Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Water Health ; 21(12): 1747-1760, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38153709

RESUMO

Small water supplies face similar problems worldwide, regardless of ownership or management type. Non-compliance with water quality regulations is more frequent in small supplies than in large ones, as are waterborne disease outbreaks. The new European Union Drinking Water Directive requires risk-based approach (RBA) to secure water safety as is recommended in the World Health Organization's Guidelines for drinking water quality through 'water safety plans'. This is already in regulation in the Nordic countries, although less used in small supplies. In this research, we explore the challenges, barriers and possible solutions to implementing RBA and improving compliance in small supplies. This was achieved by conducting and analysing interviews with 53 stakeholders from all eight Nordic countries to produce recommendations for action by the different implicated actors. Our findings suggest the centrality of governmental policy, including support for continuous training, provision of simple RBA guidelines and increasing cooperation in the water sector. The Nordic experience reflects global challenges with small water supplies and the trend towards systematic preventive management epitomized in the framework for drinking water safety advocated by the World Health Organization since 2004.


Assuntos
Água Potável , Qualidade da Água , Abastecimento de Água , Surtos de Doenças , União Europeia
2.
Int J Hyg Environ Health ; 230: 113627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956900

RESUMO

Reliable safe water supply is a pillar of society and a key to public health. The Nordic countries have an abundance of clean fresh water as a source for drinking water supplies. They have followed developments in safeguarding water, both the recommendations of the World Health Organization framework for safe drinking water and European legislation. Worldwide, including the Nordic countries, small water supplies are less compliant with water safety regulation. The forthcoming EU directive on drinking water require risk-based approaches and improved transparency on water quality. This research looks at the Nordic frameworks for safe water supply, with emphasis on risk-based approaches and smaller systems. We analyzed the legal frameworks for safe water, the structure of the water sector across the Nordic countries and explored how prepared these countries are to meet these requirements. Our findings show that, while legal requirements are mostly in place, delivery of information to the public needs to be improved. Most Nordic countries are in the process of implementing risk-based management in large and medium size water supplies, whereas small supplies are lagging. We conclude that a key to success is increased training and support for small supplies. We suggest wider adoption of the Nordic model of cooperation with benchmarking of safe water for all to transfer knowledge between the countries. This work provides insights into challenges and opportunities for the Nordic countries and provides insights relevant to countries worldwide in their effort towards realization of SDG Target 6.1.


Assuntos
Água Potável , Água Doce , Saúde Pública , Qualidade da Água , Abastecimento de Água
3.
Exp Hematol ; 44(10): 982-990.e11, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27297329

RESUMO

The rare memory B cells in thymus (Thy) are considered the cells of origin for primary mediastinal large B-cell lymphoma. The objectives of the present study were to characterize the normal memory B-cell compartment in Thy and to support its association with primary mediastinal B-cell lymphoma. Seven paired human tissue samples from Thy and sternum bone marrow (BM) were harvested during cardiac surgery. B-cell subsets were phenotyped by Euroflow standard and fluorescence-activated cell sorting for microarray analysis on the Human Exon 1.0 ST Arrays platform. Differentially expressed genes between Thy and BM memory B cells were identified and correlated with the molecular subclasses of diffuse large B-cell lymphoma. Within Thy, 4% (median; range 2%-14%) of the CD45(+) hematopoietic cells were CD19(+) B cells, with a major fraction being CD27(+)/CD38(-) memory B cells (median 80%, range 76%-93%). The BM contained 14% (median; range 3%-27%), of which only a minor fraction (median 5%, range 2%-10%) were memory B cells. Global gene expression analysis of the memory B-cell subsets from the two compartments identified 133 genes upregulated in Thy, including AICDA, REL, STAT1, TNF family, SLAMF1, CD80, and CD86. In addition, exons 4 and 5 in the 3' end of AICDA were more highly expressed in Thy than in BM. The Thy memory B-cell gene profile was overexpressed in primary mediastinal B-cell lymphoma compared with other diffuse large B-cell lymphoma subclasses. The present study describes a Thy memory B-cell subset and its gene profile correlated with primary mediastinal B-cell lymphomas, suggesting origin from Thy memory B cells.


Assuntos
Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/metabolismo , Idoso , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/patologia , Linfócitos B/imunologia , Linfócitos B/patologia , Biomarcadores , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Memória Imunológica , Imunofenotipagem , Contagem de Linfócitos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos/genética , Fenótipo , Transdução de Sinais
4.
PLoS One ; 10(10): e0139329, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26448050

RESUMO

BACKGROUND: Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment. METHODS: We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included. RESULTS: We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS) in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010) * IL10 (rs1800890) (HR = 0.11 (0.02-0.50)). Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center. CONCLUSIONS: The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.


Assuntos
Linfoma Folicular/genética , Linfoma Difuso de Grandes Células B/genética , Idoso , Alelos , Feminino , Genótipo , Haplótipos , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Subunidade beta de Receptor de Interleucina-10/genética , Subunidade beta de Receptor de Interleucina-10/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Subunidade alfa de Receptor de Interleucina-4/genética , Subunidade alfa de Receptor de Interleucina-4/metabolismo , Desequilíbrio de Ligação , Linfoma Folicular/etiologia , Linfoma Folicular/mortalidade , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Risco , Análise de Sobrevida , Transcriptoma
5.
Cytometry B Clin Cytom ; 88(1): 40-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25327569

RESUMO

BACKGROUND: Cryopreservation is an acknowledged procedure to store vital cells for future biomarker analyses. Few studies, however, have analyzed the impact of the cryopreservation on phenotyping. METHODS: We have performed a controlled comparison of cryopreserved and fresh cellular aliquots prepared from individual healthy donors. We studied circulating B-cell subset membrane markers and global gene expression, respectively by multiparametric flow cytometry and microarray data. Extensive statistical analysis of the generated data tested the concept that "overall, there are no phenotypic differences between cryopreserved and fresh B-cell subsets." Subsequently, we performed an uncontrolled comparison of tonsil tissue samples. RESULTS: By multiparametric flow analysis, we documented no significant changes following cryopreservation of subset frequencies or membrane intensity for the differentiation markers CD19, CD20, CD22, CD27, CD38, CD45, and CD200. By gene expression profiling following cryopreservation, across all samples, only 16 out of 18708 genes were significantly up or down regulated, including FOSB, KLF4, RBP7, ANXA1 or CLC, DEFA3, respectively. Implementation of cryopreserved tissue in our research program allowed us to present a performance analysis, by comparing cryopreserved and fresh tonsil tissue. As expected, phenotypic differences were identified, but to an extent that did not affect the performance of the cryopreserved tissue to generate specific B-cell subset associated gene signatures and assign subset phenotypes to independent tissue samples. CONCLUSIONS: We have confirmed our working concept and illustrated the usefulness of vital cryopreserved cell suspensions for phenotypic studies of the normal B-cell hierarchy; however, storage procedures need to be delineated by tissue-specific comparative analysis.


Assuntos
Subpopulações de Linfócitos B/citologia , Criopreservação , Tonsila Palatina/citologia , Fenótipo , Antígenos CD/genética , Antígenos CD/imunologia , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Bancos de Espécimes Biológicos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Citometria de Fluxo/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Fator 4 Semelhante a Kruppel , Análise de Sequência com Séries de Oligonucleotídeos , Tonsila Palatina/efeitos dos fármacos , Tonsila Palatina/imunologia , Tonsila Palatina/metabolismo , Transcriptoma
6.
Artigo em Inglês | MEDLINE | ID: mdl-25242153

RESUMO

Background Cryopreservation is an acknowledged procedure to store vital cells for future biomarker analyses. Few studies, however, have analyzed the impact of the cryopreservation on phenotyping. Methods We have performed a controlled comparison of cryopreserved and fresh cellular aliquots prepared from individual healthy donors. We studied circulating B-cell subset membrane markers and global gene expression, respectively by multiparametric flow cytometry and microarray data. Extensive statistical analysis of the generated data tested the concept that "overall, there are phenotypic differences between cryopreserved and fresh B-cell subsets". Subsequently, we performed a consecutive uncontrolled comparison of tonsil tissue samples. Results By multiparametric flow analysis, we documented no significant changes following cryopreservation of subset frequencies or membrane intensity for the differentiation markers CD19, CD20, CD22, CD27, CD38, CD45, and CD200. By gene expression profiling following cryopreservation, across all samples, only 16 out of 18708 genes were significantly up or down regulated, including FOSB, KLF4, RBP7, ANXA1 or CLC, DEFA3, respectively. Implementation of cryopreserved tissue in our research program allowed us to present a performance analysis, by comparing cryopreserved and fresh tonsil tissue. As expected, phenotypic differences were identified, but to an extent that did not affect the performance of the cryopreserved tissue to generate specific B-cell subset associated gene signatures and assign subset phenotypes to independent tissue samples. Conclusions We have confirmed our working concept and illustrated the usefulness of vital cryopreserved cell suspensions for phenotypic studies of the normal B-cell hierarchy; however, storage procedures need to be delineated by tissue specific comparative analysis. © 2014 Clinical Cytometry Society.

7.
BMC Immunol ; 15: 3, 2014 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-24483235

RESUMO

BACKGROUND: This report describes a method for the generation of global gene expression profiles from low frequent B-cell subsets by using fluorescence-activated cell sorting and RNA amplification. However, some of the differentiating compartments involve a low number of cells and therefore it is important to optimize and validate each step in the procedure. METHODS: Normal lymphoid tissues from blood, tonsils, thymus and bone marrow were immunophenotyped by the 8-colour Euroflow panel using multiparametric flow cytometry. Subsets of B-cells containing cell numbers ranging from 800 to 33,000 and with frequencies varying between 0.1 and 10 percent were sorted, subjected to mRNA purification, amplified by the NuGEN protocol and finally analysed by the Affymetrix platform. RESULTS: Following a step by step strategy, each step in the workflow was validated and the sorting/storage conditions optimized as described in this report. First, an analysis of four cancer cell lines on Affymetrix arrays, using either 100 ng RNA labelled with the Ambion standard protocol or 1 ng RNA amplified and labelled by the NuGEN protocol, revealed a significant correlation of gene expressions (r ≥ 0.9 for all). Comparison of qPCR data in samples with or without amplification for 8 genes showed that a relative difference between six cell lines was preserved (r ≥ 0.9). Second, a comparison of cells sorted into PrepProtect, RNAlater or directly into lysis/binding buffer showed a higher yield of purified mRNA following storage in lysis/binding buffer (p < 0.001). Third, the identity of the B-cell subsets validated by the cluster of differentiation (CD) membrane profile was highly concordant with the transcriptional gene expression (p-values <0.001). Finally, in normal bone marrow and tonsil samples, eight evaluated genes were expressed in accordance with the biology of lymphopoiesis (p-values < 0.001), which enabled the generation of a gene-specific B-cell atlas. CONCLUSION: A description of the implementation and validation of commercially available kits in the laboratory has been examined. This included steps for cell sorting, cell lysis/stabilization, RNA isolation, RNA concentration and amplification for microarray analysis. The workflow described in this report will enable the generation of microarray data from minor sorted B-cell subsets.


Assuntos
Subpopulações de Linfócitos B/metabolismo , Perfilação da Expressão Gênica/métodos , Antígenos CD/metabolismo , Citometria de Fluxo , Humanos , Tecido Linfoide/citologia , Tecido Linfoide/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes
8.
Leuk Lymphoma ; 55(6): 1251-60, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23998255

RESUMO

Recent findings have suggested biological classification of B-cell malignancies as exemplified by the "activated B-cell-like" (ABC), the "germinal-center B-cell-like" (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and "recurrent translocation and cyclin D" (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.


Assuntos
Linfócitos B/metabolismo , Linfócitos B/patologia , Leucemia de Células B/diagnóstico , Leucemia de Células B/genética , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Transcriptoma , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Análise em Microsséries/métodos , Modelos Estatísticos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética
9.
BMC Genomics ; 13: 596, 2012 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-23127183

RESUMO

BACKGROUND: Malignant cells in tumours of B-cell origin account for 0.1% to 98% of the total cell content, depending on disease entity. Recently, gene expression profiles (GEPs) of B-cell lymphomas based on microarray technologies have contributed significantly to improved sub-classification and diagnostics. However, the varying degrees of malignant B-cell frequencies in analysed samples influence the interpretation of the GEPs. Based on emerging next-generation sequencing technologies (NGS) like tag sequencing (tag-seq) for GEP, it is expected that the detection of mRNA transcripts from malignant B-cells can be supplemented. This study provides a quantitative assessment and comparison of the ability of microarrays and tag-seq to detect mRNA transcripts from malignant B-cells. A model system was established by eight serial dilutions of the malignant B-cell lymphoma cell line, OCI-Ly8, into the embryonic kidney cell line, HEK293, prior to parallel analysis by exon microarrays and tag-seq. RESULTS: We identified 123 and 117 differentially expressed genes between pure OCI-Ly8 and HEK293 cells by exon microarray and tag-seq, respectively. There were thirty genes in common, and of those, most were B-cell specific. Hierarchical clustering from all dilutions based on the differentially expressed genes showed that neither technology could distinguish between samples with less than 1% malignant B-cells from non-B-cells. A novel statistical concept was developed to assess the ability to detect single genes for both technologies, and used to demonstrate an inverse proportional relationship with the sample purity. Of the 30 common genes, the detection capability of a representative set of three B-cell specific genes--CD74, HLA-DRA, and BCL6 - was analysed. It was noticed that at least 5%, 13% and 22% sample purity respectively was required for detection of the three genes by exon microarray whereas at least 2%, 4% and 51% percent sample purity of malignant B-cells were required for tag-seq detection. CONCLUSION: A sample purity-dependent loss of the ability to detect genes for both technologies was demonstrated. Taq-seq, in comparison to exon microarray, required slightly less malignant B-cells in the samples analysed in order to detect the two most abundantly expressed of the selected genes. The results show that malignant cell frequency is an important variable, with fundamental impact when interpreting GEPs from both technologies.


Assuntos
Linfoma de Células B/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Sequência de RNA/métodos , Antígenos de Diferenciação de Linfócitos B/genética , Linhagem Celular Tumoral , Análise por Conglomerados , Proteínas de Ligação a DNA/genética , Éxons , Células HEK293 , Cadeias alfa de HLA-DR/genética , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Linfoma de Células B/metabolismo , Modelos Genéticos , Proteínas Proto-Oncogênicas c-bcl-6
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...