RESUMEN
BACKGROUND: Agricultural and construction workers spend much of their work time outdoors and have higher risks of developing skin cancer when compared to indoor workers. However, there is limited research on ultraviolet radiation (UVR) exposure knowledge, sun safety practices and constraints within these occupational groups in Ireland. AIMS: This study aimed to examine self-reported time spent outdoors in a sample of Irish agricultural and construction workers; to describe and compare UVR exposure knowledge, safety practices and perceived constraints in both occupational groups, and to assess the association of demographic, personal and occupational factors with sun-related knowledge, practices and perceived constraints. METHODS: Agricultural workers (nâ =â 154) and construction workers (nâ =â 467) completed a questionnaire, which measured solar UVR exposure knowledge, safety practices, and perceived constraints to sun personal protective equipment and sunscreen use in addition to demographic, personal, and workplace characteristics. Mann-Whitney and Kruskal-Wallis tests were used to examine differences in knowledge, practices and perceived constraints by these characteristics. RESULTS: Both groups spend a significant proportion of their working week outdoors (25 hours per week on average). Although participation in sun safety training was high for both groups, UVR exposure knowledge and sunscreen use were low, and annual rates of reported sunburn were high. Knowledge, practices and perceived constraints also differed significantly according to demographic, personal, occupational and workplace characteristics. CONCLUSIONS: In addition to training by employers and advisory groups, interventions are required to address perceived barriers that impede the uptake and usage of control measures that can lower risk.
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Agricultura , Agricultores , Conocimientos, Actitudes y Práctica en Salud , Exposición Profesional , Luz Solar , Protectores Solares , Humanos , Irlanda , Masculino , Adulto , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Agricultores/estadística & datos numéricos , Encuestas y Cuestionarios , Persona de Mediana Edad , Luz Solar/efectos adversos , Femenino , Protectores Solares/uso terapéutico , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/etiología , Quemadura Solar/prevención & control , Rayos Ultravioleta/efectos adversos , Ropa de Protección/estadística & datos numéricos , Industria de la ConstrucciónRESUMEN
BACKGROUND: Workplace bullying is a pervasive problem with significant personal, social and economic costs. Estimates of the resulting lost productivity provide an important societal perspective on the impact of the problem. Understanding where these economic costs fall is relevant for policy. AIMS: We estimated the value of lost productivity to the economy from workplace bullying in the public and private sectors in Ireland. METHODS: We used nationally representative survey data and multivariable negative binomial regression to estimate the independent effect of workplace bullying on days absent from work. We applied the human capital approach to derive an estimate of the annual value of lost productivity due to bullying by sector and overall, in 2017. RESULTS: Bullying was independently associated with an extra 1.00 (95% CI: 0.38-1.62) days absent from work over a 4-week period. This differed for public and private sector employees: 0.69 (95% CI: -0.12 to 1.50) versus 1.45 (95% CI: 0.50-2.40) days respectively. Applying official data, we estimated the associated annual value of lost productivity to be 51.8 million in the public sector, 187.6 million in the private sector and 239.3 million overall. CONCLUSIONS: The economic value of lost productivity from workplace bullying in Ireland is significant. Although bullying is more prevalent in the public sector, it has a larger effect on absence in the private sector. Given this, along with the greater overall share of employees, productivity losses from bullying are considerably larger in the private sector in Ireland.
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Acoso Escolar/estadística & datos numéricos , Eficiencia Organizacional/economía , Sector Privado/economía , Sector Público/economía , Lugar de Trabajo/economía , Adulto , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Lugar de Trabajo/psicologíaRESUMEN
BACKGROUND: Influenza vaccination uptake by Irish healthcare workers remains sub-optimal despite local initiatives to increase it. AIMS: To investigate hospital workers' attitudes to influenza vaccination and how this influenced their decisions about vaccination. METHODS: A questionnaire survey of Irish hospital workers, measuring uptake of and attitudes to influenza vaccination. RESULTS: There were 747 responders, of whom 361 (48%) reported having received influenza vaccination. Attitudes predicting vaccination uptake included a belief that vaccination would protect family members (P < 0.0005, CI 1.191-1.739), a perception of susceptibility to 'flu (P < 0.0005, CI 1.182-1.685), a belief that all healthcare workers should be vaccinated (P < 0.005, CI 1.153-1.783), perceived ease of getting 'flu vaccination at work (P < 0.0005, CI 1.851-2.842) and encouragement by line managers (P < 0.05, CI 1.018-1.400). Attitudes negatively associated with vaccination uptake included fear of needles (P < 0.05, CI 0.663-0.985) and a belief that vaccination would cause illness (P < 0.0005, CI 0.436-0.647). Medical staff were significantly more likely to be vaccinated. Healthcare students were least likely to be vaccinated (P < 0.0005). CONCLUSION: Addressing specific barriers to influenza vaccination in healthcare workers may improve uptake.
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Conocimientos, Actitudes y Práctica en Salud , Vacunas contra la Influenza , Personal de Hospital/estadística & datos numéricos , Vacunación/estadística & datos numéricos , Adulto , Familia , Femenino , Humanos , Gripe Humana/prevención & control , Inyecciones/psicología , Irlanda , Masculino , Persona de Mediana Edad , Personal de Hospital/psicología , Estudiantes/psicología , Encuestas y Cuestionarios , Vacunación/psicologíaRESUMEN
Work-related respiratory disease is a significant risk in the farming community. We assessed respiratory symptoms using a validated work-related respiratory questionnaire in 126 dairy farmers (19-75 years; 91.3% male). The prevalence of cough symptoms was 34.4%. Thirty-seven farmers (29.4%) complained of upper airway symptoms while forty (31.7%) complained of eye problems. Cumulated symptoms scores did not indicate higher than normal rates of chronic lung disease. Only 10 farmers (7.9%) were taking medication for lung conditions. Only 7 (5.6%) were current smokers. The rate of respiratory symptoms did not relate to the herd size or the method of animal feeding used by the farmers. The incidence of respiratory symptoms remains high among Irish dairy farmers. While the exact reason for this is unknown it may be related to continuing work- related dust exposure.
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Enfermedades de los Trabajadores Agrícolas/epidemiología , Agricultores/estadística & datos numéricos , Trastornos Respiratorios/epidemiología , Adulto , Anciano , Animales , Tos/epidemiología , Polvo , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Exposición Profesional , Prevalencia , Trastornos Respiratorios/etiología , Fumar/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Workaholism is recognized as a health risk for academics given the open-ended nature of academic work; however, current prevalence rates of workaholism in the academic setting are unknown. AIMS: To assess the prevalence of workaholism within academics and determine the impact of workaholism on psychological well-being, work-life conflict, work-life fit, job satisfaction and perceived work effort. METHODS: Academics in three Irish universities completed a survey including measures of workaholism, psychological well-being, work-life conflict and job satisfaction. Analysis of variance tests were used to compare workaholism types on the outcome measures. RESULTS: A total of 410 academics completed the survey and were categorized by workaholism type: workaholics (27%), enthusiastic workaholics (23%), relaxed workers (27%) and uninvolved workers (23%). Workaholics reported poorer functioning across all the outcome measures in comparison to the other three groups. CONCLUSIONS: This study demonstrates the high levels of workaholism within academia and highlights the negative impact of workaholism on work-related outcomes and psychological well-being. These findings are significant given the highly intensive nature of academic work today and reducing resources within this sector.
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Conducta Adictiva/epidemiología , Satisfacción en el Trabajo , Ocupaciones , Satisfacción Personal , Estrés Psicológico/etiología , Universidades , Trabajo/psicología , Adulto , Conducta Adictiva/complicaciones , Conducta Adictiva/psicología , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Administración del Tiempo , Adulto JovenRESUMEN
Galectin-3 (Gal-3) is a multifunctional protein involved in cancer through regulation of cell adhesion, cell growth, apoptosis and metastasis, while p21 (Cip1/WAF1) is a negative regulator of the cell cycle, involved in apoptosis, transcription, DNA repair and metastasis. The results presented here demonstrate for the first time that the level of Gal-3 protein is associated with the level of p21 protein expression in human prostate cancer cells and the effects of Gal-3 on cell growth and apoptosis were reversed by modulating p21 expression level. Furthermore, Gal-3 regulates p21 expression at the post-translational level by stabilizing p21 protein via the carbohydrate-recognition domain. This is the first report suggesting a molecular function not yet described for Gal-3 as the regulator of p21 protein stability. This study provides a unique insight into the relationship of these two molecules during prostate cancer progression, and may provide a novel therapeutic target.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Galectina 3/metabolismo , Neoplasias de la Próstata/metabolismo , Apoptosis , Secuencia de Bases , Proteínas Sanguíneas , Simulación por Computador , Galectina 3/genética , Galectinas , Humanos , Masculino , Datos de Secuencia Molecular , Neoplasias de la Próstata/patología , Estabilidad Proteica , Estructura Terciaria de Proteína , Células Tumorales CultivadasRESUMEN
UNLABELLED: The role of B cells in inflammatory bone formation and resorption is controversial. We investigated this in patients with rheumatoid arthritis (RA) treated with rituximab, a B-cell depleting antibody. We found a significant suppression in bone turnover, possibly a direct effect or as a consequence of a reduction in inflammation and disease activity. INTRODUCTION: RA is the most prevalent inflammatory joint disease, in which B cells play an important role. However, the role of B cells in bone turnover is controversial and RA subjects treated with rituximab, a B-cell depleting monoclonal antibody, provide an ideal model for determining the role of B cells in inflammatory bone resorption. METHODS: Serum from 46 RA patients, collected pre- and post-rituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, ß-isomerised carboxy-terminal telopeptide of type 1 collagen [ßCTX] and osteoprotegerin [OPG]). RESULTS: A significant decrease in bone resorption was observed 6 months after rituximab (median change ßCTX -50 ng/L, 95%CI -136, -8 p < 0.001, this equates to -37%; 95%CI -6, -49), mirrored by a reduction in disease activity. Similarly, there was a significant increase in P1NP, a marker of bone formation (median change P1NP 5.0 µg/L, 95%CI -1.0, 11.2, p = 0.02; 13%; 95%CI -3, 39), but no significant change in osteocalcin or OPG levels. The percentage change from baseline of ßCTX in a subgroup of patients (not on prednisolone or bisphosphonate) was significantly correlated with the percentage reduction in DAS28 score (r (s) = 0.570, p = 0.014). CONCLUSIONS: In conclusion, we have found that B-cell depletion increases bone formation and decreases bone resorption in RA patients; this may be a direct effect on osteoblasts and osteoclasts, respectively, and be at least partially explained by the decreased inflammation and disease activity.
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Anticuerpos Monoclonales de Origen Murino/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Linfocitos B/metabolismo , Remodelación Ósea/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/sangre , Regeneración Ósea/efectos de los fármacos , Colágeno Tipo I/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoprotegerina/sangre , Fragmentos de Péptidos/sangre , Péptidos/sangre , Procolágeno/sangre , RituximabRESUMEN
Prostate cancer will develop chemoresistance following a period of chemotherapy. This is due, in part, to the acquisition of antiapoptotic properties by the cancer cells and, therefore, development of novel strategies for treatment is of critical need. Here, we attempt to clarify the role of the antiapoptotic molecule galectin-3 in prostate cancer cells using siRNA and antagonist approaches. The data showed that Gal-3 inhibition by siRNA or its antagonist GCS-100/modified citrus pectin (MCP) increased cisplatin-induced apoptosis of PC3 cells. Recent studies have indicated that cisplatin-induced apoptosis may be mediated by calpain, a calcium-dependent protease, as its activation leads to cleavage of androgen receptor into an androgen-independent isoform in prostate cancer cells. Thus, we examined whether calpain activation is associated with the Gal-3 function of regulating apoptosis. Here, we report that Gal-3 inhibition by siRNA or GCS-100/MCP enhances calpain activation, whereas Gal-3 overexpression inhibits it. Inhibition of calpain using its inhibitor and/or siRNA attenuated the proapoptotic effect of Gal-3 inhibition, suggesting that calpain activation may be a novel mechanism for the proapoptotic effect of Gal-3 inhibition. Thus, a paradigm shift for treating prostate cancer is suggested whereby a combination of a non-toxic anti-Gal-3 drug together with a toxic chemotherapeutic agent could serve as a novel therapeutic modality for chemoresistant prostate cancers.
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Antineoplásicos/uso terapéutico , Calpaína/metabolismo , Cisplatino/uso terapéutico , Galectina 3/antagonistas & inhibidores , Neoplasias de la Próstata/tratamiento farmacológico , Línea Celular Tumoral , Galectina 3/genética , Galectina 3/metabolismo , Humanos , Masculino , Polisacáridos/farmacología , Interferencia de ARN , ARN Interferente Pequeño/metabolismoRESUMEN
OBJECTIVES: Maternal infection, particularly bacterial vaginosis (BV) in pregnancy, is one of the leading causes of adverse perinatal outcomes. The determinants of individual differences in susceptibility, or vulnerability, to maternal infections are poorly understood. This study examines whether chronic maternal stress predisposes women to infection during pregnancy, and if so, whether the effects of chronic stress on infection are independent of other established risk factors. METHODS: We conducted a cross-sectional, clinical prevalence study of chronic maternal stress and BV status in a sample of 454 pregnant women at 14.3+/-0.3 weeks gestation (+/-SEM). BV was diagnosed by Gram-stain of vaginal fluid samples; chronic maternal stress was assessed using the Cohen Perceived Stress Scale. Other established risk factors for BV, including maternal age, race/ethnicity, marital status, SES, and behaviors related to feminine hygiene, sexual practices, and substance use, were measured using a structured interview. RESULTS: Of the 454 women enrolled in this study, 224 (49%) were BV positive (Nugent score 7-10), 64 (14%) had intermediate vaginal flora (Nugent score 4-6), and 166 (37%) were BV negative (Nugent score 0-3). BV+ women had significantly higher chronic stress levels than BV- women (24.6+/-0.5 vs. 22.2+/-0.6 units (+/-SEM), respectively; t = 3.19; p < .01). Maternal sociodemographic variables (African-American race/ethnicity) and behavioral characteristics (vaginal douching, number of lifetime sexual partners, and use of illicit drugs) also were significantly associated with the presence of BV. After controlling for the effects of these variables, using a multivariable logistic regression model, chronic maternal stress remained a significant and independent predictor of BV status. Women in the moderate-stress group (third quartile) and high-stress (fourth quartile) group were 2.3 times (95% CI = 1.2-4.3) and 2.2 times (95% CI = 1.1-4.2) more likely to be BV+ than women in the low-stress group (bottom quartile). CONCLUSIONS: High levels of chronic stress during pregnancy are associated with bacterial vaginosis. The effect of chronic maternal stress is independent of the effects of other established sociodemographic and behavioral risk factors for BV.
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Complicaciones Infecciosas del Embarazo , Estrés Fisiológico/etiología , Vaginosis Bacteriana/complicaciones , Enfermedad Crónica , Estudios Transversales , Femenino , Conductas Relacionadas con la Salud , Humanos , Entrevistas como Asunto , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Análisis de Regresión , Factores de Riesgo , Vaginosis Bacteriana/epidemiologíaRESUMEN
The disparity between blacks and whites in perinatal health ranges from a 2.3-fold excess risk among black women for preterm delivery and infant mortality to a 4-fold excess risk among black women for maternal mortality. To stimulate concerted public health action to address such racial and ethnic disparities in health, the national Healthy People objectives call for elimination of all health disparities by the year 2010. Eliminating health disparities requires a greater understanding of the factors that contribute to their development. This commentary summarizes the state of the science of reducing such disparities and proposes a framework for using the results of qualitative studies on the social context of pregnancy to understand, study, and address disparities in infant mortality and preterm delivery. Understanding the social context of African American women's lives can lead to an improved understanding of the etiology of preterm birth, and can help identify promising new interventions to reduce racial and ethnic disparities in preterm delivery.
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Negro o Afroamericano , Resultado del Embarazo , Femenino , Humanos , Mortalidad Infantil , Recién Nacido , Recien Nacido Prematuro , Embarazo , Factores de Riesgo , Condiciones Sociales , Muerte Súbita del Lactante/prevención & control , Estados Unidos , Población BlancaRESUMEN
Preterm birth is currently the most important problem in maternal-child health in the United States. Epidemiological studies have suggested that two factors, maternal stress and maternal urogenital tract infection, are significantly and independently associated with an increased risk of spontaneous preterm birth. These factors are also more prevalent in the population of sociodemographically disadvantaged women who are at increased risk for preterm birth. Studies of the physiology of parturition suggest that neuroendocrine and immune processes play important roles in the physiology and pathophysiology of normal and preterm parturition. However, not all women with high levels of stress and/or infection deliver preterm, and little is understood about factors that modulate susceptibility to pathophysiological events of the endocrine and immune systems in pregnancy. We present here a comprehensive, biobehavioural model of maternal stress and spontaneous preterm delivery. According to this model, chronic maternal stress is a significant and independent risk factor for preterm birth. The effects of maternal stress on preterm birth may be mediated through biological and/or behavioural mechanisms. We propose that maternal stress may act via one or both of two physiological pathways: (a) a neuroendocrine pathway, wherein maternal stress may ultimately result in premature and/or greater degree of activation of the maternal-placental-fetal endocrine systems that promote parturition; and (b) an immune/inflammatory pathway, wherein maternal stress may modulate characteristics of systemic and local (placental-decidual) immunity to increase susceptibility to intrauterine and fetal infectious-inflammatory processes and thereby promote parturition through pro-inflammatory mechanisms. We suggest that placental corticotropin-releasing hormone may play a key role in orchestrating the effects of endocrine and inflammatory/immune processes on preterm birth. Moreover, because neuroendocrine and immune processes extensively cross-regulate one another, we further posit that exposure to both high levels of chronic stress and infectious pathogens in pregnancy may produce an interaction and multiplicative effect in terms of their combined risk for preterm birth. Finally, we hypothesise that the effects of maternal stress are modulated by the nature, duration and timing of occurrence of stress during gestation. A discussion of the components of this model, including a theoretical rationale and review of the available empirical evidence, is presented. A major strength of this biobehavioural perspective is the ability to explore new questions and to do so in a manner that is more comprehensive than has been previously attempted. We expect findings from this line of proposed research to improve our present state of knowledge about obstetric risk assessment for preterm birth by determining the characteristics of pregnant women who are especially susceptible to stress and/or infection, and to broaden our understanding of biological (endocrine, immune, and endocrine-immune interactions) mechanisms that may translate social adversity during pregnancy into pathophysiology, thereby suggesting intervention strategies.
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Trabajo de Parto Prematuro/etiología , Complicaciones Infecciosas del Embarazo , Estrés Fisiológico/complicaciones , Vaginosis Bacteriana/complicaciones , Femenino , Predicción , Humanos , Recién Nacido , Sistemas Neurosecretores/fisiología , Trabajo de Parto Prematuro/fisiopatología , Embarazo , Complicaciones Infecciosas del Embarazo/fisiopatología , Investigación , Estrés Fisiológico/fisiopatología , Vaginosis Bacteriana/fisiopatologíaRESUMEN
The Healthy People 2010 objectives call for the elimination of racial disparities in health, along with reductions in several multifactorial perinatal outcomes. Evidence-based interventions have been the focus of discussion to date. We propose a 6-component framework based on knowledge from the social, medical, psychological, and epidemiological literatures to guide development of interventions to reduce preterm delivery and eliminate disparities. Pilot testing and rigorous evaluation of the interventions developed from this framework are encouraged.
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Negro o Afroamericano , Accesibilidad a los Servicios de Salud/normas , Modelos Organizacionales , Trabajo de Parto Prematuro/prevención & control , Atención Prenatal/normas , Práctica de Salud Pública , Población Blanca , Medicina Basada en la Evidencia , Femenino , Guías como Asunto , Humanos , Embarazo , Desarrollo de Programa , Factores Socioeconómicos , Estados Unidos , Salud de la MujerRESUMEN
Bacterial vaginosis (BV) remains a moderately prevalent condition with clearly observed links to adverse reproductive, gynecological, and other outcomes in women, including human immunodeficiency virus infection. Because of inconsistent findings from clinical studies concerning BV's etiologic role, no definitive policies with respect to screening and treatment have yet been established. Of concern is the high, unexplained prevalence of BV among African-American women, who are also at extremely high risk for preterm birth. The complexity of the sociodemographic picture challenges the field of public health to continue to explore the role of BV and its relationship to a whole host of social and biomedical conditions that may contribute to adverse health outcomes among society's most vulnerable members. Future decisions about screening and treatment, currently based on the biomedical model, may need to take into consideration issues of social context and expanded views of causality if we are to better understand and eliminate those factors that place individual women at risk of adverse outcomes, as well as the conditions that underlie racial and ethnic disparities in health.
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Tamizaje Masivo , Vaginosis Bacteriana/diagnóstico , Salud de la Mujer , Adulto , Etnicidad , Femenino , Humanos , Trabajo de Parto Prematuro , Evaluación de Resultado en la Atención de Salud , Embarazo , Complicaciones Infecciosas del Embarazo , Medición de Riesgo , Clase Social , Vaginosis Bacteriana/complicacionesRESUMEN
BACKGROUND: Galectin-3 is a carbohydrate-binding protein whose level of expression has been shown to be correlated with metastatic potential in a number of different tumor types. The purpose of this investigation was to examine galectin-3 expression in several tumorigenic and nontumorigenic prostate cell lines and prostate tissue samples. METHODS: The expression of galectin-3 in cell lines and tissue samples was evaluated by tissue immunohistochemistry and Western blot analysis. RESULTS: Human cell lines PC-3M, PC-3, DU-145, PrEC-1, and MCF10A demonstrated the presence of galectin-3. Galectin-3 was not detected in TSU-pr1 and LNCaP by Western blot analysis. We furthered our studies by examining a series of human prostate tissue samples for expression of galectin-3. Overall, approximately 60-70% of the normal tissue examined demonstrated heterogenous expression of galectin-3. In stage II tumors, however, there was a dramatic decrease in galectin-3 expression in both PIN and tumor sections, with only 10.5% (2/19) of these samples expressing this protein. Stage III tumors also demonstrated a decreased expression of galectin-3, although this downregulation was not as dramatic, with 35% of PIN samples and 52% of tumor tissue expressing galectin-3 (P < 0.01). CONCLUSIONS: These data demonstrate that galectin-3 is downregulated in prostate cancer. The altered downregulation pattern of galectin-3 observed between tumor stages suggests different roles for galectin-3 in the progression of prostate cancer.
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Antígenos de Diferenciación/biosíntesis , Regulación Neoplásica de la Expresión Génica , Próstata/patología , Neoplasias de la Próstata/patología , Antígenos de Diferenciación/análisis , Antígenos de Diferenciación/genética , Western Blotting , Línea Celular , Galectina 3 , Humanos , Inmunohistoquímica , Masculino , Próstata/citología , Neoplasias de la Próstata/química , Neoplasias de la Próstata/genética , Células Tumorales CultivadasRESUMEN
Increasing evidence suggests that carbohydrate-binding proteins play an essential role in tumor growth and metastasis. However, conflicting results on their function in the regulation of cell proliferation and differentiation during angiogenesis have been reported. We have examined the role of galectin-3 in the regulation of human umbilical vein endothelial cell proliferation, differentiation, migration, and neovascularization. Galectin-3, a carbohydrate-binding protein, with specificity for type 1 and 11 ABH blood group epitopes and polylactosamine glycan containing cell surface glycoproteins, is the major nonintegrin cellular laminin-binding protein. Because galectin-3 expression was shown to be associated in some tumor systems with metastasis, we questioned whether it induces endothelial cell morphogenesis. Here we show that galectin-3 affects chemotaxis and morphology and stimulates capillary tube formation of HUV-EC-C in vitro and angiogenesis in vivo. Endothelial cell morphogenesis is a carbohydrate-dependent process, as it is neutralized by specific sugars and antibodies. These findings demonstrate that endothelial cell surface carbohydrate recognition event(s) can induce a signaling cascade leading to the differentiation and angiogenesis of endothelial cells.
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Antígenos de Diferenciación/farmacología , Quimiotaxis/efectos de los fármacos , Endotelio Vascular/citología , Glicoproteínas de Membrana/farmacología , Neovascularización Patológica/inducido químicamente , Neoplasias Cutáneas/irrigación sanguínea , Animales , Antígenos de Diferenciación/metabolismo , Capilares/citología , Medios de Cultivo Condicionados/farmacología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Galectina 3 , Humanos , Técnicas para Inmunoenzimas , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Desnudos , Neovascularización Patológica/patología , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Neoplasias Cutáneas/patología , Transfección , Células Tumorales Cultivadas , Venas Umbilicales/citologíaAsunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/efectos adversos , Fallo Hepático/inducido químicamente , Pemolina/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos , Canadá , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Industria Farmacéutica , Humanos , Comercialización de los Servicios de Salud , Pemolina/uso terapéutico , Medición de RiesgoRESUMEN
Galectin-3 is a member of the beta-galactoside-binding protein family shown to be involved in tumor progression and metastasis. It has a unique primary structure consisting of three domains: a 12-amino acid leader sequence containing a casein kinase I serine phosphorylation site, which is preceded by a collagenase-sensitive Pro-Gly-rich motif, and a COOH-terminal half encompassing the carbohydrate-binding site. To study the functional role of the unusual leader sequence of galectin-3, a mutant cDNA that causes an 11-amino acid deletion in the NH2-terminal region was generated and expressed in galectin-3-null BT-549 human breast carcinoma cells. Deletion of the NH2 terminus resulted in abolition of the secretion of truncated galectin-3, loss of nuclear localization, and reduced carbohydrate-mediated functions compared with the wild-type protein. When green fluorescent protein was fused to the galectin-3 leader sequence and transiently transfected into BT-549 cells, the uniform cellular distribution of native green fluorescent protein was changed mainly to a nuclear pattern. To further investigate whether the functional changes observed in a galectin-3 with the 11 NH2-terminal amino acids deleted were due to loss of phosphorylation at Ser6, two point mutations were created at this serine: Ser6-->Ala and Ser6-->Glu. No obvious difference was observed in cellular localization between wild-type and Ser6-mutated transfectants. These results suggest a structural role for the NH2 terminus leader motif of galectin-3 in determining its cellular targeting and biological functions independent of phosphorylation.