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1.
J Evol Biol ; 22(4): 805-17, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19226415

RESUMO

Synodontis catfish are a species-rich, tropical pan-African genus that predominately occur in fluviatile environments, but which also form a small radiation within Lake Tanganyika (LT). Here we estimate Synodontis relationships, based on mitochondrial and nuclear DNA, greatly expanding previous sampling. Data were analysed using different methods of phylogenetic inference: Bayesian (also testing compositional heterogeneity), likelihood and parsimony, in order to investigate biogeographic history and the extent of intralacustrine speciation within this group. Bayesian-relaxed clock analyses were used to estimate timings of radiations. Our analyses reveal a single origin of the LT flock with the inclusion of the nonendemic S. victoriae, and that these taxa evolved relatively recently (5.5 Ma), considerably later than the formation of LT (9-12 Ma). Two internal endemic clades diversified at a similar time (2-2.5 Ma), corresponding to a period of climate change, when lake levels dropped. We find evidence for a further species flock, composed of riverine southern African taxa, the diversification of which is very rapid, 0.8 Ma (95% HPD: 0.4-1.5) and infer a similar scenario for the diversification of this flock to southern African serrachromine cichlids in that they radiated in the now extinct lake Makgadikgadi. We also reveal that the biogeographic history of Synodontis catfish is more complex than previously thought, with nonmonophyletic geographic species groupings.


Assuntos
Peixes-Gato/classificação , Filogenia , África , Animais , Peixes-Gato/genética , DNA Mitocondrial/genética , Dados de Sequência Molecular
2.
Toxicology ; 212(1): 10-23, 2005 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15963385

RESUMO

BACKGROUND: Iron is an essential micronutrient but also a major catalyst of oxidative and inflammatory reactions. OBJECTIVE: To evaluate the potential utility of selected biomarkers in blood or urine to indicate in vivo oxidative or inflammatory response to oral iron intake at pharmacological doses. METHODS: Three healthy volunteers provided morning, fasting samples of blood and urine on up to 13 study days--3 before, 7 during and 3 following a 7-consecutive-day period of receiving 120 mg of iron per day as ferrous sulfate in commercially available syrup. A series of 23 biomarkers were measured on each collection of biological fluids to monitor iron-responsive changes in biomarkers related to hematological or iron status, inflammation and in vivo oxidation. RESULTS: Among the inflammatory biomarkers measured, white blood cells, serum CRP and urinary neopterin showed no response to iron dosing. Only circulating interleukin-4 (IL-4) and TNF-alpha had abnormal responses with a time association to the oral iron intake. Among the oxidative biomarkers, expression of blood superoxide dismutase (SOD), hemoxygenase-1, catalase as well as circulating thiobarbituric acid reactive substances (TBARS), total oxidative capacity and carbonyl proteins were stable in response to iron exposure. Only urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes evidenced consistent or suggestive responses to ingestion of the iron challenge. Serum hepcidin concentration increased dramatically in all three subjects after only the first 120 mg dose of iron, and remained elevated even 9 days after cessation of the iron intervention. CONCLUSIONS: Most of the candidate biomarkers show very limited promise as response-indicators to oral iron dosing at the 120 mg dosages or lower, but circulating IL-4, TNF-alpha as well as urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes showed potential utility as reliable indicators of oxidative and inflammatory response to oral ferrous sulfate.


Assuntos
Compostos Ferrosos/toxicidade , Inflamação/sangue , Inflamação/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Testes Hematológicos/métodos , Humanos , Inflamação/urina , Masculino , Estresse Oxidativo/fisiologia , Projetos Piloto
4.
Med Hypotheses ; 61(4): 419-30, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-13679005

RESUMO

To date, relatively little is known about the etiology, pathophysiology, diagnosis, therapy, prevention and prognosis of environment-related syndromes like multiple chemical sensitivity (MCS), idiopathic environmental intolerance (IEI), sick building syndrome (SBS), chronic fatigue syndrome (CFS), candida syndrome (CS) and burnout syndrome (BS). Part of the reason is that these syndromes have not been clearly defined and classified in scientific categories distinct from each other, and that they show clinical similarities to classified somatoform disorders. Furthermore, there are at least three possible explanations for the existence of these syndromes: (1) The syndromes may result from the interaction of environmental factors, individual susceptibility and psychological factors (i.e., how they are perceived and seen by the patient); (2) they may reflect socially and culturally accepted methods of expressing distress; and/or (3) they may be iatrogenic. Despite all the uncertainties in evaluation of environmental syndromes, physicians have the duty to take the affected person's problems seriously. A comprehensive systematic classification which better accounts for these complex clinical manifestations is long overdue. Until these syndromes are well defined, the terms used for them should definitely not be applied to connote a specific disease process.


Assuntos
Medicina Ambiental , Transtornos Somatoformes/diagnóstico , Meio Ambiente , Doença Ambiental/diagnóstico , Síndrome de Fadiga Crônica/diagnóstico , Humanos , Modelos Teóricos , Sensibilidade Química Múltipla/diagnóstico , Síndrome do Edifício Doente/diagnóstico , Síndrome
5.
Med Sci Monit ; 9(8): RA203-15, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12942047

RESUMO

The existence of a 'chronic whiplash injury' has been a source of debate in the medical literature for many years. Some authors have published articles suggesting that chronic whiplash syndrome is the result of chronic pathology (injury), and that this injury may occur at any collision speed; others have stated that any psychological factors are secondary rather than primary (etiologic) to the problem of chronic pain, or that secondary gain is a rare or uncommon phenomenon. These articles contradict scientific measures and efforts which show that for Quebec Task Force Grade 1 and 2 whiplash-associated disorders, the highly prevalent problem of chronic pain may be a culturally and psychosocially determined phenomenon, in which confounding psychosocial variables determine the behaviour and outcome following an otherwise benign acute injury. The authors of the current literature critique reviewed the biomedical and engineering literature relating to whiplash syndrome, searching for articles that supported the construct of 'chronic whiplash injuries'. Thirty seven articles containing fourteen distinct statements supporting the construct of 'chronic whiplash injuries' were found that fit the inclusion criteria. The methodology described in these articles was evaluated critically to determine if the authors' conclusions regarding 'chronic whiplash injuries' were scientifically sound. The authors of the current critique found that all of the articles contained significant methodologic errors relative to their respective authors' statements regarding chronic whiplash. The most frequent concerns reside with sampling, experimental design and interpretation of data.


Assuntos
Traumatismos em Chicotada , Acidentes de Trânsito/legislação & jurisprudência , Lesões Encefálicas/fisiopatologia , Vértebras Cervicais/anatomia & histologia , Vértebras Cervicais/patologia , Estudos de Avaliação como Assunto , Humanos , Cervicalgia/etiologia , Cervicalgia/fisiopatologia , Reprodutibilidade dos Testes , Transtornos da Articulação Temporomandibular/etiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Traumatismos em Chicotada/patologia , Traumatismos em Chicotada/fisiopatologia , Traumatismos em Chicotada/psicologia
10.
Med Hypotheses ; 57(4): 459-64, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11601869

RESUMO

Since the introduction of the concept of tertiary gain by Dansak in 1973, there has been little further publication or research on this topic. Yet, tertiary gain is often the subject of debate amongst physicians, therapists, insurers, the media, and even at times the general public. Much of the controversy of disability syndromes and the health and economic burden they present has focused on secondary gain and illness behaviour. The role of tertiary gain in illness behaviour is likely also relevant, and a model of tertiary gain is needed to begin further understanding the implications of this phenomenon for patients and those who treat them. This article introduces a phraseology for tertiary gain, and models the effects of tertiary gain on illness behaviour and the interactions of secondary and tertiary gain in the setting of disability syndromes.


Assuntos
Pessoas com Deficiência/psicologia , Papel do Doente , Humanos
11.
Endocrinology ; 142(11): 4983-93, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11606467

RESUMO

PTH and PTHrP both act in the regulation of fetal mineral metabolism. PTHrP regulates placental calcium transfer, fetal blood calcium, and differentiation of the cartilaginous growth plate into endochondral bone. PTH has been shown to influence fetal blood calcium, but its role in skeletal formation remains undefined. We compared skeletal morphology, mineralization characteristics, and gene expression in growth plates of fetal mice that lack parathyroids and PTH (Hoxa3 null) with the effects of loss of PTHrP (Pthrp null), loss of PTH/PTHrP receptor (Pthr1 null), and loss of both PTH and PTHrP (Hoxa3 null x Pthrp null). Loss of PTH alone does not affect morphology or gene expression in the skeletal growth plates, but skeletal mineralization and blood calcium are significantly reduced. In double-mutant fetuses (Hoxa3 null/Pthrp null), combined loss of PTH and PTHrP caused fetal growth restriction, limb shortening, greater reduction of fetal blood calcium, and reduced mineralization. These findings suggest that 1) PTH may play a more dominant role than PTHrP in regulating fetal blood calcium; 2) blood calcium and PTH levels are rate-limiting determinants of skeletal mineral accretion; and 3) lack of both PTH and PTHrP will cause fetal growth restriction.


Assuntos
Densidade Óssea/fisiologia , Cálcio/sangue , Sangue Fetal , Hormônio Paratireóideo/fisiologia , Proteínas/fisiologia , Animais , Osso e Ossos/embriologia , Retardo do Crescimento Fetal/etiologia , Feto/anatomia & histologia , Feto/metabolismo , Expressão Gênica , Lâmina de Crescimento/fisiologia , Proteínas de Homeodomínio/genética , Camundongos , Camundongos Knockout/genética , Glândulas Paratireoides/anormalidades , Glândulas Paratireoides/embriologia , Hormônio Paratireóideo/deficiência , Proteína Relacionada ao Hormônio Paratireóideo , Proteínas/genética , Esqueleto
12.
Virology ; 288(1): 139-44, 2001 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-11543666

RESUMO

Foamy viruses have several qualities favorable for vector development: they are not known to cause disease; they can transduce stationary cells; and the foamy virus receptor is expressed on a wide variety of cells. Here, we analyzed the level of virus receptor expression on hematopoietic progenitor cells. Foamy virus binding was measured by a flow cytometric assay and was found to be considerably reduced in hematopoietic progenitors cell lines as well as in primary CD34(+) cells when compared to fibroblasts. Retroviral vectors based on murine leukemia virus (MLV) pseudotyped with a foamy virus envelope transduced hematopoietic cell lines with a more than 10-fold lower efficiency than fibroblasts. Moreover, less than 1% of primary CD34(+) hematopoietic progenitor cells were transduced with the foamy virus pseudotypes, while gene transfer efficiencies of 8-40% were achieved using pseudotypes with amphotropic envelope or the G protein of vesicular stomatitis virus. In conclusion, the expression of functional foamy virus receptors on hematopoietic progenitors cells was found to be insufficient to achieve high levels of gene transfer into CD34(+) hematopoietic progenitor cells with cell-free vector supernatants using current transduction protocols.


Assuntos
Células-Tronco Hematopoéticas/virologia , Receptores Virais/fisiologia , Spumavirus/fisiologia , Proteínas Virais/genética , Animais , Antígenos CD34/análise , Linhagem Celular , Fibroblastos , Técnicas de Transferência de Genes , Humanos , Rim , Células L , Vírus da Leucemia Murina/fisiologia , Camundongos , Especificidade da Espécie , Spumavirus/genética , Linfócitos T/virologia , Transfecção , Proteínas do Envelope Viral/fisiologia , Proteínas Virais/metabolismo
13.
Surgery ; 130(2): 242-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11490356

RESUMO

BACKGROUND: Prolonged polymorphonuclear neutrophil (PMN) survival has been implicated in tissue injury after sepsis. Previously we reported that lipopolysaccharide (LPS) inhibits PMN apoptosis via the activation of the extracellular signal-regulated kinase (ERK). Conversely, the p38 mitogen activated protein kinase (MAPK) pathway is involved in the spontaneous apoptosis of PMNs. The interaction between these 2 pathways and their ability to regulate apoptosis during sepsis remain largely undefined. We hypothesize that there is interaction between the ERK and p38 pathways during sepsis. METHODS: PMNs were isolated from healthy volunteers by Ficoll gradient centrifugation and red blood cell sedimentation. Cells were then pretreated for 1 hour with the ERK inhibitor (PD98059, 10 micromol/L), p38 inhibitor (SB203580, 1 micromol/L), or vehicle. After treatment with LPS, apoptosis and MAPK activity were correlated. RESULTS: LPS stimulation significantly inhibits PMN apoptosis compared with unstimulated cells. Furthermore, inhibition of ERK significantly abrogates this effect, whereas inhibition of p38 augments LPS induced inhibition of apoptosis. Elk-1 phosphorylation (ERK target) is significantly increased by LPS alone and by inhibition of the p38 pathway during LPS stimulation. This correlates with ERK phosphorylation by Western blot. CONCLUSIONS: These data show that p38 inhibition enhances ERK activity during endotoxemia. Furthermore, these data suggest that cooperation between ERK and p38 MAPK pathways dictates the apoptotic potential of PMNs during inflammatory states.


Assuntos
Apoptose/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neutrófilos/citologia , Adulto , Apoptose/imunologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Humanos , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Neutrófilos/enzimologia , Fosforilação , Piridinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno
14.
J Pediatr ; 139(2): 254-60, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11487753

RESUMO

OBJECTIVES: To investigate the effect of increased iron intakes on hematologic status and cognition in low birth weight infants. STUDY DESIGN: We randomly assigned 58 infants to receive formula with 13.4 mg iron/L (normal iron) or 20.7 mg iron/L (high iron). At baseline, discharge, and at 3, 6, 9, and 12 months' corrected age, we assessed anthropometry; infections; red blood cell hemoglobin, catalase, glutathione peroxidase, red blood cell fragility (hydrogen peroxide test), and superoxide dismutase values; plasma malondialdehyde, ferritin, iron, transferrin, zinc and copper levels; and diet intake. Griffiths' Development Assessment was done at 3, 6, 9, and 12 months only. RESULTS: No statistical differences (P <.05) were noted for weight, catalase or malondialdehyde levels, red blood cell fragility, or Griffith's Development Assessment. Iron intakes were greater in the high iron group except at 12 months. Hemoglobin (high iron, 123 +/- 9; normal iron, 118 +/- 8) was not different at 3 months (P =.07). Plasma zinc levels (high iron, 70 +/- 14; normal iron, 89 +/- 27) and copper levels (high iron, 115 +/- 26; normal iron, 132 +/- 27; P =.06) at 12 months suggested inhibition of absorption by high iron formula. Glutathione peroxidase levels were higher in the high iron group. The total number of respiratory tract infections was greater in the high iron group (3.3 +/- 0.9) than in the normal iron group (2.5 +/- 0.9). CONCLUSION: In terms of cognitive outcome, there is no advantage associated with elevated iron intake for low birth weight infants.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Recém-Nascido de Baixo Peso , Ferro/uso terapêutico , Análise de Variância , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Humanos , Recém-Nascido , Ferro/administração & dosagem , Zinco/sangue
15.
J Pediatr Gastroenterol Nutr ; 33(1): 64-9, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11479410

RESUMO

BACKGROUND: There is a paucity of data about water soluble vitamin status in low birthweight infants. Therefore, the authors' objective was to assess current feeding protocols. METHODS: The authors measured serum concentrations for riboflavin, pyridoxine, and vitamin C and functional assays for thiamine and riboflavin longitudinally in 16 premature infants (birthweight, 1,336 +/- 351 g; gestational age, 30 +/- 2.5 weeks) before receiving nutrition (time 1, 2 +/- 1 days), during supplemental or parenteral nutrition (time 2, 16 +/- 10 days) and while receiving full oral feedings (time 3, 32 +/- 15 days). In plasma, vitamin C was measured colorimetrically, and riboflavin and pyridoxine were measured using high-performance liquid chromatography. The erythrocyte transketolase test as a functional evaluation of thiamine and the erythrocyte glutathione reductase test for riboflavin were measured colorimetrically. RESULTS: At time 1, nutrient intake of vitamins were negligible because infants were receiving intravenous glucose and electrolytes only. Intakes differed between time 2 and time 3 for thiamine (510 +/- 280 and 254 +/- 115 microg. kg-1. d-1, respectively), riboflavin (624 +/- 305 and 371 +/- 193 microg. kg-1. d-1, respectively), and pyridoxine (394 +/- 243 and 173 +/- 85 microg/100 kcal, respectively), but not for vitamin C (32 +/- 17 and 28 +/- 12 mg. kg-1. d-1, respectively). Blood levels at times 1, 2, and 3 were for thiamine (4.9 +/- 2.7%, 3.3 +/- 6.6%, and 4.1 +/- 9% erythrocyte transketolase test, respectively), riboflavin (0.91 +/- 0.31, 0.7 +/- 0.3, 0.91 +/- 0.18 erythrocyte glutathione reductase test, respectively), riboflavin (19.5 +/- 17, 23.3 +/- 8.6, 17.6 +/- 10 ng/mL, respectively), pyridoxine (32 +/- 25, 40 +/- 16, 37 +/- 26 ng/mL, respectively), and vitamin C (5.2 +/- 3, 5 +/- 2.2, 10 +/- 5 microg/mL, respectively) and did not differ at those times. CONCLUSIONS: Current intakes of these vitamins, except for possibly vitamin C, during parenteral and enteral nutrition seem to result in adequate plasma concentrations and normal functional indices.


Assuntos
Nutrição Enteral , Recém-Nascido de Baixo Peso/sangue , Estado Nutricional , Nutrição Parenteral , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Cromatografia Líquida de Alta Pressão/métodos , Colorimetria/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/sangue , Masculino , Necessidades Nutricionais , Piridoxina/administração & dosagem , Piridoxina/sangue , Riboflavina/administração & dosagem , Riboflavina/sangue , Tiamina/administração & dosagem , Tiamina/sangue
16.
J Surg Res ; 99(1): 129-33, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11421614

RESUMO

BACKGROUND: Prolonged neutrophil(PMN) survival has been implicated in tissue injury following sepsis. A variety of bacterial products have been identified which inhibit PMN apoptosis including lipopolysaccharide(LPS). Extracellular heat shock proteins(Hsp) have recently been identified as potent regulatory signals for the innate immune system during the inflammatory response. We hypothesized that Hsp 27 can affect PMN phenotype with respect to apoptosis and cytokine profile. MATERIALS AND METHODS: PMN were isolated from the peripheral blood of healthy human volunteers by red blood cell sedimentation and gradient centrifugation. Cells were placed in media and cultured for 18 h with and without recombinant human Hsp 27 at various concentrations. In parallel experiments, PMN were stimulated with LPS, a known inhibitor of PMN apoptosis, for comparison. Apoptosis was quantified using annexin V and propidium iodide staining with flow cytometric analysis. Culture supernatants were assayed for secretion of TNF-alpha, IL-10, and IL-12. RESULTS: Hsp 27 significantly inhibits PMN apoptosis [control; 81.8 +/- 3.6%, vs Hsp 27, 60.4 +/- 4.1% p < 0.05]. The reduction is similar to that signaled by LPS, alone. Together their effect is not synergistic. The Hsp 27 response is dose-dependent. Hsp 27 does not induce secretion of TNF-alpha, IL-10, or IL-12, whereas LPS does signal IL-12 and TNF-alpha secretion. CONCLUSION: These data demonstrate that exogenous Hsp 27 may play a role in neutrophil-mediated tissue injury during trauma and sepsis via its ability to inhibit neutrophil apoptosis. However, Hsp 27 does not significantly alter neutrophil phenotype with respect to cytokine production profile.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Choque Térmico/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Concentração Osmolar , Fator de Necrose Tumoral alfa/metabolismo
17.
Med Hypotheses ; 57(1): 68-75, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11421629

RESUMO

There are many controversial disability syndromes, representing medicolegal and social dilemmas for a variety of medical disciplines. While illness behavior and sick role phenomena are often invoked to explain many of these syndromes, the extent to which such phenomena are under volitional control has not been thoroughly explored. The volitional control of illness behavior has important treatment implications, and may explain why cognitive therapy can be effective in these patients. Further understanding of the relevance of cognitive theory to illness behavior, the sick role, secondary gain, and disability may render even more effective cognitive therapy approaches. This review explores the consciousness states, the role of each state in information processing (in this case processing illness information), the automaticity and hence volitional state of each level of information processing, and the likelihood that illness behavior in disability syndromes is volitional. The cognitive model of these syndromes considers the interaction of automaticity, volition, and illness behavior and likely has numerous clinical, social, and legal applications.


Assuntos
Cognição , Pessoas com Deficiência/psicologia , Modelos Teóricos , Papel do Doente , Humanos
18.
J Pediatr Gastroenterol Nutr ; 31(3): 270-4, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10997371

RESUMO

BACKGROUND: Human milk contains various bioactive compounds including numerous immunologic factors, enzymes, growth factors, and hormones. However, the change during the course of lactation in many of these compounds has not been fully characterized. Therefore, the objective of the present study was to measure the activity of the enzymes superoxide dismutase (SOD; Enzyme Commission number [EC] 1.15.1.1) and glutathione peroxidase (SeGSHPx; EC 1.11.1.9) in human milk, to record changes in enzyme activity over time and to determine whether there are differences in activity between the milk of mothers of full-term (FT) and premature (PT) infants. METHODS: Nine samples were collected from each of 15 mothers (32 +/- 4 years of age; mean +/- standard deviation) of FT infants (gestational age, 40 +/- 1 weeks; birth weight, 3544 +/- 417 g) and 19 mothers (28 +/- 5 years of age) of healthy PT infants (gestational age, 29 +/- 4 weeks; birth weight, 1312 +/- 479 g). Samples were collected within a week of birth (+/- 1 day) and thereafter for 8 weeks, with a final collection at 12 weeks. RESULTS: During the 12-week study period, in both groups, total milliunits of GHSPx and SeGHSPx per milligram protein and SOD per per milligram protein increased, whereas protein content declined. SeGHSPx per milliliter milk was higher in the PT group at week 1 (92 +/- 30 mU/mL vs. 73 +/- 21 mU/mL), week 2 (93 +/- 28 mU/mL vs. 75 +/- 24 mU/mL), and week 7 (85 +/- 24 mU/mL vs. 68 +/- 22 mU/mL). The SOD activity per milliliter milk and milligram protein was higher throughout the entire study in the FT milk. CONCLUSIONS: Because mothers of PT infants may produce less milk than those of FT infants, PT infants may be at a disadvantage for antioxidant protection from these enzymes.


Assuntos
Glutationa Peroxidase/análise , Recém-Nascido Prematuro , Lactação/metabolismo , Leite Humano/enzimologia , Superóxido Dismutase/análise , Adulto , Antioxidantes , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Leite Humano/fisiologia , Fatores de Tempo
19.
Exp Cell Res ; 259(1): 1-11, 2000 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-10942574

RESUMO

Retroviral insertional mutagenesis has proven to be a powerful in vivo approach for identifying genetic mutations involved in tumorigenesis or developmental abnormalities. Applying this approach to an in vitro system, where experimental design can be readily manipulated, would greatly increase its efficacy. In this study, we sought to determine whether retroviral insertional mutagenesis could be used to isolate cell mutants, in which the transcriptional activation of a receptor gene has occurred. Cells of the myeloid progenitor cell line FDC-P1(M), which do not express the alpha receptor subunit (GMRalpha) for granulocyte-macrophage colony-stimulating factor (GM-CSF), were infected and selected for growth in GM-CSF. Over 100 mutants were isolated at a frequency up to ninefold higher than that of uninfected controls. Expression of GMRalpha in these mutants was confirmed by blocking proliferation with GM-CSF antibodies, detection of high-affinity receptors, and Northern blot analysis. Significantly, in 7/18 mutants analyzed, gross DNA rearrangements had occurred in the GMRalpha locus. These rearrangements were demonstrated to be due to intergenic rearrangements, juxtaposing an active enhancer/promoter upstream of the GMRalpha gene. In one mutant it could be demonstrated that the wild-type allele was also expressed, providing evidence that secondary mutations had occurred. The implications of these results for retroviral insertional mutagenesis are discussed.


Assuntos
Vetores Genéticos , Mutagênese Insercional/fisiologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Retroviridae/genética , Ativação Transcricional/fisiologia , Animais , Anticorpos/farmacologia , Divisão Celular/fisiologia , Linhagem Celular , Clonagem Molecular , Expressão Gênica/fisiologia , Rearranjo Gênico/fisiologia , Células-Tronco Hematopoéticas/citologia , Íntrons/genética , Testes de Neutralização , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/imunologia , Proteínas Recombinantes de Fusão/genética
20.
CMAJ ; 162(11): 1557-9, 2000 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-10862228

RESUMO

BACKGROUND: Newfoundland has one of the highest rates of neural tube defects in North America. Given the association between low maternal folic acid levels and neural tube defects, a cross-sectional study was conducted to obtain base-line data on the folate and vitamin B12 status of a sample of women in Newfoundland who were pregnant. METHODS: Blood samples were collected between August 1996 and July 1997 from 1424 pregnant women in Newfoundland during the first prenatal visit (at approximately 16 weeks' gestation); this represented approximately 25% of the women in Newfoundland who were pregnant during this period. The samples were analysed for serum folate, vitamin B12, red blood cell folate and homocysteine. RESULTS: Median values for serum folate, red blood cell folate and serum vitamin B12 were 25 nmol/L, 650 nmol/L and 180 pmol/L, respectively. On the basis of the interpretive criteria used for red blood cell folate status, 157 (11.0%) of the 1424 women were deficient (< 340 nmol/L) and a further 180 (12.6%) were classified as indeterminate (340-420 nmol/L). Serum homocysteine levels, measured in subsets of the red blood cell folate status groups, supported the inadequate folate status. Serum vitamin B12 levels of 621 (43.6%) women were classified as deficient or marginal; however, the validity of the interpretive criteria for pregnant women is questionable. INTERPRETATION: A large proportion of pregnant women surveyed in Newfoundland in 1997 had low red blood cell folate levels.


Assuntos
Ácido Fólico/sangue , Vitamina B 12/sangue , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Terra Nova e Labrador , Gravidez , Cuidado Pré-Natal , Estudos Soroepidemiológicos
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