RESUMEN
BACKGROUND: The present study aimed to analyse the nutritional quality of childrens' breakfasts using data collected during a cross-sectional observational study on the prevalence of urinary osmolality in 529 French children aged 9-11 years. METHODS: Total nutrient intake, mean adequacy ratio (MAR), energy density and solid energy density were calculated from breakfast food and fluid nutritional composition. To identify the main qualitative breakfast patterns, each breakfast item was categorised into 15 solid and liquid food categories and a principal component analysis followed by a cluster analysis was performed. RESULTS: Only 9.8% included skipped breakfast. Breakfast provided, on average, 22.9% of the recommended daily energy intake and 24.7% of the mean adequacy ratio of 23 key nutrients. Four breakfast patterns were identified: 'Sweets breakfast' (40.0% of children), 'Traditional French breakfast' (27.2%), 'Ready-to-eat cereal (RTEC) + milk' (18.1%) and 'Dairy and juice breakfast' (9.5%). Nutritionally, the 'RTEC + milk' pattern was the most advantageous. Flavoured milk was the most frequently consumed food (50.5%) and the major component of the 'Traditional French breakfast'. CONCLUSIONS: Although breakfast provided a substantial contribution to a range of nutrients, opportunity for improvement, particularly to less nutrient breakfast patterns, should not be overlooked.
Asunto(s)
Desayuno , Evaluación Nutricional , Población Blanca , Animales , Niño , Estudios Transversales , Dieta , Grano Comestible , Estudios de Evaluación como Asunto , Femenino , Calidad de los Alimentos , Francia , Humanos , Masculino , Leche , Encuestas Nutricionales , Ingesta Diaria Recomendada , EstudiantesRESUMEN
The 2010 Dietary Guidelines recommended that Americans increase potassium and decrease sodium intakes to reduce the burden of hypertension. One reason why so few Americans meet the recommended potassium or sodium goals may be perceived or actual food costs. This study explored the monetary costs associated with potassium and sodium intakes using national food prices and a representative sample of US adults. Dietary intake data from the 2001-2002 National Health and Nutrition Examination Survey were merged with a national food prices database. In a population of 4744 adults, the association between the energy-adjusted sodium and potassium intakes, and the sodium-to-potassium ratio (Na:K) and energy-adjusted diet cost was evaluated. Diets that were more potassium-rich or had lower Na:K ratios were associated with higher diet costs, while sodium intakes were not related to cost. The difference in diet cost between extreme quintiles of potassium intakes was $1.49 (95% confidence interval: 1.29, 1.69). A food-level analysis showed that beans, potatoes, coffee, milk, bananas, citrus juices and carrots are frequently consumed and low-cost sources of potassium. Based on existing dietary data and current American eating habits, a potassium-dense diet was associated with higher diet costs, while sodium was not. Price interventions may be an effective approach to improve potassium intakes and reduce the Na:K ratio of the diet. The present methods helped identify some alternative low-cost foods that were effective in increasing potassium intakes. The identification and promotion of lower-cost foods to help individuals meet targeted dietary recommendations could accompany future dietary guidelines.
Asunto(s)
Alimentos/economía , Hipertensión/prevención & control , Potasio en la Dieta/administración & dosificación , Potasio en la Dieta/economía , Ingesta Diaria Recomendada/economía , Factores Socioeconómicos , Sodio en la Dieta/administración & dosificación , Sodio en la Dieta/economía , Adulto , Anciano , Presión Sanguínea , Conducta Alimentaria , Femenino , Alimentos/efectos adversos , Conductas Relacionadas con la Salud , Promoción de la Salud/economía , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Potasio en la Dieta/efectos adversos , Conducta de Reducción del Riesgo , Sodio en la Dieta/efectos adversos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: There is overwhelming evidence that experiences during early life could have long-term health consequences. However, the role of early nutrition in programming obesity and leptin resistance is still poorly understood. OBJECTIVE: We aimed at determining whether nutritional intakes in early life are associated with body composition and hormonal status at 20 years. SUBJECTS: Healthy infants participating in the two-decade-long prospective ELANCE (Etude Longitudinale Alimentation Nutrition Croissance des Enfants) study were examined at 10 months and 2 years. At 20 years, weight, height, subscapular and triceps skinfold thicknesses, fat mass (FM) and fat-free mass (FFM) assessed via bioelectrical impedance analysis, and serum leptin concentration were recorded in 73 subjects still participating in the follow-up. RESULTS: In adjusted linear regression models, an increase by 100 kcal in energy intake at 2 years was associated with higher subscapular skinfold thickness (ß=6.4% SF, 95% confidence interval 2.53-10.30, P=0.002) and higher FFM (0.50 kg, 0.06-0.95, P=0.03) at 20 years. An increase by 1% energy from fat at 2 years was associated with lower subscapular skinfold thickness (-2.3% SF, -4.41 to -0.18, P=0.03), lower FM (-0.31 kg, -0.60 to -0.01, P=0.04) and lower serum leptin concentration (-0.21 µg l(-1), -0.39 to -0.03, P=0.02) at 20 years. CONCLUSIONS: Low-fat intake in early life was negatively associated with body fat (particularly at the trunk site) and serum leptin concentration at 20 years, suggesting that early low-fat intake could increase the susceptibility to develop overweight and leptin resistance at later ages. These findings substantiate current recommendations against restricting fat intake in early life and open new directions for investigating the origin of obesity.
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Tejido Adiposo , Registros de Dieta , Fenómenos Fisiológicos Nutricionales del Lactante , Leptina/sangre , Obesidad/sangre , Biomarcadores/sangre , Estatura , Índice de Masa Corporal , Peso Corporal , Preescolar , Susceptibilidad a Enfermedades , Ingestión de Energía , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Lactante , Masculino , Estado Nutricional , Obesidad/epidemiología , Estudios Prospectivos , Grosor de los Pliegues Cutáneos , Aumento de Peso , Adulto JovenRESUMEN
BACKGROUND: The beneficial impact of the traditional Mediterranean diet pattern on adiposity is still under debate, and this has never been assessed in a developing Mediterranean country. OBJECTIVES: To assess the relationships between adherence to a traditional Mediterranean diet and adiposity indexes, that is, body mass index (BMI) and waist circumference (WC), in a sample from rural Lebanon. DESIGN: A sample of 798 adults, aged 40-60 years, was selected in continental rural areas of Lebanon for a cross-sectional study. The questionnaire included socio-demographic, anthropometric and dietary sections. The daily consumption frequencies of selected food groups, categorized as positive or negative components, were calculated based on a food frequency questionnaire. Adherence to the Mediterranean diet was assessed using six a priori scores; including the widely used Mediterranean diet score (MDS). Associations between diet scores and BMI and WC were assessed. RESULTS: Overall, the diet of the study sample only partially matched the traditional Mediterranean diet. A total of 17.0% of men and 33.7% women were obese. The MDS was negatively associated (P<0.05) with WC, but not BMI, in men and women. The constructed composite Mediterranean score combining positive components of the diet (whole cereals, vegetables, legumes and fruit, olive oil and fish) and negative components adapted to this sample (refined cereals and pastries, and liquid sweets) was consistently and negatively associated with both BMI and WC for men and women in multivariate models. A 2-point increase in that score was associated with a decrease in BMI of 0.51 and 0.78 kg m(-2) and a decrease in WC of 2.77 and 4.76 cm in men and women, respectively. CONCLUSION: The results demonstrate that a Mediterranean diet is negatively associated with obesity and visceral adiposity in a rural population of a developing Mediterranean country.
Asunto(s)
Adiposidad/fisiología , Dieta Mediterránea , Carbohidratos de la Dieta/administración & dosificación , Grano Comestible , Obesidad/dietoterapia , Adiposidad/etnología , Adulto , Índice de Masa Corporal , Estudios Transversales , Carbohidratos de la Dieta/efectos adversos , Grano Comestible/efectos adversos , Conducta Alimentaria/etnología , Femenino , Humanos , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/etnología , Salud Rural , Factores Sexuales , Encuestas y Cuestionarios , Circunferencia de la CinturaRESUMEN
BACKGROUND/OBJECTIVES: Nutrient profiling of foods is defined as the science of ranking or classifying foods based on their nutrient content. Nutrient profiles can be calculated based on 100 g or 100 kcal of food or on standard serving sizes. The objective of this study was to compare the performance of nutrient profiles based on 100 g, 100 kcal and government-mandated serving sizes, and to identify the optimal base of calculation. SUBJECTS/METHODS: Nutrient profiles tested were composed of positive subscores based on nutrients to encourage and negative subscores based on nutrients to limit. Alternative profiles, computed using different bases of calculation, were used to rank order 378 commonly consumed foods from a food frequency instrument. Profile performance was tested with respect to the foods' energy density. RESULTS: Serving sizes, defined by the US Food and Drug Administration as reference amounts customarily consumed (RACC), were inversely linked to energy density of foods. Positive subscores based on 100 kcal were equivalent to those calculated using RACC values. Negative subscores performed better when based on 100 g as opposed to 100 kcal. CONCLUSIONS: Models based on serving sizes and on 100 kcal were preferable for positive subscores and models based on 100 g of food were preferable for negative subscores. RACC-based profiles may represent an attractive option for the US consumer.
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Bebidas/normas , Análisis de los Alimentos/normas , Etiquetado de Alimentos/normas , Valor Nutritivo , Algoritmos , Bebidas/análisis , Bases de Datos como Asunto/normas , Unión Europea , Análisis de los Alimentos/métodos , Humanos , Política Nutricional , Estados UnidosRESUMEN
BACKGROUND: Nutrient profiling of foods is defined as the science of classifying foods based on their nutrient content. Food rankings generated by nutrient profile models need to be tested against objective reality as opposed to public opinion. OBJECTIVE: To test the performance of selected nutrient profile models in relation to the foods' energy density (kcal g(-1)) and energy cost (Dollar per 1000 kcal). SUBJECTS/METHODS: Analyses were based on 378 component foods of a food frequency instrument. The models tested were the French nutrient adequacy models NAS23 and NAS16 and nutrient density models NDS23 and NDS16; and a family of nutrient-rich models (NR(n), where n=5-7; 10-12, and 15). Also tested were LIM scores and a modified British Food Standards Agency model WXYfm. Profiles were calculated based on 100 g, 100 kcal and on Reference Amounts Customarily Consumed. Food rankings generated by different models were correlated with each other and with the foods' energy density and energy cost. RESULTS: Nutrient profile models based on protein, fiber, vitamins and minerals showed an inverse correlation with energy density that diminished as more micronutrients were introduced into the model. Models based on fat, sugar and sodium were highly correlated with energy density. Foods classified as healthier were generally associated with higher energy costs. CONCLUSIONS: Not all models accurately reflected the foods' content of nutrients known to be beneficial to health. High correlations with energy density meant that some models classified foods based on their energy density as opposed to nutrient content.
Asunto(s)
Ingestión de Energía , Análisis de los Alimentos , Alimentos/clasificación , Valor Nutritivo , Dieta , Encuestas sobre Dietas , Alimentos/economía , Alimentos/normas , Humanos , Modelos Biológicos , Necesidades Nutricionales , Encuestas y Cuestionarios , Oligoelementos/análisis , Oligoelementos/economía , Oligoelementos/normas , Vitaminas/análisis , Vitaminas/economía , Vitaminas/normasRESUMEN
Childhood obesity is an important public health problem, with a rapidly increasing frequency worldwide. Identification of critical periods for the development of childhood and adolescent obesity could be very useful for targeting prevention measures. Weight status in early childhood is a poor predictor of adult adiposity status, and most obese adults were not obese as children. We first proposed to use the body mass index (BMI) charts to monitor individual BMI development. The adiposity rebound (AR) corresponds to the second rise in BMI curve that occurs between ages 5 and 7 years. It is not as direct a measure as BMI at any age, but because it involves the examination of several points during growth, and because it is identified at a time when adiposity level clearly change directions, this method provides information that can help us understand individual changes and the development of health risks. An early AR is associated with an increased risk of overweight. It is inversely associated with bone age, and reflects accelerated growth. The early AR recorded in most obese subjects and the striking difference in the mean age at AR between obese subjects (3 years) and non-obese subjects (6 years) suggest that factors have operated very early in life. The typical pattern associated with an early AR is a low BMI followed by increased BMI level after the rebound. This pattern is recorded in children of recent generations as compared to those of previous generations. This is owing to the trend of a steeper increase of height as compared to weight in the first years of life. This typical BMI pattern (low, followed by high body fatness level) is associated with metabolic diseases such as diabetes and coronary heart diseases. Low body fatness before the AR suggests that an energy deficit had occurred at an early stage of growth. It can be attributable to the high-protein, low-fat diet fed to infants at a time of high energy needs, the former triggering height velocity and the latter decreasing the energy density of the diet and then reducing energy intake. The high-fat, low-protein content of human milk may contribute to its beneficial effects on growth processes. Early (pre- and postnatal) life is a critical period during which environmental factors may programme adaptive mechanisms that will persist in adulthood. Under-nutrition in fetal life or during the first years after birth may programme a thrifty metabolism that will exert adverse effects later in life, especially if the growing child is exposed to overnutrition. These observations stress the importance of an adequate nutritional status in childhood and the necessity to provide nutritional intakes adapted to nutritional needs at various stages of growth. Because the AR reflects particular BMI patterns, it is a useful tool for the paediatrician to monitor the child's adiposity development and for researchers to investigate the different developmental patterns leading to overweight. It contributes to the understanding of chronic disease programming and suggests new approaches to obesity prevention.
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Adiposidad/fisiología , Composición Corporal/fisiología , Índice de Masa Corporal , Ingestión de Energía/fisiología , Estado Nutricional/fisiología , Obesidad/prevención & control , Adolescente , Adulto , Niño , Preescolar , Humanos , Masculino , Obesidad/fisiopatología , Oportunidad Relativa , Factores de Riesgo , Aumento de Peso/fisiología , Adulto JovenRESUMEN
Apical internodes of tall fescue (Festuca arundinacea Schreb. var. Clarine) harvested at flowering were sectioned into 5 or 10 equal parts to study in situ degradability and cell wall composition, respectively. The basal (youngest) section had the greatest primary wall content. Cell walls in the upper (older) sections had the highest xylose/arabinose ratio and lignin content and a lignin rich in syringyl units, all typical of extensive secondary wall development. Almost all of the p-coumaric (p-CA) and about half of the ferulic acid (FA) were released by 1 M NaOH and presumed to be ester-linked. The total FA content was approximately double that of p-CA in all sections other than the youngest with a distribution similar to that of total p-CA. However, the ratio of esterified to ether and ether plus ester linked (Et & Et+Es) FA differed with age. Whereas the esterified form remained essentially constant ( approximately 4.5 g/kg of cell wall), Et & Et+Es ferulate increased with increasing age of the tissue and was significantly related to lignin deposition (r = 0.79, P < 0.01). The extent of cell wall degradation after 48 h of incubation in the rumen was inversely related to maturity, falling from 835 g/kg of dry matter in the youngest section to 396 g/kg in the oldest. Both the rate and extent of cell wall degradation were significantly negatively related to the ratio of xylose to arabinose, lignin content, proportion of syringyl units present in lignin, and concentration of Et & Et+Es FA present. A positive relationship between Et & Et+Es FA was also found, with the rate (P < 0.01) being better correlated than the extent (P < 0.05) of cell wall degradation. Application of the newly extended internode model to fescue produced results consistent with the view that both the lignin content and the extent to which lignin was covalently bound to the other wall polymers crucially influenced the rate and extent of degradation.
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Hidroxibenzoatos/química , Poaceae/química , Alimentación Animal , Animales , Biodegradación Ambiental , Pared Celular/química , Digestión , Hidroxibenzoatos/análisis , Lignina/química , Lignina/metabolismo , Estructura Molecular , Poaceae/ultraestructura , Polisacáridos/química , Polisacáridos/metabolismo , Rumen/microbiología , Rumen/fisiologíaRESUMEN
Myasthenia gravis (MG) is an autoimmune disease targeting the skeletal muscle acetylcholine receptor. We have previously demonstrated a selection bias of CD4+ T cells expressing the Vbeta5.1 T-cell receptor gene in the thymus of HLA-DR3 patients with MG. To evaluate the pathogenicity of these cells, severe combined immunodeficiency mice engrafted with MG thymic lymphocytes were treated with anti-Vbeta5.1 antibody. Signs of pathogenicity (eg, acetylcholine receptor loss and complement deposits at the muscle end plates of chimeric mice) were prevented in anti-Vbeta5.1-treated severe combined immunodeficiency chimeras. Pathogenicity was mediated by autoantibodies against acetylcholine receptor. Thymic cells depleted of Vbeta5.1-positive cells in vitro before cell transfer were nonpathogenic, indicating that Vbeta5.1-positive cells are involved in the production of pathogenic autoantibodies. Acetylcholine receptor loss was prevented by Vbeta5.1 targeting in HLA-DR3 patients only, demonstrating specificity for HLA-DR3-peptide complexes. The action of the anti-Vbeta5.1 antibody involved both the in vivo depletion of Vbeta5.1-expressing cells and an increase in the interferon-gamma/interleukin-4 ratio, pointing to an immune deviation-based mechanism. This demonstration that a selective and specific T-helper cell population is involved in controlling pathogenic autoantibodies in MG holds promise for the treatment of MG.
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Autoinmunidad/inmunología , Placa Motora/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Adolescente , Adulto , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones SCID , Receptores Colinérgicos/inmunologíaRESUMEN
We analyzed the production and the roles of IL-6, IL-10, and IL-13 in B-lymphoid malignancies and in specific diseases with B-lymphocyte hyperactivity. Both IL-13 and IL-10 genes are expressed in B-cell lymphomas. However, their contribution to tumor progression is unclear. In certain lymphoproliferative disorders that develop in transplanted patients, IL-6 is produced by malignant cells and is a major factor of their proliferation. In other lymphomas, the IL-6 gene is expressed only in malignancies where differentiated malignant cells are present. In these lymphomas, IL-6 is produced by stromal cells, and the malignant cells express the IL-6 receptor. In patients with HIV infection, the level of production of IL-6, IL-10, and IL-13 is not higher than those of other conditions with immune activation. However, IL-6 contributes to increased production of IgG and IgA in vivo. In Castleman's disease, IL-6 is produced in the lymph node germinal centers, partly originating from follicular dendritic cells, which may explain some of the pathogenesis of this disease. In systemic lupus erythematosus, the critical cytokine is IL-10, which is produced in large amounts by B lymphocytes and monocytes and is responsible for autoantibody production. Taken together, these data emphasize the roles of IL-6 and IL-10, usually produced by nonlymphoid cells, on B lymphocytes, either malignant or hyperactivated.
Asunto(s)
Linfocitos B/metabolismo , Interleucinas/farmacología , Linfoma de Células B/metabolismo , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Linfocitos B/efectos de los fármacos , Enfermedad de Castleman/metabolismo , Línea Celular , Fiebre/tratamiento farmacológico , Infecciones por VIH/metabolismo , Humanos , Inmunoglobulina G/metabolismo , Interleucina-10/metabolismo , Interleucina-10/farmacología , Interleucina-13/farmacología , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-6/farmacología , Trastornos Linfoproliferativos/metabolismo , Ratones , Ratones SCID , Modelos InmunológicosRESUMEN
Competitive reverse transcription-polymerase chain reaction (RT-PCR) is a new technique allowing quantification of cytokine gene expression from either experimental or clinical samples. In this assay, a time-consuming step is the quantification of amplified products. To improve this step, we set up a colorimetric assay in which the amplified product from either the cDNA or the competitor can be reliably quantified. Using this approach, which can be completely automatized, up to 320 PCR products can be quantified each day. In this report, we describe the quantification of IL-10 mRNA molecules as compared to that of beta-actin mRNA molecules. The sensitivity of the quantification was 7.7 x 10(7) molecules for the amplified beta-actin cDNA and the amplified IL-10 cDNA, corresponding to approximately 9.6 pg amplified beta-actin cDNA and 11 pg amplified IL-10 cDNA, respectively. The intra-assay variation coefficient was < 12%. This technique can be readily extended to all cytokines, and it thus allows routine monitoring of cytokine gene expression, either from experimental samples or from clinical trials.
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Citocinas/genética , Expresión Génica , Reacción en Cadena de la Polimerasa/métodos , Actinas/genética , Secuencia de Bases , Unión Competitiva , Colorimetría/métodos , Cartilla de ADN/genética , ADN Complementario/genética , Estudios de Evaluación como Asunto , Amplificación de Genes , Humanos , Técnicas In Vitro , Interleucina-10/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/estadística & datos numéricos , ARN Mensajero/análisis , ARN Mensajero/genética , Sensibilidad y EspecificidadRESUMEN
Expression of the IL-13 gene in malignant tissues from 26 human B-cell lymphoid malignancies was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). A positive signal was detected in 16 cases, which included high grade B lymphomas, follicular lymphomas and B-cell chronic lymphocytic leukemias. IL-13 mRNA was also detected in the 9 malignant B cell lines and in the 6 lymphoblastoid cell lines tested, as well as in freshly isolated malignant B cells from 2 patients with a Burkitt's lymphoma. Two of 8 T-cell lymphomas and 2 of 4 T-cell lines expressed the IL-13 gene. In contrast, IL-13 gene expression was not detected in any of the 5 non-lymphoid cell lines tested. No specific binding of radiolabeled IL-13 was detected on B cell lines, suggesting an absence of IL-13 receptors on such cells. This conclusion was also supported by the inability of IL-13 or anti-IL-13 antibodies to affect the growth of malignant B cells. Taken together, these results show that both malignant and EBV-transformed B lymphocytes, either freshly isolated or maintained as cell lines, express the IL-13 gene. This raises the question of the role of B lymphocyte-derived IL-13, a B lymphocyte stimulating cytokine, on the in vivo function of normal B lymphocytes as well as on the in vivo behaviour of B lymphoid malignancies.
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Linfocitos B/inmunología , Expresión Génica , Herpesvirus Humano 4/genética , Interleucina-1/biosíntesis , Linfoma de Células B/inmunología , Animales , Linfocitos B/patología , Secuencia de Bases , Linfoma de Burkitt/inmunología , Línea Celular , Línea Celular Transformada , Cartilla de ADN , Herpesvirus Humano 4/inmunología , Humanos , Linfoma de Células B/patología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Linfocitos T/inmunologíaRESUMEN
Human immunodeficiency virus infection leads to a deregulated production of a number of cytokines. Some of them (IL-1, IL-6, TNF-alpha, interferon-gamma) are produced in increased amounts in vivo, whereas the production of IL-2 is decreased. This latter abnormality plays a pivotal role in the establishment of the immunodeficiency. Some cytokines (IL-1, IL-6, TNF-alpha) stimulate the in vitro replication of HIV, whereas others (mainly the interferons) inhibit it. The effect of cytokines in vivo in the spreading of HIV remains, however, largely unknown. Cytokines may also be involved in the development of many clinical manifestations associated with HIV infection. IL-1, IL-6 and TNF-alpha may play a role in tissue damages associated with opportunistic infections, in HIV-related encephalopathy and in cachexia. Cytokines, mainly IL-6, IL-10 and IL-13, may stimulate the growth of malignant cells during Kaposi sarcoma or lymphomas. Better knowledge of the role of cytokines during HIV infection should allow new therapeutic approaches based on the use of either recombinant cytokines or specific antagonists, with the aim of limiting both HIV spreading and the clinical manifestations of this infection.
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Citocinas/fisiología , Infecciones por VIH/inmunología , Citocinas/uso terapéutico , Infecciones por VIH/terapia , HumanosRESUMEN
Interleukin-10 (IL-10) production by B lymphocytes has previously been demonstrated for malignant cells and for in vitro activated normal B cells. Spontaneous in vivo production of IL-10 by normal B lymphocytes has only been demonstrated in mice, in which autoreactive Ly 1 + B cells are involved. In the present study, spontaneous expression of the IL-10 gene by peripheral blood mononuclear cells was investigated in systemic lupus erythematosus (SLE), a human disease involving autoreactive B cells. Of the 47 SLE patients tested by coupled reverse transcriptase-polymerase chain reaction, 34 scored positive, contrasting with only 1 positive out of 34 normal subjects (p < 0.001). Spontaneous in vitro production of IL-10 by PBMC, determined using an ELISA assay, was 33 times higher in SLE than in controls (2623 +/- 728 pg/ml vs 79.3 +/- 34.5 pg/ml, respectively) (p < 0.001). The level of production of IL-10 in SLE was unrelated to either clinical or biological markers of disease activity. Among PBMC, monocytes and B lymphocytes both contributed to IL-10 production, whereas T cells did not. IL-10 overproduction in SLE suggests that this Th2-type interleukin plays a role in the production of autoantibodies through pathways involving both paracrine production by monocytes and autocrine IL-10 production by autoreactive B cells.
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Linfocitos B/metabolismo , Interleucina-10/biosíntesis , Lupus Eritematoso Sistémico/metabolismo , Monocitos/metabolismo , Adolescente , Adulto , Secuencia de Bases , ADN , Femenino , Humanos , Interleucina-10/genética , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
Interferon-gamma (IFN-gamma) has been shown to inhibit human immunodeficiency virus (HIV) replication in macrophages. However, the site of its effect on the HIV infectious cycle is unknown. We show here that IFN-gamma inhibits the transactivation of HIV long terminal repeat (LTR) during viral infection and that it antagonizes tat effect in HT4LacZ-1 cells. HT4LacZ-1 is an indicator CD4+ HeLa cell line for HIV infectivity, because it harbors a HIV LTR-LacZ gene susceptible to transactivation by tat. It was used in combination with a computer-assisted image analyzer to quantify: (i) the number of transactivated foci following HIV infection, (ii) their individual level of transactivation, and (iii) the fusion potency of infected cells. IFN-gamma induced a 75% decrease of the number of transactivated foci following infection of HT4LacZ-1 cells by HIV. The remaining 25% foci still susceptible to transactivation were transactivated at a lower level than in control cultures, and the fusion potency of infected cells was strongly decreased. IFN-gamma acted after HIV entry into the cell and independently of reverse transcription. IFN-gamma antagonized tat-induced LTR transactivation: it inhibited transactivation of HT4LacZ-1 cells when tat was provided either from a SV40-based expression vector of tat or by polyethylene glycol-induced cell fusion with HeLa-tat-III cells. These results suggest that IFN-gamma affects the expression or the activity of cellular factors interacting with tat and that the high level of IFN-gamma production associated with HIV infection plays a role in the establishment of HIV latency.
Asunto(s)
Genes tat , Duplicado del Terminal Largo de VIH , VIH-1/genética , Interferón gamma/farmacología , Activación Transcripcional/efectos de los fármacos , Células Gigantes/efectos de los fármacos , Células Gigantes/fisiología , VIH-1/fisiología , Células HeLa , Humanos , Cinética , Transfección , Replicación Viral , Zidovudina/farmacología , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismoRESUMEN
Whenever an innovative treatment or a research protocol is proposed to a patient, the "loi Huriet" requires a written consent from the patient. This is an important change in the field of the interrelation between the doctor and his patient. To evaluate the impact of this written consent we asked 215 patients who have signed a consent form to answer a questionnaire at the end of their radiation treatment. The signature appears as an important event. The majority of the patients (70%) is not shocked by this procedure. In 97% of cases, in spite of this written relation, the patients keep intact their confidence in their doctor. Sometimes this consent form may improve the information given to the patient and it should not be seen as an obstacle for the development of research trials. There are still many problems to be solved as regards the information of the patient and the application of the "loi Huriet".
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Ensayos Clínicos como Asunto/legislación & jurisprudencia , Consentimiento Informado , Relaciones Médico-Paciente , Francia , Humanos , Neoplasias/radioterapia , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
Serine esterase B (SE B) is a protein contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells; SE B gene is transcribed upon activation of these cytotoxic cells. In order to show the in vivo interactions between HIV-infected cells and anti-HIV cytotoxic cells we analysed, by in situ hybridization, the expression of the SE B gene in eight hyperplastic lymph nodes from HIV-1-infected patients presenting with persistent generalized lymphadenopathy. We detected numerous cells expressing the SE B gene. The mean number of positive cells was 3.2 times higher in HIV lymph nodes than in six non-HIV hyperplastic lymph nodes studied in parallel (P less than 0.05). In control lymph nodes, the SE B gene was expressed only in interfollicular areas; virtually no cells expressed the SE B gene within follicles. In contrast, in HIV lymph nodes cells expressing the SE B gene were distributed either in interfollicular areas or within follicles. Expression of the SE B gene inside follicles was thus a specific feature of HIV lymph nodes (P less than 0.001) and was associated with the presence of HIV antigens and RNA at the same site. These results suggest that cytotoxic cells are activated in follicles of HIV lymph nodes and may be involved in the lysis of HIV-infected cells. Such a phenomenon may explain the development of follicle lysis, a specific feature of HIV lymph nodes. It may also inhibit the spreading of HIV infection.
Asunto(s)
Esterasas/genética , Infecciones por VIH/inmunología , VIH-1/inmunología , Ganglios Linfáticos/microbiología , Linfocitos T Citotóxicos/microbiología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/microbiología , Northern Blotting , Expresión Génica/genética , Antígenos VIH/análisis , Infecciones por VIH/microbiología , VIH-1/fisiología , Humanos , Hiperplasia/inmunología , Hiperplasia/microbiología , Interleucina-2/genética , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , ARN Viral/análisis , Linfocitos T Citotóxicos/enzimología , Linfocitos T Citotóxicos/inmunología , Replicación ViralRESUMEN
We used a quantitative bioassay (the beta-gal assay) to visualize and quantify syncytium induction by fresh HIV isolates. This bioassay is based on the transactivation by tat of a chimeric gene comprising an HIV-1 long terminal repeat (LTR) fused to a modified lacZ gene of Escherichia coli. The chimeric gene encodes a beta-galactosidase which is translocated to the nucleus. It allows the enzymatic staining of all nuclei from HIV-induced syncytia. Using this unequivocal assay (the beta-gal assay), we could assess the syncytium-inducing properties of fresh HIV isolates after only 4 days of coculture of patient lymphocytes with activated normal lymphocytes. Syncytium-inducing HIV isolates were detected in 11 out of 40 seropositive patients studied. They were isolated mainly from AIDS patients: eight out of 17 grade IV (according to Centers for Disease Control criteria) patients were infected with syncytium-inducing strains. However, of 23 grade II and III patients tested, syncytium-inducing HIV strains were isolated from three cases. These three patients displayed no detectable p24 antigenaemia and had a CD4+ cell count of greater than 300 cells/microliter. The in vitro replication rate of HIV grown from 36 patient blood samples was then examined by sequential p24 antigen measurements in coculture supernatants. The 10 samples leading to syncytium formation also exhibited the highest replication rate. The possibility of unequivocally detecting syncytium-inducing strains after only a few days of coculture will make this detection routine and rapid. In addition, the limited period of amplification required is a significant advantage as it minimizes the emergence of HIV variants selected during long-term in vitro cultures.