Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Environ Health ; 23(1): 55, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858670

RESUMEN

BACKGROUND: Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of alternative PFAS, as well as PFAS precursors. Biomonitoring data for PFAS are critical for assessing exposure and human health risk. METHODS: We collected serum samples from 289 adult female participants in a 2018-2021 follow-up study of the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort. Samples were analyzed for 40 PFAS using ultra-performance liquid chromatography-tandem mass spectrometry. For those compounds with > 50% detection, as well as the sum of these compounds, we describe serum concentrations and patterns of exposure according to sociodemographic and obstetrical history characteristics. RESULTS: 17 out of 40 PFAS were detected in > 50% of samples with 7 of these detected in > 97% of samples. Median [95th percentile] concentrations (µg/L) were highest for PFOS (1.62 [4.56]), PFOA (0.69 [1.52]), PFNA (0.38 [0.81]), and PFHxS (0.33 [0.92]). Geometric mean concentrations of PFOA and PFHxS were approximately 2-fold lower among those with more children (≥ 3 vs. 1), greater number of children breastfed (≥ 3 vs. ≤ 1), longer lifetime duration of breastfeeding (> 4 years vs. ≤ 9 months), and shorter time since last pregnancy (≤ 4 years vs. > 8 years). We observed similar patterns for PFOS, PFHpS, and the sum of 17 PFAS, though the differences between groups were smaller. Concentrations of PFOA were higher among "White" participants, while concentrations of N-MeFOSE, N-EtFOSE, 7:3 FTCA, and 4:2 FTS were slightly higher among participants reporting a race or ethnicity other than "White". Concentrations of legacy, alternative, and precursor PFAS were generally similar across levels of age, education, household income, body mass index, and menopausal status. CONCLUSIONS: We report the first Canadian biomonitoring data for several alternative and precursor PFAS. Our findings suggest that exposure to PFAS, including several emerging alternatives, may be widespread. Our results are consistent with previous studies showing that pregnancy and breastfeeding are excretion pathways for PFAS.


Asunto(s)
Contaminantes Ambientales , Fluorocarburos , Humanos , Femenino , Fluorocarburos/sangre , Adulto , Contaminantes Ambientales/sangre , Canadá , Monitoreo Biológico , Embarazo , Adulto Joven , Estudios de Cohortes
2.
Nature ; 513(7517): 219-23, 2014 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-25209800

RESUMEN

The hydroxyl radical (OH) is a key oxidant involved in the removal of air pollutants and greenhouse gases from the atmosphere. The ratio of Northern Hemispheric to Southern Hemispheric (NH/SH) OH concentration is important for our understanding of emission estimates of atmospheric species such as nitrogen oxides and methane. It remains poorly constrained, however, with a range of estimates from 0.85 to 1.4 (refs 4, 7-10). Here we determine the NH/SH ratio of OH with the help of methyl chloroform data (a proxy for OH concentrations) and an atmospheric transport model that accurately describes interhemispheric transport and modelled emissions. We find that for the years 2004-2011 the model predicts an annual mean NH-SH gradient of methyl chloroform that is a tight linear function of the modelled NH/SH ratio in annual mean OH. We estimate a NH/SH OH ratio of 0.97 ± 0.12 during this time period by optimizing global total emissions and mean OH abundance to fit methyl chloroform data from two surface-measurement networks and aircraft campaigns. Our findings suggest that top-down emission estimates of reactive species such as nitrogen oxides in key emitting countries in the NH that are based on a NH/SH OH ratio larger than 1 may be overestimated.


Asunto(s)
Atmósfera/química , Radical Hidroxilo/química , Modelos Teóricos , Contaminantes Atmosféricos/química , Cloroformo/química , Simulación por Computador , Óxidos de Nitrógeno/química
3.
Int J Obes (Lond) ; 40(10): 1566-1573, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27273607

RESUMEN

BACKGROUND/OBJECTIVES: The use of bisphenol A (BPA) in consumer products and food packaging has been associated under certain conditions with a risk of negative health outcomes. This prompted its removal from many products and replacement with structural analogs. Bisphenol S (BPS) is one such analog, but its metabolic effects have not been fully characterized. The objective of our study was to determine whether BPS functions similarly to BPA at inducing adipogenesis. METHODS: Murine 3T3-L1 preadipocytes were used to evaluate and compare the adipogenic potential of BPS to BPA. Cells were treated with 0.01-50 µM BPS or 0.01-50 µM BPA and adipogenic effects were measured. Further, their ability to activate peroxisome proliferator-activated receptor gamma (PPARγ), an adipogenic transcription factor, was also determined. RESULTS: Our results indicate that treatment of 3T3-L1 cells with BPS induced lipid accumulation and increased mRNA and protein expression of key adipogenic markers (1-50 µM; P<0.05). BPS treatment resulted in a higher expression of adipogenic markers as well as greater lipid accumulation when compared with BPA treatment. We showed that BPS can upregulate lipoprotein lipase, adipocyte protein 2, PPARγ, perilipin, adipsin and CCAAT/enhancer-binding protein alpha mRNA expression levels. Furthermore, using transcriptional assays, we showed that BPS and BPA can modestly activate PPARγ using a PPRE (PPARγ response element)-dependent luciferase construct by 1.5-fold (P<0.05). However, BPS but not BPA was able to competitively inhibit rosiglitazone (ROSI)-activated PPARγ, suggesting that BPS interacts with PPARγ distinctly from BPA. Co-treatment of cells with the selective PPARγ antagonist GW9662 inhibits BPS-, BPA-, ROSI- but not dexamethasone-dependent adipogenic differentiation. CONCLUSIONS: Both BPA and BPS can enhance 3T3-L1 adipocyte differentiation in a dose-dependent manner and require PPARγ to induce adipogenesis. Through direct comparison, we show that BPS is a more potent adipogen than BPA.


Asunto(s)
Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , PPAR gamma/metabolismo , Fenoles/farmacología , Células Madre/efectos de los fármacos , Sulfonas/farmacología , Células 3T3-L1 , Adipocitos/metabolismo , Animales , Western Blotting , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Ratones , Células Madre/citología , Células Madre/metabolismo
4.
Geophys Res Lett ; 42(11): 4573-4580, 2015 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-27570318

RESUMEN

We have developed a chemical mechanism describing the tropospheric degradation of chlorine containing very short-lived substances (VSLS). The scheme was included in a global atmospheric model and used to quantify the stratospheric injection of chlorine from anthropogenic VSLS ( ClyVSLS) between 2005 and 2013. By constraining the model with surface measurements of chloroform (CHCl3), dichloromethane (CH2Cl2), tetrachloroethene (C2Cl4), trichloroethene (C2HCl3), and 1,2-dichloroethane (CH2ClCH2Cl), we infer a 2013 ClyVSLS mixing ratio of 123 parts per trillion (ppt). Stratospheric injection of source gases dominates this supply, accounting for ∼83% of the total. The remainder comes from VSLS-derived organic products, phosgene (COCl2, 7%) and formyl chloride (CHClO, 2%), and also hydrogen chloride (HCl, 8%). Stratospheric ClyVSLS increased by ∼52% between 2005 and 2013, with a mean growth rate of 3.7 ppt Cl/yr. This increase is due to recent and ongoing growth in anthropogenic CH2Cl2-the most abundant chlorinated VSLS not controlled by the Montreal Protocol.

5.
J Prosthodont ; 24(3): 194-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25143068

RESUMEN

PURPOSE: The prevalence of Candida infections has been rising with an increasingly aging population and a larger population of immunocompromised individuals. The use of probiotics may be an alternative approach to antifungal agents in the prevention and treatment of oral candidiasis. This study aimed to evaluate the short-term effect of probiotics in reducing the infection level of oral Candida in candidiasis-asymptomatic elderly denture wearers. MATERIALS AND METHODS: In a double-blind randomized study, 59 denture wearers harboring Candida spp. in the oral cavity with no clinical symptoms were allocated into two groups: probiotic and placebo. All patients were instructed to clean the denture daily. The probiotic group poured a capsule containing lyophilized Lactobacillus rhamnosus HS111, Lactobacillus acidophillus HS101, and Bifidobacterium bifidum daily on the palatal surface of the maxillary denture, whereas the placebo group was submitted to the same regimen using placebo capsules. Candida spp. infection levels were evaluated in palate mucosa samples obtained before and after a 5-week experimental period. RESULTS: All patients harbored Candida in the palate mucosa at baseline. Fifty-five individuals completed the experimental period. The detection rate of Candida spp. was 92.0% in the placebo group after the experimental period, whereas it was reduced to 16.7% in the probiotic group. The reduction promoted by the probiotic regimen was independent of baseline characteristics such as Candida infection level and colonizing species, age of denture, and other variables. CONCLUSION: The probiotic product was effective in reducing the colonization of the oral cavity with Candida in candidiasis-asymptomatic elderly denture wearers, suggesting that this multispecies probiotic could be used to prevent oral candidiasis. CLINICAL IMPLICATIONS: Colonization of oral surfaces by Candida is considered a risk factor for invasive fungal infections. The use of a product with L. rhamnosus, L. acidophilus, and B. bifidum may represent an alternative treatment for reduction of Candida infections in elderly denture wearers.


Asunto(s)
Candida/efectos de los fármacos , Candidiasis Bucal/prevención & control , Candidiasis Bucal/terapia , Dentaduras/microbiología , Boca/microbiología , Probióticos/uso terapéutico , Anciano , Bifidobacterium bifidum , Brasil , Alisadura de la Restauración Dental/efectos adversos , Método Doble Ciego , Femenino , Humanos , Lactobacillus acidophilus , Lacticaseibacillus rhamnosus , Masculino , Persona de Mediana Edad , Hueso Paladar/microbiología
6.
Int J Clin Pract Suppl ; (170): 20-5, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21323809

RESUMEN

Closed-loop algorithms can be found in every aspect of everyday modern life. Automation and control are used constantly to provide safety and to improve quality of life. Closed-loop systems and algorithms can be found in home appliances, automobiles, aviation and more. Can one imagine nowadays driving a car without ABS, cruise control or even anti-sliding control? Similar principles of automation and control can be used in the management of diabetes mellitus (DM). The idea of an algorithmic/technological way to control glycaemia is not new and has been researched for more than four decades. However, recent improvements in both glucose-sensing technology and insulin delivery together with advanced control and systems engineering made this dream of an artificial pancreas possible. The artificial pancreas may be the next big step in the treatment of DM since the use of insulin analogues. An artificial pancreas can be described as internal or external devices that use continuous glucose measurements to automatically manage exogenous insulin delivery with or without other hormones in an attempt to restore glucose regulation in individuals with DM using a control algorithm. This device as described can be internal or external; can use different types of control algorithms with bi-hormonal or uni-hormonal design; and can utilise different ways to administer them. The different designs and implementations have transitioned recently from in silico simulations to clinical evaluation stage with practical applications in mind. This may mark the beginning of a new era in diabetes management with the introduction of semi-closed-loop systems that can prevent or minimise nocturnal hypoglycaemia, to hybrid systems that will manage blood glucose (BG) levels with minimal user intervention to finally fully automated systems that will take the user out of the loop. More and more clinical trials will be needed for the artificial pancreas to become a reality but initial encouraging results are proof that we are on the right track. We attempted to select recent publications that will present these current achievements in the quest for the artificial pancreas and that will inspire others to continue to progress this field of research.


Asunto(s)
Diabetes Mellitus/terapia , Sistemas de Infusión de Insulina , Páncreas Artificial , Humanos , Bombas de Infusión Implantables
7.
Int J Clin Pract Suppl ; (166): 20-5, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20377660

RESUMEN

The dream of closing the loop is actually the dream of creating an artificial pancreas and freeing the patients from being involved with the care of their own diabetes. Insulin-dependent diabetes (type 1) is a chronic incurable disease which requires constant therapy without the possibility of any 'holidays' or insulin-free days. It means that patients have to inject insulin every day of their life, several times per day, and in order to do it safely they also have to measure their blood glucose levels several times per day. Patients need to plan their meals, their physical activities and their insulin regime - there is only very small room for spontaneous activities. This is why the desire for an artificial pancreas is so strong despite the fact that it will not cure the diabetic patients. Attempts to develop a closed-loop system started in the 1960s but never got to a clinical practical stage of development. In recent years the availability of continuous glucose sensors revived those efforts and stimulated the clinician and researchers to believe that closing the loop might be possible nowadays. Many papers have been published over the years describing several different ideas on how to close the loop. Most of the suggested systems have a sensing arm that measures the blood glucose repeatedly or continuously, an insulin delivery arm that injects insulin upon command and a computer that makes the decisions of when and how much insulin to deliver. The differences between the various published systems in the literature are mainly in their control algorithms. However, there are also differences related to the method and site of glucose measurement and insulin delivery. SC glucose measurements and insulin delivery are the most studied option but other combinations of insulin measurements and glucose delivery including intravascular and intraperitoneal (IP) are explored. We tried to select recent publications that we believe had influenced and inspired people interested in the field.


Asunto(s)
Diabetes Mellitus/terapia , Sistemas de Infusión de Insulina , Páncreas Artificial , Humanos , Bombas de Infusión Implantables
8.
Science ; 211(4478): 163-5, 1981 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-17757266

RESUMEN

Concentrations of organic pollutants in the air and in precipitation have been measured at Enewetak Atoll in the North Pacific Ocean. These data from a site removed from industrial and human activity indicate the present concentrations of synthetic organic pollutants in the atmosphere and establish the long-range atmospheric transport of organic pollutants to remote marine areas. Hexachlorobenzene and hexachlorocyclohexane isomers are present in the remote marine atmosphere. Polychlorobiphenyls, total DDT, dieldrin, chlordane, and two phthalate ester plasticizers were also found in the samples. The concentrations of pollutants in the atmosphere remote from continental sources are good measures of the minimum concentrations of air pollutants on Earth.

9.
Science ; 199(4327): 419-21, 1978 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-413194

RESUMEN

Phthalate ester plasticizers have been detected in the open-ocean environment. Samples consisting of water, sediment, air, and biota from the Gulf of Mexico and of water and air from the North Atlantic were analyzed and found to contain two phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) and di-n-dibutyl phthalate (DBP): the concentrations of polychlorinated biphenyls (PCB's) and DDT's (p,p'-DDT and p,p'-DDE) were also determined. Like the ubiquitous PCB's and DDT's, the phthalate plasticizers were found in almost all samples analyzed; DEHP was present at higher concentrations than the PCB's or DDT's in water and sediment. The environmental impact of the concentrations found in these studies, coupled with the continued high production and wise use of these plasticizers, requires assessment.


Asunto(s)
Contaminantes Ambientales/análisis , Ácidos Ftálicos/análisis , Contaminantes Atmosféricos/análisis , DDT/análisis , Bifenilos Policlorados/análisis , Agua de Mar , Contaminantes del Suelo/análisis , Contaminantes Químicos del Agua/análisis
10.
Science ; 292(5517): 719-23, 2001 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-11326097

RESUMEN

Data taken in aircraft transects of emissions plumes from rural U.S. coal-fired power plants were used to confirm and quantify the nonlinear dependence of tropospheric ozone formation on plume NO(x) (NO plus NO(2)) concentration, which is determined by plant NO(x) emission rate and atmospheric dispersion. The ambient availability of reactive volatile organic compounds, principally biogenic isoprene, was also found to modulate ozone production rate and yield in these rural plumes. Differences of a factor of 2 or greater in plume ozone formation rates and yields as a function of NO(x) and volatile organic compound concentrations were consistently observed. These large differences suggest that consideration of power plant NO(x) emission rates and geographic locations in current and future U.S. ozone control strategies could substantially enhance the efficacy of NO(x) reductions from these sources.

11.
Science ; 291(5506): 1026-31, 2001 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-11161213

RESUMEN

Large particles containing nitric acid (HNO3) were observed in the 1999/2000 Arctic winter stratosphere. These in situ observations were made over a large altitude range (16 to 21 kilometers) and horizontal extent (1800 kilometers) on several airborne sampling flights during a period of several weeks. With diameters of 10 to 20 micrometers, these sedimenting particles have significant potential to denitrify the lower stratosphere. A microphysical model of nitric acid trihydrate particles is able to simulate the growth and sedimentation of these large sizes in the lower stratosphere, but the nucleation process is not yet known. Accurate modeling of the formation of these large particles is essential for understanding Arctic denitrification and predicting future Arctic ozone abundances.

12.
Sci Rep ; 8(1): 4669, 2018 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-29549350

RESUMEN

The East Asian Summer Monsoon driven by temperature and moisture gradients between the Asian continent and the Pacific Ocean, leads to approximately 50% of the annual rainfall in the region across 20-40°N. Due to its increasing scientific and social importance, there have been several previous studies on identification of moisture sources for summer monsoon rainfall over East Asia mainly using Lagrangian or Eulerian atmospheric water vapor models. The major source regions for EASM previously proposed include the North Indian Ocean, South China Sea and North western Pacific. Based on high-precision and high-frequency 6-year measurement records of hydrofluorocarbons (HFCs), here we report a direct evidence of rapid intrusion of warm and moist tropical air mass from the Southern Hemisphere (SH) reaching within a couple of days up to 33°N into East Asia. We further suggest that the combination of direct chemical tracer record and a back-trajectory model with physical meteorological variables helps pave the way to identify moisture sources for monsoon rainfall. A case study for Gosan station (33.25°N, 126.19°E) indicates that the meridional transport of precipitable water from the SH accompanying the southerly/southwesterly flow contributes most significantly to its summer rainfall.

13.
Front Microbiol ; 8: 2280, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29238325

RESUMEN

Probiotics are live microorganisms that confer benefits to the host health. The infection rate of potentially pathogenic organisms such as Candida albicans, the most common agent associated with mucosal candidiasis, can be reduced by probiotics. However, the mechanisms by which the probiotics interfere with the immune system are largely unknown. We evaluated the effect of probiotic bacteria on C. albicans challenged human macrophages. Macrophages were pretreated with lactobacilli alone (Lactobacillus rhamnosus LR32, Lactobacillus casei L324m, or Lactobacillus acidophilus NCFM) or associated with Escherichia coli lipopolysaccharide (LPS), followed by the challenge with C. albicans or LPS in a co-culture assay. The expression of pattern-recognition receptors genes (CLE7A, TLR2, and TLR4) was determined by RT-qPCR, and dectin-1 reduced levels were confirmed by flow cytometry. The cytokine profile was determined by ELISA using the macrophage cell supernatant. Overall probiotic lactobacilli down-regulated the transcription of CLEC7A (p < 0.05), resulting in the decreased expression of dectin-1 on probiotic pretreated macrophages. The tested Lactobacillus species down-regulated TLR4, and increased TLR2 mRNA levels in macrophages challenged with C. albicans. The cytokines profile of macrophages challenged with C. albicans or LPS were altered by the probiotics, which generally led to increased levels of IL-10 and IL-1ß, and reduction of IL-12 production by macrophages (p < 0.05). Our data suggest that probiotic lactobacilli impair the recognition of PAMPs by macrophages, and alter the production of pro/anti-inflammatory cytokines, thus modulating inflammation.

14.
Bull Am Meteorol Soc ; 98(1): 106-128, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29636590

RESUMEN

The Convective Transport of Active Species in the Tropics (CONTRAST) experiment was conducted from Guam (13.5° N, 144.8° E) during January-February 2014. Using the NSF/NCAR Gulfstream V research aircraft, the experiment investigated the photochemical environment over the tropical western Pacific (TWP) warm pool, a region of massive deep convection and the major pathway for air to enter the stratosphere during Northern Hemisphere (NH) winter. The new observations provide a wealth of information for quantifying the influence of convection on the vertical distributions of active species. The airborne in situ measurements up to 15 km altitude fill a significant gap by characterizing the abundance and altitude variation of a wide suite of trace gases. These measurements, together with observations of dynamical and microphysical parameters, provide significant new data for constraining and evaluating global chemistry climate models. Measurements include precursor and product gas species of reactive halogen compounds that impact ozone in the upper troposphere/lower stratosphere. High accuracy, in-situ measurements of ozone obtained during CONTRAST quantify ozone concentration profiles in the UT, where previous observations from balloon-borne ozonesondes were often near or below the limit of detection. CONTRAST was one of the three coordinated experiments to observe the TWP during January-February 2014. Together, CONTRAST, ATTREX and CAST, using complementary capabilities of the three aircraft platforms as well as ground-based instrumentation, provide a comprehensive quantification of the regional distribution and vertical structure of natural and pollutant trace gases in the TWP during NH winter, from the oceanic boundary to the lower stratosphere.

15.
Cancer Res ; 51(2): 612-8, 1991 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-1845956

RESUMEN

BALB/c 3T3 cells transformed in vitro with polyoma virus were cloned and passaged once in syngeneic mice. Resulting tumors from each clone were explanted and recultured. Expression of receptor for Fc of IgG (Fc gamma RII) in the original in vitro maintained clones and in cells derived from tumors elicited by the respective cells was measured at the protein level as well as at the mRNA level. Clones were assayed in pairs. The ancestor in vitro maintained clones [designated cultured cells (C)] were compared with cells derived from the same clones after a single passage in vivo followed by explantation and reculturing [designated cultured-tumor-cultured cells (CTC)]. C cells of any of the tested clones did not express Fc gamma RII. On the other hand, certain CTC cells were positive. The Fc gamma RII-positive cells were derived from tumors appearing after a long precancer latency period (greater than 140 days). CTC cells derived from tumors that appeared after shorter latency periods (less than 80 days) were Fc gamma RII negative. These results were obtained both by using radioimmunoassay and monoclonal antibodies against mouse Fc gamma RII as well as by Northern blot analysis using the Fc gamma RII complementary DNA probe. The involvement of macrophages as the Fc gamma RII-expressing cells in CTC cells was excluded. Fc gamma RII expression was down-regulated in CTC cells as a function of time following their explantation into culture. Fc gamma RII expression could be up-regulated in these cells and induced on C cells by maintaining the cultured cells in the presence of normal mouse serum or recombinant interferon. We also tested the expression of Fc gamma RII on CTC cells following their inoculation into syngeneic mice for a second time (CTCx2 cells). The results showed a positive correlation between Fc gamma RII expression in the inoculated ancestor CTC cells and on the CTCx2 cell progeny.


Asunto(s)
Antígenos de Diferenciación/genética , Transformación Celular Neoplásica , Neoplasias Experimentales/genética , Poliomavirus/genética , Receptores Fc/genética , Animales , Antígenos de Diferenciación/análisis , Biomarcadores de Tumor/análisis , Línea Celular , Membrana Celular/inmunología , Células Clonales , Inmunoglobulina G/metabolismo , Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/patología , ARN Neoplásico/genética , Receptores Fc/análisis , Receptores de IgG
16.
Oncogene ; 20(48): 7110-4, 2001 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-11704836

RESUMEN

Transcriptional regulation of the BRCA1 proximal promoter has been suggested to play a role in the decreased expression of BRCA1 observed in sporadic breast cancer. Computer analysis of the sequence of the proximal promoter reveals the presence of a potential CREB site. We have identified CREB/ATF-1 as the factor interacting with this site in nuclear extracts from MCF-7 and T-47D cells. This site is shown to be important for the constitutive expression of the promoter in these cells, as well as in Hep G2 cells. Despite the presence of this site, the BRCA1 promoter is not responsive to cAMP induction. It appears that CREB acts as a constitutive positive element for BRCA1 expression and that any mechanism inactivating CREB function would have a dramatic effect on BRCA1 expression.


Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas de Unión al ADN , Regulación Neoplásica de la Expresión Génica/genética , Genes BRCA1 , Regiones Promotoras Genéticas/genética , Factores de Transcripción/metabolismo , Transcripción Genética/genética , Factor de Transcripción Activador 1 , Adenocarcinoma/genética , Adenocarcinoma/patología , Secuencia de Bases , Sitios de Unión , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Colforsina/farmacología , Islas de CpG , AMP Cíclico/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/química , Metilación de ADN , ADN de Neoplasias/genética , Dimerización , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes Reporteros , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Unión Proteica , Factores de Transcripción/química , Transfección , Células Tumorales Cultivadas/efectos de los fármacos
17.
Oncogene ; 19(15): 1933-40, 2000 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-10773883

RESUMEN

Decreased expression of BRCA1 may play a role in the etiology of sporadic breast cancer. Deletion and point mutant analysis of proximal promoter elements in the BRCA1 1a promoter revealed a 22 bp region which was critical for the expression of the promoter in MCF-7 cells, but had a much reduced effect in T47D cells. The main transcription factor interacting with this site was identified as GABPalpha/beta, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells. Cotransfection experiments with GABPalpha and beta1 expression vectors produced transactivation of this element in both lines. These results suggest that GABPalpha/beta is a critical activator of BRCA1 expression, and that its activity may differ in human breast cell lines.


Asunto(s)
Proteína BRCA1/genética , Neoplasias de la Mama/genética , Proteínas de Unión al ADN/fisiología , Factores de Transcripción/fisiología , Animales , Factor de Transcripción de la Proteína de Unión a GA , Regulación de la Expresión Génica , Humanos , Ratones , Mutagénesis , Regiones Promotoras Genéticas , Activación Transcripcional , Células Tumorales Cultivadas
18.
Mol Immunol ; 27(12): 1219-28, 1990 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2177146

RESUMEN

We analyzed several cellular and molecular properties of BALB/c 3T3 cellular clones transformed in vitro with polyoma virus and exhibiting a high or low tumorigenicity phenotype. We also analyzed the same clones after a single in vivo passage in syngeneic mice. This passage invariably induced and/or selected variants exhibiting a very high tumorigenicity phenotype. BALB/c mice bearing tumors induced by the inoculation of the above cells, regardless of their tumorigenicity phenotype, have a lower number of L3T4 positive splenocytes than appropriate controls. The response to Con-A of spleen cells from such mice was also suppressed. Concomitantly, an increase in Mac-1 positive splenocytes could be measured. In spite of the non-specific suppression of T cells, spleen cells from tumor-bearers showed a specific proliferative response to polyoma antigens. Molecular analysis of polyoma transformed cells showed no differences between the various cells with respect to integration of the polyoma viral genes or with respect to src, myc and fos proto-oncogenes. In vitro maintained cells and in vivo passaged cells seemed to differ, however, in the content of polyoma middle T. Whereas polyoma virus transformed cells maintained only in culture never expressed low affinity receptors for IgG (Fc gamma RII), certain in vivo passaged cells did. This expression could be measured both at the protein and the mRNA level. Those in vivo passaged cells which expressed F alpha RII gave tumors following a long latency period. Ongoing experiments will indicate whether or not Fc gamma RII expression is linked to long latency of tumor development.


Asunto(s)
Transformación Celular Neoplásica/inmunología , Transformación Celular Viral/genética , Animales , Antígenos de Diferenciación/biosíntesis , Antígenos Transformadores de Poliomavirus/inmunología , Línea Celular Transformada , Mapeo Cromosómico , Células Clonales , ADN Viral/genética , Variación Genética , Tolerancia Inmunológica , Ratones , Fenotipo , Poliomavirus/genética , Proto-Oncogenes/genética , ARN Mensajero/análisis , Receptores Fc/biosíntesis , Receptores de IgG
19.
Am J Med ; 75(5): 877-81, 1983 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6638054

RESUMEN

Many opportunistic infections have been associated with an acquired immunodeficiency state in which cellular immune status has been altered. Two homosexual patients are described who presented with fever, peripheral eosinophilia, and a travel history to Haiti and were found to have central nervous system toxoplasmosis. Despite definitive diagnosis and appropriate therapy, both died. Techniques for diagnosis of central nervous system toxoplasmosis are discussed, and the importance of brain biopsy in this clinical situation is stressed. Eosinophilia may serve as an early diagnostic marker for disseminated toxoplasmosis in homosexual patients.


Asunto(s)
Encefalopatías/diagnóstico , Homosexualidad , Toxoplasmosis/diagnóstico , Adulto , Antibacterianos/uso terapéutico , Biopsia , Encefalopatías/tratamiento farmacológico , Encefalopatías/patología , Haití , Humanos , Masculino , Persona de Mediana Edad , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/patología , Viaje
20.
Am J Med ; 65(3): 507-13, 1978 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-362918

RESUMEN

Nosocomial respiratory tract infection with Acinetobacter calcoaceticus occurs frequently in many hospitals. An outbreak of respiratory tract infections in an intensive care unit provided an opportunity to study clinical and epidemiologic characteristics of such infections. Retrospective studies demonstrated that A. calcoaceticus in sputum was significantly associated with endotracheal intubation (p = 0.03) and continuous positive pressure ventilation (p less than 0.02). After control measures had interrupted the outbreak, a prospective microbiologic investigation demonstrated that one third of the hospital personnel had transient hand colonization with multiple strains of A. calcoaceticus. Pharyngeal, vaginal and rectal carriage was rare. A pulmonary therapist with chronic dermatitis had persistent hand colonization with the epidemic strain, and he contaminated respiratory therapy equipment. Cross contamination of respiratory therapy equipment occurred while in use, but no other inanimate reservoir was demonstrated. Although previous studies have implied that the inanimate hospital environment has unique reservoirs of A. calcoaceticus, these reservoirs were not implicated in this outbreak. Human skin must be considered an important reservoir of A. calcoaceticus.


Asunto(s)
Infecciones por Acinetobacter/epidemiología , Infección Hospitalaria/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Acinetobacter/aislamiento & purificación , Connecticut , Infección Hospitalaria/microbiología , Femenino , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal/efectos adversos , Masculino , Persona de Mediana Edad , Personal de Hospital , Faringe/microbiología , Respiración con Presión Positiva/efectos adversos , Estudios Prospectivos , Infecciones del Sistema Respiratorio/microbiología , Estudios Retrospectivos , Piel/microbiología , Esputo/microbiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA