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1.
BMC Pediatr ; 21(1): 308, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243738

RESUMO

BACKGROUND: Less than 2% of overweight children and adolescents in Switzerland can participate in multi-component behaviour changing interventions (BCI), due to costs and lack of time. Stress often hinders positive health outcomes in youth with obesity. Digital health interventions, with fewer on-site visits, promise health care access in remote regions; however, evidence for their effectiveness is scarce. METHODS: This randomized controlled not blinded trial (1:1) was conducted in a childhood obesity center in Switzerland. Forty-one youth aged 10-18 years with body mass index (BMI) > P.90 with risk factors or co-morbidities or BMI > P.97 were recruited. During 5.5 months, the PathMate2 group (PM) received daily conversational agent counselling via mobile app, combined with standardized counselling (4 on-site visits). Controls (CON) participated in a BCI (7 on-site visits). We compared the outcomes of both groups after 5.5 (T1) and 12 (T2) months. Primary outcome was reduction in BMI-SDS (BMI standard deviation score: BMI adjusted for age and sex). Secondary outcomes were changes in body fat and muscle mass (bioelectrical impedance analysis), waist-to-height ratio, physical capacities (modified Dordel-Koch-Test), blood pressure and pulse. Additionally, we hypothesized that less stressed children would lose more weight. Thus, children performed biofeedback relaxation exercises while stress parameters (plasma cortisol, stress questionnaires) were evaluated. RESULTS: At intervention start median BMI-SDS of all patients (18 PM, 13 CON) was 2.61 (obesity > + 2SD). BMI-SDS decreased significantly in CON at T1, but not at T2, and did not decrease in PM during the study. Muscle mass, strength and agility improved significantly in both groups at T2; only PM reduced significantly their body fat at T1 and T2. Average daily PM app usage rate was 71.5%. Cortisol serum levels decreased significantly after biofeedback but with no association between stress parameters and BMI-SDS. No side effects were observed. CONCLUSIONS: Equally to BCI, PathMate2 intervention resulted in significant and lasting improvements of physical capacities and body composition, but not in sustained BMI-SDS decrease. This youth-appealing mobile health intervention provides an interesting approach for youth with obesity who have limited access to health care. Biofeedback reduces acute stress and could be an innovative adjunct to usual care.


Assuntos
Obesidade Infantil , Telemedicina , Adolescente , Índice de Massa Corporal , Criança , Humanos , Sobrepeso , Obesidade Infantil/terapia , Suíça
2.
Phys Chem Chem Phys ; 19(34): 23357-23361, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28825734

RESUMO

The growth of two-dimensional materials into three-dimensional geometries holds the promise for high performance hybrid materials and novel architectures. The synthesis of such structures, however, proceeds in fundamentally different flow regimes compared to conventional CVD where pressure differences and wall collisions are neglected. We here demonstrate the remarkable stability of graphene growth under varying fluid dynamic flow regimes. We investigate the growth process across different flow conditions using confined growth in refractory pores. Analysis of the growth rate reveals a transport-limited process which allows experimental determination of the gas diffusion coefficient. The diffusion coefficient was found to be constant for large pore dimension but scales with pore dimension as the pore size decreases below the mean free path providing clear evidence for previously predicted Knudsen molecular-flow conditions for atomic confinement. Surprisingly, changes to the flow conditions by two orders of magnitude do not cause qualitative changes of the graphene growth process. This unique behavior was attributed to rarefied flow conditions by scaling analysis and an analytical relation between growth rate and constriction could be extracted that proves accurate throughout the investigated conditions. Our results demonstrate a fundamentally different growth process compared to traditional CVD processes that is akin to atomic layer deposition and highlight the feasibility of high-quality 2D-material growth on 3D morphologies with ultra-high aspect ratios.

3.
Gene Ther ; 19(1): 25-33, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21562593

RESUMO

Chronic hepatitis B virus (HBV) infection is closely related to the development of severe liver complications, including hepatocellular carcinoma. In previous studies, we reported that in vivo long-term HBV suppression in transgenic mice can be achieved without apparent toxicity by short hairpin RNA sequentially delivered using adeno-associated viral (AAV) vectors of different serotypes. Our goal herein was to address the clinical utility of this delivery system and, in particular, to determine whether RNA interference (RNAi) and its ability to induce long-term HBV suppression will modulate the development of HBV-associated liver pathology. As a model system, we used a unique HBV transgenic mouse model, containing a 1.3 times over length of the HBV genome, on the ICR mouse background. These transgenic mice produce high serum HBV titers comparable with human chronic HBV patients, and, importantly, manifest characteristic HBV-associated pathology, including progressive hepatocellular injury and the development of hepatocellular adenoma. Using this system, we injected animals with AAV vectors expressing either HBV-specific or a control luciferase-specific short hairpin RNA and followed animals for a total of 18 months. We report herein that AAV-mediated RNAi therapy profoundly inhibits HBV replication and gene expression, with a significant reduction in hepatic regeneration, liver enzymes and, importantly, the appearance of liver adenomas. Indeed, the therapeutic effect of RNAi correlated with the reduction in HBV titers. Our data demonstrate that appropriately designed RNAi therapy has the potential to prevent formation of HBV-associated hepatocellular adenoma.


Assuntos
Adenoma de Células Hepáticas/terapia , Regulação Viral da Expressão Gênica , Vírus da Hepatite B/patogenicidade , Neoplasias Hepáticas/terapia , Interferência de RNA , RNA Viral/genética , Adenoma de Células Hepáticas/sangue , Adenoma de Células Hepáticas/patologia , Adenoma de Células Hepáticas/virologia , Animais , Northern Blotting , Dependovirus/genética , Dependovirus/metabolismo , Feminino , Técnicas de Transferência de Genes , Antígenos de Superfície da Hepatite B/análise , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Hepatite B Crônica/terapia , Hepatite B Crônica/virologia , Hepatócitos/citologia , Hepatócitos/metabolismo , Hepatócitos/virologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas Experimentais , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , RNA Viral/metabolismo , Transgenes , Carga Viral , Replicação Viral
4.
Eur Respir J ; 31(5): 957-62, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18216048

RESUMO

All-trans retinoic acid (ATRA) can induce acute respiratory distress syndrome in patients with acute promyelocytic leukaemia (APL). The current study investigated the role of monocyte chemotactic protein (MCP)-1 in the chemotactic transmigration of ATRA-treated NB4 (ATRA-NB4) APL cells toward A549 alveolar epithelial cells. NB4 and A549 cells were separately cultured with ATRA and/or dexamethasone (DEX). ATRA-NB4 cells were then placed in an upper insert and co-incubated with A549 cells or their conditioned medium (CM) located in a lower plate to test their transmigration activity. ATRA stimulated NB4 cells to transmigrate toward the A549 cells. The secretion of MCP-1 was enhanced by ATRA treatment in both A549 and NB4 cells. The binding assay demonstrated that ATRA-NB4 cells bound MCP-1. Pre-treatment of both CM-A549 cells with antibodies against MCP-1 and of ATRA-NB4 cells with antibodies against MCP-1 receptors reduced ATRA-NB4 cell transmigration. DEX did not suppress MCP-1 secretion and transmigration in ATRA-NB4 cells, although when applied to A549 cells, MCP-1 secretion was suppressed and ATRA-NB4 cell transmigration was attenuated. Monocyte chemotactic protein-1 secreted from alveolar epithelial cells plays an important role in the cell-cell interaction involved in the chemotactic transmigration of all-trans retinoic acid-treated acute promyelocytic leukaemia cells toward alveolar epithelial cells.


Assuntos
Antineoplásicos/efeitos adversos , Quimiotaxia/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Precursoras de Granulócitos/efeitos dos fármacos , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/efeitos dos fármacos , Técnicas de Cocultura , Humanos , Alvéolos Pulmonares/citologia , Alvéolos Pulmonares/efeitos dos fármacos , Receptores CCR2
5.
Intern Med J ; 38(6): 422-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18336541

RESUMO

BACKGROUND: The Janus kinase-2 (JAK-2) V617F mutation has been recently reported in patients with myeloproliferative disorders (MPD), which is believed to underlie growth factor hypersensitivity displayed by haematopoietic progenitors in these disorders. However, its frequency has been rarely determined in Taiwanese patients. METHODS: The frequency of JAK2-V617F mutation in patients with polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis (IMF) was determined in the DNA from the peripheral blood leucocytes of 108 patients by genomic polymerase chain reaction and restriction enzyme-based assay. RESULTS: The JAK2-V617F mutation could be detected in 28 of 33 polycythaemia vera patients (85%), 29 of 49 essential thrombocythaemia patients (59%) and 2 of 6 IMF patients (33%), but was not detected in 11 patients with myelodysplastic syndrome or another 10 with other haematological diseases. The presence of the JAK2 mutation was associated with specific MPD disease subtypes (P = 0.007), longer disease duration (P = 0.005), splenomegaly (P = 0.019), a higher white blood cell count (P = 0.002) and a higher haemoglobin level (P = 0.036). However, the overall risk of thrombosis or bleeding was not affected by the presence of the JAK2 mutation (32 vs 17%; P = 0.22). CONCLUSION: The JAK2-V617F mutation can be frequently detected in the Taiwanese patients with MPD disorders and therefore should be incorporated into the initial evaluation of patients suspected of MPD.


Assuntos
DNA/genética , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/genética , Idoso , Éxons , Feminino , Predisposição Genética para Doença , Humanos , Técnicas Imunoenzimáticas , Incidência , Masculino , Transtornos Mieloproliferativos/enzimologia , Transtornos Mieloproliferativos/epidemiologia , Reação em Cadeia da Polimerase , Taiwan/epidemiologia
6.
Mol Cell Biol ; 11(3): 1480-7, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1996105

RESUMO

C/EBP is a rat liver DNA-binding protein which can act as a transcription factor. Its N-terminal portion contains three distinct domains. The first domain (amino acids 1 to 107) appears to be a highly potent transactivator. The second domain (amino acids 107 to 170) does not appear to exhibit either activation or repression activity. This domain is defined as an "attenuator domain" because its presence under four different sequence contexts reproducibly decreases the effect of transactivation of C/EBP. The third domain (amino acids 171 to 245) is a relatively weaker transactivator with a striking proline-rich motif. Deletional analysis of this third domain has shown that a 45-amino-acid region is sufficient for transactivation. This region (amino acids 171 to 215) contains 12 proline, 6 histidine, and mainly hydrophobic or noncharged amino acids. Further mutational analysis of a highly conserved proline-octamer region within this domain indicates that a specific proline content is not crucial for transactivation.


Assuntos
Proteínas de Ligação a DNA/ultraestrutura , Proteínas Nucleares/ultraestrutura , Proteínas de Saccharomyces cerevisiae , Fatores de Transcrição/ultraestrutura , Sequência de Bases , Proteínas Estimuladoras de Ligação a CCAAT , Células Cultivadas , Clonagem Molecular , Análise Mutacional de DNA , Proteínas Fúngicas/genética , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , Oligonucleotídeos/química , Proteínas Recombinantes de Fusão , Proteínas Repressoras/fisiologia , Relação Estrutura-Atividade , Transativadores/genética , Transfecção
7.
Poult Sci ; 96(5): 1191-1203, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339512

RESUMO

This study evaluated the antioxidant ability of Taisung No. 3 mulberry leaf extract (MLE) as well as the potential of mulberry leaf (ML)-based dietary supplementation for modulating the antioxidative status of laying hens. The results showed that the MLE had a total phenolic compound content of 7.4 ± 0.15 mg of gallic acid equivalent/g dry weight (DW) and a total flavonoid content of 4.4 ± 0.19 mg of quercetin equivalent/g DW. The 2, 2-diphenyl-1-picrylhydrazyl free-radical-scavenging ability was 45.9% when 0.1 mg/mL MLE was added. The lipid oxidation inhibition ability was 43.9% when 50 mg/mL MLE was added. We subjected 96 laying hens (Hendrix Genetics) to 4 treatments, namely diets supplemented with dry ML at 0 (control), 0.5, 1, or 2% for 12 weeks. Each treatment involved 8 replicates with 3 hens each. The results indicated that the 0.5% ML-supplemented group exhibited significantly higher mRNA levels of antioxidant-regulated genes, such as Nrf2, HO-1, and GST, and significantly lower ROMO1 gene expression levels at wk 12. The serum malondialdehyde level was lower and the catalase activity and superoxide dismutase activity were higher in all the ML-supplemented groups than in the control group. The egg mass and feed conversion rate significantly improved in the ML-supplemented groups compared with the control group, and, overall, 1% ML supplementation had the most favorable effects at one to 12 weeks. The egg yolk weight, shell weight, shell strength, shell thickness, yolk color, and Haugh unit were increased among all ML-supplemented groups at one to 12 weeks. On the basis of these observations, we conclude that 0.5% ML can be used as a new feed additive to potentially modulate the antioxidative status of laying hens and improve their production performance and egg quality.


Assuntos
Ração Animal/análise , Antioxidantes/análise , Galinhas , Ovos/análise , Morus/química , Extratos Vegetais/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Feminino , Flavonoides/análise , Malondialdeído/sangue , Oviposição/efeitos dos fármacos , Fenóis/análise , Folhas de Planta/química , Transcriptoma
8.
Oncogene ; 36(47): 6542-6554, 2017 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-28759046

RESUMO

Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers. Our data further reveal a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower trimethylation of histone H3 lysine 27 suppressive modification, relaxes chromatin, and promotes the accessibility of the transcription factor STAT1 to the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions. Down-regulation of ROS1 in highly invasive OSCC cells, nevertheless, reduces cell proliferation and inhibits metastasis to lung in the tail-vein injection and the oral cavity xenograft models. Our findings highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Finally, we demonstrate that co-targeting of ROS1 and EGFR could potentially offer an effective oral cancer therapy.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/secundário , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CXCL1/metabolismo , Regulação para Baixo , Receptores ErbB/antagonistas & inibidores , Histonas/metabolismo , Humanos , Masculino , Metilação , Camundongos , Terapia de Alvo Molecular/métodos , Neoplasias Bucais/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Fator de Transcrição STAT1/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína GLI1 em Dedos de Zinco/metabolismo
9.
Oncogene ; 6(2): 237-43, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1847999

RESUMO

We have examined p53 oncogene/anti-oncogene alleles in 10 different human hepatoma cell lines and 18 primary hepatocellular carcinomas. The p53 allele in these hepatoma cell lines appears to be a frequent target of mutation as demonstrated by Southern and Northern blotting, immunoprecipitation and Western blot analysis. In general, the steady state level of p53 specific RNA or protein in these hepatoma cell lines is higher than in normal liver. However, in three out of ten cell lines, normal-sized p53 mRNA cannot be detected. In contrast, the involvement of the p53 allele in primary hepatocellular carcinoma appears to be an exceedingly rare event. Steady state levels of p53 specific RNA in primary hepatomas are practically indistinguishable from those in normal adult liver. Using the polymerase chain reaction technique, we have amplified and subcloned exons 5, 6, 7 and 8 of p53 from 10 different hepatoma samples. DNA sequence analysis of these exon subclones reveals no apparent structural alterations. Finally, synthesis of p53 specific mRNA or protein in a HepG2 human hepatoblastoma cell line does not appear to be affected by gene expression and replication of human hepatitus B virus. Surprisingly, unlike many other kinds of human solid tumors, point mutations in p53 do not appear to be important in primary tumors of hepatocellular carcinomas.


Assuntos
Alelos , Carcinoma Hepatocelular/genética , Genes p53 , Neoplasias Hepáticas/genética , Northern Blotting , Southern Blotting , Éxons , Vírus da Hepatite B/genética , Humanos , Dados de Sequência Molecular , Mutação , RNA Mensageiro/análise , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/biossíntese , Replicação Viral
10.
Clin Cancer Res ; 6(3): 1161-8, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10741747

RESUMO

Vascular endothelial growth factor (VEGF) expression and tumor microvessel density (MVD) were examined by immunohistochemical staining in 117 cases of thoracic esophageal squamous cell carcinoma. Thirty-six (31%) of the 117 cases were evaluated as VEGF-positive. The average number of metastatic lymph nodes at surgery was 5.6 in the VEGF-positive cases and 3.0 in the VEGF-negative cases and was significantly higher in those with VEGF-positive cases (P = 0.04). The incidence of pathological tumor (PT)2-4 cases among the high-MVD cases was significantly higher than among the low-MVD cases (P = 0.01). MVD was 59.4 +/- 4.7 (mean +/- SE)/mm2 in the VEGF-positive cases and 47.9 +/- 3.8/mm2 in the VEGF-negative cases. The MVD of the VEGF-positive tumors was higher than that of VEGF-negative tumors, but the difference was not significant (P = 0.08). The survival rate of the patients with high-MVD tumors was significantly poorer than those with low-MVD tumors, and the survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.009 and P = 0.04, respectively). The cumulative survival rates in the VEGF-positive groups were found to be significantly poorer in the pT3 and pathological node (pN)1 groups when stratified according to pT factor (pathological T category) and pN factor (pathological N category) in the tumor-node-metastasis (TNM) classification. VEGF expression had the second highest hazard ratio in the multivariate analysis, after pN factor. These results indicate that VEGF is a useful marker for predicting the outcome in patients with more advanced esophageal squamous cell carcinoma. It seems that TNM factors and VEGF expression are important factors in the selection of appropriate treatments.


Assuntos
Carcinoma de Células Escamosas/patologia , Fatores de Crescimento Endotelial/biossíntese , Neoplasias Esofágicas/patologia , Linfocinas/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Esôfago/química , Esôfago/efeitos dos fármacos , Esôfago/patologia , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/química , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
11.
Clin Cancer Res ; 3(12 Pt 1): 2229-36, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9815619

RESUMO

The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate cyclin-dependent kinase 4-mediated phosphorylation of pRB in the cell cycle of normal cells. p16/CDKN2 gene and cyclin D1/PRAD-1 gene alterations have been detected in squamous cell carcinoma cell lines and in several primary squamous cell carcinomas of the esophagus. We immunohistochemically assessed p16 and cyclin D1 expression in 111 squamous cell carcinomas of the esophagus after evaluation of the antibodies against p16 and cyclin D1 protein using four squamous cell carcinoma cell lines. Loss of p16 expression was detected in 56 of 111 cases (50%). The mean number of metastatic lymph nodes without p16 expression was significantly higher than the number of nodes with p16 expression (P = 0.04). The postoperative survival rate for patients without p16 expression was significantly lower than that of patients with p16 expression (P = 0.04). Cyclin D1 overexpression was found in 28 of the 111 cases (25%) and correlated with distant organ metastasis after curative surgery (P = 0.05). The survival rate of patients with cyclin D1 overexpression was significantly lower than that of patients without cyclin D1 overexpression (P = 0.01). A positive correlation between the loss of p16 expression and cyclin D1 overexpression was observed (P = 0. 03). The loss of p16 expression and overexpression of cyclin D1 may be useful prognostic indicators in patients with squamous cell carcinomas of the esophagus. It may be possible to select more suitable treatment for patients with squamous cell carcinomas of the esophagus by evaluating the status of p16 and cyclin D1 expression.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Ciclina D1/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/cirurgia , Regulação Neoplásica da Expressão Gênica , Genes p16 , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Ciclina D1/análise , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Fatores de Tempo , Células Tumorais Cultivadas
12.
J Bone Joint Surg Br ; 87(6): 770-5, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15911656

RESUMO

We have carried out in 24 patients, a two-stage revision arthroplasty of the hip for infection with massive bone loss. We used a custom-made, antibiotic-loaded cement prosthesis as an interim spacer. Fifteen patients had acetabular deficiencies, eight had segmental femoral bone loss and one had a combined defect. There was no recurrence of infection at a mean follow-up of 4.2 years (2 to 7). A total of 21 patients remained mobile in the interim period. The mean Merle D'Aubigné and Postel hip score improved from 7.3 points before operation to 13.2 between stages and to 15.8 at the final follow-up. The allograft appeared to have incorporated into the host bone in all patients. Complications included two fractures and one dislocation of the cement prosthesis. The use of a temporary spacer maintains the function of the joint between stages even when there is extensive loss of bone. Allograft used in revision surgery after septic conditions restores bone stock without the risk of recurrent infection.


Assuntos
Antibacterianos/administração & dosagem , Artroplastia de Quadril , Infecções Relacionadas à Prótese/cirurgia , Adulto , Idoso , Artrografia , Cimentos Ósseos , Transplante Ósseo , Terapia Combinada , Sistemas de Liberação de Medicamentos , Feminino , Seguimentos , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Desenho de Prótese , Infecções Relacionadas à Prótese/diagnóstico por imagem , Infecções Relacionadas à Prótese/tratamento farmacológico , Reoperação/métodos , Índice de Gravidade de Doença
13.
J Endocrinol ; 179(3): 367-77, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14656206

RESUMO

Thyroid hormones (THs) regulate growth, development, differentiation and metabolic processes by interacting and activating thyroid hormone receptors (TRs). Although much progress has been made in our understanding of the transcriptional regulation of many TR target genes, little is known of the regulation of plasma protein gene expression by TRs. To investigate the role of TRs in plasma protein expression we used human hepatocellular carcinoma cell lines and carried out cDNA microarray analysis. Our results indicate that several plasma proteins including transferrin, prothrombin, angiotensinogen, haptoglobin, alpha-2-HS-glycoprotein alpha and beta chain, complement, lipoproteins and fibrinogen are up-regulated by THs. Furthermore, clusterin, alpha-2-macroglobulin precursor, prothymosin alpha and alpha-fetoprotein were found to be down-regulated by THs.Transferrin, an iron-binding protein expressed in all mammals, and mainly synthesized in the liver, was investigated further. Immunoblot and Northern blot analyses revealed that exposure of HepG2-TRalpha1 sub-lines and HepG2-Neo cells to tri-iodothyronine (T(3)) induced time- and dose-dependent increases in the abundance of transferrin mRNA and protein, with the extent of these effects correlating with the level of expression of TRalpha1. Nuclear run-on experiments indicate that this induction is functioning at the transcriptional level. Moreover, cyclohexamide treatment did not eliminate the induction of transferrin by TH. Thus, our results suggest that the induction of transferrin by TH is direct and may in fact be mediated by an as yet unidentified response element in the promoter region.


Assuntos
Proteínas Sanguíneas/metabolismo , Regulação da Expressão Gênica/fisiologia , Hormônios Tireóideos/fisiologia , Proteínas Sanguíneas/genética , Northern Blotting , DNA Complementar/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , RNA Mensageiro/genética , Receptores alfa dos Hormônios Tireóideos/metabolismo , Transcrição Gênica , Ativação Transcricional , Transferrina/biossíntese , Transferrina/genética , Tri-Iodotironina/farmacologia , Tri-Iodotironina/fisiologia , Células Tumorais Cultivadas
14.
J Clin Epidemiol ; 46(6): 545-8, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8501481

RESUMO

Several studies of childhood cancer, especially leukemia, in residential areas have reported an association with wire configuration codes. These codes were suggested to be surrogates of electromagnetic field exposure. However, the selection criteria used in several of the studies caused the case and control populations to be non-comparable, especially with respect to residential mobility. Specifically, controls were required to be residentially stable but cases were not. Thus, an artificial association between residential mobility and cancer was created by the subject selection procedure. The present study of 5721 residences in Columbus, Ohio was conducted to learn if bias due to differences in residential mobility, rather than electromagnetic fields, could explain the reported association between wire configuration codes and childhood cancer. It was found that the proportion of homes classified as "high" wire code in the non-stable population was 31% greater than the corresponding proportion in the stable population. This finding shows that high wire codes are associated with homes in which the residents are mobile and low wire codes are associated with homes occupied by stable residents. Thus, as a consequence of this association between residential mobility and high wire codes, studies that created an artificial association between residential mobility and childhood cancer will also produce a false association between high wire codes and cancer.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Habitação/legislação & jurisprudência , Neoplasias Induzidas por Radiação/epidemiologia , Dinâmica Populacional/estatística & dados numéricos , Estudos de Casos e Controles , Criança , Humanos , Neoplasias Induzidas por Radiação/etiologia , Ohio/epidemiologia , Viés de Seleção
15.
J Orthop Res ; 19(4): 696-702, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11518281

RESUMO

The mechanism underlying chronic destructive arthropathy after pyogenic arthritis is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus infected human articular chondrocytes and investigated the signal transduction pathways activated by bacterial infection. Chondrocytes cultured in monolayer were challenged with bacteria for 6 h and were analyzed after incubation for 2, 18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of apoptosis after infection and the following incubation period. Although treatment with extensive washing and vancomycin could ameliorate the amount of apoptosis from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the infected samples with treatment still had higher amount of apoptosis than the un-infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of apoptosis, the caspase activity was upregulated in bacteria infected samples and remained high in samples with treatment (ANOVA P < 0.05). Signal transduction pathways activated by bacterial infection were assessed by co-transfection technique. After infection, the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and cyclic AMP-dependent protein kinase activities were elevated by 7.6-, 7.3-, and 3.2-fold, respectively, compared to the uninfected controls. The data support the hypothesis that human chondrocytes will undergo apoptosis after infection by a single organism. Apoptosis and activated intracellular kinase activities may be related to the pathogenesis of post-infectious destructive arthropathy.


Assuntos
Apoptose/fisiologia , Condrócitos/enzimologia , Condrócitos/microbiologia , Proteínas Quinases JNK Ativadas por Mitógeno , Transdução de Sinais/fisiologia , Infecções Estafilocócicas/fisiopatologia , Células Cultivadas , Condrócitos/citologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Citometria de Fluxo , Humanos , MAP Quinase Quinase 4 , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo
16.
J Epidemiol Community Health ; 56(7): 492-6, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12080155

RESUMO

STUDY OBJECTIVE: s: Social epidemiologists have hypothesised that neighbourhood quality may exert an important contextual influence on mental and physical health. However, validated instruments do not exist for measuring neighbourhood quality in Taiwan. A self reported instrument to measure perceived neighbourhood quality in Taiwan was developed and tested. DESIGN: Community survey. SETTING: Southern Taiwan, including the metropolitan Kaohsiung area and eight surrounding communities, representing urban, suburban, and rural districts. PARTICIPANTS: A total of 1084 residents, aged 18 to 75, were surveyed during 1999 to 2000. MAIN RESULTS: Using factor analysis with varimax rotation, three subscales explained 54.8% of the variance in our 15 item Neighbourhood Quality Index: perceived social capital (Cronbach alpha=0.84), perceived security (alpha=0.78), and adequacy of services and facilities (alpha=0.67). Lower perceived neighbourhood social capital (odds ratio, OR, 1.26; 95% CI: 1.21 to 1.32), lower neighbourhood security (OR 1.37; 95% CI: 1.26 to 1.48), and inadequate neighbourhood services and facilities (OR 1.17; 95% CI: 1.06 to 1.28) were all related to higher residential dissatisfaction. CONCLUSIONS: A Neighbourhood Quality Index was developed for use in Taiwan with good internal consistency and test-retest reliability, as well as convergent validity. Future studies will examine the association between this index and measures of individual mental and physical health.


Assuntos
Saúde Mental , Qualidade de Vida , Características de Residência , Adulto , Idoso , Atitude , Comportamento do Consumidor , Feminino , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Saúde da População Rural , Fatores Socioeconômicos , Saúde Suburbana , Inquéritos e Questionários/normas , Taiwan , Saúde da População Urbana
17.
J Bone Joint Surg Br ; 85(6): 818-21, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12931797

RESUMO

We retrospectively reviewed 45 hip arthroplasties which were performed over a period of 20 years in 38 patients with cirrhosis of the liver. There was a high perioperative 30-day complication rate (26.7%). Advanced cirrhosis was associated with a higher risk of complications (p = 0.004) as also was increased age, a high level of creatinine, a low level of albumin, a low platelet count, ascites, encephalopathy and an increased operative blood loss. The survival of the prosthesis at five years was 77.8% and infection was a major cause of failure. In view of the high rate of early complications and the limited longevity of the prosthesis, surgeons who perform hip arthroplasty on such patients should counsel them appropriately preoperatively.


Assuntos
Artroplastia de Quadril/métodos , Cirrose Hepática/complicações , Adulto , Idoso , Artroplastia de Quadril/instrumentação , Feminino , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Falha de Prótese , Reoperação , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
18.
J Bone Joint Surg Br ; 79(3): 361-5, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9180309

RESUMO

We made a clinical study of polyethylene wear in 240 hips of 187 patients having primary total hip arthroplasties from 1989 to 1990, using uncemented Osteonics components, with a head size of 26 mm. We excluded cups with anteversion of over 20 degrees and measured linear wear by a new method using a digitiser and special software of our design. Follow-up was from two to five years (mean 4.3). The mean age at operation was 50.3 years, with more men than women (1.4:1). The mean linear wear per year was 0.15 mm; this did not increase with the longevity of the prosthesis (p = 0.54). In 59 hips showing evidence of osteolysis, the mean linear wear rate was significantly higher at 0.23 mm/year (p <0.001). The mean linear wear rate also correlated significantly with age at the time of operation (p = 0.008), but we found no significant correlations with body-weight, gender, aetiology of the disease, thickness of polyethylene, or cup position. Our new method of measurement is time-saving and reproducible. The results confirm the greater rate of linear wear of polyethylene in patients showing osteolysis and in those who are younger.


Assuntos
Materiais Biocompatíveis , Prótese de Quadril , Polietilenos , Falha de Prótese , Adulto , Idoso , Cimentos Ósseos , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteólise/diagnóstico por imagem , Desenho de Prótese/estatística & dados numéricos , Radiografia , Reprodutibilidade dos Testes , Fatores de Tempo
19.
J Orthop Trauma ; 7(5): 468-72, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8229384

RESUMO

Thirty-eight segmental tibial shaft fractures were treated with closed Grosse-Kempf interlocking nails and retrospectively followed up for > or = 1 year (average 32 months). There was a 97% union rate and a 4.5 +/- 1.6 month union period. Knee as well as ankle range of motion was satisfactory. Significant complications included one aseptic nonunion (3%), which healed after the static locked nail was dynamized. We recommend that whenever possible, closed interlocking nailing should be used to treat closed or mild open (wound size < 1 cm) segmental tibial shaft fractures.


Assuntos
Fixação Intramedular de Fraturas/métodos , Fraturas Expostas/cirurgia , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
20.
J Orthop Trauma ; 10(1): 45-9, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8926554

RESUMO

Seventeen distal tibial nonunions were treated by a combination of metal removal with closed intramedullary reaming for internal bone graft and application of a long leg cast for aseptic nonunions and an external fixator for quiescent septic nonunions. The nonunions were present for a median of 1.8 years (range, 1.2-3.4 years). All achieved a solid union with a union period of 5.2 +/- 1.6 months. There was one complication of a renewed infection in a septic nonunion. The functional rating score improved from all unsatisfactory before treatment to 13 satisfactory after treatment. The other four (all were infected nonunions) also improved from poor to a fair outcome. In conclusion, the technique described is a simple and effective method to treat some complex distal tibial nonunions.


Assuntos
Transplante Ósseo/métodos , Moldes Cirúrgicos , Fixadores Externos , Fixação Intramedular de Fraturas/métodos , Consolidação da Fratura , Fraturas não Consolidadas/cirurgia , Fraturas da Tíbia/cirurgia , Adulto , Feminino , Seguimentos , Fraturas não Consolidadas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Fraturas da Tíbia/diagnóstico por imagem , Resultado do Tratamento
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