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1.
Am J Hum Genet ; 103(1): 100-114, 2018 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-29979980

RESUMEN

The tRNA synthetases catalyze the first step of protein synthesis and have increasingly been studied for their nuclear and extra-cellular ex-translational activities. Human genetic conditions such as Charcot-Marie-Tooth have been attributed to dominant gain-of-function mutations in some tRNA synthetases. Unlike dominantly inherited gain-of-function mutations, recessive loss-of-function mutations can potentially elucidate ex-translational activities. We present here five individuals from four families with a multi-system disease associated with bi-allelic mutations in FARSB that encodes the beta chain of the alpha2beta2 phenylalanine-tRNA synthetase (FARS). Collectively, the mutant alleles encompass a 5'-splice junction non-coding variant (SJV) and six missense variants, one of which is shared by unrelated individuals. The clinical condition is characterized by interstitial lung disease, cerebral aneurysms and brain calcifications, and cirrhosis. For the SJV, we confirmed exon skipping leading to a frameshift associated with noncatalytic activity. While the bi-allelic combination of the SJV with a p.Arg305Gln missense mutation in two individuals led to severe disease, cells from neither the asymptomatic heterozygous carriers nor the compound heterozygous affected individual had any defect in protein synthesis. These results support a disease mechanism independent of tRNA synthetase activities in protein translation and suggest that this FARS activity is essential for normal function in multiple organs.


Asunto(s)
Aminoacil-ARNt Sintetasas/genética , Enfermedades Pulmonares/genética , Mutación/genética , Adolescente , Alelos , Enfermedad de Charcot-Marie-Tooth/genética , Preescolar , Femenino , Genes Recesivos/genética , Heterocigoto , Humanos , Lactante , Masculino , Biosíntesis de Proteínas/genética
2.
Nucleic Acids Res ; 44(3): 1247-55, 2016 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-26773056

RESUMEN

Many human tRNA synthetases evolved alternative functions outside of protein synthesis. These functions are associated with over 200 splice variants (SVs), most of which are catalytic nulls that engender new biology. While known to regulate non-translational activities, little is known about structures resulting from natural internal ablations of any protein. Here, we report analysis of two closely related, internally deleted, SVs of homodimeric human tyrosyl-tRNA synthetase (TyrRS). In spite of both variants ablating a portion of the catalytic core and dimer-interface contacts of native TyrRS, each folded into a distinct stable structure. Biochemical and nuclear magnetic resonance (NMR) analysis showed that the internal deletion of TyrRSΔE2-4 SV gave an alternative, neomorphic dimer interface 'orthogonal' to that of native TyrRS. In contrast, the internal C-terminal splice site of TyrRSΔE2-3 prevented either dimerization interface from forming, and yielded a predominantly monomeric protein. Unlike ubiquitous TyrRS, the neomorphs showed clear tissue preferences, which were distinct from each other. The results demonstrate a sophisticated structural plasticity of a human tRNA synthetase for architectural reorganizations that are preferentially elicited in specific tissues.


Asunto(s)
Empalme Alternativo , Multimerización de Proteína , Estructura Secundaria de Proteína , Tirosina-ARNt Ligasa/química , Tirosina-ARNt Ligasa/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Western Blotting , Dominio Catalítico/genética , Línea Celular , Línea Celular Tumoral , Perfilación de la Expresión Génica , Humanos , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Células Jurkat , Espectroscopía de Resonancia Magnética , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Eliminación de Secuencia , Homología de Secuencia de Aminoácido , Tirosina-ARNt Ligasa/metabolismo
3.
J Biol Chem ; 289(28): 19269-75, 2014 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-24898250

RESUMEN

Inflammatory and debilitating myositis and interstitial lung disease are commonly associated with autoantibodies (anti-Jo-1 antibodies) to cytoplasmic histidyl-tRNA synthetase (HisRS). Anti-Jo-1 antibodies from different disease-afflicted patients react mostly with spatially separated epitopes in the three-dimensional structure of human HisRS. We noted that two HisRS splice variants (SVs) include these spatially separated regions, but each SV lacks the HisRS catalytic domain. Despite the large deletions, the two SVs cross-react with a substantial population of anti-Jo-l antibodies from myositis patients. Moreover, expression of at least one of the SVs is up-regulated in dermatomyositis patients, and cell-based experiments show that both SVs and HisRS can be secreted. We suggest that, in patients with inflammatory myositis, anti-Jo-1 antibodies may have extracellular activity.


Asunto(s)
Empalme Alternativo , Autoanticuerpos/metabolismo , Epítopos/metabolismo , Histidina-ARNt Ligasa/metabolismo , Miositis/enzimología , Autoanticuerpos/inmunología , Línea Celular Tumoral , Epítopos/genética , Epítopos/inmunología , Histidina-ARNt Ligasa/genética , Histidina-ARNt Ligasa/inmunología , Humanos , Inflamación/enzimología , Inflamación/genética , Inflamación/inmunología , Inflamación/patología , Miositis/genética , Miositis/inmunología , Miositis/patología , Estructura Terciaria de Proteína
4.
Int J Behav Med ; 22(2): 268-75, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25189290

RESUMEN

BACKGROUND: Adolescent smoking has been associated with general parenting style, although potential differences between fathers and mothers were seldom investigated, especially in non-Western populations. PURPOSE: The aim of this study is to investigate associations between Hong Kong adolescents' smoking and their perceptions of paternal and maternal parenting styles. METHOD: In a school-based survey in 2006-2007, 33,408 adolescents (44.6 % boys; mean age 14.5 ± 1.3 years) provided information on smoking and the frequency of care and control by each parent, who was classified into one of four adolescent-reported parenting styles: authoritative (high care, high control), authoritarian (low care, high control), permissive (high care, low control), or neglectful (low care, low control). Logistic regression was used to calculate adjusted odds ratios (AORs) of current smoking (past 30 days) for parenting variables, considering potential effect modification by age, sex and parental smoking. RESULTS: Maternal care and control were strongly and significantly associated with lower odds of adolescent current smoking. However, such association was weak for paternal care and observed only in girls. Conversely, paternal control was positively associated with current smoking, especially if the father smoked. The lowest AORs of current smoking were associated with authoritative mothers, permissive fathers and combinations of maternal and paternal parenting styles with an authoritative mother whether or not the father was authoritative. CONCLUSION: Maternal care, control and authoritative parenting were associated with lower odds of adolescent smoking in Hong Kong. Paternal care was only weakly associated with lower odds of adolescent smoking, and paternal control was even associated with higher odds of smoking.


Asunto(s)
Padre/psicología , Madres/psicología , Responsabilidad Parental/psicología , Fumar/epidemiología , Adolescente , Estudios Transversales , Femenino , Hong Kong , Humanos , Masculino , Percepción , Autoinforme , Encuestas y Cuestionarios
5.
J Biol Chem ; 288(41): 29223-8, 2013 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-24003230

RESUMEN

Although tRNA synthetases are enzymes that catalyze the first step of translation in the cytoplasm, surprising functions unrelated to translation have been reported. These studies, and the demonstration of novel activities of splice variants, suggest a far broader reach of tRNA synthetases into cell biology than previously recognized. Here we show that mRNAs for most tRNA synthetases can be detected in exosomes. Also detected in exosomes was an mRNA encoding a unique splice variant that others had associated with prostate cancer. The exosomal mRNAs encoding the native synthetase and its cancer-associated splice variant could be translated in vitro and in mammalian cells into stable proteins. Other results showed that selection by exosomes of the splice variant mRNA could be regulated by an external stimulus. Thus, a broad and diverse regulated pool of tRNA synthetase-derived mRNAs is packaged for genetic exchange.


Asunto(s)
Aminoacil-ARNt Sintetasas/genética , Exosomas/genética , Regulación Neoplásica de la Expresión Génica , ARN Mensajero/genética , Empalme Alternativo , Aminoacil-ARNt Sintetasas/metabolismo , Western Blotting , Neoplasias de la Mama , Línea Celular Tumoral , Citoplasma/genética , Citoplasma/metabolismo , Exosomas/metabolismo , Células HEK293 , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Células Jurkat , Células MCF-7 , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
6.
Alcohol Alcohol ; 49(6): 668-74, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25288615

RESUMEN

AIMS: We investigated the prevalence of various parental pro-drinking practices and its association with parental drinking status. METHODS: A school-based survey was completed by 2200 students (mean age 14.8, SD 2.0; boys 51.4%) from 4 randomly selected secondary schools in Hong Kong. Students reported whether they had ever experienced each of nine parental pro-drinking practices (PPDPs). RESULTS: Overall, 67.5% of students reported at least one PPDP, but the prevalence was much higher if both parents were drinkers (89.0%) compared with non-drinkers (38.8%). The adjusted odds ratio (AOR) (95% CI) of experiencing at least one PPDP was 6.79 (4.98, 9.26) if either parent drank and 15.71 (10.50, 23.50) if both drank compared with none (P for trend <0.001). Compared with non-drinking, the AORs (95% CI) of experiencing at least one PPDP for occasional drinking and frequent drinking were 6.72 (5.03, 8.98) and 18.11 (9.88, 33.18) in fathers (P for trend <0.001), and 7.33 (5.15, 10.44) and 5.33 (1.98, 14.45) in mothers. CONCLUSION: The prevalence of PPDPs was generally low in non-drinking parents, but increased dramatically with the number of drinking parents and the frequency of paternal drinking.


Asunto(s)
Conducta del Adolescente/etnología , Consumo de Bebidas Alcohólicas/etnología , Recolección de Datos , Relaciones Padres-Hijo/etnología , Adolescente , Conducta del Adolescente/psicología , Consumo de Bebidas Alcohólicas/psicología , Niño , Recolección de Datos/métodos , Femenino , Hong Kong/etnología , Humanos , Masculino
7.
Nicotine Tob Res ; 15(1): 185-91, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22547778

RESUMEN

INTRODUCTION: This study investigated the associations of smoking family and secondhand smoke (SHS) exposure at home with quit attempts and smoking cessation among adolescents. METHODS: Students from 85 randomly selected secondary schools in Hong Kong were surveyed using an anonymous self-administered questionnaire on SHS exposure at home and outside the home in the past 7 days, quit attempts, smoking cessation, sociodemographic characteristics, and smoking status of family members and peers. Families with 1 or more smoking members (excluding the subject) were classified as smoking families and otherwise as nonsmoking families. Logistic regression yielded adjusted odds ratios (AORs) for quit attempts and smoking cessation in smoking families with or without SHS exposure at home compared with nonsmoking families. RESULTS: Of 4,361 students who had smoked in the past 12 months, 70.3% were living with smokers and 52.8% were exposed to SHS at home. Compared with nonsmoking families, the AORs (95% CI) for making at least 1 quit attempt in the past 12 months were 0.80 (0.61-1.05) for 0 day, 0.80 (0.63-1.04) for 1-3 days, and 0.65 (0.50-0.86) for 4-7 days of SHS exposure at home. The corresponding AORs (95% CI) for smoking cessation were 0.58 (0.48-0.70), 0.45 (0.35-0.58), and 0.49 (0.41-0.60) (p for trend <.001). Any SHS exposure at home was associated with 28% and 53% lower odds of quit attempts and smoking cessation, respectively. CONCLUSIONS: Living with smoker(s) and especially being exposed to SHS at home may hinder quit attempts and smoking cessation among Chinese adolescent smokers.


Asunto(s)
Familia , Cese del Hábito de Fumar/psicología , Cese del Hábito de Fumar/estadística & datos numéricos , Contaminación por Humo de Tabaco , Adolescente , Estudios Transversales , Femenino , Hong Kong , Humanos , Modelos Logísticos , Masculino , Instituciones Académicas , Medio Social , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/estadística & datos numéricos
8.
BMC Fam Pract ; 14: 141, 2013 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-24070145

RESUMEN

BACKGROUND: Few studies have examined how common physicians assess various weight-related variables and patient characteristics that predict such assessments based on adolescents' reports. We aimed to examine how common adolescents received weight-related physical measurements and lifestyle enquiries (dietary habits and physical activity) from private practitioners and to identify factors associated with these assessments. METHODS: In the Hong Kong Student Obesity Surveillance (HKSOS) project, 33692 students (44.9% boys; mean age 14.8, SD 1.9 years, age range 11-18) from 42 randomly selected schools completed an anonymous questionnaire. The students were asked "In the past 12 months, has any private practitioners (or their nurses) measured or asked about these items?" Response options included height, weight, waist circumference (WC), blood pressure (BP), BMI, diet, and physical activity. Weight status was based on self-reported weight and height. Logistic regression was used to identify student characteristics associated with each assessment. Analyses were conducted using STATA 10.0. RESULTS: Among 13283 students who had doctor consultations in the past 12 months, 37.9% received physical measurements or lifestyle enquiries, with weight (20.8%), height (16.8%) and blood pressure (11.5%) being the most common, followed by diet (8.1%), BMI (6.3%), WC and physical activity (both 4.6%). In general, adolescents who were female, older, underweight or overweight/obese, had parents with higher education level, and had actively asked private practitioners for advice about weight were more likely to receive assessments of weight-related factors. CONCLUSIONS: Weight-related factors in adolescents were infrequently assessed by private practitioners in Hong Kong. Generally, unhealthy weight, higher parental education and advice-seeking by adolescents predicted these assessments.


Asunto(s)
Ejercicio Físico , Conducta Alimentaria , Anamnesis/métodos , Sobrepeso/diagnóstico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Práctica Privada/estadística & datos numéricos , Delgadez/diagnóstico , Adolescente , Factores de Edad , Determinación de la Presión Sanguínea/estadística & datos numéricos , Estatura , Peso Corporal , Niño , Recolección de Datos/métodos , Escolaridad , Femenino , Hong Kong , Humanos , Modelos Logísticos , Masculino , Obesidad/diagnóstico , Factores Sexuales , Encuestas y Cuestionarios , Circunferencia de la Cintura
9.
Nicotine Tob Res ; 14(6): 682-7, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22180586

RESUMEN

INTRODUCTION: To investigate the association between smoking and self-rated health (SRH) among adolescents in Hong Kong. METHODS: Form 1 (U.S. Grade 7) to 5 students (N = 36,225) from 85 randomly selected secondary schools were surveyed using anonymous, self-administered questionnaires to collect information about smoking, SRH, secondhand smoke exposure, drinking, illicit drug use, physical activities, medical services use, health complaints, and sociodemographic characteristics. Logistic regression yielded adjusted odds ratios (AORs) for poor SRH due to smoking in boys and girls. RESULTS: Compared with never-smoking, smoking experimentation, ex-smoking, and current smoking were associated with AORs (95% CI) for poor SRH of 1.22 (1.07-1.40), 1.43 (1.12-1.83), and 1.31 (1.13-1.53), p for trend <.001, in boys and 1.26 (1.10-1.39), 1.42 (1.08-1.85), and 1.75 (1.53-2.00, p for trend <.001, in girls. The AOR of poor SRH for current smoking was higher in girls than boys, p for interaction <.001. Current and experimental smoking but not ex-smoking were significantly associated with poor SRH among healthy students who had no health complaints or recent medical consultations. Increasing cigarette consumption, years of smoking, and smoking urge were also significantly associated with poor SRH. CONCLUSIONS: Smoking was associated with poor SRH among Chinese adolescents, especially girls. This finding is useful for discouraging smoking initiation and motivating quitting in adolescent smokers.


Asunto(s)
Estado de Salud , Autoevaluación (Psicología) , Fumar/psicología , Adolescente , Desarrollo del Adolescente , Consumo de Bebidas Alcohólicas/psicología , Femenino , Encuestas Epidemiológicas/estadística & datos numéricos , Hong Kong/epidemiología , Humanos , Modelos Logísticos , Masculino , Actividad Motora , Oportunidad Relativa , Instituciones Académicas , Fumar/epidemiología , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/efectos adversos
10.
Cancer Lett ; 548: 215898, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36075487

RESUMEN

Uracil misincorporation during DNA replication is a major cell toxic event, of which cancer cells overcome by activating the dUTPase enzyme. The DUT gene is the only known dUTPase in human. Despite reports on common upregulations in cancers, the role of DUT in human hepatocellular carcinoma (HCC) remains largely undetermined. In this study, we investigated the mechanism underlying DUT biology in HCC and tumor susceptibility to drug targeting dUTPase. Overexpression of DUT was found in 42% of HCC tumors and correlated with advanced stage HCC. Knockout of DUT in HCC cell lines showed suppressed proliferation through cell cycle arrest and a spontaneous induction of DNA damage. A protective effect from oxidative stress was also demonstrated in both knockout and overexpression DUT assays. Transcriptome analysis highlighted the NF-κB survival signaling as the downstream effector pathway of DUT in overriding oxidative stress-induced cell death. Interestingly, stably expressed DUT in liver progenitor organoids conferred drug resistance to TKI Sorafenib. Targeting dUTPase activity by TAS-114, could potentiate suppression of HCC growth that synergized with Sorafenib for better treatment sensitivity. In conclusion, upregulated DUT represents a nucleotide metabolic weakness and therapeutic opportunity in HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , FN-kappa B , Nucleótidos , Pirofosfatasas , Sorafenib/farmacología , Uracilo/metabolismo
11.
Int J Behav Nutr Phys Act ; 8: 3, 2011 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-21251295

RESUMEN

Non-exercise physical activity (NEPA) is an important part of energy expenditure. This study aimed to investigate the prevalence of exercise and NEPA among adolescents. In the HKSOS project 2006-2007, the proportions of Hong Kong Chinese adolescents (N=32,005) achieving 60-minute exercise and 60-minute NEPA per day were analyzed. Exercise was defined as structured and planned physical activities, and NEPA was defined as unstructured and unplanned physical activities including walking for transportation and climbing stairs. The prevalence of exercise was higher in boys than girls (after school: 63.8% vs 39.6%; holidays: 78.7% vs 60.0%), but the prevalence of NEPA in boys was similar to that in girls (after school: 72.2% vs 68.0%; holidays: 80.3% vs 79.4%). In general, the prevalence of both exercise and NEPA decreased with age in boys and girls, but was more marked for exercise than NEPA. In conclusion, the prevalence of exercise was lower in adolescent girls than boys, and decreased more rapidly with age than NEPA. NEPA seems to be easier to accumulate than exercise among adolescents regardless of sex and age.


Asunto(s)
Conducta del Adolescente , Ejercicio Físico , Actividad Motora , Adolescente , Factores de Edad , Metabolismo Energético , Femenino , Hong Kong , Humanos , Masculino , Sobrepeso/prevención & control , Autoinforme , Caracteres Sexuales , Factores de Tiempo
12.
J Paediatr Child Health ; 47(4): 173-82, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21244545

RESUMEN

AIM: This study aimed to establish the normative values for the 12-item Short Form Health Survey version 2 (SF-12v2) and examine demographic differences among Hong Kong Chinese adolescents. METHODS: A total of 28,981 Hong Kong Chinese adolescents aged 12-18 participated in a school-based survey in 2006-2007. Sex- and age-specific SF-12v2 scores were obtained. Ordinal logistic regression models and linear regression models were used to examine the demographic differences for the eight subscales including physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health, and two component summary scores of Physical Component Summary and Mental Component Summary. RESULTS: The mean (standard deviation) Physical Component Summary score was 50.28 (6.82) for boys and 49.37 (6.47) for girls. The corresponding Mental Component Summary score was 45.86 (9.86) for boys and 44.77 (9.56) for girls. Ceiling effects were observed in some of the eight subscales but not the two component summary scores. Ordinal logistic regression showed that girls had significantly lower scores than boys in most subscales including physical functioning with odds ratio (95% confidence interval) of 0.89 (0.84-0.93); role physical, 0.94 (0.90-0.98); bodily pain, 0.76 (0.73-0.80); general health, 0.55 (0.53-0.57); vitality, 0.72 (0.69-0.75); role emotional, 0.78 (0.74-0.81); and mental health, 0.91 (0.88-0.95). In general, older and non-local-born adolescents had lower component summary scores than their peers. CONCLUSIONS: This study has provided norms and identified demographic differences of the Chinese SF-12v2.


Asunto(s)
Encuestas Epidemiológicas/instrumentación , Encuestas y Cuestionarios/normas , Adolescente , Niño , Femenino , Hong Kong , Humanos , Masculino , Calidad de Vida
13.
Drug Alcohol Depend ; 227: 108932, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34365224

RESUMEN

BACKGROUND: The association of depressive symptoms with moderate and heavy drinking in adolescents have been reported in many studies, but that with light drinking is unclear. METHODS: In a 2012-13 school-based survey, 20,951 secondary school students (aged 11-20 years, 51.3 % boys) from 44 schools in Hong Kong reported their sociodemographic information, depressive symptoms, drinking patterns and other lifestyle factors. The associations of depressive symptoms with drinking status, drinking frequency and quantity, and the usual type of alcohol beverage consumed were examined using robust Poisson regression accounting for school clustering and covariates. RESULTS: The prevalence of current drinking and depressive symptoms was 13.6 % and 19.0 %, respectively. Depressive symptoms were associated with former drinking (adjusted prevalence ratio 1.48, 95 % confidence interval 1.30-1.68) and measures of light drinking: experimental drinking (1.29, 1.19-1.39), less-than-monthly drinking (1.40, 1.18-1.67) and consuming half a drink or less (1.33, 1.12-1.58), and such associations were stronger in younger adolescents. Associations were also observed for light drinking patterns of 1-2 drinks less than monthly (1.72, 1.40-2.11) and half a drink monthly (1.51, 1.21-1.88). Consuming fruit wine (1.51, 1.27-1.79) and beer (1.63, 1.42-1.88) with relatively low alcohol contents was also associated with depressive symptoms. CONCLUSIONS: Our study provided first evidence that even light drinking in terms of the amount, frequency and type of alcohol beverages or light drinking patterns such as consuming 1-2 drinks less than monthly and half a drink monthly were associated with depressive symptoms in adolescents. Our results support total alcohol abstinence in adolescents.


Asunto(s)
Consumo de Bebidas Alcohólicas , Depresión , Adolescente , Consumo de Bebidas Alcohólicas/epidemiología , Bebidas Alcohólicas , Cerveza , Estudios Transversales , Depresión/epidemiología , Femenino , Humanos , Masculino , Instituciones Académicas
14.
Cell Mol Immunol ; 18(6): 1463-1475, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-31797905

RESUMEN

His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+ and CD8+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome.


Asunto(s)
Histidina-ARNt Ligasa/sangre , Inmunidad , Especificidad de Órganos , Animales , Autoanticuerpos/sangre , Estudios de Casos y Controles , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Histidina-ARNt Ligasa/inmunología , Humanos , Inmunidad/efectos de los fármacos , Inmunomodulación/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/farmacología , Pulmón/efectos de los fármacos , Pulmón/patología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Células Musculares/efectos de los fármacos , Células Musculares/enzimología , Músculos/efectos de los fármacos , Músculos/patología , Miositis/sangre , Miositis/diagnóstico por imagen , Miositis/inmunología , Especificidad de Órganos/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Tomografía Computarizada por Rayos X
15.
Tob Control ; 19(2): 129-33, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20378586

RESUMEN

OBJECTIVE: To investigate the effect of comprehensive smoke-free legislation in 2007 on the exposure of children to secondhand smoke (SHS) in Hong Kong. METHODS: Two cross-sectional questionnaire surveys were conducted, before (2006) and after (2008) the implementation of smoke-free legislation, among primary 2-4 students (equivalent to US grades 2-4) from 19 and 24 randomly selected schools, respectively. Adjusted ORs for SHS exposure at home and outside home post-legislation compared with pre-legislation were calculated. The strength of the association between SHS exposure and respiratory symptoms in each survey was used as an indirect indicator of the intensity of exposure. RESULTS: Among 3243 and 4965 never smoking students in the 2006 and 2008 surveys, the prevalence of SHS exposure in the past 7 days increased both at home (from 10.2% to 14.1%) and outside home (from 19.8% to 27.2%). Post-legislation, students were 56% more likely (p<0.01) to report SHS exposure at home coupled with an insignificantly stronger association between SHS exposure and respiratory symptoms. Similarly, students were 60% more likely (p<0.001) to report SHS exposure outside home in 2008, but the association between SHS exposure and respiratory symptoms became insignificantly weaker. Parental smoking rates were similar before and after legislation. CONCLUSIONS: The prevalence of exposure to SHS at home and outside home have both increased among primary school students in Hong Kong post-legislation. Comprehensive smoke-free legislation without strong support for smoking cessation might have displaced smoking into the homes of young children.


Asunto(s)
Fumar/epidemiología , Fumar/legislación & jurisprudencia , Contaminación por Humo de Tabaco/legislación & jurisprudencia , Contaminación por Humo de Tabaco/estadística & datos numéricos , Niño , Estudios Transversales , Femenino , Cabello/química , Hong Kong/epidemiología , Humanos , Modelos Logísticos , Masculino , Nicotina/química , Nicotina/metabolismo , Agonistas Nicotínicos/química , Agonistas Nicotínicos/metabolismo , Padres , Enfermedades Respiratorias/epidemiología , Encuestas y Cuestionarios
16.
BMC Public Health ; 10: 88, 2010 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-20178615

RESUMEN

BACKGROUND: This study was designed to investigate the relation between health-related physical fitness and weight status in Hong Kong adolescents. METHODS: 3,204 students aged 12-18 years participated in the Hong Kong Student Obesity Surveillance (HKSOS) project in 2006-2007. Anthropometric measures (height, weight) and health-related fitness (push-up, sit-up, sit-and-reach, 9-minute run) were assessed. Body mass index (BMI) was computed to classify participants into normal weight, underweight (Grade I, II/III), overweight, and obese groups. The associations of health-related physical fitness with BMI and weight status were examined by partial correlation coefficients and analysis of covariance, respectively. RESULTS: More boys than girls were overweight or obese (18.0% vs 8.7%), but more girls than boys were underweight (22.3% vs 16.7%). Boys performed significantly (P < 0.001) better in sit-up (38.8 vs 31.6 times/min) and 9-minute run (1632.1 vs 1353.2 m), but poorer in sit-and-reach (27.4 vs 32.2 cm) than girls. All four physical fitness tests were significantly positively correlated with each other in both sexes, and BMI was only weakly correlated with sit up and sit-and-reach tests in boys. Decreasing performance (P for trend < 0.05) was observed from normal weight to overweight and obese for push-up, sit-up, and 9-minute run in both sexes. From normal weight to Grade I and Grade II/III underweight, decreasing performance (P for trend < 0.05) for sit-up and sit-and-reach in both sexes and for push-up in boys was observed. CONCLUSIONS: The relations between BMI and health-related physical fitness in adolescents were non-linear. Overweight/obese and underweight adolescents had poorer performance in push-up and sit-up tests than normal weight adolescents. Different aspects of health-related physical fitness may serve as immediate indicators of potential health risks for underweight and overweight adolescents.


Asunto(s)
Índice de Masa Corporal , Aptitud Física/fisiología , Adolescente , Peso Corporal , Niño , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Fuerza Muscular , Obesidad/epidemiología , Sobrepeso/epidemiología , Factores Sexuales
17.
Int J Environ Health Res ; 20(3): 219-30, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20352550

RESUMEN

Respiratory ill-health effects due to particulate air exposure at different geographical locations in Hong Kong that aggregate individual living locations were estimated based on satellite information. We assessed the presence of respiratory symptoms of a frequent cough or sputum in school students aged 11-20 years old (n = 9,881). Daily particulate air pollution levels at students' living locations were derived from the surface extinction coefficients measured by satellite and measurements from the air pollutant monitoring stations at ground level. Adjusted odds ratio (OR) [95% CI] of respiratory symptoms was 1.047 [1.005, 1.091] per 10 microg m(-3) increase in PM(10) concentration. Specificity tests showed that adjusted OR of having other symptoms is not significant (p = 0.20-0.94). Exposures to PM(10) at different geographical locations is associated with increased odds of having respiratory symptoms (cough or sputum) but not with other symptoms unrelated to air pollution.


Asunto(s)
Contaminación del Aire/análisis , Material Particulado/análisis , Enfermedades Respiratorias/inducido químicamente , Nave Espacial , Topografía Médica/métodos , Adolescente , Adulto , Contaminación del Aire/efectos adversos , Niño , Estudios Transversales , Interpretación Estadística de Datos , Hong Kong/epidemiología , Humanos , Material Particulado/efectos adversos , Enfermedades Respiratorias/epidemiología , Adulto Joven
18.
Biochem Soc Trans ; 37(Pt 6): 1415-8, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19909288

RESUMEN

The SCZ (schizophrenia)-associated GABA(A) receptor (gamma-aminobutyric acid type A receptor) beta(2) subunit gene GABRB2 was recently associated with BPD (bipolar disorder). Although weaker than its association with SCZ, significant association of GABRB2 with BPD was found in both German and Chinese, especially for the haplotypes rs1816071-rs187269 and rs1816072-rs187269 for which the M-M variants showed higher frequency in disease than the control. Significant genotype-dependent reduction in GABRB2 expression was shown for BPD, but to a lesser extent than that for SCZ. Temporal effects on GABRB2 expression were observed. Moreover, for the homozygous major genotypes of rs1816071, rs1816072 and rs187269, expression increased with time in CON but decreased in SCZ and BPD. The genotypes of these three SNPs (single nucleotide polymorphisms) were further correlated with antipsychotics dosage in SCZ cohorts. The findings highlight the importance of GABRB2 in neuropsychiatric disease aetiology, with respect to haplotype association, as well as reduction of and temporal effects on gene expression in both SCZ and BPD, but to a lesser extent in the latter, supporting the suggestion that functional psychosis can be conceptualized as a continuous spectrum of clinical phenotypes rather than as distinct categories.


Asunto(s)
Trastorno Bipolar/genética , Expresión Génica , Receptores de GABA-A/genética , Esquizofrenia/genética , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Polimorfismo de Nucleótido Simple , Trastornos Psicóticos/genética , Receptores de GABA-A/metabolismo , Población Blanca/genética
19.
BMC Public Health ; 9: 271, 2009 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-19642972

RESUMEN

BACKGROUND: Weight comments are commonly received by adolescents, but the accuracy of the comments and their effects on weight misperception are unclear. We assessed the prevalence and accuracy of weight comments received by Chinese adolescents from different sources and their relation to weight misperception. METHODS: In the Hong Kong Student Obesity Surveillance (HKSOS) project 2006-07, 22612 students aged 11-18 (41.5% boys) completed a questionnaire on obesity. Students responded if family members, peers and professionals had seriously commented over the past 30 days that they were "too fat" or "too thin" in two separate questions. The accuracy of the comments was judged against the actual weight status derived from self-reported height and weight. Self-perceived weight status was also reported and any discordance with the actual weight status denoted weight misperception. Logistic regression yielded adjusted odd ratios for weight misperception by the type of weight comments received. RESULTS: One in three students received weight comments, and the mother was the most common source of weight comments. Health professional was the most accurate source of weight comments, yet less than half the comments were correct. Adolescents receiving incorrect comments had increased risk of having weight misperception in all weight status groups. Receiving conflicting comments was positively associated with weight misperception among normal weight adolescents. In contrast, underweight and overweight/obese adolescents receiving correct weight comments were less likely to have weight misperception. CONCLUSION: Weight comments, mostly incorrect, were commonly received by Chinese adolescents in Hong Kong, and such incorrect comments were associated with weight misperception.


Asunto(s)
Peso Corporal , Autoimagen , Adolescente , Femenino , Hong Kong , Humanos , Masculino , Análisis Multivariante , Vigilancia de la Población , Prevalencia
20.
Acta Paediatr ; 98(12): 1959-64, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19673720

RESUMEN

AIM: To investigate the prospective effects of weight perception of self and weight comments by others on psychological health problems among Chinese adolescents. METHODS: In the Hong Kong Student Obesity Surveillance project, 8716 adolescents (41.3% boys) aged 14.2 +/- 1.7 years were followed prospectively. Logistic regression yielded odds ratios (ORs) for psychological health problems at 1-year follow-up by weight comments received and weight perception at baseline (2006), adjusting for each other sociodemographic factors and body mass index. RESULTS: Perceived fatness at baseline predicted subsequent headache and feeling stressful with adjusted ORs (95% confidence intervals) of 1.17 (1.03-1.33) and 1.20 (1.03-1.39), respectively. Perceived thinness at baseline did not predict any subsequent health problems. Receiving incorrect weight comments at baseline also predicted headache, feeling stressful and feeling depressed at follow-up, with adjusted ORs of 1.19 (1.08-1.31), 1.26 (1.04-1.53) and 1.38 (1.10-1.74) respectively. No gender difference was found in the effects of weight perception and weight comments on psychological outcomes. CONCLUSIONS: In adolescents, perceived fatness and incorrect weight comments predicted psychological health problems at 1-year follow-up. Family members, peers and other social contacts should realize the potential adverse effects of their weight comments, and adolescents should be taught how to correctly assess their weight status.


Asunto(s)
Peso Corporal , Psicología del Adolescente , Autoimagen , Adolescente , Imagen Corporal , Femenino , Estudios de Seguimiento , Estado de Salud , Hong Kong , Humanos , Relaciones Interpersonales , Modelos Logísticos , Masculino , Trastornos Mentales/psicología , Salud Mental , Oportunidad Relativa , Estudios Prospectivos
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