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Introduction: Field work with bats is an important contribution to many areas of research in environmental biology and ecology, as well as microbiology. Work with bats poses hazards such as bites and scratches, and the potential for exposure to infectious pathogens such as rabies virus. It also exposes researchers to many other potential hazards inherent to field work, such as environmental conditions, delayed emergency responses, or challenging work conditions. Methods: This article discusses the considerations for a thorough risk assessment process around field work with bats, pre- and post-occupational health considerations, and delves into specific considerations for areas related to biosafety concerns-training, personal protective equipment, safety consideration in field methods, decontamination, and waste. It also touches on related legal and ethical issues that sit outside the realm of biosafety, but which must be addressed during the planning process. Discussion: Although the focal point of this article is bat field work located in northern and central America, the principles and practices discussed here are applicable to bat work elsewhere, as well as to field work with other animal species, and should promote careful considerations of how to safely conduct field work to protect both researchers and animals.
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RATIONALE: The basis for gender influences on allergen-specific IgEs is unclear. OBJECTIVES: To perform regular and sex-stratified genomewide linkage analyses of IgE to each of three allergens (Ascaris lumbricoides, Blatella germanica [German cockroach]), and Dermatophagoides pteronyssinus [dust mite]) and to conduct an association study of a candidate gene in a linked genomic region. METHODS: Genomewide linkage analyses of allergen-specific IgEs were conducted in 653 members of eight large families of Costa Rican children with asthma. An analysis of the association between single-nucleotide polymorphisms in thymic stromal lymphopoietin (TSLP) and IgE measurements was conducted in 417 parent-child trios in Costa Rica. Significant results were replicated in 470 families of white children in the Childhood Asthma Management Program (CAMP). MEASUREMENTS AND MAIN RESULTS: Among all subjects, there was suggestive evidence of linkage (LOD >/= 2.72) to IgE to Ascaris (on chromosome 7q) and IgE to dust mite (on chromosomes 7p and 12q). In a sex-stratified analysis, there was significant evidence of linkage to IgE to cockroach on chromosome 5q23 (peak LOD, 4.14 at 127 cM) in female subjects. TSLP is located within the 1.5 LOD-unit support interval for this linkage peak and has female-specific effects on lung disease in mice. In a sex-stratified analysis, the T allele of single-nucleotide polymorphism rs2289276 in TSLP was associated with reductions in IgE to cockroach (in Costa Rican girls) and total IgE (in girls in Costa Rica and in CAMP; P value for sex-by-genotype interaction, <0.01 in both studies). CONCLUSIONS: Consistent with findings in murine models, a variant in TSLP may have female-specific effects on allergic phenotypes.
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Asma/genética , Baratas/imunologia , Citocinas/genética , Predisposição Genética para Doença/genética , Imunoglobulina E/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos , Animais , Criança , Costa Rica , Feminino , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fatores Sexuais , Linfopoietina do Estroma do TimoRESUMO
Serum total immunoglobulin E (IgE) is a critical intermediate phenotype of allergic diseases. Although total IgE exhibits sexual dimorphism in humans (with males demonstrating higher IgE than females), the molecular basis of this difference is unknown. A genome-wide scan of 380 short-tandem repeat (STR) markers was performed in eight extended pedigrees of asthmatic children (n=655) from the Central Valley of Costa Rica. Genome-wide linkage analysis of total IgE was performed by variance component models. Among all subjects, only one genomic region (chromosome 7p15) showed modest evidence of linkage to total IgE (LOD=1.60). In contrast, a sex-stratified analysis revealed distinct genetic architectures of total IgE in males and females and identified significant linkage to total IgE on a novel male-specific locus on chromosome 20p12 (LOD=3.63 at 36 cM). Genotyping of additional STRs on chromosome 20 resulted in improved evidence for linkage (LOD=3.75 at 33 cM) and a 1.5 LOD-unit support interval for the linkage peak between 26 and 38 cM. Three polymorphisms in two genes on chromosome 20p12 (JAG1 and ANKRD5) were then found to be associated with total IgE in 420 nuclear families of Costa Rican children with asthma. Two of these polymorphisms (in JAG1) were significantly associated with total IgE in families of boys (n=264) but not in families of girls (n=156) with asthma. JAG1 is a hematopoetic cell growth factor that may regulate normal B-cell development. This is the first demonstration of a possible genetic basis for differences in total IgE between sexes.
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Asma/sangue , Asma/genética , Família , Ligação Genética , Imunoglobulina E/sangue , Caracteres Sexuais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Mapeamento Cromossômico , Cromossomos Humanos Par 20 , Costa Rica , Feminino , Genoma Humano , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Although asthma is highly prevalent among certain Hispanic subgroups, genetic determinants of asthma and asthma-related traits have not been conclusively identified in Hispanic populations. A study was undertaken to identify genomic regions containing susceptibility loci for pulmonary function and bronchodilator responsiveness (BDR) in Costa Ricans. METHODS: Eight extended pedigrees were ascertained through schoolchildren with asthma in the Central Valley of Costa Rica. Short tandem repeat (STR) markers were genotyped throughout the genome at an average spacing of 8.2 cM. Multipoint variance component linkage analyses of forced expiratory volume in 1 second (FEV(1)) and FEV(1)/ forced vital capacity (FVC; both pre-bronchodilator and post-bronchodilator) and BDR were performed in these eight families (pre-bronchodilator spirometry, n = 640; post-bronchodilator spirometry and BDR, n = 624). Nine additional STR markers were genotyped on chromosome 7. Secondary analyses were repeated after stratification by cigarette smoking. RESULTS: Among all subjects, the highest logarithm of the odds of linkage (LOD) score for FEV(1) (post-bronchodilator) was found on chromosome 7q34-35 (LOD = 2.45, including the additional markers). The highest LOD scores for FEV(1)/FVC (pre-bronchodilator) and BDR were found on chromosomes 2q (LOD = 1.53) and 9p (LOD = 1.53), respectively. Among former and current smokers there was near-significant evidence of linkage to FEV(1)/FVC (post-bronchodilator) on chromosome 5p (LOD = 3.27) and suggestive evidence of linkage to FEV(1) on chromosomes 3q (pre-bronchodilator, LOD = 2.74) and 4q (post-bronchodilator, LOD = 2.66). CONCLUSIONS: In eight families of children with asthma in Costa Rica, there is suggestive evidence of linkage to FEV(1) on chromosome 7q34-35. In these families, FEV(1)/FVC may be influenced by an interaction between cigarette smoking and a locus (loci) on chromosome 5p.
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Asma/genética , Ligação Genética/genética , Adolescente , Adulto , Idoso , Asma/etnologia , Asma/fisiopatologia , Broncodilatadores , Criança , Costa Rica/etnologia , Volume Expiratório Forçado/fisiologia , Genoma Humano , Genótipo , Humanos , Pessoa de Meia-Idade , Fenótipo , Fumar/efeitos adversos , Fumar/fisiopatologia , Capacidade Vital/fisiologiaRESUMO
Although asthma is a major public health problem in certain Hispanic subgroups in the United States and Latin America, only one genome scan for asthma has included Hispanic individuals. Because of small sample size, that study had limited statistical power to detect linkage to asthma and its intermediate phenotypes in Hispanic participants. To identify genomic regions that contain susceptibility genes for asthma and airway responsiveness in an isolated Hispanic population living in the Central Valley of Costa Rica, we conducted a genome-wide linkage analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of eight large pedigrees of Costa Rican children with asthma. Nonparametric multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele-sharing statistic, and variance component models were used for the multipoint linkage analysis of airway responsiveness as a quantitative phenotype. All linkage analyses were repeated after exclusion of the phenotypic data of former and current smokers. Chromosome 12q showed some evidence of linkage to asthma, particularly in nonsmokers (P < 0.01). Among nonsmokers, there was suggestive evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 2.33 at 146 cM). After genotyping 18 additional short-tandem repeat markers on chromosome 12q, there was significant evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 3.79 at 144 cM), with a relatively narrow 1.5-LOD unit support interval for the observed linkage peak (142-147 cM). Our results suggest that chromosome 12q24.31 contains a locus (or loci) that influence a critical intermediate phenotype of asthma (airway responsiveness) in Costa Ricans.
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Asma/genética , Cromossomos Humanos Par 12/genética , Ligação Genética , Sistema Respiratório/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/tratamento farmacológico , Broncoconstritores/uso terapêutico , Criança , Mapeamento Cromossômico , Costa Rica , Saúde da Família , Feminino , Genoma Humano , Humanos , Escore Lod , Masculino , Cloreto de Metacolina/uso terapêutico , Repetições de Microssatélites , Pessoa de Meia-Idade , Sistema Respiratório/efeitos dos fármacosRESUMO
Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.
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Predisposição Genética para Doença , Hanseníase/genética , Proteínas/genética , Ubiquitina-Proteína Ligases/genética , Alelos , Brasil , Estudos de Casos e Controles , Mapeamento Cromossômico , Cromossomos Humanos Par 6/genética , Perfilação da Expressão Gênica , Haplótipos , Humanos , Proteínas dos Microfilamentos , Chaperonas Moleculares , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , VietnãRESUMO
Leprosy, a chronic infectious disease caused by Mycobacterium leprae, affects an estimated 700,000 persons each year. Clinically, leprosy can be categorized as paucibacillary or multibacillary disease. These clinical forms develop in persons that are intrinsically susceptible to leprosy per se, that is, leprosy independent of its specific clinical manifestation. We report here on a genome-wide search for loci controlling susceptibility to leprosy per se in a panel of 86 families including 205 siblings affected with leprosy from Southern Vietnam. Using model-free linkage analysis, we found significant evidence for a susceptibility gene on chromosome region 6q25 (maximum likelihood binomial (MLB) lod score 4.31; P = 5 x 10(-6)). We confirmed this by family-based association analysis in an independent panel of 208 Vietnamese leprosy simplex families. Of seven microsatellite markers underlying the linkage peak, alleles of two markers (D6S1035 and D6S305) showed strong evidence for association with leprosy (P = 6.7 x 10(-4) and P = 5.9 x 10(-5), respectively).
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Masculino , Feminino , Humanos , Alelos , /genética , /genética , Escore Lod , Hanseníase/genética , Ligação Genética , Repetições de Microssatélites , VietnãRESUMO
The HemoCue system utilizes the principle of oxidation of haemoglobin to hemiglobin by sodium nitrite and the subsequent conversion of hemiglobin to hemiglobinazide by sodium azide. The reagents for these reactions are contained within a small disposable microcuvette of approximately 10 microliters in volume. A venous or capillary sample is introduced into the microcuvette by capillary action and, after reaction with the reagents, the absorbance is read in the HemoCue photometer at 565 and 880 nm. The haemoglobin concentration is then displayed as a digital reading, in either g/dl or mmol/l in 15-45 seconds. We compared haemoglobin values obtained by the HemoCue system with those from the Coulter Counter S-Plus IV in 366 pregnant women in urban Jamaica, and found a highly significant correlation (r = 0.78, P < 0.01). However, because of the convenience and ease of use of this instrument and considering the relatively high cost, we recommend it for use only as a research tool in field studies where accurate and rapid haemoglobin determinations are required.
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Anemia/sangue , Hemoglobinometria/métodos , Hemoglobinas/análise , Complicações Hematológicas na Gravidez/sangue , Adolescente , Adulto , Feminino , Humanos , Indicadores e Reagentes , Jamaica , GravidezRESUMO
High plasma ferritin has been found in all three classes of malnutrition. The aim of this study was to determine whether or not the high ferritin is the result of high iron stores or of some other condition whereby ferritin escapes into the plasma from damaged tissue. Normal plasma ferritin is largely glycosylated whereas tissue ferrritin in not. Twenty-six malnourished children (9, kwashiorkor; 7, marasmic-Kwashiorkor; 10, marasmus) were injected intramuscularly with 500 mg desferrioxamine and the urinary iron output over twenty-four hours determined (urinary iron in response to desferrioxamine is an index of the size of iron stores). Total plasma ferritin was measured by an Enzyme Labeled Immunosorbent Assay and plasma glycosylated ferritin by measuring the ferritin remaining in the supernatant after incubating with concanavalin A. Urinary iron excretion correlated significantly with total plasma ferritin and plasma glycosylated ferritin. It was significantly higher in children with oedema. The extent of glycosylation suggests secretion into the plasma via the normal pathway and not by leakage from damaged tissue. The elevation of plasma ferritin in malnutrition can therefore be interpreted as an indicator of high levels or storage iron. This study was supported by the Wellcome Trust (AU)
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Humanos , Criança , Distúrbios Nutricionais/metabolismo , Ferritinas/sangue , Ferritinas/metabolismo , Ferro/metabolismo , Jamaica , Kwashiorkor , Desnutrição Proteico-Calórica , DesferroxaminaRESUMO
The HemoCue system utilizes the principle of oxidation of haemoglobin to hemiglobin by sodium nitrite and the subsequent conversion of hemiglobin to hemiglobinazide by sodium azide. The reagents for these reactions are contained within a small disposable microcuvette of approximately 10 æ\ in volumne. A venous or capillary sample is introduced into the microcuvette by capillary action and, after reaction with the reagents, the absorbance is read in the HemoCue photometer at 565 and 880nm. The haemoglobin concentration is then displayed as a digital reading, in either g/dl or mmol/l in 15-45 seconds. We compared haemolgobin values obtained by the HemoCue system with those from the Coulter Counter S-Plus IV in 366 pregnant women in urban Jamaica, and found a highly significant correlation (r = 0.78, P < 0.01). However, because of the convenience and erase of use of this instrument and considering the relatively high cost, we recommend it for use only as a research tool in field studies where accurate and rapid haemoglobin dterminationas are required (AU)