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1.
Leukemia ; 29(3): 576-85, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25234168

RESUMO

In leukemogenesis, Notch signaling can be up and downregulated in a context-dependent manner. The transcription factor hairy and enhancer of split-1 (Hes1) is well-characterized as a downstream target of Notch signaling. Hes1 encodes a basic helix-loop-helix-type protein, and represses target gene expression. Here, we report that deletion of the Hes1 gene in mice promotes acute myeloid leukemia (AML) development induced by the MLL-AF9 fusion protein. We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity. FLT3 was consequently upregulated in MLL-AF9-expressing immortalized and leukemia cells with a Hes1- or RBPJ-null background. MLL-AF9-expressing Hes1-null AML cells showed enhanced proliferation and ERK phosphorylation following FLT3 ligand stimulation. FLT3 inhibition efficiently abrogated proliferation of MLL-AF9-induced Hes1-null AML cells. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. We also accessed two independent databases containing messenger RNA (mRNA) expression profiles and found that the expression level of FLT3 mRNA was negatively correlated with those of HES1 in patient AML samples. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development, probably by downregulating FLT3 expression.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Regulação Leucêmica da Expressão Gênica , Proteínas de Homeodomínio/genética , Leucemia Mieloide Aguda/genética , Tirosina Quinase 3 Semelhante a fms/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Proliferação de Células , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/deficiência , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Transgênicos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Transdução de Sinais , Análise de Sobrevida , Fatores de Transcrição HES-1 , Tirosina Quinase 3 Semelhante a fms/metabolismo
2.
Blood Cancer J ; 4: e264, 2014 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-25501021

RESUMO

TET2 (Ten Eleven Translocation 2) is a dioxygenase that converts methylcytosine (mC) to hydroxymethylcytosine (hmC). TET2 loss-of-function mutations are highly frequent in subtypes of T-cell lymphoma that harbor follicular helper T (Tfh)-cell-like features, such as angioimmunoblastic T-cell lymphoma (30-83%) or peripheral T-cell lymphoma, not otherwise specified (10-49%), as well as myeloid malignancies. Here, we show that middle-aged Tet2 knockdown (Tet2(gt/gt)) mice exhibit Tfh-like cell overproduction in the spleen compared with control mice. The Tet2 knockdown mice eventually develop T-cell lymphoma with Tfh-like features after a long latency (median 67 weeks). Transcriptome analysis revealed that these lymphoma cells had Tfh-like gene expression patterns when compared with splenic CD4-positive cells of wild-type mice. The lymphoma cells showed lower hmC densities around the transcription start site (TSS) and higher mC densities at the regions of the TSS, gene body and CpG islands. These epigenetic changes, seen in Tet2 insufficiency-triggered lymphoma, possibly contributed to predated outgrowth of Tfh-like cells and subsequent lymphomagenesis. The mouse model described here suggests that TET2 mutations play a major role in the development of T-cell lymphoma with Tfh-like features in humans.


Assuntos
Transformação Celular Neoplásica/metabolismo , Proteínas de Ligação a DNA/biossíntese , Linfoma Folicular/metabolismo , Linfoma de Células T/metabolismo , Neoplasias Experimentais/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Proteínas de Ligação a DNA/genética , Dioxigenases , Técnicas de Silenciamento de Genes , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma de Células T/genética , Linfoma de Células T/patologia , Camundongos , Camundongos Transgênicos , Mutação , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Proteínas Proto-Oncogênicas/genética , Linfócitos T Auxiliares-Indutores/patologia
3.
Rev Sci Instrum ; 85(2): 02A912, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24593491

RESUMO

Two methods for the feed of vapor from solid materials in the Center for Nuclear Study ECR ion source are described. A rod placed near the wall of the plasma chamber, operating up to a melting point of 2600 °C, has been used for CaO, SiO2, and FeO. An oven with a number of openings, operating up to 800 °C, has been used for P2O5, Li, and S. Typical ion beam intensities of (7)Li(2+), (6)Li(3+), (40)Ca(12+), and (56)Fe(15+) are achieved 280, 75, 28, and 7 eµA, respectively. High intensity heavy ion beams are stably supplied into the azimuthally varying field cyclotron.

4.
J Viral Hepat ; 14(1): 48-54, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17212644

RESUMO

We sought to clarify the incidence and role of Helicobacter pylori (H. pylori) seropositivity in patients with hepatitis C virus (HCV) infection and the effect of coinfection on interferon-alpha and ribavirin therapy. The presence of H. pylori was tested using a commercially available enzyme immunoassay in serum samples from 93 patients with chronic hepatitis C. Clinical features, HCV markers and response of HCV to interferon-alpha and ribavirin were compared between H. pylori-positive and H. pylori-negative patients. Anti-H. pylori antibody was detected in 45 (48%) of the 93 patients, whose median HCV-RNA level (495 vs 760 kIU/mL; P = 0.013) and platelet count (128 vs 158 x 10(3)/microL; P = 0.009) were significantly lower than in patients with HCV infection alone. Anti-H. pylori antibody levels were found to be significantly correlated with fibrosis score (P = 0.0083, r = 0.33) but inversely related to platelet count (P = 0.0037, r = -0.34). The sustained response rate for HCV clearance following interferon-alpha and ribavirin treatment did not differ between patients with and without anti-H. pylori seropositivity. The presence of H. pylori [odds ratio (OR) 8.61; 95% confidence interval (CI) 1.59-46.70] and fibrosis score (OR 30.13; 95% CI 5.44-166.78) were found by multivariate analysis to be associated with the decrease of platelet count during therapy. Coexistent H. pylori infection does not demonstrably influence the clinical course of chronic hepatitis C. A possible connection between H. pylori coinfection and thrombocytopenia was found during the treatment course, suggesting that preemptive eradication of H. pylori may facilitate completion of treatment and increased sustained virological response.


Assuntos
Antivirais/uso terapêutico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/virologia , Helicobacter pylori/crescimento & desenvolvimento , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/microbiologia , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/microbiologia , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , RNA Viral/sangue , Proteínas Recombinantes , Resultado do Tratamento
5.
Chemosphere ; 45(2): 129-36, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11572604

RESUMO

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) formation by the thermal reactions of phenols with CuCl2 under oxygen flux were carried out in relation to their formation mechanisms. To evaluate the effect of photocatalytic degradation of titanium dioxide (TiO2) thin film prepared by the sol-gel method, the photocatalysis of PCDD/DFs in acetonitrile/water solution by batch-recycle system was conducted. For the thermal reaction system of powder mixtures of 2,4,5-trichlorophenol (2,4,5-TCP) and CuCl2, the formation rates were 8.1 microg/g-2,4,5-TCP/min for total PCDD/DFs and 6.9 microg/g-2,4,5-TCP/min for PCDDs, and total PCDD/DF rate was higher by approximately 40 fold compared to phenol vapor/oxygen/CuCl2 powder system. For the system of 2,4,5-TCP, PCDDs were mainly formed via ortho-phenoxyphenols (POP) intermediate by the condensation of 2,4,5-trichlorophenate. For PCDD/DF photocatalytic degradations, most PCDD congeners photodecomposed rapidly and the rates presented more than 70% (as dechlorination rates of 76% for PCDDs) at 24 h after irradiation, using PCDD/DFs formed with 2,4,5-TCP. The rate constants were in the order of 4.8-6.1 x 10(-3) min(-1), assuming the pseudo-first-order reactions for their low levels.


Assuntos
Benzofuranos/química , Corantes/química , Fenóis/química , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/química , Poluentes do Solo/análise , Poluentes Atmosféricos , Catálise , Incineração , Fotoquímica , Dibenzodioxinas Policloradas/análise , Eliminação de Resíduos , Temperatura , Titânio/química
6.
Chemosphere ; 45(2): 145-50, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11572606

RESUMO

Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/DF) levels in plywood combustion gas were investigated for the effects of ammonium chloride (NH4Cl) and paint. For combustion systems in which neither NH4Cl nor paint were present in the plywood samples, total amounts of PCDD/DFs in the combustion gas were in the order of 35-529 ng/Nm3, and were higher in the systems with softwood trees than broadleaf ones, depending on the Cl concentrations. For the systems with added NH4Cl and no paint, and those without NH4Cl but were painted, higher PCDD/ DF rates were observed at combustion temperatures of 270 degrees C and 500 degrees C, respectively. However, for the systems with both NH4Cl and paint, their amounts in the range of 0.6-13 ng/Nm3 were the lowest in all systems. The PCDD/DF abundance profiles were similar to their patterns in pentachlorophenol (PCP). Furthermore, it was found that the 2,3,7,8-chlorine substituted penta- and hexa-CDDs contributed more than other 2,3,7,8-chlorine substitutes to toxicity equivalency (TEQ).


Assuntos
Poluentes Atmosféricos/análise , Cloreto de Amônio/química , Benzofuranos/análise , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/análise , Poluentes do Solo/análise , Incineração , Pintura , Eliminação de Resíduos , Madeira
7.
Nihon Igaku Hoshasen Gakkai Zasshi ; 61(6): 303-9, 2001 May.
Artigo em Japonês | MEDLINE | ID: mdl-11431936

RESUMO

In a report of a nationwide survey on radiographic conditions of chest radiography in Japan, it was pointed out that the average entrance surface dose (ESD) of the computed radiography (CR) system was higher than that of the film-screen system. It seemed important that an objective index and criteria be established for dose reduction without a loss of image quality that would interfere with diagnostic observation. For this purpose, we investigated the properties of root of mean square (RMS) granularity, since it is a dominant factor in CR image quality and strongly depends on dose. The results indicated that RMS granularity showed little dependence on tube voltage when relative exposure was kept constant and that it decreased with the increment of exposure and approached a finite minimum value in a very high exposure region. For the most frequently used radiographic conditions in Japan (120 kV, 2.5 mmAl, 200 cm SID, 10: 1 grid), the decrement in RMS granularity from 6 to 16 mAs was 0.0276 to 0.0253 (9.1%). This finding suggested that exposure exceeding 6 mAs did not improve image quality, i.e., exposure reduction down to 6 mAs would not cause a significant loss of image quality. It was therefore concluded that RMS granularity was a useful objective index by which to determine the upper limit of exposure. Use of the most frequent conditions with 6 mAs seemed to be recommendable as an initial condition for the technical optimization of CR chest radiography, since ESD under this condition was 0.265 mGy, which was approximately equal to the value of the ESD distribution of a total chest radiogram in Japan.


Assuntos
Processamento de Imagem Assistida por Computador/normas , Intensificação de Imagem Radiográfica , Radiografia Torácica/normas , Adulto , Radiação de Fundo , Humanos , Imagens de Fantasmas , Doses de Radiação , Radiografia Torácica/métodos
8.
Dig Dis Sci ; 46(2): 338-44, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11281183

RESUMO

We previously reported that the gastric mucosa emits fluorescence of porphyrins at the onset of gastric lesions induced by hemorrhagic shock. In this study, we investigated whether the fluorescent substance concerns with the gastric mucosal injuries induced by diflofenac, a nonsteroidal antiinflammatory drug (NSAID). In the gastric mucosa treated with diclofenac, lesions were generated and myeloperoxidase activity increased. Diclofenac administration also increased thiobarbituric acid-reactive substances, a index of tissue peroxidation. After diclofenac treatment, the gastric mucosal fluorescence intensities rose. HPLC analysis demonstrated that the fluorescent substances were mesoporphyrin and protoporphyrin, which were the same as found in hemorrhagic shock. Pretreatment of the tissue with radical scavenging substances, catalase and troxipide, restrained the increase of mucosal fluorescence intensity, tissue peroxidation, and lesion formation. These findings indicate that diclofenac treatment induced the generation of porphyrins as well as tissue peroxidation in gastric mucosal tissue. This study suggests that autofluorescence observation is a useful tool to identify diclofenac-induced gastric injury.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Diclofenaco/efeitos adversos , Modelos Animais de Doenças , Fluorescência , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/patologia , Porfirinas/análise , Animais , Antiulcerosos/farmacologia , Catalase/farmacologia , Cromatografia Líquida de Alta Pressão , Sequestradores de Radicais Livres/farmacologia , Mucosa Gástrica/metabolismo , Gastrite/metabolismo , Gastrite/prevenção & controle , Peroxidação de Lipídeos , Masculino , Piperidinas/farmacologia , Porfirinas/química , Ratos , Ratos Wistar , Espectrometria de Fluorescência
9.
Am Heart J ; 141(4): 645-52, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11275933

RESUMO

BACKGROUND: Patients with heart failure show signs of cardiac sympathetic dysfunction such as elevation of blood norepinephrine (NE) level, as a result of reduction in the number of sympathetic nerves, decrease in myocardial NE content, accelerated NE turnover or spillover of NE, and NE reuptake disorder at sympathetic nerve endings. In dilated cardiomyopathy (DCM), iodine 123-metaiodobenzylguanidine (MIBG) used clinically as a tracer for imaging of the sympathetic function was found to be useful in evaluation of severity and prognosis. METHODS AND RESULTS: A total of 143 (123)I-MIBG myocardial single-photon emission computed tomography (SPECT) images were taken at successive intervals on 58 patients with DCM (mean age 54 +/- 11 years), as well as before and after therapy to determine the severity of DCM and the therapeutic effect of beta-blocker. Patients were divided into group A (n = 20), in which left ventricular ejection fraction (LVEF) improved by 10% or more within 6 months after the administration of beta-blocker, and group B (n = 20), in which there was less than a 10% change in LVEF. After (123)I-MIBG myocardial SPECT was taken, the washout rate for the entire left ventricle was calculated from early and delayed images. The estimations of extent score and severity score were based on the polar map prepared from short axial images taken from 17 healthy volunteers (mean age 35 +/- 5 years). There was a significant correlation between LVEF and (123)I-MIBG findings (extent score, severity score, and washout rate) obtained before and after beta-blocker therapy. After beta-blocker therapy, LVEF and (123)I-MIBG findings significantly improved in group A. On the other hand, no change occurred in (123)I-MIBG findings in group B. There was no significant difference in LVEF between group A (32.1% +/- 8.0%) and group B (29.5% +/- 7.2%). Also, there was no significant difference in the washout rate between group A (54.4% +/- 10.9%) and group B (52.9% +/- 7.2%). Comparison of (123)I-MIBG images before beta-blocker therapy of group A and group B revealed that the extent score (26.5 +/- 16.0 vs 44.5 +/- 21.1, respectively; P <.01) and the severity score (24.9 +/- 21.9 vs 58.2 +/- 35.2, respectively; P <.01) on the basis of the early (123)I-MIBG image was significantly lower for group A. CONCLUSIONS: From the above findings, patients with DCM in which (123)I-MIBG uptake is high on early images were expected to show improvement in cardiac function by beta-blocker therapy. Findings also suggested that (123)I-MIBG was useful for examining the severity of DCM, determining the applicability of beta-blocker therapy, estimating the maintenance dosage of beta-blocker, and evaluating prognosis.


Assuntos
3-Iodobenzilguanidina , Antagonistas Adrenérgicos beta/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Radioisótopos do Iodo , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico
10.
Nihon Rinsho ; 59(2): 291-5, 2001 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-11218400

RESUMO

The resistance of Helicobacter pylori (H. pylori) to antibiotics leaves great influence on treatment outcome. Agar and broth dilution techniques are difficult to perform and not practical. E-test has the advantage of allowing visualization of resistant subpopulations of bacteria within zones of inhibitions. We studied point mutation of 23s-rRNA gene for H. pylori strains. (74 clarithromycin (CAM)-resistant, 6 CAM-susceptible) The results of these assays were well correlated with these of E-test. The cure rate of triple therapy with metoronidazole (MTZ) for CAM-resistant H. pylori is 100%(11/11), and that with CAM for MTZ-resistant H. pylori is 94.4% (17/18). It is very difficult to eradicate CAM and MTZ-resistant H. pylori.


Assuntos
Helicobacter pylori/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Resistência Microbiana a Medicamentos , Quimioterapia Combinada/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Mutação Puntual , RNA Ribossômico 23S/genética
11.
Nihon Igaku Hoshasen Gakkai Zasshi ; 61(13): 721-9, 2001 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-11766397

RESUMO

The purpose of this study was to find an indexing feature for small gastric carcinoma taken by double contrast radiography, and to propose a new method for detecting lesions. We considered the method from the viewpoint of the detection and diagnosis of lesions. The inclination curve of the density of a small gastric carcinoma, Type IIc + IIa, with a depth of cancerous invasion of M, taken by the double contrast method was investigated. The curve of density that was obtained clearly showed the change and inclination of density that was proper for the shape of the surface of the lesion and seemed to be good for pointing out the lesion and for reproducing a new image of the lesion. Our results were as follows: The area surrounding the depressed lesion appeared as a steep-gradient brightness curve (with or without surrounding raised margin), and the frequency brightness-curve of the bottom of the lesion showed less frequency than that of the surrounding non-cancerous region. These results indicate that this proposed method is effective for the detection of small gastric carcinoma taken by double contrast radiography, although the process of elimination of false positives should be improved.


Assuntos
Neoplasias Gástricas/diagnóstico por imagem , Estômago/patologia , Tecnologia Radiológica/métodos , Meios de Contraste/administração & dosagem , Humanos , Radiografia , Neoplasias Gástricas/patologia , Filme para Raios X
12.
Cancer ; 89(8): 1664-9, 2000 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11042558

RESUMO

BACKGROUND: The TNM classification (International Union Against Cancer) of salivary gland carcinoma was revised in 1997. In this study, the authors have evaluated the validity of this new TNM classification and clinical staging in 1683 patients with parotid gland carcinoma. METHODS: Reclassification was conducted according to the new classification based on the clinical data of 1683 patients registered to the salivary gland division of the Japanese Joint Committee on TNM classification. The 5- and 10-year survival rates according to TNM classification were calculated for 1074 patients whose prognosis could be followed up. Finally, the distribution of the total patient population was analyzed using the new staging and the survival curves for each disease stage. RESULTS: The variance of the patients for T1 to T4 was appropriate using the new T classification. The 5- and 10-year survival rates corresponded well to the degree of progression of TNM. However, there were only nine patients with Stage III, and marked nonuniformity in the staging was observed. The separation of the survival curves for each stage was not clear, and no significant differences between the survival curves of Stages II and III and Stages III and IV were observed. When the authors classified T1N1M0, T2N1M0, T3N1N0, and T4N0M0, which have 5- and 10-year survival rates similar to Stage III, distribution of patients and separation of the survival curves in each stage improved markedly. CONCLUSIONS: The results of the current study confirm that the new TNM classification system is valid. However, a significant problem was observed with respect to the new clinical staging. The authors propose that T1N1M0, T2N1M0, T3N1M0, and T4N0M0 be classified as Stage III.


Assuntos
Neoplasias das Glândulas Salivares/classificação , Neoplasias das Glândulas Salivares/patologia , Intervalo Livre de Doença , Neoplasias de Cabeça e Pescoço/classificação , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Japão , Metástase Linfática , Metástase Neoplásica , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/mortalidade , Taxa de Sobrevida , Fatores de Tempo
13.
J Gastroenterol Hepatol ; 15(7): 744-51, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10937679

RESUMO

BACKGROUND AND AIMS: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia. METHODS: Using reverse transcription-polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol. RESULTS: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P=0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA. CONCLUSIONS: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.


Assuntos
Domínio Catalítico/genética , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/enzimologia , Helicobacter pylori , Lesões Pré-Cancerosas/genética , RNA , Neoplasias Gástricas/genética , Telomerase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/enzimologia , Lesões Pré-Cancerosas/patologia , RNA Mensageiro/biossíntese , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia
14.
Nihon Igaku Hoshasen Gakkai Zasshi ; 60(7): 389-95, 2000 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-10921298

RESUMO

The purpose of this work was to propose guidance levels of entrance surface doses for radiographic examinations of Japanese patients based on a nationwide survey. Questionnaires asking about the technical conditions of radiography were sent to 2,000 hospitals in Japan. The entrance doses (1st quartile, median, 3rd quartile, and mean) were calculated by the Numerical Dose Determination (NDD) method described in this paper and by using the conditions reported in the questionnaires. Our results for all types of examinations showed that the median was lower than the mean, whereas the median was higher than the mean in the results reported in the British NRPB 21. The median of our results was lower than that in the NRPB in England (Present work/NRPB in England = 0.27-0.74). We propose guidance levels of entrance surface doses for examinations carried out in Japanese institutions as the 3rd quartile of the dose distributions. The present proposed levels are lower than those described by IAEA. The calculated entrance surface doses exceeded the guidance levels set by IAEA in less than 10% of the institutions surveyed.


Assuntos
Doses de Radiação , Proteção Radiológica/normas , Radiografia , Guias como Assunto , Humanos , Japão , Valores de Referência
15.
J Gastroenterol ; 35(7): 510-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10905358

RESUMO

Autofluorescence observations enable scientists to sensitively identify various lesions. Non-steroidal anti-inflammatory drugs such as aspirin and indomethacin are well known to induce gastric mucosal injuries. Our purpose was to clarify whether the observation of mucosal autofluorescence could help us to recognize indomethacin-induced gastric lesion formation. Gastric mucosal fluorescence intensity and gastric lesion scores were time-sequentially measured after indomethacin treatment in rats. To identify the localization of autofluorescent substances, stomach cryosections were observed with an epifluorescence microscope. Fluorescent substances from damaged tissue were also analyzed by high-performance liquid chromatography. In addition, to elucidate whether oxidative stress directly generates fluorescent substances from heme, we investigated the reaction between hydrogen peroxide and hemoglobin in a cell-free system. Treatment with indomethacin induced gastric lesions by tissue peroxidation, with mucosal fluorescence intensity increasing time-dependently. The fluorescence products were mesoporphyrin and protoporphyrin, and they were localized in disrupted mucosal tissue. In the cell-free system, porphyrins were directly generated by hydrogen peroxide from hemoglobin. These findings indicate that indomethacin treatment increased the intensity of porphyrin fluorescence. Gastric mucosal lesion formation can be sensitively detected with fluorescence observations.


Assuntos
Mucosa Gástrica/metabolismo , Estresse Oxidativo , Porfirinas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Cromatografia Líquida de Alta Pressão , Fluorescência , Sequestradores de Radicais Livres , Mucosa Gástrica/patologia , Indometacina/farmacologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
16.
Am J Physiol Gastrointest Liver Physiol ; 279(1): G107-17, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10898752

RESUMO

The present study was conducted to elucidate the mechanisms by which Helicobacter pylori (HP)-derived ammonia causes gastric mucosal injury. Intact sheets of guinea pig gastric fundic mucosae were incubated in Ussing chambers. Both the luminal and the serosal pH were kept at 7.4. Transmucosal potential difference (PD) and electrical resistance (R) were monitored as indices of mucosal integrity. Restitution was evaluated by recovery of PD, R, and transmucosal [(3)H]mannitol flux after Triton X-100-induced mucosal injury. The effects of luminal or serosal NH(4)Cl on function and morphology of uninjured or injured mucosae were examined. In uninjured mucosae, serosal NH(4)Cl induced more profound decreases in PD and R and more prominent vacuolation in gastric epithelial cells than did luminal NH(4)Cl. In contrast, luminal NH(4)Cl markedly inhibited restitution in injured mucosae and caused an extensive vacuolation in gastric epithelial cells, as did serosal NH(4)Cl. Transmucosal ammonia flux was greater in the injured than in the uninjured mucosae. These results suggest that 1) basolateral membrane of gastric epithelial cells is more permeable to ammonia than apical membrane and 2) luminal ammonia, at concentrations detected in HP-infected gastric lumen, retards restitution in injured mucosae.


Assuntos
Amônia/metabolismo , Mucosa Gástrica/metabolismo , Úlcera Gástrica/metabolismo , Cloreto de Amônio/farmacologia , Animais , Compostos de Bário/farmacologia , Transporte Biológico/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Cátions/metabolismo , Polaridade Celular/fisiologia , Células Cultivadas , Cloretos/farmacologia , Cultura em Câmaras de Difusão , Relação Dose-Resposta a Droga , Eletrofisiologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Mucosa Gástrica/citologia , Mucosa Gástrica/microbiologia , Cobaias , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/patologia , Helicobacter pylori , Manitol/farmacocinética , Potenciais da Membrana/efeitos dos fármacos , Octoxinol/toxicidade , Canais de Potássio/metabolismo , Cloreto de Sódio/farmacologia , Simportadores de Cloreto de Sódio-Potássio , Úlcera Gástrica/microbiologia , Úlcera Gástrica/patologia , Tensoativos/toxicidade , Trítio , Vacúolos/patologia
17.
Biosci Biotechnol Biochem ; 64(4): 775-80, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10830492

RESUMO

A type IV collagen-binding protein of 41 kDa was isolated from the mushroom Hypsizigus marmoreus and the protein was designated as HM41. The Western blotting analysis with anti-HM41 antibodies demonstrated that HM41 was unrelated to HM23, which had been shown to have an affinity for type IV collagen. The microsequence analysis of the membrane-blotted peptides generated by fragmentation with cyanogen bromide showed no homologous proteins reported. HM41 had cell adhesion-promoting activity for murine Lewis lung carcinoma LL2 cells and human fibrosarcoma HT1080 cells. These results indicate that HM41 is a hitherto undescribed fungus protein that can interact both with animal extracellular matrix protein type IV collagen and with animal tumor cells.


Assuntos
Agaricales/metabolismo , Colágeno/metabolismo , Proteínas Fúngicas/farmacologia , Animais , Carcinoma Pulmonar de Lewis , Adesão Celular/efeitos dos fármacos , Cromatografia de Afinidade/métodos , Fibrossarcoma , Proteínas Fúngicas/isolamento & purificação , Humanos , Integrinas/isolamento & purificação , Camundongos , Receptores de Colágeno , Sefarose , Células Tumorais Cultivadas
18.
Mod Pathol ; 13(5): 554-61, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10824928

RESUMO

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72- and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21Waf1 and p27Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation. Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.


Assuntos
Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Parotídeas/patologia , Idoso , Sequência de Bases , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/metabolismo , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclina D1/análise , Análise Mutacional de DNA , DNA de Neoplasias/química , DNA de Neoplasias/genética , Diagnóstico Diferencial , Receptores ErbB/análise , Humanos , Queratinas/análise , Antígeno Ki-67/análise , Perda de Heterozigosidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Microscopia Eletrônica , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/metabolismo , Mutação Puntual , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genética
19.
Plant Cell ; 12(5): 757-70, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10810148

RESUMO

Organ bending through differential growth represents a major mechanism by which plants are able to adaptively alter their morphology in response to local changes in the environment. Two plant hormones, auxin and ethylene, have been implicated as regulators of differential growth responses; however, the mechanisms by which they elicit their effects remain largely unknown. Here, we describe isolation of the NPH4 gene of Arabidopsis, which is conditionally required for differential growth responses of aerial tissues, and we report that NPH4 encodes the auxin-regulated transcriptional activator ARF7. The phenotypes of nph4 mutants, which include multiple differential growth defects associated with reduced auxin responsiveness, including impaired auxin-induced gene expression, are consistent with the predicted loss of function of a transcriptional activator, and these phenotypes indicate that auxin-dependent changes in gene transcription are prerequisite for proper organ bending responses. Although NPH4/ARF7 appears to be a major regulator of differential growth, it is not the sole regulator because phenotypes of nph4 null mutants were suppressed by application of ethylene. This latter finding illustrates the intimate connection between auxin and ethylene in the control of growth in higher plants.


Assuntos
Arabidopsis/crescimento & desenvolvimento , Genes de Plantas , Genes Reguladores , Ácidos Indolacéticos/fisiologia , Arabidopsis/genética , Arabidopsis/fisiologia , Sequência de Bases , Clonagem Molecular , Primers do DNA , Etilenos/metabolismo , Gravitropismo , Mutação , Fenótipo
20.
Nihon Igaku Hoshasen Gakkai Zasshi ; 60(14): 863-7, 2000 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-11197837

RESUMO

Several previous studies have indicated that the medical exposure dose(entrance surface dose) is lower with Computed Radiography(CR) than with the Film/Screen(F/S) system. We conducted a questionnaire survey of 1,297 hospitals regarding the radiation exposure conditions of X-ray examinations. From the survey results, we calculated the entrance surface dose(first quartile, median, third quartile, and mean) using the NDD calculation method. In the case of chest radiography(adult patients) by CR, the entrance surface dose was 150% of the median value for the overall examination and 160% of the median value for orthochromatic screen systems. The CR exposure set-up using a lower voltage and higher mAs than the F/S method was found to result in a high entrance surface dose. We also found a difference in patient dose among hospitals using CR. Mean surface dose in CR system was 0.12 mGy in a quartile, 0.19 mGy in the middle and 0.27 mGy in the third quartile. Among the hospitals which showed higher doses of third quatile them above mentioned, dose differences of a quartile were distributed 2 to 10 times higher them mean exposure doses.


Assuntos
Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Radiografia Torácica , Humanos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Torácica/métodos
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