent views of the target population concerning fall risk and the necessity of fall prevention. The willingness to take up preventive measures depends on a variety of personal factors, the quality of information, guidance and decision-making, the prevention program itself and social support. THE ANALYSIS OF PAPERS REGARDING LEGAL ISSUES SHOWS THREE MAIN CHALLENGES: the uncertainty of which standard of care has to be expected with regard to fall prevention, the necessity to consider the specific conditions of every single case when measures for fall prevention are applied, and the difficulty to balance the rights to autonomous decision making and physical integrity. DISCUSSION AND CONCLUSIONS:

Balzer K; Bremer M; Schramm S; Lühmann D; Raspe H

2012-01-01

391

Fall prevention among apprentice carpenters.  

UK PubMed Central (United Kingdom)

OBJECTIVES: Falls from heights are a leading cause of mortality and morbidity in the construction industry, especially among inexperienced workers. We surveyed apprentice carpenters to identify individual and organizational factors associated with falls from heights. METHODS: We developed a 72-item survey on fall prevention with multiple domains including fall experience, fall-prevention knowledge, risk perceptions, confidence in ability to prevent falls, training experience, and perceptions of the safety climate and crew safety behaviors. We administered the questionnaire to apprentice carpenters in this cross-sectional study. RESULTS: Of the 1025 respondents, 51% knew someone who had fallen from a height at work and 16% had personally fallen in the past year, with ladders accounting for most of the falls. Despite participation in school-based and on-the-job training, fall-prevention knowledge was poor. Ladders were perceived as low risk and ladder training was rare. Apprentices reported high levels of unsafe, fall-related behaviors on their work crews. Apprentices in residential construction were more likely to fall than those in commercial construction, as were apprentices working on crews with fewer senior carpenters to provide mentorship, and those reporting more unsafe behaviors among fellow workers. CONCLUSIONS: Despite participation in a formal apprenticeship program, many apprentices work at heights without adequate preparation and subsequently experience falls. Apprenticeship programs can improve the timing and content of fall-prevention training. This study suggests that organizational changes in building practices, mentorship, and safety practices are also necessary to decrease worker falls from heights.

Kaskutas V; Dale AM; Lipscomb H; Gaal J; Fuchs M; Evanoff B

2010-05-01

392

The Money Laundering Prevention System  

Directory of Open Access Journals (Sweden)

Full Text Available The paper presents the money laundering and terrorist financing prevention system in Croatia. The basic concepts are defined, the principles and fundamentals of international regulations analysed, and the regulatory system in Croatia cover