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1.
Ultrasound Obstet Gynecol ; 61(6): 682-690, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36840981

RESUMO

OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Pré-Eclâmpsia , Diagnóstico Pré-Natal , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Estudos Prospectivos , Proteína Plasmática A Associada à Gravidez , Fator de Crescimento Placentário , Pressão Arterial , Artéria Uterina/diagnóstico por imagem , Biomarcadores , Fluxo Pulsátil , Dinamarca/epidemiologia
2.
Pharmacogenomics J ; 18(3): 494-500, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28696418

RESUMO

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1ß levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.


Assuntos
Farmacogenética/métodos , Psoríase/tratamento farmacológico , Psoríase/genética , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Dinamarca , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Interleucina-1beta/genética , Antígeno 96 de Linfócito/genética , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Psoríase/epidemiologia , Psoríase/patologia , Receptores de Interleucina-1/genética , Receptor 2 Toll-Like/genética , Receptor Toll-Like 9/genética , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos
3.
Stud Mycol ; 91: 61-78, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30425417

RESUMO

The fungal kingdom is too large to be discovered exclusively by classical genetics. The access to omics data opens a new opportunity to study the diversity within the fungal kingdom and how adaptation to new environments shapes fungal metabolism. Genomes are the foundation of modern science but their quality is crucial when analysing omics data. In this study, we demonstrate how one gold-standard genome can improve functional prediction across closely related species to be able to identify key enzymes, reactions and pathways with the focus on primary carbon metabolism. Based on this approach we identified alternative genes encoding various steps of the different sugar catabolic pathways, and as such provided leads for functional studies into this topic. We also revealed significant diversity with respect to genome content, although this did not always correlate to the ability of the species to use the corresponding sugar as a carbon source.

4.
Int J Obes (Lond) ; 36(12): 1545-51, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22270380

RESUMO

BACKGROUND: Circulating angiotensin-converting enzyme (ACE) was identified as a predictor of weight loss maintenance in overweight/obese women of the Diogenes project. OBJECTIVE: To investigate whether ACE acted also as a predictor in men of the Diogenes study and to compare it with that in women. DESIGN: Subjects, who lost ≥ 8% of body weight induced by low-caloric diet in an 8-week weight loss period, were assigned to weight loss maintenance with dietary intervention for 6 months. SUBJECTS: 125 overweight/obese healthy men from eight European countries who completed whole intervention. MEASUREMENTS: Concentrations and activity of serum ACE at baseline and after the 8-week weight loss, in addition to anthropometric and physiological parameters. RESULTS: Serum ACE concentration decreased by 11.3 ± 10.6% during the weight loss period in men. A greater reduction is associated with less body weight regain during the maintenance period (r=0.227, P=0.012). ACE change was able to predict a weight regain ≤ 20% after 6 months, with an odds ratio of 1.59 (95% confidence interval (CI): 1.09-2.33, P=0.016) for every 10% reduction, which was independent of body mass index and weight loss. The prediction power was weaker in men than in women, but without a significant sex difference (P=0.137). In pooled subjects (N=218), the odds ratio was 1.96 (95% CI: 1.46-2.64, P<0.001). CONCLUSIONS: A greater reduction of ACE during weight loss is favorable for weight maintenance in both men and women. This can offer useful information for personalized advice to improve weight loss maintenance. It also confirms the role of ACE in the metabolic pathways of weight regulation.


Assuntos
Obesidade/sangue , Peptidil Dipeptidase A/sangue , Redução de Peso , Adulto , Biomarcadores/sangue , Estudos Transversais , Dieta Redutora , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Distribuição por Sexo , Aumento de Peso
5.
Integr Cancer Ther ; 20: 15347354211058404, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34894812

RESUMO

PURPOSE: To compare disease free survival experienced by women who received usual oncologic care compared to a cohort of women who received naturopathic oncology care in addition to usual care. METHODS: Women with breast cancer who received naturopathic oncology (NO) care in Western Washington State (WA) (N = 176) were recruited to a prospective study of clinical health-related quality of life outcomes and then matched to women who received usual care (UC) only (N = 334). RESULTS: Among 510 women with breast cancer stages 1 to 3, a total of 50 women (10%) experienced a disease-free survival (DFS) ending event within the observation period; 23 (6.8% of those in the UC cohort, and 27 (15.3% of those in the NO cohort (P < .05). Although, women in the 2 cohorts received similar surgical, chemotherapy, and radiation treatment, women with breast cancer who received naturopathic oncology adjunctive care were less likely to use anti-estrogen therapy, and experienced poorer DFS (logrank test, P < .05). However, differences in DFS could not be shown to be due to cohort differences in anti-estrogen therapy, baseline HRQOL, or naturopathic oncology therapies prescribed. The stage 3 women in the naturopathic oncology group had more advanced disease at diagnosis. They were more likely to have 5 or more metastatic lymph nodes at baseline (18.5%) compared to their usual care matched control group (13%). Women in the naturopathic oncology group also had higher grade tumors at diagnosis. CONCLUSIONS: Results show that recurrence of breast cancer was associated with more advanced malignant lymph node involvement; and that naturopathic oncology services provided in 2009-2015 did not improve disease-free survival in these high-risk breast cancer patients.


Assuntos
Neoplasias da Mama , Naturologia , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida
6.
Fungal Genet Biol ; 46 Suppl 1: S180-90, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18684401

RESUMO

In this review, we present a comprehensive overview of the current status of genomics, transcriptomics, proteomics, metabolomics, and metabolic modeling in Aspergillus species. Currently, 13 Aspergillus genomes divided across seven species have been sequenced with more to come, and many applications of this information on a systems level have been published. More than 30 studies on global transcription analysis have been published, and 21 different platforms are available for Aspergillus transcription studies. Additionally, the fields of proteomics and metabolomics have, while still in their infancy, produced intriguing results and novel applications. Finally, multiple levels of Aspergillus metabolism have been reconstructed and modelled. Systems-level research of Aspergilli have in a few years added to our knowledge on processes relevant to evolution, central and secondary metabolism, cellular organization, pathogenicity and biotechnology and future efforts may lead to much improved understanding of regulation of key cellular processes in this important family of filamentous fungi.


Assuntos
Aspergillus/fisiologia , Biologia de Sistemas , Aspergillus/genética , Perfilação da Expressão Gênica , Genoma , Metaboloma , Modelos Biológicos , Proteoma
7.
Metab Eng ; 11(2): 107-16, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19271267

RESUMO

In order to improve the production of succinate and malate by the filamentous fungus Aspergillus niger the activity of the glyoxylate bypass pathway was increased by over-expression of the isocitrate lyase (icl) gene. The hypothesis was that when isocitrate lyase was up-regulated the flux towards glyoxylate would increase, leading to excess formation of malate and succinate compared to the wild-type. However,metabolic network analysis showed that an increased icl expression did not result in an increased glyoxylate bypass flux. The analysis did show a global response with respect to gene expression, leading to an increased flux through the oxidative part of the TCA cycle. Instead of an increased production of succinate and malate, a major increase in fumarate production was observed. The effect of malonate, a competitive inhibitor of succinate dehydrogenase (SDH), on the physiological behaviour of the cells was investigated. Inhibition of SDH was expected to lead to succinate production, but this was not observed. There was an increase in citrate and oxalate production in the wild-type strain. Further more, in the strain with over-expression of icl the organic acid production shifted from fumarate towards malate production when malonate was added to the cultivation medium. Overall,the icl over-expression and malonate addition had a significant impact on metabolism and on organic acid production profiles. Although the expected succinate and malate formation was not observed, a distinct and interesting production of fumarate and malate was found.


Assuntos
Aspergillus niger/metabolismo , Glioxilatos/metabolismo , Isocitrato Liase/metabolismo , Transdução de Sinais/fisiologia , Aspergillus niger/genética , Isocitrato Liase/genética , Regulação para Cima
8.
Br J Pharmacol ; 155(4): 535-46, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18622409

RESUMO

BACKGROUND AND PURPOSE: The present study investigated the mechanisms by which oleanolic acid, a component of olive oil, increases release of nitric oxide (NO). EXPERIMENTAL APPROACH: Measurements of isometric tension, NO concentration, or endothelial cell calcium were made in rat isolated mesenteric arteries. Immunoblotting for endothelial NOS (eNOS) and Akt kinase were performed in primary cultures of human umbilical vein endothelial cells (HUVECs). KEY RESULTS: Oleanolic acid (3-30 microM) evoked endothelium-dependent relaxations in noradrenaline-contracted rat superior and small mesenteric arteries. In rat superior mesenteric arteries, oleanolic acid induced simultaneous increases in NO concentration and relaxation, and these responses were inhibited by an inhibitor of NOS, asymmetric dimethyl-L-arginine (300 microM) and by the NO scavenger, oxyhaemoglobin (10 microM). Oleanolic acid-evoked NO increases were not reduced in Ca(2+)-free solution and in the presence of an inhibitor of endoplasmic reticulum calcium-ATPase, thapsigargin (1 microM). Oleanolic acid evoked relaxation without changes in endothelial cell calcium, but decreased smooth muscle calcium in arterial segments. Oleanolic acid failed to increase calcium in HUVECs, but increased time-dependently phosphorylation of Akt kinase at Serine(473) (Akt-Ser(473)) and eNOS at Serine(1177) (eNOS-Ser(1177)), which was attenuated by inhibitors of phosphoinositide-3-kinase. CONCLUSIONS AND IMPLICATIONS: This study provides direct evidence that a component of olive oil, oleanolic acid, activated endothelium-dependent release of NO and decreased smooth muscle cell calcium followed by relaxation. The oleanolic acid-evoked endothelium-derived NO release was independent of endothelial cell calcium and involved phosphoinositide-3-kinase-dependent phosphorylation of Akt-Ser(473) followed by phosphorylation of eNOS-Ser(1177).


Assuntos
Cálcio/metabolismo , Endotélio Vascular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Ácido Oleanólico/farmacologia , Animais , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Humanos , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Ácido Oleanólico/administração & dosagem , Azeite de Oliva , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Óleos de Plantas/química , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Veias Umbilicais
9.
Cancer Res ; 60(22): 6381-3, 2000 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11103801

RESUMO

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymorphism at codon 198 of hGPX1 and lung cancer risk. Cases (n = 315) were matched to controls on age (+/-5 years), intervention group, and study clinic using incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1 Pro198Leu variant allele was 58% for controls and 71% for cases (P < 0.001). Using conditional logistic regression, we found a significant association between hGPX1 genotype and lung cancer risk. The odds ratio for heterozygotes was 1.8 (95% confidence interval, 1.2-2.8) and 2.3 (95% confidence interval, 1.3-3.8) for homozygous variants compared to wild-type individuals. Due to its high prevalence, the hGPX1 variant may contribute significantly to lung cancer risk among Caucasians but not among ethnic Chinese who do not exhibit this polymorphism.


Assuntos
Glutationa Peroxidase/genética , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Polimorfismo Genético , Fatores Etários , Idoso , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Estudos de Casos e Controles , Códon , Genótipo , Mutação em Linhagem Germinativa , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/genética , Vitamina E/administração & dosagem , Vitamina E/sangue , beta Caroteno/administração & dosagem , beta Caroteno/sangue , Glutationa Peroxidase GPX1
10.
Eur J Pain ; 20(3): 408-16, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26104968

RESUMO

BACKGROUND: Sleep problems have been identified as a risk factor for several chronic pain conditions. Reduced sleep has been related to increased pain perception and it has been hypothesized that reduced pain inhibition may explain this. The aim of this study was to determine if sleep restriction (SR) affects heat pain perception and conditioned pain modulation (CPM). METHODS: In a paired cross-over design with two conditions (2 nights habitual sleep (HS) vs. 2 nights 50% SR) CPM was tested in 22 healthy individuals (14 women, 8 men). The test stimulus (TS) was 2-min contact heat stimulation (47  ± 1.3  °C) to the volar forearm. TS was delivered before and during a 7 °C cold pressor test (conditioning stimulus, CS) to the contralateral hand. RESULTS: TS was perceived as more painful after SR compared to after HS (p < 0.001). A stronger inhibitory CPM was found after SR versus after HS (p < 0.001). CONCLUSIONS: The results indicate that SR leads to increased heat pain perception, but not reduced inhibitory CPM. This contradicts general assumptions on the relation between SR and the CPM effect.


Assuntos
Percepção da Dor , Dor/psicologia , Privação do Sono/complicações , Adolescente , Adulto , Pressão Sanguínea , Temperatura Baixa , Condicionamento Psicológico , Estudos Cross-Over , Feminino , Antebraço , Temperatura Alta , Humanos , Masculino , Dor/fisiopatologia , Medição da Dor , Adulto Jovem
11.
Circulation ; 100(16): 1727-33, 1999 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-10525493

RESUMO

BACKGROUND: This study further investigated the relationship between estrogen, arterial endothelium, and nitric oxide (NO) in cholesterol-clamped rabbits. METHODS AND RESULTS: Rabbits were ovariectomized, balloon-injured in the thoracic aorta, and grouped to receive cholesterol-enriched chow together with either 17beta-estradiol or vehicle for 1, 2, 4, or 8 weeks. In the undamaged aorta, cholesterol accumulation of the placebo rabbits was significantly increased from week 4 to 8 (P<0.001). This increase was almost completely inhibited by estrogen (P<0.001). In the balloon-injured aorta, the estrogen and placebo rabbits accumulated similar amounts of cholesterol in the reendothelialized areas. In the deendothelialized areas, the estrogen group surprisingly accumulated significantly more cholesterol than the placebo group. This difference was apparent from week 2 and became significant at week 8 (P<0.01). Circulating nitrite/nitrate were significantly increased by estrogen at weeks 1, 2, and 4 but not at week 8. Similarly, in additional experiments, basal NO release was significantly higher in estrogen-treated than in placebo-treated rabbits after 4 (P<0.05) but not after 8 weeks. Stimulated NO release and endothelial NO synthase activity did not differ between groups. Mononuclear-endothelial cell binding was reduced by 50% by estrogen after 4 weeks (P<0.05). This difference, however, was abolished by coadministration of N(G)-nitro-L-arginine methyl ester, an inhibitor of NO production. CONCLUSIONS: The direct antiatherogenic effect of estrogen was present, absent, or reversed, depending on the state of the arterial endothelium, and preceded by a transient increase in NO production followed by a reduced mononuclear-endothelial cell binding.


Assuntos
Aorta Torácica/efeitos dos fármacos , Arteriosclerose/prevenção & controle , Arteriosclerose/fisiopatologia , Colesterol na Dieta , Dieta Aterogênica , Endotélio Vascular/efeitos dos fármacos , Estradiol/farmacologia , Análise de Variância , Animais , Aorta Torácica/fisiologia , Aorta Torácica/fisiopatologia , Colesterol/metabolismo , Endotélio Vascular/fisiologia , Endotélio Vascular/fisiopatologia , Feminino , Nitratos/sangue , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Nitritos/sangue , Ovariectomia , Coelhos
12.
Cardiovasc Res ; 47(1): 192-9, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10869546

RESUMO

OBJECTIVE: Several animal studies suggest that nitric oxide (NO) produced by the endothelium attenuates arterial cholesterol accumulation. In the present study we have asked the following questions: (1) is the regional variation in aortic cholesterol accumulation in hypercholesterolemic rabbits preceded by a regional variation in endothelial NO synthase (eNOS) activity in normocholesterolemic rabbits, and (2) is the antiatherogenic effect of estrogen in hypercholesterolemic rabbits preceded by a higher eNOS activity in normocholesterolemic rabbits. METHODS: The eNOS activity was determined by conversion of 14C-L-arginine to 14C-L-citrulline in freshly isolated endothelial cells of aorta in normocholesterolemic rabbits. In the regional variation study, 16 male and eight female rabbits were used. In the estrogen study, ovariectomized female rabbits were subcutaneously injected three times weekly with either 17beta-estradiol (n=7) or vehicle (n=7) for 18 weeks. RESULTS: In the regional variation study, the atherosclerosis prone aortic arch showed a significant lower eNOS activity than the more resistant abdominal aorta in both male (P<0.0001) and female (P<0.05) rabbits. In the estrogen study, the eNOS activity in the aortic arch and upper thoracic aorta was significantly higher in the estrogen than in the vehicle rabbits (P<0.05). In the lower thoracic aorta, however, the eNOS activity was the same. CONCLUSION: The findings suggest that a high NO production in the luminal endothelium of the arterial wall precedes a low cholesterol accumulation during a subsequent period of hypercholesterolemia.


Assuntos
Endotélio Vascular/enzimologia , Estradiol/uso terapêutico , Hipercolesterolemia/enzimologia , Óxido Nítrico Sintase/análise , Análise de Variância , Animais , Aorta Abdominal , Aorta Torácica , Técnicas de Cultura de Células , Células Cultivadas , Feminino , Hipercolesterolemia/tratamento farmacológico , Imuno-Histoquímica , Masculino , Óxido Nítrico Sintase Tipo III , Ovariectomia , Coelhos , Fatores de Tempo
13.
Cancer Epidemiol Biomarkers Prev ; 10(2): 119-23, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11219768

RESUMO

We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.


Assuntos
Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Polimorfismo Genético , Adulto , Distribuição por Idade , Idoso , Sequência de Bases , Estudos de Casos e Controles , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida , Estados Unidos/epidemiologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
14.
Cancer Lett ; 164(2): 161-7, 2001 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-11179831

RESUMO

In order to examine whether a polymorphism in the promoter region of the myeloperoxidase (MPO) gene is associated with lung cancer among male smokers, we conducted a case-control study nested within a Finnish clinical trial cohort. Although we found no evidence of an overall association between lung cancer risk and MPO genotype, the variant MPO genotype was associated with an increased risk of lung cancer among a subset of older men. These findings contrast with those from previous studies that report decreased lung cancer risk among MPO variant individuals.


Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Peroxidase/genética , Regiões Promotoras Genéticas , Fumar , Fatores Etários , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Finlândia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco
15.
Am J Med Genet ; 90(5): 361-8, 2000 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-10706356

RESUMO

Women with a family history of breast cancer often over-estimate their personal risk for cancer and may view themselves as candidates for genetic testing even when the likelihood of an informative test result is low. We report here on genetic counseling of women with an intermediate family history of breast cancer, defined as women who have one or more biological relatives with breast cancer but whose pedigree suggests a low likelihood of autosomal dominant transmission. A genetic counseling protocol based on traditional genetic counseling strategies was developed with additional components added to address the needs of women with moderately increased breast cancer risk. These additional components included information about non-genetic risk factors, comparisons of high and moderate risk pedigrees, and evaluation of personal risk based on both genetic and nongenetic risk factors. Most participants liked the genetic counseling and found it useful. At baseline, participants over-estimated both their personal risk of breast cancer and that of the average woman. After counseling, estimates of personal and average risk of breast cancer were lower, although both remained higher than actual risk. Most participants reported that they felt less worried about breast cancer after receiving their personal-risk estimate. At baseline, most women judged themselves to be candidates for genetic testing and expressed interest in testing. The number who considered themselves candidates for testing was reduced after counseling (60% versus 82%) but still constituted a majority. Similarly, interest in testing was partially reduced by counseling (60% versus 91%). We conclude that genetic counseling can help women with an intermediate family history of breast cancer to develop more accurate views of their risk, reduce their breast cancer worry, and aid some of them in developing a more realistic view of genetic testing.


Assuntos
Neoplasias da Mama/genética , Aconselhamento Genético/métodos , Adolescente , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2 , Protocolos Clínicos , Feminino , Aconselhamento Genético/psicologia , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Fatores de Risco , Inquéritos e Questionários , Fatores de Transcrição/genética
16.
DNA Cell Biol ; 17(3): 231-8, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9539103

RESUMO

We developed a quantitative competitive reverse transcriptase-polymerase chain reaction (QC RT-PCR) assay to measure mRNA levels of seven human cytochrome P450 (P450, CYP) genes and microsomal epoxide hydrolase (EH) simultaneously. This assay employs an exogenous recombinant RNA (rcRNA) molecule as an internal standard that shares PCR primer and hybridization probe sequences with CYP1A1, CYP1A2, CYP2A6/7, CYP2D6, CYP2E1, CYP2F1, CYP3A4/5/7, and EH mRNA. Because each rcRNA molecule contains several primer sequences, an entire battery of genes that exhibit differential responsiveness to various classes of xenobiotics may be measured simultaneously from one population of cDNA molecules. In this study, we demonstrated the precision and power of the assay using small amounts of human liver total RNA. We also report for the first time quantitative profiles of P450 and EH mRNA abundance in eight human livers. Cytochrome P450 2E1 mRNA maintained the highest abundance (average 6.67 x 10(7) molecules/microg of total RNA) and least variation (13 fold) in all livers examined. Cytochrome P450 1A2, CYP2A6/7, CYP2D6, CYP3A4/5, and EH mRNAs were approximately one order of magnitude less abundant than CYP2E1 transcripts, with CYP2D6 levels exhibiting the greatest variation (220 fold) between individuals. This QC RT-PCR assay should prove valuable for measuring basal and induced mRNAs in different cell types in vitro, as well as in biomonitoring applications where individuals are exposed or hypersusceptible to certain xenobiotic-initiated toxicities.


Assuntos
Sistema Enzimático do Citocromo P-450/análise , Sistema Enzimático do Citocromo P-450/genética , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Primers do DNA , Epóxido Hidrolases/análise , Epóxido Hidrolases/genética , Feminino , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/normas , RNA/síntese química , RNA/genética , RNA Mensageiro/análise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Obstet Gynecol ; 96(1): 70-4, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10862845

RESUMO

OBJECTIVE: To assess the prevalence of reported ovarian cancer screening among a population-based sample of women from Washington state and identify factors that influence the decision to be screened. METHODS: A population-based sample of 6749 women aged 54-84 years, living in 40 predominately rural communities in Washington state, was surveyed about their utilization of ultrasonography and CA 125 for ovarian cancer screening. We also assessed relevant demographic, family history, psychosocial, and health behavior variables. RESULTS: After exclusions, data from 4938 respondents were available. Two percent (n = 96) reported having been screened. Multiple logistic regression identified ovarian cancer worry, contact with an obstetrician-gynecologist, and family history of ovarian cancer as independently associated with screening. Based on self-reported family histories, 27 women had pedigrees consistent with high risk of ovarian cancer, but none of those women reported having been screened. CONCLUSION: Ovarian cancer screening is rare. Women at high risk of it might not be getting recommended screening.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Neoplasias Ovarianas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Washington
18.
Am J Prev Med ; 18(3): 199-207, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10722985

RESUMO

INTRODUCTION: The Community Trial of Mammography Promotion assessed the effectiveness of mammography promotion by community volunteer groups in rural areas. Three interventions were tested. One used an individual counseling strategy, one used a community activities strategy, and a third combined the two strategies. METHODS: The effects of the interventions were tested by randomizing 40 communities either to the study interventions or to a control group. A cohort of 352 women from each community was randomly selected and used to evaluate the interventions' effectiveness. Of these, 6592 women were eligible for screening mammography at baseline and follow-up and were successfully interviewed prior to and after study intervention activities. RESULTS: Although the interventions did not significantly increase women's overall use of mammography, the community activities intervention increased use at follow-up by regular users over baseline by 2.9% (p = 0.01). Intervention appears to have increased the use of mammography among certain groups of women who were not regular users at baseline, including those in communities without female physicians (10% to 16%; p < 0.05), and among women with no health insurance (10% to 23%; p

Assuntos
Neoplasias da Mama/prevenção & controle , Promoção da Saúde , Mamografia/estatística & dados numéricos , População Rural , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Washington
19.
Am J Prev Med ; 17(1): 87-90, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10429758

RESUMO

PURPOSE: Screening for prostate cancer with the prostate-specific antigen (PSA) test remains controversial. This controversy is reflected in a lack of consensus in the medical literature and among professional and policy organizations regarding routine screening by PSA. It is not known how physicians respond when recommendations from experts are inconsistent. METHODS: A questionnaire was mailed to 1369 primary care physicians in active practice in Washington State in 1994. Response rate to the survey was 63%. Chi-square tests and multivariate logistic regression analysis were used to examine the effects of physician characteristics on physicians' self report of use of the PSA test for screening asymptomatic male patients, aged 50 to 80, for prostate cancer. RESULTS: Of the 714 physicians included in the analysis, 68% reported routine use of PSA. Use of PSA varied among physicians on the basis of practice setting, years since medical school graduation, and whether compensation was fee-for-service or salaried. Male physicians trained before 1974 and physicians receiving fee-for-service were significantly more likely than other physicians to recommend screening by PSA. CONCLUSIONS: Results suggest that physicians' personal characteristics such as year of medical school graduation, gender, and mode of reimbursement are related to self-reported PSA use.


Assuntos
Padrões de Prática Médica/estatística & dados numéricos , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Distribuição de Qui-Quadrado , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento , Atenção Primária à Saúde/estatística & dados numéricos , Inquéritos e Questionários , Washington
20.
Health Psychol ; 16(5): 433-41, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9302540

RESUMO

This investigation extends prior research to apply decision-making constructs from the transtheoretical model (TTM) of behavior change to mammography screening. Study subjects were 8,914 women ages 50-80, recruited from 40 primarily rural communities in Washington State. Structural equation modeling showed that favorable and unfavorable opinions about mammography (i.e., pros and cons) fit the observed data. Analysis of variance supported the associations between readiness to obtain screening (i.e., stage of adoption) and opinions about mammography (i.e., decisional balance) previously found in research using smaller samples from another geographic region. This report extends these earlier studies by using structural equation modeling, opinion scales based both on principal component analyses and on a priori definitions, a developmental sample and a confirmatory sample, and by sampling from a different geographic region. It is recommended that future research examine whether opinions regarding the cons of mammography are more individually specific than the pros.


Assuntos
Neoplasias da Mama/prevenção & controle , Mamografia/psicologia , Programas de Rastreamento/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Técnicas de Apoio para a Decisão , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Washington
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