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1.
Endoscopy ; 45(3): 195-201, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23299524

RESUMO

BACKGROUND AND STUDY AIMS: The aim of the current study was to assess the detection rate of the right adrenal gland and the diagnostic ability of endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) for the diagnosis of adrenal metastasis in potentially resectable lung cancer. PATIENTS AND METHODS: This retrospective cohort study included a consecutive series of 150 patients undergoing EUS/EUS - FNA for staging of lung cancer. The detection rate of the right adrenal gland by EUS and the diagnostic accuracies of computed tomography (CT), positron emission tomography-CT (PET-CT), and EUS/EUS - FNA for the diagnosis of adrenal metastasis were evaluated. RESULTS: The right adrenal gland was visualized by EUS in 131 patients (87.3 %); the left adrenal gland was visualized in all patients. Findings suggestive of metastasis in either one of the adrenal glands or in both were observed in 6 patients (4.0 %) by CT, in 5 patients (3.3 %) by PET-CT, and in 11 patients (7.3 %) by EUS. EUS - FNA was performed simultaneously in the 11 patients, and in 4 patients the diagnosis of metastasis was established. The accuracy for the diagnosis of adrenal metastasis was 100 % for EUS/EUS - FNA, 96.0 % for CT, and 97.0 % for PET-CT (P = 0.1146). CONCLUSIONS: As well as the left adrenal gland, the right adrenal gland was also usually visible by EUS. EUS/EUS - FNA provided an accurate diagnosis of adrenal metastasis, although the prevalence of adrenal metastasis was relatively low in these patients with potentially resectable lung cancer.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma/secundário , Neoplasias das Glândulas Suprarrenais/secundário , Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Endossonografia , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Cuidados Pré-Operatórios , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/secundário , Tomografia Computadorizada por Raios X
2.
Endoscopy ; 43(12): 1070-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21971925

RESUMO

BACKGROUND AND STUDY AIMS: Recent studies have evaluated the efficacy of peroral cholangioscopy (POCS) for diagnosis of biliary diseases. In order to obtain clear images with POCS, saline irrigation, which is performed to replace yellow bile, is carried out for an extended duration. The aim of this study was to evaluate the feasibility of replacing saline irrigation with CO2 insufflation during POCS. PATIENTS AND METHODS: A total of 36 patients who had bile duct lesions and were due to undergo POCS were enrolled in the study. Of these patients, 18 underwent POCS using saline irrigation followed by CO2 insufflation, and 18 patients underwent the reverse approach. The two methods were compared with regard to the time required to obtain a clear endoscopic image and the quality of the images. RESULTS: The median time required to obtain a clear endoscopic image using CO2 insufflation (5.0 min) was significantly shorter than that required for saline irrigation (22.5 min; P < 0.001). The quality of the endoscopic images obtained was similar in 27 cases. However, CO2 insufflation provided better images in four cases that showed an abundance of mucin or biliary sludge, and saline irrigation was superior to CO2 insufflation in five cases that showed severe stricture with bleeding and tall papillary lesions. CONCLUSIONS: CO2 insufflation during POCS can reduce procedure time and simplify cholangioscopy. The overall image quality was similar to that obtained with conventional saline irrigation.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Ductos Biliares , Dióxido de Carbono/administração & dosagem , Endoscopia do Sistema Digestório , Cloreto de Sódio/administração & dosagem , Gravação em Vídeo , Idoso , Feminino , Humanos , Insuflação , Masculino , Pessoa de Meia-Idade , Irrigação Terapêutica
3.
Endoscopy ; 43(12): 1082-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21971924

RESUMO

BACKGROUND: Recently, transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been evaluated for mediastinal nodal staging (N staging) of lung cancer, as this technique is less invasive than mediastinoscopy and possibly more accurate than 18F-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). However, EUS-FNA does not provide access to pretracheal and hilar lymph nodes. More recently, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been introduced as a novel technique for accessing pretracheal and hilar lymph nodes. Although the combined endoscopic approach of EUS-FNA and EBUS-TBNA is presumably more accurate than PET-CT, only a few reports have quantitatively evaluated its diagnostic ability. Therefore, we prospectively assessed the diagnostic yield of this combined endoscopic approach for mediastinal N staging of lung cancer. METHODS: A consecutive series of 120 patients with suspected resectable lung cancer on CT findings underwent PET-CT and combined EUS-FNA/EBUS-TBNA. The accuracy and other diagnostic indices of the combined approach in mediastinal N staging were compared with those of PET-CT. RESULTS: Among the enrolled patients, a final pathological N stage was established in 110 patients. The accuracy of the combined approach using EUS-FNA and EBUS-TBNA was significantly higher than that of PET-CT (90.0 % vs. 73.6 %; P < 0.0001). The sensitivity, specificity, and positive and negative predictive values were respectively 71.8 %, 100 %, 100 %, and 86.6 % for the combined approach vs. 47.4 %, 87.5 %, 66.7 %, and 75.9 % for PET-CT. CONCLUSIONS: The combined endoscopic approach using EUS-FNA and EBUS-TBNA provided excellent diagnostic performance. Therefore, this approach is strongly recommended before surgery or mediastinoscopy to avoid futile thoracotomy and surgical intervention.


Assuntos
Biópsia por Agulha Fina , Broncoscopia , Endossonografia , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática , Masculino , Mediastino , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
4.
Endoscopy ; 42(6): 441-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20432207

RESUMO

BACKGROUND AND STUDY AIMS: A small amount of free air, visible on CT but not on plain chest radiography, which appeared following endoscopic submucosal dissection (ESD) of a gastric neoplasm without endoscopically visible perforation, was defined as a "transmural air leak", and a prospective, consecutive entry study was performed to determine its incidence and clinical significance. PATIENTS AND METHODS: Between January 2006 and September 2008, ESD was performed for 246 gastric lesions in 246 consecutive patients. Abdominal CT scan was performed 1 day after ESD. In addition, chest radiography and blood biochemistry tests were performed at different time points before and after ESD. RESULTS: Two hundred and nineteen lesions (89 %) were curatively removed by ESD. Among the total of 246 patients, we encountered endoscopically visible perforation during ESD in 2 patients (0.8 %), and clinically suspected perforation diagnosed by the presence of free air on chest radiography but invisible during ESD in 3 patients (1 %), while transmural air leak was observed in another 33 (13 %). Air leak occurred in cases where resection size was larger, procedure time longer, and the muscularis propria on the ulcer base was exposed at the end of ESD. Patients with air leaks developed pyrexia at a higher rate than those without (36 % vs. 16 %, P = 0.018). These patients recovered with antibiotics and required no endoscopic or surgical intervention. The presence of an air leak did not affect the duration of hospital stay. CONCLUSIONS: A transmural air leak was observed in 13 % of the patients undergoing ESD. Larger resection size, prolonged procedure time, and exposure of the muscularis propria on the ulcer base were risk factors for transmural air leak, but the outcome of patients with this complication was good.


Assuntos
Adenocarcinoma/cirurgia , Adenoma/cirurgia , Gastroscopia/efeitos adversos , Neoplasias Gástricas/cirurgia , Estômago/lesões , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Ar , Dissecação/efeitos adversos , Feminino , Mucosa Gástrica/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos
5.
Endoscopy ; 41(2): 179-82, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19214901

RESUMO

Splenic tumors are occasionally found in clinical practice but the diagnosis is often difficult if only serologic and imaging tests are used. Therefore, pathologic sampling is required in such cases. Endoscopic ultrasonography (EUS) provides a good image of the spleen through the gastric wall, and a transgastric EUS-guided fine needle aspiration (EUS-FNA) biopsy may be easier than the percutaneous approach. Furthermore, a large-gauge needle may raise the capability of EUS-FNA for the histopathologic diagnosis. The aim of this study was to evaluate the yield of EUS-FNA using a large-gauge needle for a splenic tumor. Five patients with splenic tumor were subjected to EUS-FNA with a 19-gauge needle to obtain histopathologic materials. A pathologic sample was obtained in all cases, and the diagnoses were lymphoma (n = 2), sarcoidosis (n = 2), and inflammatory pseudotumor (n = 1). EUS-FNA using a 19-gauge needle is safe and useful for the diagnosis of splenic tumors.


Assuntos
Biópsia por Agulha Fina/métodos , Endossonografia , Granuloma de Células Plasmáticas/patologia , Linfoma/patologia , Sarcoidose/patologia , Esplenopatias/patologia , Idoso , Feminino , Seguimentos , Granuloma de Células Plasmáticas/diagnóstico por imagem , Humanos , Linfoma/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Agulhas , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Sarcoidose/diagnóstico por imagem , Esplenopatias/diagnóstico por imagem
6.
Endoscopy ; 40(5): 400-5, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18494134

RESUMO

BACKGROUND AND STUDY AIM: Sarcoidosis is a systemic disorder of unknown cause that is characterized by a pathological hallmark, noncaseating granuloma. Bilateral hilar lymphadenopathy (BHL) is a major clinical feature, but it is sometimes difficult to exclude other diseases, especially in cases where there are no pulmonary abnormalities (stage I). Bronchoscopic transbronchial biopsy is currently a popular method by which to obtain pathological material, but its diagnostic power is insignificant. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), also attempted recently, makes the sampling of pathological material easier and better, but the diagnoses are still based on cytological findings. Our study aimed to evaluate the yield of transesophageal EUS-FNA for histological confirmation of stage I sarcoidosis. METHODS: The study was a prospective comparative study to investigate the diagnostic sensitivities of FNA cytology and FNA histology. Subjects were consecutive patients with BHL without lung lesions on chest radiographs or chest CT who were referred to our hospitals between December 2003 and April 2006. Transesophageal EUS-FNA was performed with 19-gauge needles instead of the conventional 22-gauge needles. RESULTS: Forty-one patients were included in this study, and both histological and cytological materials were obtained successfully by EUS-FNA in all patients. Histopathological examination of the FNA sample showed noncaseating granuloma in 34 (94.4%) of the 36 patients with a final diagnosis of sarcoidosis. In contrast, only 28 of the 36 (77.8%) were diagnosed as having sarcoidosis on the basis of cytological findings. The difference was statistically significant (P = 0.0444). CONCLUSION: FNA histology is better suited than FNA cytology to establishing the diagnosis of stage I sarcoidosis, and EUS-FNA with a 19-gauge needle plays a important role in this process.


Assuntos
Biópsia por Agulha Fina/métodos , Endossonografia , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Cirurgia Assistida por Computador , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/instrumentação , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agulhas , Valor Preditivo dos Testes , Índice de Gravidade de Doença
7.
Sci Total Environ ; 403(1-3): 230-4, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18593638

RESUMO

Pb-LIII edge XANES spectra of atmospheric particles are directly obtained by fluorescent XAFS spectroscopy using a 19-element solid state detector (SSD). Particulate sample was collected on a quartz fiber filter using a high-volume air sampler, and the filter was cut into small pieces (25x25 mm). Then, surface layer of the filter piece was scaled and accumulated in order to enhance the particle density per filter unit. Use of 10 pieces of the surface layer enables the measurement of Pb-LIII edge XANES spectra on beamline BL01B1 at SPring-8, Hyogo, Japan. The shape of the Pb-LIII edge XANES spectra of the particulate sample is similar to the shapes of the spectra for PbS, PbCO(3), PbSO(4) and/or PbCl(2). Additionally, the filter sample is also divided into water-soluble, 0.1 M HCl-extractable, and residual fractions of Pb compounds by a simple acid extraction procedure. We discuss the possibility of Pb speciation in the particulate samples with combination of highly sensitive XANES spectroscopy and simple acid extraction.


Assuntos
Monitoramento Ambiental/métodos , Chumbo/química , Material Particulado/química , Espectrometria por Raios X/métodos , Cidades , Ácido Clorídrico/química , Chumbo/análise , Material Particulado/análise , Água/química
8.
J Natl Cancer Inst ; 73(6): 1389-93, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6439933

RESUMO

Studies were conducted for investigation of the inhibitory effect on the development of experimental tumors of the skin and liver with vitamin A-like compounds, with a particular focus on a new synthetic derivative of the polyprenoic acid 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166). Incidence of skin papilloma, chemically induced in mice, was significantly influenced by dietary vitamin A contents. When given orally at a dose of 200 mg/kg body weight, beta-carotene regressed the skin papilloma to some extent (-16% at 14 days), although its effect was much weaker than that of E-5166 (-43%). E-5166 also significantly reduced tumor incidences of experimental hepatomas induced by chemical carcinogen in rats as well as in "spontaneous" hepatoma-bearing mice (C3H/HeNCrj) genetically determined. Further chemical studies revealed that retinol was locally deficient in the hepatomas but not in adjacent normal livers: In particular, anhydroretinol was newly detected in the tumors of spontaneous hepatoma-bearing mice, suggesting increased conversion of retinol into the inactive metabolite. Moreover, cellular retinoid-binding protein, F-type (an oncofetal protein), also newly appeared exclusively in the hepatoma tissues, suggesting that the preventive effect of E-5166 on hepatocarcinogenesis was mediated, at least in part, through its binding with the new retinoid receptor.


Assuntos
Antineoplásicos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Papiloma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Vitamina A/análogos & derivados , Vitamina A/uso terapêutico , 9,10-Dimetil-1,2-benzantraceno , Animais , Dieta , Relação Dose-Resposta a Droga , Feminino , Metildimetilaminoazobenzeno , Camundongos , Camundongos Endogâmicos , Relação Estrutura-Atividade
9.
Cancer Res ; 61(20): 7675-82, 2001 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11606411

RESUMO

Retinoids induce apoptosis and differentiation of hepatocellular carcinoma (HCC) cells and are used clinically in the chemoprevention of HCC. We have shown previously that hepatocarcinogenesis is accompanied by accumulation of full-length retinoid X receptor alpha (RXRalpha), although the underlying mechanisms and biological implications have remained unclear. The present studies were based on the finding that the accumulated full-length RXRalpha was phosphorylated at serine/threonine residues both in all human HCC tissues examined and in human HCC-derived HuH7 cells. Phosphorylation at serine 260 of RXRalpha, a consensus site of mitogen-activated protein kinase, was closely linked to its retarded degradation, low transactivating activity, and the promotion of cancer cell growth. There was no genomic mutation in the RXRalpha gene, and abrogation of phosphorylation by mitogen-activated protein kinase-specific inhibitors restored the degradation of RXRalpha in an RXR ligand-dependent manner. These results suggest that phosphorylation of RXRalpha may interfere with its metabolism and signaling in human HCC, which could lead to growth promotion of these tumors.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Receptores do Ácido Retinoico/metabolismo , Fatores de Transcrição/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Divisão Celular/fisiologia , Humanos , Ligantes , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutagênese Sítio-Dirigida , Fosforilação , Receptores do Ácido Retinoico/antagonistas & inibidores , Receptores do Ácido Retinoico/genética , Receptores X de Retinoides , Serina/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Ativação Transcricional/fisiologia , Transfecção
10.
Biochim Biophys Acta ; 923(1): 116-24, 1987 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-2432942

RESUMO

Cellular retinoic acid-binding protein (CRABP) has been purified to homogeneity from human placenta by a series of procedures, including acetone powder extraction, gel filtration on Sephadex G-50, and ion-exchange chromatography on DEAE-cellulose and on SP-Sephadex. Cellular retinol-binding protein (CRBP) was isolated concurrently. CRABP was purified 75,400-fold, based on total soluble acetone powder extract of placenta. The protein is a single polypeptide chain with a molecular mass of 14,600 Da, estimated by sodium dodecyl sulfate (SDS) gel electrophoresis or gel filtration, and has an isoelectric point of 4.78 (apo-CRABP, 4.82). On analysis of absorption and fluorescence spectra, the protein was seen to exhibit an absorption peak at 350 nm, fluorescence excitation maxima at 350 and 370 nm, and a fluorescence emission maximum at 475 nm. Human CRABP was immunologically distinct from human CRBP and serum retinol-binding protein.


Assuntos
Proteínas de Transporte/isolamento & purificação , Placenta/análise , Proteínas de Transporte/imunologia , Cromatografia em Gel , Cromatografia por Troca Iônica , Eletroforese em Gel de Poliacrilamida , Epitopos/imunologia , Feminino , Humanos , Ponto Isoelétrico , Peso Molecular , Gravidez , Receptores do Ácido Retinoico , Espectrometria de Fluorescência , Espectrofotometria
11.
Circulation ; 99(24): 3110-7, 1999 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-10377073

RESUMO

BACKGROUND: Oxidized LDL (Ox-LDL) seems to play key roles in atherogenesis. Lectinlike Ox-LDL receptor-1 (LOX-1) is a recently identified cell-surface receptor for Ox-LDL. The relationship of this novel receptor for Ox-LDL to atherogenesis, however, has not yet been clarified. In this study, we explored the expression of LOX-1 in the atherosclerotic lesions of human carotid arteries. METHODS AND RESULTS: Using carotid endarterectomy specimens obtained from 21 patients and 2 samples of normal human aortas, we examined LOX-1 expression by reverse transcription-polymerase chain reaction and immunohistochemistry. In aortas without atherosclerosis, LOX-1 expression was undetectable by immunohistochemistry and negligible by reverse transcription-polymerase chain reaction. In carotid arteries, luminal endothelial cells covering early atherosclerotic lesions were more frequently positive for LOX-1 expression than those in advanced atherosclerotic lesions. Endothelial cells in the intimal neovasculature of advanced lesions also expressed LOX-1. In addition, macrophages and smooth muscle cells in the intima of advanced atherosclerotic plaques were positive for LOX-1 expression. CONCLUSIONS: LOX-1 may play important roles in Ox-LDL uptake and subsequent functional alteration in the luminal endothelium in early atherosclerotic lesions and in intimal neovascular endothelial cells in advanced plaques. Furthermore, LOX-1 may also be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages and smooth muscle cells in the atherosclerotic intima.


Assuntos
Arteriosclerose/metabolismo , Arteriosclerose/patologia , Receptores de LDL/genética , Idoso , Animais , Anticorpos Monoclonais , Antígenos CD/análise , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Diferenciação Mielomonocítica/imunologia , Células CHO , Artérias Carótidas/química , Artérias Carótidas/patologia , Cricetinae , Endotélio Vascular/química , Endotélio Vascular/metabolismo , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Regulação da Expressão Gênica/fisiologia , Humanos , Lectinas , Macrófagos/química , Macrófagos/fisiologia , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/química , Músculo Liso Vascular/metabolismo , Neovascularização Fisiológica/fisiologia , RNA Mensageiro/análise , Receptores de LDL/análise , Receptores de LDL/imunologia , Receptores de LDL Oxidado , Receptores Depuradores Classe E , Transfecção , Túnica Íntima/química , Túnica Íntima/patologia
12.
Clin Cancer Res ; 3(5): 727-31, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9815742

RESUMO

A goal of cancer chemoprevention is the deletion of latent premalignant or malignant clones before they expand to a clinically detectable tumor. However, such clonal deletion has not been demonstrated in clinical studies. We have evaluated serum levels of lectin-reactive alpha-fetoprotein (AFP-L3), which suggests the presence of latent hepatoma cells, in a randomized controlled trial that used acyclic retinoid to prevent second primary hepatomas in patients who had received treatments that cured initial hepatomas. The trial involved 21 patients in each acyclic retinoid (600 mg daily) and placebo group and consisted of a 12-month period of drug administration and a subsequent follow-up period. Serum AFP-L3 was determined at entry and at the end of the 12-month treatment period using lectin-affinity electrophoresis and antibody-affinity blotting. Although neither treatment affected serum levels of total AFP, acyclic retinoid significantly reduced AFP-L3 levels after a 12-month administration (P < 0.01). Acyclic retinoid not only deleted AFP-L3 from patients who had been positive for AFP-L3 at entry but also prevented the appearance of AFP-L3 in patients who had been negative at entry (P < 0.01). In contrast, placebo significantly raised the incidence of AFP-L3-positive patients after a 12-month administration from that at entry (P < 0.05). Patients positive for AFP-L3 after a 12-month treatment had a significantly higher risk of second primary hepatomas in the subsequent follow-up period (P = 0.03). Acyclic retinoid may have deleted a clone of latent hepatoma cells producing AFP-L3 and thereby inhibited second primary hepatomas. Serum AFP-L3 may be a useful intermediate biomarker in the chemoprevention of second primary hepatomas by acyclic retinoid.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Segunda Neoplasia Primária/prevenção & controle , Tretinoína/análogos & derivados , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lectinas , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/sangue , Placebos , Fatores de Tempo , Tretinoína/uso terapêutico
13.
FEBS Lett ; 411(1): 102-6, 1997 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-9247151

RESUMO

We studied the mechanism by which 9,13-di-cis-retinoic acid (9,13dcRA), a novel and endogenous stereoisomer of all-trans-RA, induces TGF-beta formation in a human liver stellate cell line, LI90. 9,13dcRA induced the expression of RAR alpha and RARbeta, enhanced the production of tissue-type plasminogen activator (tPA), thereby, surface plasmin levels, and induced the activation of latent TGF-beta. Similar effects were obtained with RAR alpha-selective retinoid, but not with RARbeta- or RARgamma-selective retinoid, and the induction was inhibited by RAR alpha-selective antagonist. These results suggest that 9,13dcRA up-regulates tPA expression, resulting in the formation of TGF-beta by LI90 cells, at least in part, via induction and activation of RAR alpha.


Assuntos
Fígado/metabolismo , Receptores do Ácido Retinoico/metabolismo , Ativador de Plasminogênio Tecidual/biossíntese , Fator de Crescimento Transformador beta/metabolismo , Tretinoína/análogos & derivados , Animais , Linhagem Celular , Células Cultivadas , Humanos , Fígado/citologia , Fígado/efeitos dos fármacos , RNA Mensageiro , Ratos , Receptores do Ácido Retinoico/agonistas , Receptores do Ácido Retinoico/antagonistas & inibidores , Receptores do Ácido Retinoico/biossíntese , Receptores do Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico , Fator de Crescimento Transformador beta/genética , Tretinoína/farmacologia
14.
FEBS Lett ; 440(1-2): 29-32, 1998 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-9862418

RESUMO

Uptake of oxidized low density lipoprotein (Ox-LDL) and subsequent foam cell transformation have been implicated in early atherogenesis. Although multiple molecules, including class A and B scavenger receptors, have been identified as Ox-LDL receptors, additional receptors may also be involved in this process. Here, we provide evidence that lectin-like Ox-LDL receptor-1 (LOX-1), a novel Ox-LDL receptor initially identified in vascular endothelial cells, is also expressed in macrophages in humans and mice. Expression of LOX-1 can be induced after macrophage-like differentiation in vitro in human peripheral blood monocytes and the related cell line THP-1 cells. Furthermore, LOX-1 expression can also be detected in resident peritoneal macrophages, and can be upregulated by an inflammatory cytokine TNF-alpha. These results suggest that LOX-1 in macrophages may play an important role in Ox-LDL uptake and subsequent foam cell formation in this cell type.


Assuntos
Macrófagos/metabolismo , Receptores de LDL/biossíntese , Fator de Necrose Tumoral alfa/farmacologia , Animais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Northern Blotting , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Imuno-Histoquímica , Lectinas , Leucócitos Mononucleares , Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais , Camundongos , Monócitos , Receptores de LDL/genética , Receptores de LDL Oxidado , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptores Depuradores Classe E , Acetato de Tetradecanoilforbol/farmacologia , Regulação para Cima
15.
FEBS Lett ; 457(2): 241-5, 1999 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-10471787

RESUMO

Lysophosphatidylcholine (lyso-PC), a polar phospholipid increased in atherogenic lipoproteins and atherosclerotic lesions, has been shown to induce transcription of a variety of endothelial genes relevant to atherogenesis. Lyso-PC has been shown to activate c-jun N-terminal kinase (JNK) and activator protein 1 (AP-1) and thereby stimulate transcription of the c-jun gene. Here we provide evidence that lyso-PC can phosphorylate cyclic AMP responsive element binding protein (CREB) and thereby activate the jun2 12-O-tetradecanoylphorbol 13-acetate response element (jun2TRE) site of the c-jun promoter, which appears to be the major molecular mechanism involved in lyso-PC-induced c-jun gene expression in cultured bovine aortic endothelial cells (BAEC). Transient transfection of BAEC with a 1.6-kbp c-jun promoter and luciferase reporter fusion gene resulted in a 12.9-fold increase in luciferase activity by lyso-PC treatment. Serial deletion mutation in c-jun promoter and luciferase reporter gene assay revealed that the 5' promoter region between nucleotide numbers -268 and -127, which contains a jun2TRE binding sequence, was most crucial for lyso-PC-induced transcription. The 5' promoter region between -76 and -27, which contains an AP-1 site, also affected lyso-PC-induced transcription of the c-jun gene. Point mutation in the jun2TRE site reduced lyso-PC-induced transcription of the c-jun promoter-luciferase fusion gene by a 70.3% decrease in c-jun promoter activity. Electrophoretic mobility shift assays showed increased binding of (32)P-labeled oligonucleotides with jun2TRE in nuclear extracts isolated from lyso-PC-treated BAEC, which was abolished or supershifted by anti-CREB antibody. Immunoblotting with anti-phosphorylated CREB antibody showed rapid phosphorylation of this protein after lyso-PC treatment. These results indicate that lyso-PC phosphorylates CREB, which was then bound to the jun2TRE site of the c-jun promoter and activated transcription. Activation of jun2TRE may play a key role in the transcriptional activation of c-jun as well as other endothelial genes depending upon these transcription factors.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Genes jun , Lisofosfatidilcolinas/metabolismo , Regiões Promotoras Genéticas , Animais , Bovinos , Núcleo Celular/metabolismo , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Lisofosfatidilcolinas/farmacologia , Fosforilação , Transcrição Gênica/efeitos dos fármacos
16.
Am J Clin Nutr ; 62(6 Suppl): 1535S-1540S, 1995 12.
Artigo em Inglês | MEDLINE | ID: mdl-7495256

RESUMO

We used newly established cervical dysplasia-derived cell lines to elucidate a molecular mechanism of the preventive action of beta-carotene in cervical multi-step carcinogenesis. Liposomal beta-carotene was added to the culture medium for human cervical dysplasia cell lines, CICCN-2 from cervical intraepithelial neoplasia grade I (CIN I), CICCN-3 from CIN II, and CICCN-4 from CIN III, and human cervical carcinoma-derived cell lines such as CICCN-6, CICCN-18, and HeLa cells. beta-Carotene (10 mumol/L) induced significant growth retardation in three cervical dysplasia cell lines but not in three cervical carcinoma-derived cell lines. Binding activities of epidermal growth factor (EGF) and cellular amounts of either messenger RNA for EGF receptor gene or EGF receptor protein were all highest in CICCN-4 cells. Cell surface binding, as well as internalization, of 125I-labeled EGF was rapidly reduced after beta-carotene treatment in dysplasia cell lines and 170-kD protein bands of EGF receptor disappeared from protein immunoblots at day 3 of the treatment. Cellular amounts of EGF receptor messenger RNA remained constant until day 3 of the treatment and were substantially reduced after day 7. Chromatin condensations, morphologic evidence for apoptotic cell death, were observed at day 1 by staining. From these results, we contend that prevention of cervical carcinogenesis by beta-carotene is due to induction of apoptosis in cervical dysplastic cells, which are premalignant cells in cervical multi-step carcinogenesis, via down-regulation of EGF receptor protein.


Assuntos
Anticarcinógenos/farmacologia , Antioxidantes/farmacologia , Carotenoides/farmacologia , Receptores ErbB/efeitos dos fármacos , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Apoptose/efeitos dos fármacos , Regulação para Baixo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/análise , Receptores ErbB/genética , Feminino , Humanos , RNA Mensageiro/análise , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia , beta Caroteno , Displasia do Colo do Útero/patologia
17.
J Nucl Med ; 36(4): 690-6, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7699466

RESUMO

UNLABELLED: To better understand cortical perfusion, we developed a method for a three-dimensional display technique with 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT. METHODS: Twelve patients with higher cortical dysfunction due to Alzheimer's disease and 18 age-matched controls were examined. Data acquisition was performed after intravenous injection of 740 MBq of 99mTc-HMPAO. After reconstructing the transaxial images, the three-dimensional images were obtained by modified volume rendering, where the surfaces were displayed in the corresponding colors as the maximum cortical value within a depth of 2 cm. RESULTS: In the control studies, almost all surface cortices were over 60% of the maximum cerebellar value. In Alzheimer's disease patients, areas of perfusion below 60% were detected in the temporo-parietal lesions and frontal lobe lesions in 6 of 12. These findings correlated with the neurological dysfunction. CONCLUSION: This method provides realistic three-dimensional information about surface cortical perfusion, which was found to be useful in clinical investigations of higher cortical dysfunction due to degenerative or cerebrovascular diseases.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio , Oximas , Tecnécio Tc 99m Exametazima
18.
J Nucl Med ; 36(12): 2180-5, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8523101

RESUMO

UNLABELLED: This study was designed to visualize the motor function area related to finger movements in normal human brain using super-early (first 640 sec of acquisition) [123l]iodoamphetamine ([123I]IMP) SPECT. METHODS: Seven healthy male volunteers performed paired, isolated baseline and task sessions. The task was a right thumb-to-fingers opposition task, which was loaded for the initial 11 min of the session. A high-performance, four-head SPECT camera was used. At each session, administration of 222 MBq [123I]IMP was followed by 16 serial 160-sec dynamic SPECT acquisitions. To obtain matched brain anatomical images, MRI was also performed using the same slice formation as in the SPECT study. After image reconstruction, ROIs were set on bilateral sensorimotor hand areas (SMHA), the supplementary motor area (SMA), the frontal, temporal and occipital lobes and the cerebellar hemispheres. The percent increase of ROI activity (%INC) in the task session compared with that in the baseline session was calculated in each ROI after normalization to the global brain radioactivity. RESULTS: There was significant activation of the left SMHA by the task, the amplitude of which was maximal in the initial phase of dynamic images (the super-early phase). This area was located in the left peri-central area identified on the analogous slice in the MR image. The left SMHA showed gradual and statistically significant decrease of %INC during the three phases. CONCLUSION: Super-early [123I]IMP may be used to identify the primary motor cortex and to evaluate its function in some pathological conditions.


Assuntos
Anfetaminas , Radioisótopos do Iodo , Córtex Motor/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Dedos/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Iofetamina , Imageamento por Ressonância Magnética , Masculino , Atividade Motora/fisiologia , Córtex Motor/anatomia & histologia , Córtex Motor/fisiologia , Fatores de Tempo
19.
J Nucl Med ; 35(7): 1226-33, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8014687

RESUMO

UNLABELLED: At least two quantitative rCBF measurements are needed to evaluate rCBF changes with pharmacological intervention. We have developed the split dose 123I-IMP SPECT method, which enables measurement of rCBF to be repeated in a short time. METHODS: Thirty-one cerebrovascular disease patients were investigated to assess reproducibility and vasoreactivity to acetazolamide. During 44-min dynamic SPECT imaging, 123I-IMP injection and respective arterial sampling were performed twice at an interval of about 25 min. The rCBF values were calculated using a microsphere model in which the washout of 123I-IMP from the brain can be negligible in the first several minutes after injection. For the second rCBF measurement, the remaining activity due to the first 123I-IMP injection was estimated and subtracted from the total brain activity. RESULTS: In ten patients, two consecutive resting mean rCBF values in the MCA territory (CBF1 and CBF2) had good correlation (CBF1 = 47.4 +/- 4.0 (ml/min/100 ml: mean +/- s.d.), CBF2 = 45.2 +/- 8.2, CBF2 = 0.900*CBF1 + 2.9, r = 0.915). In 11 patients with occlusive lesions in the unilateral ICA system, mean rCBF in the MCA territory was increased by only 27.7% +/- 14.0% in the affected side by a 1-g intravenous acetazolamide injection, while 44.5% +/- 12.3% increase was found in the nonaffected side. In 10 patients without a major arterial lesion, a 49.7% +/- 17.0% increase of rCBF was demonstrated. CONCLUSIONS: This split dose method 123I-IMP SPECT can be useful to estimate vascular reserve.


Assuntos
Acetazolamida/farmacologia , Anfetaminas , Isquemia Encefálica/diagnóstico por imagem , Circulação Cerebrovascular , Radioisótopos do Iodo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Feminino , Humanos , Iofetamina , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
20.
J Nucl Med ; 38(7): 1109-11, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9225799

RESUMO

UNLABELLED: Regional distributions of 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) and 99mTc-ethyl cysteinate dimer (99mTc-ECD) were compared in the normal brain. METHODS: Six paid, healthy volunteers (mean age 26 yr) had high-resolution neuroperfusion SPECT using both 99mTc-HMPAO and 99mTc-ECD on separate days. RESULTS: Regional distribution of the two tracers differed. Technetium-99m-HMPAO accumulated more in the thalamus, frontal lobe, temporal lobe and cerebellum than 99mTc-ECD, which accumulated more in the occipital and parietal lobes. There was a considerable difference in the accumulation of the two tracers in the medial temporal lobe. The percent accumulations of 99mTc-HMPAO and 99mTc-ECD in the medial temporal lobe compared with the mean global cerebral cortical accumulation were 93.9% +/- 2.4% and 83.1% +/- 4.1% (mean +/- s.d.), respectively. CONCLUSION: The results suggest that 99mTc-HMPAO and 99mTc-ECD require specific and separate criteria for diagnosing temporal lobe pathologies, such as dementia and temporal lobe epilepsy.


Assuntos
Cisteína/análogos & derivados , Compostos de Organotecnécio , Oximas , Compostos Radiofarmacêuticos , Lobo Temporal/diagnóstico por imagem , Adulto , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Tecnécio Tc 99m Exametazima , Tálamo/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único
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