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Football is a global game which is constantly evolving, showing substantial increases in physical and technical demands. Nutrition plays a valuable integrated role in optimising performance of elite players during training and match-play, and maintaining their overall health throughout the season. An evidence-based approach to nutrition emphasising, a 'food first' philosophy (ie, food over supplements), is fundamental to ensure effective player support. This requires relevant scientific evidence to be applied according to the constraints of what is practical and feasible in the football setting. The science underpinning sports nutrition is evolving fast, and practitioners must be alert to new developments. In response to these developments, the Union of European Football Associations (UEFA) has gathered experts in applied sports nutrition research as well as practitioners working with elite football clubs and national associations/federations to issue an expert statement on a range of topics relevant to elite football nutrition: (1) match day nutrition, (2) training day nutrition, (3) body composition, (4) stressful environments and travel, (5) cultural diversity and dietary considerations, (6) dietary supplements, (7) rehabilitation, (8) referees and (9) junior high-level players. The expert group provide a narrative synthesis of the scientific background relating to these topics based on their knowledge and experience of the scientific research literature, as well as practical experience of applying knowledge within an elite sports setting. Our intention is to provide readers with content to help drive their own practical recommendations. In addition, to provide guidance to applied researchers where to focus future efforts.
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Rendimiento Atlético/fisiología , Dieta Saludable , Política Nutricional , Fútbol/fisiología , Traumatismos en Atletas/rehabilitación , Composición Corporal , Conducta Competitiva/fisiología , Diversidad Cultural , Suplementos Dietéticos , Ambiente , Femenino , Humanos , Masculino , Necesidades Nutricionales , Acondicionamiento Físico Humano/fisiología , ViajeRESUMEN
BACKGROUND: Children with intellectual disabilities (ID) frequently have feeding problems, but there has been limited research on nutrient intake, dietary patterns and diet quality in this population. METHOD: Nutrient intakes, dietary patterns and the Healthy Eating Index were compared between 48 children with ID and 55 typically developing (TD) children aged 3-8 years who participated in the Children's Mealtime Study. Three-day food records that included two weekdays and one weekend day were used to assess dietary intake. Food intake was entered into the Nutrition Data System for Research for analysis of nutrient intake, dietary patterns and diet quality. Height and weight were measured to determine body mass index (BMI). The relation of dietary patterns to weight status was also assessed. RESULTS: Typically developing children and children with ID met the Estimated Average Requirement/Adequate Intake (EAR/AI) for most nutrients. However, a substantial number of children in both groups did not meet the EAR for vitamins E and D and calcium and the AI for vitamin K. Only one TD child met the AI for potassium. A small percentage of children in both groups did not meet the EAR for vitamin A and vitamin C, and in the ID group, a small percentage did not meet the EAR for vitamin B12 . Children in the ID group consumed, on average, fewer servings of vegetables than TD children (0.5 vs. 1.2, P < 0.001), but there was no significant difference in servings of fruit (0.8 vs. 1.1, respectively), fruit juice (less than a half serving in both groups), sugar-sweetened beverages (less than a half serving in both groups) or snacks (1.1 vs. 1.4, respectively) after adjusting for BMI z-score, parental education and race. We found a significant correlation between snack intake and BMI z-score among children with ID but not among TD children (r = 0.48, P < 0.0001 vs. r = 0.19, P = 0.16, respectively). The Healthy Eating Index indicated, on average, poor overall diet quality in both groups (58.2 in the ID group and 59.1 in the TD group). CONCLUSIONS: This study suggests that the diets of children with ID, as in TD children, need improvement. Targeting healthy eating in children with ID would improve diet quality and overall health.
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Discapacidad Intelectual , Niño , Dieta , Ingestión de Alimentos , Ingestión de Energía , Humanos , Discapacidad Intelectual/epidemiología , NutrientesRESUMEN
BACKGROUND: Physical activity has beneficial effects on the health of cancer survivors. We aimed to investigate accelerometer-assessed physical activity and sedentary time in cancer survivors, and describe activity profiles. Additionally, we identify demographic and clinical correlates of physical activity, sedentary time and activity profiles. METHODS: Accelerometer, questionnaire and clinical data from eight studies conducted in four countries (n = 1447) were pooled. We calculated sedentary time and time spent in physical activity at various intensities using Freedson cut-points. We used latent profile analysis to identify activity profiles, and multilevel linear regression analyses to identify demographic and clinical variables associated with accelerometer-assessed moderate to vigorous physical activity (MVPA), sedentary time, the highly active and highly sedentary profile, adjusting for confounders identified using a directed acyclic graph. RESULTS: Participants spent on average 26 min (3%) in MVPA and 568 min (66%) sedentary per day. We identified six activity profiles. Older participants, smokers and participants with obesity had significantly lower MVPA and higher sedentary time. Furthermore, men had significantly higher MVPA and sedentary time than women and participants who reported less fatigue had higher MVPA time. The highly active profile included survivors with high education level and normal body mass index. Haematological cancer survivors were less likely to have a highly active profile compared to breast cancer survivors. The highly sedentary profile included older participants, males, participants who were not married, obese, smokers, and those < 12 months after diagnosis. CONCLUSIONS: Cancer survivors engage in few minutes of MVPA and spend a large proportion of their day sedentary. Correlates of MVPA, sedentary time and activity profiles can be used to identify cancer survivors at risk for a sedentary and inactive lifestyle.
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Supervivientes de Cáncer/estadística & datos numéricos , Ejercicio Físico , Conducta Sedentaria , Acelerometría , Estudios de Cohortes , Femenino , Monitores de Ejercicio , Humanos , MasculinoRESUMEN
Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is 'sensed' have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-(13)C2]Leu and [(2)H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A-V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70% vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling 90 min vs. 30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; -57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.
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Leucina/farmacología , Músculo Esquelético/metabolismo , Biosíntesis de Proteínas/efectos de los fármacos , Proteolisis/efectos de los fármacos , Valeratos/farmacología , Administración Oral , Humanos , Leucina/administración & dosificación , Leucina/farmacocinética , Masculino , Distribución Tisular , Valeratos/administración & dosificación , Valeratos/farmacocinética , Adulto JovenRESUMEN
We examined postprandial branched-chain amino acid (BCAA), insulin, and glucose responses in blood for 4 h following the consumption of two isonitrogenous doses (2 × 20 g protein) of Greek-style yogurt (GY) and skimmed milk (MILK) in young males. Peak leucine and BCAA concentrations and areas under the curve were greater after GY versus MILK, and time to maximal leucine/BCAA concentrations was similar between conditions. We demonstrated that different protein-matched wholefood dairy products elicit different postprandial aminoacidemic responses.
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Aminoácidos de Cadena Ramificada , Yogur , Masculino , Animales , Leucina/metabolismo , Aminoácidos de Cadena Ramificada/metabolismo , Leche/química , Glucosa/metabolismo , InsulinaRESUMEN
A progressive decrement in muscle mass and muscle function, sarcopoenia, accompanies ageing. The loss of skeletal muscle mass and function is the main feature of sarcopoenia. Preventing the loss of muscle mass is relevant since sarcopoenia can have a significant impact on mobility and the quality of life of older people. Dietary protein and physical activity have an essential role in slowing muscle mass loss and helping to maintain muscle function. However, the current recommendations for daily protein ingestion for older persons appear to be too low and are in need of adjustment. In this review, we discuss the skeletal muscle response to protein ingestion, and review the data examining current dietary protein recommendations in the older subjects. Furthermore, we review the concept of protein quality and the important role that nutrient-dense protein (NDP) sources play in meeting overall nutrient requirements and improving dietary quality. Overall, the current evidence endorses an increase in the daily ingestion of protein with emphasis on the ingestion of NDP choices by older adults.
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Envejecimiento Saludable , Anciano , Anciano de 80 o más Años , Dieta , Proteínas en la Dieta , Humanos , Músculo Esquelético , Nutrientes , Calidad de VidaRESUMEN
Objective: To assess early care and education professionals' breastfeeding knowledge and practices before and after an e-learning program. Participants: Early care and education professionals from New Hampshire (U.S.A.) licensed child care programs were invited to complete a pre-assessment followed by a 90-minute e-learning breastfeeding program. Three months post-training, participants were invited to complete the post-assessment. Analysis: McNemar tests were used to assess changes from pre-post-assessment for dichotomous variables. McNemar-Bowker tests were used to determine differences from pre-post for variables with more than two categories. When the McNemar-Bowker test was significant, a multiple comparison correction (Bonferroni) was used. Results: 114 participants completed the e-learning program and pre-post assessment. Results showed significant improvement from pre-post in 10 of 15 breastfeeding knowledge questions related to health of baby, mother and child care centers, economics, and environmental impact. There were significant changes from pre-post in 24 of 50 breastfeeding practice questions in handling breast milk, promoting breastfeeding, and supporting mothers. Conclusions and Implications: This study indicates improvement in early care and education professionals' breastfeeding knowledge and practices; however, opportunities exist to design targeted initiatives to further strengthen practices that support breastfeeding families in the child care environment.
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BACKGROUND: Using residual values calculated from models regressing appendicular lean mass on fat mass and height is one of several suggested strategies for adjusting appendicular lean mass for body size when measuring sarcopenia. However, special consideration is required when using this technique in different subgroups in order to capture the correct individuals as sarcopenic. OBJECTIVES: To provide guidance about how to conduct stratified analyses for the regression adjustment technique using age groups as an example. DESIGN: Cross-sectional study. SETTING: Data collected at baseline (2012-2015) for the Canadian Longitudinal Study on Aging. PARTICIPANTS: Community dwelling participants of European descent aged 45 to 85 years (n=25,399). MEASUREMENTS: Appendicular lean mass, height, and weight were measured. Sex-specific residuals were calculated in participants before and after stratifying participants by age group (45-54, 55-64, 65-74, 75-85 years). Cut offs corresponding to the sex-specific 20th percentile residual values in participants ≥65 years were determined first in the residuals calculated in all participants and residuals calculated in only those aged ≥65 years. For each set of cut offs, the percentage of age and sex-stratified participants with low appendicular lean mass were compared for the residuals calculated in all participants and the residuals calculated after stratifying by age. RESULTS: In 12,622 males and 12,737 females, regardless of the cut off used, the percentage of participants with low appendicular lean mass decreased with age when residuals were calculated after age stratification. When the residuals were calculated in all participants, the percentage of participants with sarcopenia increased from the youngest to the oldest age groups. CONCLUSIONS: Sex-specific residuals in all participants should be calculated prior to stratifying the sample by age group, or other stratification variables, for the purposes of developing appendicular lean mass cut offs or subgroup analyses.
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Proyectos de Investigación , Sarcopenia , Distribución por Edad , Anciano , Anciano de 80 o más Años , Envejecimiento , Composición Corporal , Canadá/epidemiología , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Sarcopenia/diagnóstico , Sarcopenia/epidemiologíaRESUMEN
The mechanism of suppression, of delayed hypersensitivity to tuberculoprotein by 6-mercaptopurine (6-MP) was studied in guinea pigs. Under the conditions of the protocol, suppression of tuberculin delayed skin test reactivity was not associated with a significantly altered end-organ response to mediators of permeability. No significant alteration of in vivo lymphoid activity, as measured by reconstitution studies, was found. In addition, lymphoid cells from 6-MP-treated animals reacted in a fashion similar to those of placebo-treated animals with respect to (a) antigen-induced lymphocyte proliferation, (b) antigen-induced liberation of macrophage inhibitory factor activity, (c) direct inhibition by antigen of peritoneal exudate cell migration. Conversely, suppression was seen in levels of blood monocytes and in vitro function of macrophages from 6-MP-treated animals in several respects: (a) adherence to glass, (b) migratory rate, (c) phagocytic capacity. Therefore, it would appear that a ma]or mechanism of 6-MP-induced suppression of delayed hypersensitivity is through its action on effector cells.
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Hipersensibilidad Tardía/inmunología , Linfocitos/inmunología , Macrófagos/inmunología , Mercaptopurina/farmacología , Animales , Diferenciación Celular , Inhibición de Migración Celular , Cobayas , Inmunidad Celular/efectos de los fármacos , Terapia de Inmunosupresión , Recuento de Leucocitos , Linfocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Fagocitosis , Prueba de TuberculinaRESUMEN
Previous work has indicated that tetraparental mice, chimeric since the eight-cell stage because of embryo fusion using histoincompatible strain combinations, possess autospecific immune cells and blocking antibodies. Although this phenomenon has been demonstrated in vitro, it may have relevance to the self-tolerance shown by these mice in vivo. The experiments described here indicate that spleen cells from tetraparental mice can block mixed lymphocyte reactions between the two parental cell types, but not between unrelated strains. Furthermore, this suppressive ability is not affected by an otherwise effective treatment of the tetraparental spleen cells with anti-theta antibody and complement. The in vitro experimental system elaborated here should help to characterize the cell type responsible for the suppression.
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Células Híbridas/inmunología , Tolerancia Inmunológica , Terapia de Inmunosupresión , Animales , Células Productoras de Anticuerpos , Fusión Celular , Proteínas del Sistema Complemento , Prueba de Histocompatibilidad , Sueros Inmunes , Activación de Linfocitos , Ratones , Mosaicismo , Bazo/inmunología , Linfocitos T/inmunologíaRESUMEN
Anti-tubular basement membrance (alpha TBM) disease-producing interstitial nephritis in mice is not dependent on the generation of alpha TBM antibodies. Susceptibility seems to be defined by very private specificities in H-2K. These specificities are pleiomorphic, providing both immune-response genes and identity restrictions for cytotoxic effector functions expressed by a Thy-1.2+, Lyt-2,3+ T cell. These studies establish a role for T cells in the pathogenesis in interstitial nephritis as well as providing further evidence for the role of H-2K in the expression of an autoimmune disease.
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Genes MHC Clase II , Antígenos H-2/genética , Nefritis Intersticial/genética , Biosíntesis de Proteínas , Animales , Membrana Basal/inmunología , Sitios de Unión de Anticuerpos , Nitrógeno de la Urea Sanguínea , Citotoxicidad Inmunológica , Susceptibilidad a Enfermedades , Túbulos Renales/inmunología , Macrófagos/inmunología , Ratones , Ratones Endogámicos A , Ratones Endogámicos AKR , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nefritis Intersticial/inmunología , Conejos , Linfocitos T/inmunologíaRESUMEN
Antiidiotypic immunity can successfully inhibit the development of antitubular basement membrane (alpha TBM) disease that produces interstitial nephritis. Rats normally immunized to produce disease, however, do not develop this regulatory and protective antiidiotypic effect. The failure to see such a regulatory response is functionally related to the influence of a nonspecific, RT7.1+, OX8-suppressor T cell that appears shortly after immunization. While this suppressor cell system can partially reduce the intensity of disease, it also limits the host's ability to specifically regulate the alpha TBM immune response and, hypothetically, leaves the disease process in an operationally active mode.
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Anticuerpos Antiidiotipos/biosíntesis , Antígenos de Histocompatibilidad/inmunología , Idiotipos de Inmunoglobulinas/inmunología , Nefritis Intersticial/inmunología , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Antiidiotipos/fisiología , Anticuerpos Monoclonales/inmunología , Membrana Basal/inmunología , Modelos Animales de Enfermedad , Hipersensibilidad Tardía/inmunología , Inmunización Pasiva , Idiotipos de Inmunoglobulinas/administración & dosificación , Túbulos Renales/inmunología , Nefritis Intersticial/etiología , Ratas , Ratas Endogámicas BN , Linfocitos T Reguladores/trasplanteRESUMEN
Unloading-induced atrophy is a relatively uncomplicated form of muscle loss, dependent almost solely on the loss of mechanical input, whereas in disease states associated with inflammation (cancer cachexia, AIDS, burns, sepsis, and uremia), there is a procatabolic hormonal and cytokine environment. It is therefore predictable that muscle loss mainly due to disuse alone would be governed by mechanisms somewhat differently from those in inflammatory states. We suggest that in vivo measurements made in human subjects using arterial-venous balance, tracer dilution, and tracer incorporation are dynamic and thus robust by comparison with static measurements of mRNA abundance and protein expression and/or phosphorylation in human muscle. In addition, measurements made with cultured cells or in animal models, all of which have often been used to infer alterations of protein turnover, appear to be different from results obtained in immobilized human muscle in vivo. In vivo measurements of human muscle protein turnover in disuse show that the primary variable that changes facilitating the loss of muscle mass is protein synthesis, which is reduced in both the postabsorptive and postprandial states; muscle proteolysis itself appears not to be elevated. The depressed postprandial protein synthetic response (a phenomenon we term "anabolic resistance") may even be accompanied by a diminished suppression of proteolysis. We therefore propose that most of the loss of muscle mass during disuse atrophy can be accounted for by a depression in the rate of protein synthesis. Thus the normal diurnal fasted-to-fed cycle of protein balance is disrupted and, by default, proteolysis becomes dominant but is not enhanced.
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Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Trastornos Musculares Atróficos/metabolismo , Animales , Humanos , Ratones , Músculo Esquelético/anatomía & histología , Tamaño de los Órganos/fisiología , Ratas , Especificidad de la EspecieRESUMEN
Administration of 6-mercaptopurine suppressed appearance of tuberculin skin test reactivity for up to 6 weeks after mycobacterial injection. Lymphocytes obtained during the period of suppressed tuberculin reactivity exhibited normal in vitro proliferative responses to tuberculin, suggesting that the drug may not be qualitatively affecting function of immunologically competent cells.
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Hipersensibilidad Tardía , Linfocitos/inmunología , Mercaptopurina/farmacología , Prueba de Tuberculina , Animales , Células Productoras de Anticuerpos , Depresión Química , Cobayas , Técnicas In Vitro , Activación de Linfocitos , Linfocitos/efectos de los fármacos , Masculino , Mercaptopurina/uso terapéuticoRESUMEN
OBJECTIVE: The aim of this study was to analyse the outcome of emergency laparoscopic surgical management of complicated diverticular disease. METHOD: A prospectively collected electronic database of all colorectal laparoscopic procedures between April 2001 and September 2007 has been used to identify outcomes in patients presenting with complicated diverticular disease. RESULTS: Sixty-six patients (28 men), median age 69 years (23-95), ASA grade II (12), III (38), IV (16) have undergone emergency surgery for complicated diverticulitis--Hinchey grades I (27), II (29), III (7) and diverticular bleeding (3) over a 6(1/2)-year period: 43 high anterior resections, 17 Hartmann's resections and seven low anterior resections. Diverticular fistulas were seen in 16 patients: colovaginal (7), colovesical (2), colo-fallopian (4), entero-colic (3). The median operation time was 110 min (45-195 min). There was one conversion to open surgery. Postoperative analgesia was provided by intravenous Paracetamol in 33 patients (50%), patient-controlled analgesia in 24 (36%), oral Paracetamol and Oramorph (12%) and epidural opioid infusion (1.5%). The median time to normal diet was 24 h (4 h-6 days) and median hospital stay 5 days (2-30). There were two deaths (3.3%); anastomotic leak, ventricular fibrillation (VF) cardiac arrest. Other complications included: wound infection eight (12%), anastomotic leak four (8%), port-site hernia one and one case of Clostridium difficile colitis requiring colectomy. There were five (7.5%) returns to theatre and two readmissions (3%). CONCLUSION: Laparoscopic resectional surgery in complicated diverticular disease is a feasible, safe and a largely predictable operation that allows for early hospital discharge and, in our opinion, improved patient care. We are encouraged to continue to offer our patients the option of an emergency laparoscopic resection.
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Colectomía/métodos , Diverticulitis del Colon/cirugía , Laparoscopía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Colectomía/efectos adversos , Femenino , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infección de la Herida Quirúrgica , Análisis de Supervivencia , Adulto JovenRESUMEN
This report describes our isolation of pGM21, a novel gene showing enhanced expression in rat mammary adenocarcinoma cell lines with high metastatic potential. We constructed a library of 25,000 complementary DNA (cDNA) clones enriched for genes associated with metastasis. To build this library, we hybridized messenger RNA (mRNA) from a poorly metastatic rat mammary adenocarcinoma cell line (DMBA8) with cDNA from the highly metastatic variant line (DMBA8 ascites). One-fifth of the library was screened by differential cDNA hybridization. After three rounds of screening, we had isolated 14 cDNA clones that showed higher mRNA expression in the more metastatic cells. When we used Northern blot screening of these cDNA clones against several related rat mammary adenocarcinoma cell lines and a line that was independently derived, one of the clones showed levels of expression consistently correlating with high metastatic potential. Southern blot analysis indicated that no gene rearrangement or amplification accounted for this change. Partial sequencing of this isolated clone revealed a 45-nucleotide segment homologous to mRNA from human elongation factor 1 subunit alpha, which is involved in protein synthesis. Our results demonstrate that overexpression of the gene corresponding to pGM21 may be important in the development of metastasis.
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Neoplasias Mamarias Experimentales/genética , Metástasis de la Neoplasia , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Línea Celular , Clonación Molecular , ADN/genética , Genes , Datos de Secuencia Molecular , ARN Neoplásico/genética , Ratas , Mapeo RestrictivoRESUMEN
Urokinase plasminogen activator (uPA) is a serine protease which has frequently been implicated in the process of tumor cell invasion and metastasis. The degree of expression and mode(s) of regulation of the uPA gene in metastatic compared with nonmetastatic tumor cells have not yet been addressed. We have cloned and sequenced a full-length rat uPA complementary DNA and utilized Northern blot analysis to report that the uPA gene is expressed at levels 3.5- to 70-fold higher in metastatic cell lines than in nonmetastatic cell lines derived from two independent rat mammary adenocarcinomas. Nuclear run-on assays and RNA half-life estimations indicated that metastatic MAT 13762 rat mammary adenocarcinoma cells expressed 3.5-fold higher levels of uPA RNA than a nonmetastatic derivative (J-clone), due to a combined increase in uPA gene transcription and cytoplasmic RNA stability. By contrast, uPA RNA (and enzyme) levels were elevated by up to 70-fold in metastatic clones of dimethylbenz(a)anthracene-induced rat mammary adenocarcinoma (DMBA-8) due to predominantly posttranscriptional mechanisms. Moreover, treatment of nonmetastatic DMBA-8 cell lines with protein synthesis inhibitors led to an increase in nuclear and cytoplasmic uPA RNA levels, without altering the rate of uPA gene transcription. These results suggest that in addition to gene transcription, posttranscriptional events localized in the nucleus and cytoplasm are key determinants of uPA gene activation in rat mammary adenocarcinomas.
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ADN/química , Regulación Enzimológica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Mamarias Experimentales/enzimología , Transcripción Genética/genética , Activador de Plasminógeno de Tipo Uroquinasa/genética , 9,10-Dimetil-1,2-benzantraceno , Secuencia de Aminoácidos , Animales , Regulación hacia Abajo , Activación Enzimática/genética , Femenino , Neoplasias Mamarias Experimentales/genética , Datos de Secuencia Molecular , ARN Mensajero/análisis , Ratas , Ratas Endogámicas F344 , Activación Transcripcional , Activador de Plasminógeno de Tipo Uroquinasa/biosíntesisRESUMEN
Loss of the chromosomal region 10q23-25 is a frequent event in the progression of prostate adenocarcinoma. A candidate tumor suppressor gene from this region, Mxi1 at 10q25, has recently been shown to be mutated in a small number of prostate tumors. To more strictly define those regions of 10q loss that are likely to be involved in tumor advancement, we have constructed a detailed deletion map spanning 10q23-25 that incorporates Mxi1. Sixty-two % (23 of 37) of tumors analyzed exhibited some degree of 10q23-25 loss. Our data suggest the presence of a prostate tumor suppressor gene(s) near the 10q23-24 boundary, which was deleted in the overwhelming majority (22 of 23) of tumors showing loss. In contrast, specific loss of Mxi1, as opposed to loss of other 10q23-25 regions or of the entire region, was observed in only 1 of 23 tumors and was accompanied by loss of markers at the 10q23-24 boundary. Furthermore, we failed to detect any mutations in Mxi1 in those tumors showing Mxi1-associated marker loss by either single-strand conformation polymorphism analysis or direct DNA sequencing.