RESUMO
Shelf sediments underlying temperate and oxic waters of the Celtic Sea (NW European Shelf) were found to have shallow oxygen penetrations depths from late spring to late summer (2.2-5.8 mm below seafloor) with the shallowest during/after the spring-bloom (mid-April to mid-May) when the organic carbon content was highest. Sediment porewater dissolved iron (dFe, <0.15 µm) mainly (>85%) consisted of Fe(II) and gradually increased from 0.4 to 15 µM at the sediment surface to ~100-170 µM at about 6 cm depth. During the late spring this Fe(II) was found to be mainly present as soluble Fe(II) (>85% sFe, <0.02 µm). Sub-surface dFe(II) maxima were enriched in light isotopes (δ56Fe -2.0 to -1.5), which is attributed to dissimilatory iron reduction (DIR) during the bacterial decomposition of organic matter. As porewater Fe(II) was oxidised to insoluble Fe(III) in the surface sediment layer, residual Fe(II) was further enriched in light isotopes (down to -3.0). Ferrozine-reactive Fe(II) was found in surface porewaters and in overlying core top waters, and was highest in the late spring period. Shipboard experiments showed that depletion of bottom water oxygen in late spring can lead to a substantial release of Fe(II). Reoxygenation of bottom water caused this Fe(II) to be rapidly lost from solution, but residual dFe(II) and dFe(III) remained (12 and 33 nM) after >7 h. Iron(II) oxidation experiments in core top and bottom waters also showed removal from solution but at rates up to 5-times slower than predicted from theoretical reaction kinetics. These data imply the presence of ligands capable of complexing Fe(II) and supressing oxidation. The lower oxidation rate allows more time for the diffusion of Fe(II) from the sediments into the overlying water column. Modelling indicates significant diffusive fluxes of Fe(II) (on the order of 23-31 µmol m-2 day-1) are possible during late spring when oxygen penetration depths are shallow, and pore water Fe(II) concentrations are highest. In the water column this stabilised Fe(II) will gradually be oxidised and become part of the dFe(III) pool. Thus oxic continental shelves can supply dFe to the water column, which is enhanced during a small period of the year after phytoplankton bloom events when organic matter is transferred to the seafloor. This input is based on conservative assumptions for solute exchange (diffusion-reaction), whereas (bio)physical advection and resuspension events are likely to accelerate these solute exchanges in shelf-seas.
RESUMO
Iron overload phenotypes in persons with and without hemochromatosis are variable. To investigate this further, probands with hemochromatosis or evidence of elevated iron stores and their family members were recruited for a genome-wide linkage scan to identify potential quantitative trait loci (QTL) that contribute to variation in transferrin saturation (TS), unsaturated iron-binding capacity (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were evaluated from 174 families. After adjusting for age, gender, and race/ethnicity, there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds (LOD) = 2.08, p = 0.001) and of UIBC (LOD = 9.52), TS (LOD = 4.78), and SF (LOD = 2.75) to the chromosome 6p region containing HFE (each p < 0.0001). After adjustments for HFE genotype and other covariates, there was evidence of linkage of SF to chromosome 16p (LOD = 2.63, p = 0.0007) and of UIBC to chromosome 5q (LOD = 2.12, p = 0.002) and to chromosome 17q (LOD = 2.19, p = 0.002). We conclude that these regions should be considered for fine mapping studies to identify QTL that contribute to variation in SF and UIBC.
Assuntos
Testes Genéticos/métodos , Genoma Humano , Hemocromatose/genética , Ferro/metabolismo , Locos de Características Quantitativas , Adulto , Negro ou Afro-Americano/genética , Idoso , Povo Asiático/genética , Feminino , Frequência do Gene , Genótipo , Hemocromatose/etnologia , Hemocromatose/prevenção & controle , Proteína da Hemocromatose , Hispânico ou Latino/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Indígenas Norte-Americanos/genética , Ferro/sangue , Escore Lod , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Fenótipo , População Branca/genéticaRESUMO
We compared initial screening transferrin saturation (TfSat) and serum ferritin (SF) phenotypes and HFE C282Y and H63D genotypes of 645 Native American and 43,453 white Hemochromatosis and Iron Overload Screening Study participants who did not report a previous diagnosis of hemochromatosis or iron overload. Elevated measurements were defined as TfSat >50% in men and >45% in women and SF >300 ng/ml in men and >200 ng/ml in women. Mean TfSat was 31% in Native American men and 32% in white men (p = 0.0337) and 25% in Native American women and 27% in white women (p < 0.0001). Mean SF was 153 microg/l in Native American and 151 microg/l in white men (p = 0.8256); mean SF was 55 microg/l in Native American women and 63 microg/l in white women (p = 0.0015). The C282Y allele frequency was 0.0340 in Native Americans and 0.0683 in whites (p < 0.0001). The H63D allele frequency was 0.1150 in Native Americans and 0.1532 in whites (p = 0.0001). We conclude that the screening TfSat and SF phenotypes of Native Americans are similar to those of whites. The allele frequencies of HFE C282Y and H63D are significantly lower in Native Americans than in whites.
Assuntos
Ferritinas/metabolismo , Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Indígenas Norte-Americanos/genética , Sobrecarga de Ferro/genética , Proteínas de Membrana/genética , Transferrina/metabolismo , População Branca/genética , Adulto , Idoso , Feminino , Ferritinas/genética , Frequência do Gene , Genótipo , Hemocromatose/diagnóstico , Hemocromatose/metabolismo , Proteína da Hemocromatose , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/diagnóstico , Masculino , Pessoa de Meia-Idade , Fenótipo , Transferrina/genéticaRESUMO
OBJECTIVES: To test whether the T variant of the C677T polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) would associate with three distinct forms of vascular disease, abdominal aortic aneurysm (AAA), coronary artery disease (CAD) and peripheral vascular disease (PVD). BACKGROUND: Increases in homocysteine induce elastolytic activity in the arterial wall, a condition which may favour vascular pathogenesis including aneurysm formation. Homozygosity of the common T variant of the C677T polymorphism in the gene for MTHFR has been shown to associate with increased levels of homocysteine. Thus, this functional polymorphism may lead to an increased propensity to develop cardiovascular disease and, in particular, AAA. METHODS: An association study was conducted across 1207 subjects; 428 patients with AAA, 271 CAD patients, 226 PVD patients and 282 controls being genotyped for the C667T variants of MTHFR. RESULTS: There were no significant differences in the frequency of the MTHFR C677T variant between any of the groups examined. AAA patients who were homozygotes for the 677T allele did, however, appear to have significantly larger aneurysms than C allele carriers. CONCLUSION: This study provides no evidence that the T variant of MTHFR is associated with susceptibility to AAA, CAD or PVD. It may, however, be a contributory factor in AAA severity as indicated by aneurysm size.
Assuntos
Aneurisma da Aorta Abdominal/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação Puntual/genética , Polimorfismo Genético/genética , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/genética , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/genética , Índice de Gravidade de DoençaRESUMO
This paper highlights the increasing concerns relating to hydroenvironmetal issues and cites recent examples of the challenges now being regularly faced by hydroenvironmetal scientists and engineers. The limitations and restrictions of both physical (or laboratory) and numerical (or computer based) hydraulic models used in the planning and management of aquatic basins are discussed. General details are given of numerical models used for flow and water quality concentration predictions in estuarine waters, with particular application to the challenges occurring along the South Wales coast. A highly accurate and non-diffusive finite difference scheme that solves the transport equation for predicting water quality indicators and suspended sediment concentration distributions is also discussed. In particular, details are outlined of the extension of the water quality indicators of faecal coliforms, as required to comply with the EU Bathing Water Directive, to predict health risk assessment, in the form of predicting the risk of gastroenteritis. Three example research projects along the South Wales coast are described; the projects involve the application of two-dimensional and three-dimensional hydroenvironmetal models to predict flow patterns and water quality indicator organism distributions in the coastal receiving waters. These studies include: (i) a curvilinear finite difference approach to modelling flows in the Bristol Channel, (ii) coastal health risk predictions in Swansea Bay using combined water quality and epidemiological models, and (iii) combined sewer overflow discharges into Cardiff Bay.
Assuntos
Modelos Teóricos , Microbiologia da Água , Purificação da Água , Abastecimento de Água , Simulação por Computador , Coleta de Dados , Engenharia , Meio Ambiente , Imageamento Tridimensional , Matemática , Chuva , Medição de Risco , País de Gales , Abastecimento de Água/normasRESUMO
BACKGROUND: A common germline polymorphism of p53 produces a protein with an Arg to Pro change at codon 72. This Pro variant has altered biochemical properties suggesting altered cancer susceptibility. METHODS: A case control study with 115 men with prostate cancer and 181 community control male subjects was conducted. Demographics, family history of cancer, and blood were obtained. Codon 72 genotypes were determined using PCR. RESULTS: The Pro/Pro genotype was associated with a markedly lower risk of prostate cancer (OR = 0.23, CI = 0.07-0.79, P = 0.012). Similar reduction in risk was observed when the analysis was limited to Caucasian subjects (86% of total). Reduction in risk remained significant in a logistic regression model after correcting for age and family history of prostate cancer (OR = 0.14, CI = 0.03-0.71, P = 0.017). CONCLUSIONS: Men with the p53 codon 72 Pro/Pro genotype appear to be at reduced risk of prostate cancer.
Assuntos
Adenocarcinoma/genética , Genes p53/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Códon , DNA de Neoplasias/química , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Eletroforese em Gel de Ágar , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Inquéritos e QuestionáriosRESUMO
A putative 1079A-->T mutation in the alpha1 isoform of the Na(+), K(+)-ATPase (Atp1a1) gene of the Dahl salt-sensitive rat inbred by John Rapp (SS/Jr) strain was projected to cause a conformation change in the membrane hydrophobic region of the protein product, possibly resulting in hypertension. The existence of the mutation was challenged, but the challenge was apparently rebutted. The New Zealand genetically hypertensive (GH) rat is known to have a blood pressure quantitative trait locus on chromosome 2 containing the gene for the ATPase. Thus, we sought to determine whether the GH rat carried the 1079A-->T transversion. We chose a method, first nucleotide change analysis, that can detect point mutations in a mixed population of polymerase chain reaction (PCR) products, even in the presence of PCR bias, and confirmed our analysis by restriction enzyme digestion of PCR products. To ensure the validity of our analyses, we used site-directed mutagenesis to create positive controls containing the mutation. Surprisingly, we found that neither the GH nor the SS/Jr strain had the A1079T transversion. Indeed, the transversion was not found in any strain tested. As an incidental observation, we have sequenced the intron preceding the exon containing the putative A1079T transversion. Within this intron, a single-base C/T polymorphism was observed at base 132. Our results definitively eliminate the putative A1079T transversion in Atp1a1 as a causative factor underlying hypertension in the GH, spontaneously hypertensive, and SS/Jr rat strains and indicate that alternative candidate genes in the region defined by the chromosome 2 hypertension quantitative trait locus should be examined.
Assuntos
Hipertensão/genética , ATPase Trocadora de Sódio-Potássio/genética , Trifosfato de Adenosina/metabolismo , Substituição de Aminoácidos , Animais , Sítios de Ligação/genética , DNA/química , DNA/genética , DNA/metabolismo , Análise Mutacional de DNA , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Feminino , Hipertensão/enzimologia , Isoenzimas/química , Isoenzimas/genética , Masculino , Mutação Puntual , Estrutura Terciária de Proteína , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Dahl , Ratos Endogâmicos Lew , Ratos Endogâmicos SHR , Ratos Endogâmicos , Ratos Endogâmicos WKY , ATPase Trocadora de Sódio-Potássio/química , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
A trait of vascular fragility, characterized by the formation of abrupt defects within the elastic laminae of the abdominal aorta, has been identified in Brown Norway (BN) rats. These lesions are greatly exacerbated in F(1) rats from a BN x New Zealand genetically hypertensive (GH) intercross, implying that the genetic background provided by the GH rat influences lesion severity. The F(2) progeny of the BN x GH intercross were used to identify susceptibility loci for the lesions as well as exacerbating loci. Two major quantitative trait loci (QTLs) for number of internal elastic lamina lesions were identified on rat chromosomes 5 and 10, with the maximum "log of the odds ratio" (LOD) scores at D5Rat119 (LOD 5.0) and at D10Mit2 (LOD 4.5), respectively, together contributing 33.5% to the genetic variance. Further analysis revealed that the chromosome 10 locus exhibits a dominant mode of inheritance, with BN alleles being associated with increased lesion number (P < 0.0002) compared with GH homozygotes. This locus was in epistasis to a modifier locus on rat chromosome 2 at D2Mit14 (LOD score 2.12). A second major locus was identified on chromosome 5, exhibiting a semidominant mode of inheritance, again with the BN allele being significantly associated with increased lesion number (P < 0.0001). Furthermore, a locus influencing lesion severity was identified on chromosome 3 wherein GH alleles associated with increased severity. This is the first study to identify susceptibility loci for vascular elastic tissue fragility.
Assuntos
Predisposição Genética para Doença/genética , Doenças Vasculares/genética , Animais , Aorta Abdominal/patologia , Mapeamento Cromossômico , Cruzamentos Genéticos , Feminino , Ligação Genética , Marcadores Genéticos , Genótipo , Escore Lod , Masculino , Fenótipo , Característica Quantitativa Herdável , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos SHR , Doenças Vasculares/patologiaRESUMO
PURPOSE: To investigate the familial incidence and phenotypic characteristics of patients with abdominal aortic aneurysms (AAA) in the Otago region of New Zealand. METHODOLOGY: A retrospective audit based pilot study and a prospective study of patients having abdominal aortic aneurysm repair from September 1988 to September 1999 was performed. RESULTS: 248 probands were enrolled, of which 19.4% had one or more first degree relative affected. The age at diagnosis of the familial (70.2) and non-familial (70.5) patients was similar. The proportion of females was increased in the familial subgroup. Hypercholesterolaemia was the only phenotypic feature to differentiate familial from non-familial patients and was associated with an earlier age of presentation. In the familial families, brothers were the most common relative affected and 77% of the families had two patients with AAA. CONCLUSION: 19.4% of patients operated on in the Otago area for AAA had a familial component to their aneurysm.
Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/genética , Distribuição por Idade , Idade de Início , Idoso , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/cirurgia , Feminino , Humanos , Hipercolesterolemia/complicações , Incidência , Masculino , Nova Zelândia/epidemiologia , Linhagem , Fenótipo , Projetos Piloto , Vigilância da População , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Distribuição por SexoRESUMO
PURPOSE: A familial component has previously been identified in 11% to 20% of patients with abdominal aortic aneurysms (AAAs). The genetic basis of familial AAA remains elusive, however. Matrix metalloproteinases have been implicated in aneurysm development; and plasmin, a serine protease, activates metalloproteinases. Plasminogen activator inhibitor-1 (PAI-1) regulates plasmin activation through the tissue plasminogen activators. A polymorphism within the promoter area of PAI-1 has been described that modifies PAI-1 expression and consequently plasminogen activation. The 4G homozygous variant is associated with increased PAI-1 expression and consequently reduced plasmin activity and therefore may be selected against in-familial AAA. The purpose of this study was to investigate the incidence of the 4G/5G insertion/deletion polymorphism in the promoter area of the PAI-1 gene in a population with AAA. METHODS: Patients seen at a tertiary referral center for repair of abdominal aortic aneurysms were recruited. DNA was extracted from blood. Primers were designed to amplify a 99 (5G)-base pair (bp) and a 98 (4G)-bp fragment bracketing the polymorphism. The 5' primer was mutated to allow a restriction endonuclease to cleave the 5G polymorphism into a 77-bp and a 22-bp fragment. Samples were run on agarose gels and stained with ethidium bromide. RESULTS: One hundred ninety patients with AAAs, including 39 patients with strong family histories and 163 controls were examined. The frequency of the 4G:5G alleles in the AAA population and in the control population was 0.6:0.4. However, 26% of patients with familial AAA were homozygous 5G compared with 13% of the control population. The 4G-allele frequency was 0.47 in the familial AAAs, compared with 0.62 in the nonfamilial patients (P =.02) and 0.61 in the control population (P =.03). CONCLUSION: The selection against the 4G4G genotype in the familial AAA population may indicate a role for PAI in the development of AAA in this population.
Assuntos
Aneurisma da Aorta Abdominal/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Idoso , Estudos de Casos e Controles , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genéticaRESUMO
XPD codes for a DNA helicase involved in transcription and nucleotide excision repair. Rare XPD mutations diminish nucleotide excision repair resulting in hypersensitivity to UV light and increased risk of skin cancer. Several polymorphisms in this gene have been identified but their impact on DNA repair is not known. We compared XPD genotypes at codons 312 and 751 with DNA repair proficiency in 31 women. XPD genotypes were measured by PCR-RFLP. DNA repair proficiency was assessed using a cytogenetic assay that detects X-ray induced chromatid aberrations (breaks and gaps). Chromatid aberrations were scored per 100 metaphase cells following incubation at 37 degrees C (1.5 h after irradiation) to allow for repair of DNA damage. Individuals with the Lys/Lys codon 751 XPD genotype had a higher number of chromatid aberrations (132/100 metaphase cells) than those having a 751Gln allele (34/100 metaphase cells). Individuals having greater than 60 chromatid breaks plus gaps were categorized as having sub-optimal repair. Possessing a Lys/Lys751 genotype increased the risk of sub-optimal DNA repair (odds ratio = 7.2, 95% confidence interval = 1.01-87.7). The Asp312Asn XPD polymorphism did not appear to affect DNA repair proficiency. These results suggest that the Lys751 (common) allele may alter the XPD protein product resulting in sub-optimal repair of X-ray-induced DNA damage.
Assuntos
DNA Helicases/genética , Reparo do DNA , Proteínas de Ligação a DNA , Polimorfismo Genético , Proteínas/genética , Fatores de Transcrição , Neoplasias da Mama/genética , Aberrações Cromossômicas , DNA/efeitos da radiação , Feminino , Genótipo , Humanos , Tolerância a Radiação , Proteína Grupo D do Xeroderma PigmentosoRESUMO
Models of human disease have long been used to understand the basic pathophysiology of disease and to facilitate the discovery of new therapeutics. However, as long as models have been used there have been debates about the utility of these models and their ability to mimic clinical disease at the phenotypic level. The application of genetic studies to both humans and model systems allows for a new paradigm, whereby a novel comparative genomics strategy combined with phenotypic correlates can be used to bridge between clinical relevance and model utility. This study presents a comparative genomic map for "candidate hypertension loci in humans" based on translating QTLs between rat and human, predicting 26 chromosomal regions in the human genome that are very likely to harbor hypertension genes. The predictive power appears robust, as several of these regions have also been implicated in mouse, suggesting that these regions represent primary targets for the development of SNPs for linkage disequilibrium testing in humans and/or provide a means to select specific models for additional functional studies and the development of new therapeutics.
Assuntos
Genoma Humano , Hipertensão/genética , Animais , Humanos , Funções Verossimilhança , Desequilíbrio de Ligação/genética , Camundongos , Valor Preditivo dos Testes , Característica Quantitativa Herdável , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos BN , Ratos Endogâmicos Dahl , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
In this study, phenotypic expression of spontaneous elastic laminae defects within the rat abdominal aorta was examined. Lesions in Brown Norway (BN) rats were compared with those of New Zealand genetically hypertensive (GH) rats. BN and GH rats were cross-bred to determine the phenotypic expression of these lesions in successive F(1) and F(2) generations. Lesions were assessed by distribution, number and a semiquantitative index of severity. All BN aortae contained numerous elastic tissue defects. In comparison, GH aortae contained only occasional elastic tissue lesions. F(1) aortae contained lesions in numbers similar to those of the parental BN strain; however, F(1) lesions were of significantly greater severity. Within the F(2) generation, a wide range in both lesion numbers and severity indices was observed, with approximately a quarter of animals having lesion numbers analogous to the GH parental strain. In conclusion, this study indicates that the spontaneous elastic tissue lesions observed within BN rats are consistent with an autosomal dominant, possibly single gene, effect. Moreover, epistatic effects, derived from the GH strain, may influence the severity of these lesions. The gene(s) responsible may be important in the development of conditions such as arteriosclerosis and aneurysms in humans.
Assuntos
Aorta Abdominal/patologia , Doenças da Aorta/genética , Doenças da Aorta/patologia , Tecido Elástico/patologia , Animais , Aorta Abdominal/anormalidades , Aorta Abdominal/ultraestrutura , Tecido Elástico/anormalidades , Tecido Elástico/ultraestrutura , Feminino , Masculino , Fenótipo , Ratos , Ratos Endogâmicos BN/genética , Ratos Endogâmicos SHR/genéticaRESUMO
Geobacter sulfurreducens contains a 9.6-kDa c-type cytochrome that was previously proposed to serve as an extracellular electron shuttle to insoluble Fe(III) oxides. However, when the cytochrome was added to washed-cell suspensions of G. sulfurreducens it did not enhance Fe(III) oxide reduction, whereas similar concentrations of the known electron shuttle, anthraquinone-2,6-disulfonate, greatly stimulated Fe(III) oxide reduction. Furthermore, analysis of the extracellular c-type cytochromes in cultures of G. sulfurreducens demonstrated that the dominant c-type cytochrome was not the 9.6-kDa cytochrome, but rather a 41-kDa cytochrome. These results and other considerations suggest that the 9.6-kDa cytochrome is not an important extracellular electron shuttle to Fe(III) oxides.
Assuntos
Grupo dos Citocromos c/metabolismo , Compostos Férricos/metabolismo , Bactérias Anaeróbias Gram-Negativas/enzimologia , Transporte de Elétrons , Eletroforese em Gel de Poliacrilamida , Bactérias Anaeróbias Gram-Negativas/metabolismo , Peso Molecular , Periplasma/metabolismoRESUMO
The dissimilatory Fe(III) reducer Geobacter metallireducens reduced Fe(III) bound in humic substances, but the concentrations of Fe(III) in a wide range of highly purified humic substances were too low to account for a significant portion of the electron-accepting capacities of the humic substances. Furthermore, once reduced, the iron in humic substances could not transfer electrons to Fe(III) oxide. These results suggest that other electron-accepting moieties in humic substances, such as quinones, are the important electron-accepting and shuttling agents under Fe(III)-reducing conditions.
Assuntos
Deltaproteobacteria/metabolismo , Compostos Férricos/metabolismo , Substâncias Húmicas/metabolismo , Ferro/metabolismo , Transporte de Elétrons , Substâncias Húmicas/química , OxirreduçãoRESUMO
OBJECTIVE: To assess racial differences in risk of developing retinopathy among individuals with type 2 diabetes, after taking into account differences in the distribution of risk factors for retinopathy. RESEARCH DESIGN AND METHODS: The participants were 105 individuals with type 2 diabetes, aged 40-69 years, who had no evidence of retinopathy at the time of a diabetic eye disease screening project. After an average of 4 years of follow-up, the subjects were reevaluated using nonmydriatic funds photography. RESULTS: Retinopathy occurred more often among black than white participants (50 vs. 19%). This difference could not be explained by differences in risk factors for retinopathy or potential confounders (odds ratio [95% CI] 2.96 [1.00-8.78] after adjustment for level of glycosylated hemoglobin, systolic blood pressure, type of diabetes treatment, and sex). CONCLUSIONS: These results are consistent with the concept that racial differences in risk of developing retinopathy exist among individuals with type 2 diabetes and that these differences may be caused by differential (genetic) susceptibility to the adverse effects of increased levels of blood glucose and/or blood pressure. Discovery of the etiology of this differential susceptibility would allows us to identify and target secondary prevention efforts to individuals with type 2 diabetes who are at increased risk of retinopathy.
Assuntos
População Negra , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus/fisiopatologia , Retinopatia Diabética/epidemiologia , Obesidade , População Branca , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Glicemia/análise , Pressão Sanguínea , Diabetes Mellitus Tipo 2/sangue , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Branca/estatística & dados numéricosRESUMO
The possibility that microorganisms might use reduced humic substances (humics) as an electron donor for the reduction of electron acceptors with a more positive redox potential was investigated. All of the Fe(III)- and humics-reducing microorganisms evaluated were capable of oxidizing reduced humics and/or the reduced humics analogue anthrahydroquinone-2,6,-disulphonate (AHODS), with nitrate and/or fumarate as the electron acceptor. These included Geobacter metallireducens, Geobacter sulphurreducens, Geothrix fermentans, Shewanella alga, Wolinella succinogenes and 'S. barnesii'. Several of the humics-oxidizing microorganisms grew in medium with AHQDS as the sole electron donor and fumarate as the electron acceptor. Even though it does not reduce Fe(III) or humics, Paracoccus denitrificans could use AHQDS and reduced humics as electron donors for denitrification. However, another denitrifier, Pseudomonas denitrificans, could not. AHODS could also serve as an electron donor for selenate and arsenate reduction by W. succinogenes. Electron spin resonance studies demonstrated that humics oxidation was associated with the oxidation of hydroquinone moieties in the humics. Studies with G. metallireducens and W. succinogenes demonstrated that the anthraquinone-2,6-disulphonate (AQDS)/AHQDS redox couple mediated an interspecies electron transfer between the two organisms. These results suggest that, as microbially reduced humics enter less reduced zones of soils and sediments, the reduced humics may serve as electron donors for microbial reduction of several environmentally significant electron acceptors.
Assuntos
Anaerobiose , Bactérias/metabolismo , Substâncias Húmicas/metabolismo , Aerobiose , Antraquinonas/metabolismo , Arseniatos/metabolismo , Bactérias/crescimento & desenvolvimento , Transporte de Elétrons , Fumaratos/metabolismo , Ácido Selênico , Compostos de Selênio/metabolismo , Células Tumorais CultivadasRESUMO
The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Using polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicroscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation (BMT) for childhood ALL. Remission BM specimens were taken 6 to 81 days (median, 23) before transplant. All patients received similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplanted in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor delta or gamma rearrangements, electrophoresis, and allele-specific oligoprobing. Samples were rated high-level positive (clonal band evident after electrophoresis; sensitivity 10(-2) to 10(-3)), low-level positive (MRD detected only after oligoprobing; sensitivity 10(-3) to 10(-5)), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all MRD-), MRD was detected at high level in 12 patients, low level in 11, and was undetectable in 33. Two-year event-free survival for these groups was 0%, 36%, and 73%, respectively (P <.001). Follow-up in patients remaining in continuing remission is 20 to 96 months (median, 35). These results suggest that MRD analysis could be used routinely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) and of those with more responsive disease (who may be candidates for randomized trials of BMT versus modern intensive relapse chemotherapy).
Assuntos
Transplante de Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neoplasia Residual , Valor Preditivo dos Testes , Prognóstico , Transplante Homólogo , Resultado do TratamentoRESUMO
Parkinson disease (PD) is a prevalent movement disorder of unknown cause whose incidence rises with increasing age. Nearly 20% of PD is familial, a small subset of which exhibits autosomal dominant transmission. However, in most families, the inheritance is not clear. To determine the most likely mode of inheritance of PD, we performed complex segregation analyses using kindreds of 136 PD patients randomly ascertained from a clinic population. The hypotheses of a nontransmissible environmental factor, no major gene or type (sporadic), and all Mendelian inheritance (dominant, recessive, additive, decreasing) were rejected (P <0.001). Familial clustering of PD in this data set is best explained by a rare familial factor which a) is transmitted in a nonMendelian fashion, and b) influences the age at onset of PD. If confirmed, our results have immediate implications in gene-mapping studies which often search for genes that behave in a Mendelian fashion that affect susceptibility rather than age at onset and long term implications in understanding the pathogenesis of PD.
Assuntos
Predisposição Genética para Doença , Doença de Parkinson/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Meio Ambiente , Feminino , Genes Dominantes , Genes Recessivos , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estatística como AssuntoRESUMO
It is generally considered that sulphur reduction was one of the earliest forms of microbial respiration, because the known microorganisms that are most closely related to the last common ancestor of modern life are primarily anaerobic, sulphur-reducing hyperthermophiles. However, geochemical evidence indicates that Fe(III) is more likely than sulphur to have been the first external electron acceptor of global significance in microbial metabolism. Here we show that Archaea and Bacteria that are most closely related to the last common ancestor can reduce Fe(III) to Fe(II) and conserve energy to support growth from this respiration. Surprisingly, even Thermotoga maritima, previously considered to have only a fermentative metabolism, could grow as a respiratory organism when Fe(III) was provided as an electron acceptor. These results provide microbiological evidence that Fe(III) reduction could have been an important process on early Earth and suggest that microorganisms might contribute to Fe(III) reduction in modern hot biospheres. Furthermore, our discovery that hyperthermophiles that had previously been thought to require sulphur for cultivation can instead be grown without the production of toxic and corrosive sulphide, should aid biochemical investigations of these poorly understood organisms.