Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
2.
BMC Public Health ; 21(1): 307, 2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549071

RESUMO

BACKGROUND: Polytobacco product use is increasingly popular, but little is known about the prevalence, trend, and factors of such use particularly in non-western countries. METHOD: A representative sample of 1139 current cigarette smokers aged 15+ (84.1% male) were telephone interviewed in Tobacco Control Policy-related Surveys in 2015-2017. Information collected included poly-tobacco use (PTU), smoking and socio-demographic characteristics. Associations of current PTU with related factors were analyzed using logistic regression with adjustment for confounders. Prevalence was weighted by age and sex of current cigarette users in the general population. RESULTS: Eighty-four point one percent (95% CI 81.4-86.6%) were exclusive cigarette smokers. Fifteen point nine percent (13.4-18.6%) were current polytobacco product users, 12.3% (10.2-14.8%) used one tobacco product and 2.52% (1.59-3.97%) used two tobacco products in addition to cigarette. Cigarette use with cigar was more common (6.28%, 4.75-8.27%), and the least used product with cigarette was e-cigarette (1.05%, 0.44-2.50%). The changes in overall prevalence of PTU by number of products use varied in 3 years. Current PTU was associated with being male (AOR 2.01, 95% CI 1.12-3.61), younger age (AORs range from 1.34-4.65, P for trend < .001) and less ready to quit (2.08, 1.09-3.97). CONCLUSIONS: Prevalence of PTU increased slowly by year, one tobacco product use with cigarette was more common. The most used tobacco product with cigarette was cigar. Being male, younger and less ready to quit were associated with current PTU.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adolescente , China/epidemiologia , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Fumantes , Uso de Tabaco/epidemiologia
3.
Br J Anaesth ; 118(3): 391-399, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28186224

RESUMO

Numerous risk prediction models are available for predicting delirium after cardiac surgery, but few have been directly compared with one another or been validated in an independent data set. We conducted a systematic review to identify validated risk prediction models of delirium (using the Confusion Assessment Method-Intensive Care Unit tool) after cardiac surgery and assessed the transportability of the risk prediction models on a prospective cohort of 600 consecutive patients undergoing cardiac surgery at a university hospital in Hong Kong from July 2013 to July 2015. The discrimination (c-statistic), calibration (GiViTI calibration belt), and clinical usefulness (decision curve analysis) of the risk prediction models were examined in a stepwise manner. Three published high-quality intensive care unit delirium risk prediction models (n=5939) were identified: Katznelson, the original PRE-DELIRIC, and the international recalibrated PRE-DELIRIC model. Delirium occurred in 83 patients (13.8%, 95% CI: 11.2-16.9%). After updating the intercept and regression coefficients in the Katznelson model, there was fair discrimination (0.62, 95% CI: 0.58-0.66) and good calibration. As the original PRE-DELIRIC model was already validated externally and recalibrated in six countries, we performed a logistic calibration on the recalibrated model and found acceptable discrimination (0.75, 95% CI: 0.72-0.79) and good calibration. Decision curve analysis demonstrated that the recalibrated PRE-DELIRIC risk model was marginally more clinically useful than the Katznelson model. Current models predict delirium risk in the intensive care unit after cardiac surgery with only fair to moderate accuracy and are insufficient for routine clinical use.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Técnicas de Apoio para a Decisão , Delírio/diagnóstico , Unidades de Terapia Intensiva , APACHE , Delírio/prevenção & controle , Hong Kong , Humanos , Tempo de Internação , Reprodutibilidade dos Testes , Fatores de Risco
4.
Hong Kong Med J ; 17(1): 61-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21282828

RESUMO

This is a retrospective review of the clinico-radiological features and neurological outcomes of reversible posterior leukoencephalopathy syndrome episodes in Chinese cancer children receiving chemotherapy in a regional hospital in Hong Kong from 1998 to 2008. Five children (3 males and 2 females) with a mean age of 7 years were identified, four of whom had acute lymphoblastic leukaemia and one had a central nervous system germ cell tumour. Presenting symptoms included seizures (100%), altered mental function (100%), headache (40%), and visual disturbance (60%). The mean systolic blood pressure at presentation was 158 mm Hg. Approximately 80% had typical radiological features of reversible posterior leukoencephalopathy syndrome. All showed complete recovery after the acute stage, but one subsequently developed epilepsy. Two patients ultimately died of refractory malignant disease. Two others were followed up for a mean of 6 years, and remained neurologically normal. This report was the first case review documenting reversible posterior leukoencephalopathy syndrome in Chinese cancer children. The clinico-radiological features and neurological outcomes were similar to those reported in western series. Early recognition of the syndrome is important to facilitate appropriate treatment. The central nervous system damage may not be reversible and thus long-term follow-up is warranted.


Assuntos
Antineoplásicos/efeitos adversos , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/patologia , Radiografia , Estudos Retrospectivos
5.
Eur J Paediatr Dent ; 9(3): 149-52, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18844445

RESUMO

AIM: Kabuki make-up Syndrome is so named because of the characteristic facies of the affected patient. The face is similar to a Kabuki actor's mask. The main aim of this report was to describe the oral features in Kabuki Syndrome, focusing on the tooth anomalies. PATIENTS AND METHODS: Five subjects with Kabuki Syndrome, identified by the Child Neuropsychiatric Clinic of the University of Sassari, Italy, were enrolled. Their medical records were reviewed and oral and dental examinations were completed. The diagnosis was based upon the typical pattern of malformations and dysmorphic features reviewed by Matsumoto and Niikawa. RESULTS: All patients showed typical characteristics of the Syndrome such as a long palpebral fissure, lower palpebral eversion, arched eyebrows, short nasal septum, prominent and large ears, fingertip pads, mental retardation, and paramedian elevation of the lower lip. CONCLUSION: Kabuki make-up Syndrome is of unknown origin but a genetic aetiopathogenesis has been proposed. It is extremely rare; in Japan, where it is most frequent, it affects 1:32000 newborns. The typical facies of the syndrome, combined with general medical and dental examinations, are very important for diagnosis confirmation.


Assuntos
Face/anormalidades , Anormalidades Dentárias/patologia , Anormalidades Múltiplas , Adolescente , Adulto , Anodontia/patologia , Criança , Hipoplasia do Esmalte Dentário/patologia , Fácies , Feminino , Humanos , Masculino , Má Oclusão/patologia , Retrognatismo/patologia , Síndrome
6.
AJNR Am J Neuroradiol ; 29(10): 1995-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18653682

RESUMO

Radiation-induced peripheral nerve tumor, in particular a benign entity such as a neurofibroma, is rare, with only a few cases being reported so far. We demonstrate a case of radiation-induced neurofibromata along the left cervical nerve roots in a man with a background of localized targeted hypofractionated radiation therapy as adjuvant treatment for left cervical nodal metastasis complicating nasopharyngeal carcinoma. The toxicity of high-dose radiation in a hypofractionated regime is also stressed.


Assuntos
Imageamento por Ressonância Magnética , Neurofibroma/diagnóstico , Neurofibroma/etiologia , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Neoplasias do Sistema Nervoso Periférico/etiologia , Radioterapia Conformacional/efeitos adversos , Raízes Nervosas Espinhais/patologia , Adulto , Fracionamento da Dose de Radiação , Humanos , Masculino
7.
AJNR Am J Neuroradiol ; 28(1): 135-7, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17213441

RESUMO

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with a variable natural history and biologic behavior, ranging from completely benign to malignant with fatal outcome. We report a case of benign IMT in the left nasal cavity with radiologic features mimicking angiofibroma. We also demonstrate the hypervascular nature of this disease on angiography and the contribution of preoperative embolization in assisting surgical excision and minimizing the potential uncontrolled intraoperative bleeding.


Assuntos
Angiografia , Cavidade Nasal , Neoplasias de Tecido Muscular/diagnóstico , Neoplasias Nasais/diagnóstico , Adolescente , Terapia Combinada , Diagnóstico Diferencial , Embolização Terapêutica , Feminino , Humanos , Inflamação/patologia , Artéria Maxilar/diagnóstico por imagem , Cavidade Nasal/irrigação sanguínea , Cavidade Nasal/patologia , Cavidade Nasal/cirurgia , Terapia Neoadjuvante , Neoplasias de Tecido Muscular/irrigação sanguínea , Neoplasias de Tecido Muscular/patologia , Neoplasias de Tecido Muscular/cirurgia , Neoplasias Nasais/irrigação sanguínea , Neoplasias Nasais/patologia , Neoplasias Nasais/cirurgia
8.
Minerva Stomatol ; 53(10): 571-9, 2004 Oct.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-15531872

RESUMO

AIM: The study evaluates the repair of residual alveolar cleft through secondary bone graft, consisting in the transplantation of autologous bone to restore the continuity of the maxillary arch and achieve normal functioning and esthetics. METHODS: During 2001-2002, 15 patients (age range 9-26 years; 7 males, 8 females) were submitted to secondary bone graft at the Maxillo-facial Surgery Operative Unit, University Hospital, Sassari. Eleven patients had complete unilateral cleft, 4 had complete bilateral cleft. All patients were operated upon by the same surgeon; they received a graft of autologous bone from the iliac crest. For preoperative and postoperative evaluation at 1 year, the following were utilised: plaster casts of the tooth arches, OPT, photographs and complete clinical documentation. RESULTS: Postoperative results were: 100% formation of a bone bridge between the maxillary segments; 70% closure of oro-nasal fistula; 100% maxillary stability; 80% spontaneous eruption of the canine within the graft; 70% height of alveolar ridge level I, 25% level II, 5% level III; 70% orthodontic closure; 80% optimal periodontal condition and 20% presence of gingival recession. In 1 subject the graft site became infected, in 4 cases an oro-nasal fistula remained. CONCLUSION: This method was found to be the most valid one at present. The best period to intervene is during late childhood (9 years). Results and functional and esthetic recovery were satisfactory and encouraging to continue utilising this technique.


Assuntos
Alveoloplastia , Transplante Ósseo , Fissura Palatina/cirurgia , Adolescente , Adulto , Transplante Ósseo/métodos , Criança , Feminino , Humanos , Masculino
9.
Br J Cancer ; 89(8): 1428-32, 2003 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-14562012

RESUMO

The incidence of gastric cancer (GC) increases significantly after the fifth decade and palliative chemotherapy is the ultimate treatment in the majority of patients. We investigated safety and efficacy of a weekly regimen with cisplatin, fluorouracil and leucovorin as first-line chemotherapy for elderly patients with advanced GC. Chemotherapy-naive patients older than 65 years were considered eligible for study entry. Frail elderly patients were identified and excluded according to the following criteria: age >85 years, dependence in one or more activities of daily living (activities of daily living and instrumental activities of daily living scales), three or more comorbid conditions, one or more geriatric syndromes. Chemotherapy consisted of 1-day per week administration of intravenous cisplatin 35 mg m(-2), 6S-stereoisomer leucovorin 250 mg m(-2) and fluorouracil 500 mg m(-2) (PLF). Patients were re-evaluated after eight weekly cycles and six additional weekly administrations were planned for patients without disease progression. A 5-day subcutaneous filgrastim (5 mug Kg(-1) day(-1), days +1-+5) was used after the first treatment delay for neutropenia and maintained thereafter. In the whole group, the best intention-to-treat overall response rate was 43% (95% CI: 30-56%). The time to disease progression and the median survival time were 5.3 and 8.6 months, respectively. Fatigue was the commonest nonhaematologic toxicity (71% of the patients). Filgrastim was used in 30 patients who showed grade II (20 patients) or grade III (10 patients) neutropenia. Neither grade IV toxicity nor toxic deaths were observed. The weekly PLF regimen resulted safe and effective in elderly patients with advanced GC. This outpatient regimen is based on old and low-cost drugs and it may represent an alternative to new and more expensive combinations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Cisplatino/administração & dosagem , Controle de Custos , Progressão da Doença , Esquema de Medicação , Custos de Medicamentos , Feminino , Filgrastim , Fluoruracila/administração & dosagem , Fluoruracila/química , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Leucovorina/química , Masculino , Proteínas Recombinantes , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento
10.
Br J Cancer ; 86(12): 1854-7, 2002 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-12085175

RESUMO

Ifosfamide and cisplatin cause urinary loss of carnitine, which is a fundamental molecule for energy production in mammalian cells. We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients. Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry. Patients were excluded if they had anaemia or other conditions thought to be causing asthenia. Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire. Treatment consisted of oral levocarnitine 4 g daily, for 7 days. Fifty patients were enrolled; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients. In the whole group, baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 (+/-6.4; standard deviation) and the mean plasma carnitine value was 20.9 microM (+/-6.8; standard deviation). After 1 week, fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 (+/-5.4; standard deviation) (P<.001). All patients achieved normal plasma carnitine levels. Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy. In selected patients, levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue. This compound deserves further investigations in a randomised, placebo-controlled study.


Assuntos
Acetilcarnitina/uso terapêutico , Antineoplásicos/efeitos adversos , Fadiga/terapia , Neoplasias/tratamento farmacológico , Nootrópicos/uso terapêutico , Idoso , Carnitina/sangue , Carnitina/urina , Cisplatino/efeitos adversos , Fadiga/induzido quimicamente , Fadiga/metabolismo , Feminino , Humanos , Ifosfamida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/metabolismo , Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
11.
Virus Res ; 75(2): 179-87, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11325472

RESUMO

The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is an RNA-dependent RNA polymerase (RdRp) which plays an essential role in viral RNA replication. Antibodies that specifically recognize NS5B will have utilities in monitoring NS5B production and subcellular localization, as well as in structure-function studies. In this report, three mouse monoclonal antibodies (mAbs), 16A9C9, 16D9A4 and 20A12C7, against a recombinant NS5B protein (genotype 1a, H-77 strain) were produced. These mAbs specifically recognize HCV NS5B, but not RdRps of polivirus (PV), bovine viral diarrhea virus (BVDV) or GB virus B (GBV-B). The mAbs can readily detect NS5B in cellular lysates of human osteosarcoma Saos2 cells constitutively expressing the nonstructural region of HCV (NS3-NS4A-NS4B-NS5A-NS5B). NS5B proteins of different HCV genotypes/subtypes (1a, 1b, 2a, 2c, 5a) showed varied affinity for these mAbs. Interestingly, the epitopes for the mAbs were mapped to the palm subdomain (amino acid 188-370) of the HCV RdRp as determined by immunoblotting analysis of a panel of HCV/GBV-B chimeric NS5B proteins. The binding site was mapped between amino acid 231 and 267 of NS5B for 16A9C9, and between 282 and 372 for 16D9A4 and 20A12C7. Furthermore, these mAbs showed no inhibitory effect on the NS5B polymerase activity in vitro.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/metabolismo , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/química , Anticorpos Anti-Hepatite C/metabolismo , RNA Polimerase Dependente de RNA/imunologia , Proteínas não Estruturais Virais/imunologia , Genoma Viral , Hepacivirus/enzimologia , Humanos , Estrutura Terciária de Proteína , RNA Polimerase Dependente de RNA/metabolismo , Células Tumorais Cultivadas , Proteínas não Estruturais Virais/metabolismo
12.
Cancer ; 91(1): 106-12, 2001 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11148566

RESUMO

BACKGROUND: Increased expression of the proto-oncogene c-myc is a common phenomenon in hepatocellular carcinoma (HCC). The proto-oncogenes c-fos and c-jun are involved in cell cycle progression and cellular proliferation. METHODS: The objective of this study was to elucidate the mechanism of hepatocarcinogenesis with regard to the expressions of c-myc, c-fos, and c-jun. One hundred fifty biopsied HCC specimens were stained immunohistochemically for the above phenotypic markers both in tumor tissue and in adjacent nontumor tissue. RESULTS: Although the expression of c-myc was high (74%) in tumor tissue, it was significantly less compared with the expression in nontumor tissue (100%; P = 0.0002). The expression of c-myc was inversely proportional to the grade of differentiation in tumor tissue (P = 0.0108; correlation coefficient [r] = -0.244); that is, tissue with poorer histologic differentiation had a lower level of c-myc expression. There were inverse associations between the expression of c-myc and the expression of mutated p53 (P = 0.0017; r = -0.285) as well as the expression of Ki67 (P = 0.057; r = -0.147). There was significantly high expression of c-fos in tumor tissue compared with the expression in nontumor tissue (91% vs. 0%; P < 0.0001). Both the tumor tissue and the nontumor tissue had high levels of expression of c-jun (96.53% and 100%, respectively). There was a trend toward a positive association between the expression of c-fos and the expression of c-jun in tumor tissue (P = 0.07; r = 0.162). CONCLUSIONS: Because c-myc is a known inducer of wild type p53, decreased c-myc expression may lead to uncontrolled cell growth because of the lack of p53 expression that normally induces apoptosis. The coordinated expression of c-fos and c-jun in HCC may reflect the coordinated tumor cell cycle of progression and proliferation; however, future studies are required to elucidate this possibility.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Genes fos/genética , Genes jun/genética , Genes myc/genética , Neoplasias Hepáticas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biópsia , Carcinoma Hepatocelular/fisiopatologia , Ciclo Celular , Transformação Celular Neoplásica , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Proto-Oncogene Mas
13.
Ann Oncol ; 11(10): 1263-6, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11106114

RESUMO

BACKGROUND: Docetaxel has shown some activity in advanced gastric cancer. Recent phase I studies found low hematologic toxicity and a favourable toxicity profile when docetaxel was administered on a weekly schedule. In this study, we explored the activity of weekly docetaxel in patients with advanced gastric cancer who failed first-line chemotherapy. MATERIALS AND METHODS: Patients with stable or progressing disease after first-line chemotherapy received 36 mg/m2 weekly docetaxel. One cycle consisted of six administrations followed by a two-weeks rest, patients were re-evaluated at week eight. The optimal two-stage design was adopted for early stopping of the trial if responses were one or less in 21 patients (< 20% response rate with alpha and beta error probabilities 0.05 and 0.010 respectively). RESULTS: Twenty-one patients have been enrolled and they are fully evaluable for response and toxicity. One patient achieved partial response, 8 patients had stable disease and 12 patients progressed. Median overall survival from the onset of salvage chemotherapy was 3.5 months. Hematologic toxicity was observed in two patients who experienced grade III leukopenia. Beginning from the third week of treatment, most of the patients (90%) showed grade II asthenia which resulted the commonest side-effect. CONCLUSIONS: This schedule of weekly docetaxel did not show significant activity in pretreated patients with advanced gastric cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Paclitaxel/análogos & derivados , Neoplasias Gástricas/tratamento farmacológico , Taxoides , Idoso , Docetaxel , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Terapia de Salvação
14.
J Virol ; 74(14): 6339-47, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10864644

RESUMO

Unique to pestiviruses, the N-terminal protein encoded by the bovine viral diarrhea virus (BVDV) genome is a cysteine protease (Npro) responsible for a self-cleavage that releases the N terminus of the core protein (C). This unique protease is dispensable for viral replication, and its coding region can be replaced by a ubiquitin gene directly fused in frame to the core. To develop an antiviral assay that allows the assessment of anti-hepatitis C virus (HCV) NS3 protease inhibitors, a chimeric BVDV in which the coding region of Npro was replaced by that of an NS4A cofactor-tethered HCV NS3 protease domain was generated. This cofactor-tethered HCV protease domain was linked in frame to the core protein of BVDV through an HCV NS5A-NS5B junction site and mimicked the proteolytic function of Npro in the release of BVDV core for capsid assembly. A similar chimeric construct was built with an inactive HCV NS3 protease to serve as a control. Genomic RNA transcripts derived from both chimeric clones, P(H/B) (wild-type HCV NS3 protease) and P(H/B(S139A)) (mutant HCV NS3 protease) were then transfected into bovine cells (MDBK). Only the RNA transcripts from the P(H/B) clone yielded viable viruses, whereas the mutant clone, P(H/B(S139A)), failed to produce any signs of infection, suggesting that the unprocessed fusion protein rendered the BVDV core protein defective in capsid assembly. Like the wild-type BVDV (NADL), the chimeric virus was cytopathic and formed plaques on the cell monolayer. Sequence and biochemical analyses confirmed the identity of the chimeric virus and further revealed variant viruses due to growth adaptation. Growth analysis revealed comparable replication kinetics between the wild-type and the chimeric BVDVs. Finally, to assess the genetic stability of the chimeric virus, an Npro-null BVDV (BVDV-Npro in which the entire Npro coding region was deleted) was produced. Although cytopathic, BVDV-Npro was highly defective in viral replication and growth, a finding consistent with the observed stability of the chimeric virus after serial passages.


Assuntos
Cisteína Endopeptidases/genética , Vírus da Diarreia Viral Bovina/genética , Proteínas não Estruturais Virais/genética , Sequência de Aminoácidos , Animais , Northern Blotting , Western Blotting , Linhagem Celular , Efeito Citopatogênico Viral , Vírus da Diarreia Viral Bovina/metabolismo , Vírus da Diarreia Viral Bovina/patogenicidade , Vírus da Diarreia Viral Bovina/fisiologia , Dados de Sequência Molecular , RNA Viral/análise , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas não Estruturais Virais/metabolismo , Ensaio de Placa Viral , Montagem de Vírus
16.
Mol Cell Biol ; 19(12): 8169-79, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10567542

RESUMO

The Grb2 and Shc adapter proteins play critical roles in coupling activated growth factor receptors to several cellular signaling pathways. To assess the role of these molecules in mammary epithelial development and tumorigenesis, we have generated transgenic mice which individually express the Grb2 and Shc proteins in the mammary epithelium. Although mammary epithelial cell-specific expression of Grb2 or Shc accelerated ductal morphogenesis, mammary tumors were rarely observed in these strains. To explore the potential role of these adapter proteins in mammary tumorigenesis, mice coexpressing either Shc or Grb2 and a mutant form of polyomavirus middle T (PyV mT) antigen in the mammary epithelium were generated. Coexpression of either Shc or Grb2 with the mutant PyV mT antigen resulted in a dramatic acceleration of mammary tumorigenesis compared to parental mutant PyV mT strain. The increased rate of tumor formation observed in these mice was correlated with activation of the epidermal growth factor receptor family and mitogen-activated protein kinase pathway. These observations suggest that elevated levels of the Grb2 or Shc adapter protein can accelerate mammary tumor progression by sensitizing the mammary epithelial cell to growth factor receptor signaling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular , Antígenos Transformantes de Poliomavirus/fisiologia , Neoplasias Mamárias Experimentais/patologia , Proteínas/fisiologia , Animais , Antígenos Transformantes de Poliomavirus/genética , Feminino , Proteína Adaptadora GRB2 , Expressão Gênica , Vetores Genéticos , Humanos , Vírus do Tumor Mamário do Camundongo , Camundongos , Camundongos Transgênicos , Morfogênese , Biossíntese de Proteínas , Proteínas/genética , Coelhos , Proteínas Adaptadoras da Sinalização Shc , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src
17.
Liver ; 19(5): 444-51, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10533805

RESUMO

AIM/BACKGROUND: Hepatocellular carcinoma (HCC) is known for its rapid growth. This study was undertaken to determine the expression of proliferative markers, apoptosis (DNA fragmentation) and oncogene products known to regulate apoptosis (p53, bcl-2) in HCC. METHODS: 150 Chinese patients with HCC were studied (M:F 128:22, age 14-88 years). Immunohistochemistry was employed to detect cell proliferative markers (PCNA, Ki67), and oncogene products known to regulate apoptosis (p53, bcl-2). DNA fragmentation was determined by terminal dUTP nick end labeling (TUNEL). RESULTS: 98% and 95% of HCC had PCNA (median 2+) and Ki67 (median 2+) detected respectively. TUNEL labeling was detected in only a small number of tumor cells (no labeling in 11%, median 1/1000 cell labeled, range: 0-70/1000 cells). There was no correlation between TUNEL labeling and the clinical parameters (sex, age, cirrhosis, and survival) and the expression of cell proliferative markers. p53 was detected in 53% of the patients (median 1+, range: 0-4+) and bcl-2 was detected in a small proportion of tumor cells in only 13% of the HCCs (range: 0-1 +). The expression of p53 and Bcl-2 did not correlate with TUNEL labeling or the natural survival. CONCLUSIONS: Cell proliferation in HCC is unmatched by apoptosis, accounting for the rapid growth of this tumor. This lack of apoptosis in HCC is unrelated to the expression of p53 or bcl-2 over-expression.


Assuntos
Carcinoma Hepatocelular/patologia , Fragmentação do DNA , Neoplasias Hepáticas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Divisão Celular , DNA de Neoplasias/análise , Feminino , Humanos , Técnicas Imunoenzimáticas , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo
18.
Otolaryngol Head Neck Surg ; 117(4): 349-54, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9339795

RESUMO

Acoustic rhinometry (AR) evaluates the geometry of the nasal cavity with acoustic reflections and provides information about nasal cross-sectional areas (CSA) and nasal volume within a given distance. The accuracy of the information obtained by AR was compared with that of magnetic resonance imaging (MRI) of the nasal cavity. Five healthy subjects were evaluated with AR and the MRI before and after the application of a long-acting nasal decongestant spray, to eliminate possible interference of the nasal cycle with both measurement techniques. The MRI images of 2 mm coronal sections of the nasal cavity were traced by three independent observers and the CSAs were calculated by computer-aided imaging digitization, to be compared with the calculated CSAs obtained with the AR at the corresponding distance from the nasal tip. Digitized data from the MRI images were also used to calculate the nasal volume within the first 6 cm from the nasal tip and compared with the AR volume measurements. The interobserver variation of digitized MRI data predecongestant and postdecongestant was not significant. The correlations of CSA and volume measurements between the AR and MRI were high (0.969) after the application of the decongestant. The correlation between the AR and MRI measurements before the decongestant was low (0.345). This may have been the result of interference of the nasal cycle during the long MRI measurements (1 hour) or other unknown factors. We conclude that AR measurements of nasal CSAs and volumes provide accurate information when compared with the MRI of the decongested nasal airway.


Assuntos
Acústica , Cefalometria/instrumentação , Imageamento por Ressonância Magnética , Cavidade Nasal/anatomia & histologia , Feminino , Humanos , Masculino , Análise de Regressão , Acústica da Fala
19.
Proc Natl Acad Sci U S A ; 93(3): 963-8, 1996 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-8577769

RESUMO

The Shc adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules--an N-terminal Tyr(P) binding (PTB) domain and a C-terminal Src homology 2 (SH2) domain. We have compared the ability of the Shc PTB domain to bind the receptors for nerve growth factor and insulin, both of which contain juxtamembrane Asn-Pro-Xaa-Tyr(P) motifs implicated in PTB binding. The Shc PTB domain binds with high affinity to a phosphopeptide corresponding to the nerve growth factor receptor Tyr-490 autophosphorylation site. Analysis of individual residues within this motif indicates that the Asn at position -3 [with respect to Tyr(P)], in addition to Tyr(P), is critical for PTB binding, while the Pro at position -2 plays a less significant role. A hydrophobic amino acid 5 residues N-terminal to the Tyr(P) is also essential for high-affinity binding. In contrast, the Shc PTB domain does not bind stably to the Asn-Pro-Xaa-Tyr(P) site at Tyr-960 in the activated insulin receptor, which has a polar residue (Ser) at position -5. Substitution of this Ser at position -5 with Ile markedly increased binding of the insulin receptor Tyr-960 phosphopeptide to the PTB domain. These results suggest that while the Shc PTB domain recognizes a core sequence of Asn-Pro-Xaa-Tyr(P), its binding affinity is modulated by more N-terminal residues in the ligand, which therefore contribute to the specificity of PTB-receptor interactions. An analysis of residues in the Shc PTB domain required for binding to Tyr(P) sites identified a specific and evolutionarily conserved Arg (Arg-175) that is uniquely important for ligand binding and is potentially involved in Tyr(P) recognition.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular , Fosfotirosina , Proteínas/química , Proteínas/metabolismo , Células 3T3 , Sequência de Aminoácidos , Animais , Antígenos Transformantes de Poliomavirus/química , Antígenos Transformantes de Poliomavirus/metabolismo , Sítios de Ligação , Células CHO , Cricetinae , Ligantes , Camundongos , Modelos Estruturais , Dados de Sequência Molecular , Fosfopeptídeos/química , Fosforilação , Biossíntese de Proteínas , Receptor de Insulina/biossíntese , Receptor de Insulina/química , Receptor de Insulina/metabolismo , Receptores de Fator de Crescimento Neural/química , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Adaptadoras da Sinalização Shc , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Transfecção
20.
Otolaryngol Head Neck Surg ; 112(6): 665-9, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7777349

RESUMO

Improved technology in in vitro tests for allergen-specific immunoglobulin E has led to increased efficiency and faster turnaround times. ImmunoCAP (Pharmacia Diagnostics, Clayton, N.C.) is an in vitro-specific immunoglobulin E test that uses a three-dimensional cellulose solid allergen phase, which allows quick results in 6 hours. In comparison, modified Phadezym-RAST (Pharmacia Diagnostics) uses a two-dimensional solid phase, and results take 3 days to obtain. This study compares the sensitivity and specificity of CAP with that of modified RAST in the detection of specific immunoglobulin E, and it assesses the correlation of the individual class scores of CAP and modified RAST with end points obtained from skin-dilutional end-point titration. The reproducibility of CAP was also assessed. Patients evaluated at the University of Chicago Allergy Clinic who had a history and physical examination consistent with immunoglobulin E-mediated allergy and in whom skin testing was clinically indicated as part of their allergy management, were asked to donate some blood for simultaneous in vitro testing by PhadezymRAST and ImmunoCAP. Testing was performed in batches. Random samples from the CAP batches were chosen for duplicate runs under conditions blinded to the technician. Receiver operating curve analysis was used for comparison of the sensitivity and specificity of RAST vs. that of CAP. We used Pearson product-moment correlation coefficients to compare the correlation of RAST and CAP classes with the end points from skin testing. Our results indicate that the sensitivity and specificity of RAST and CAP are similar, that the classes of these two tests correlate well with the end points from skin testing, and that duplicate samples of CAP also correlate well.


Assuntos
Hipersensibilidade/diagnóstico , Imunoglobulina E/análise , Testes Intradérmicos , Teste de Radioalergoadsorção , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA