Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 133
Filtrar
1.
Leukemia ; 24(2): 335-44, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20016539

RESUMO

We analyzed the long-term outcomes of 1021 patients with acute lymphoblastic leukemia (ALL), enrolled in four successive clinical trials (ALL811, ALL841, ALL874 and ALL911) between 1981 and 1993. All patients received risk-adopted therapy according to leukocyte count and age at the time of diagnosis. The median follow-up durations of the four studies were 17.8 years in ALL811, 15.5 years in ALL841, 11.9 years in ALL874 and 15.8 years in ALL911. Patients' event-free survival (EFS) and overall survival (OS) rates at 12 years were 41.0 and 54.3% in ALL811, 50.2 and 60.2% in ALL841, 57.3 and 64.7% in ALL874, and 63.4 and 71.7% in ALL911, respectively. Thus, cure can become a reality for about 70% of children with ALL. There is, however, still a significant difference in survival outcomes according to risk group. Late effects were observed in 70 patients out of 834 (8.4%); hepatitis and short stature were most commonly reported. Reduction of late adverse effects for all patients and development of new treatment strategies for very-high-risk patients are major issues for upcoming trials to address.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Oncologia/organização & administração , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Prognóstico , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
2.
Pediatr Surg Int ; 25(11): 995-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19693517

RESUMO

We report a rare case of choledochal cyst (CC) associated with congenital duodenal atresia (DA) and annular pancreas (AP). A girl was born at 37 weeks of gestation weighing 2,974 g with a prenatal diagnosis of DA. She underwent a duodenoduodenostomy for type III DA with an AP 1 day after birth. At 4 years of age, she was admitted for evaluation of cholangitis and pancreatitis. Radiological studies demonstrated a fusiform-type CC with pancreaticobiliary maljunction (PBMJ). Excision of the CC and hepaticojejunostomy were performed. The patient was discharged without complications. Despite the fact that CC, DA, and AP are embryologically closely related entities, to the best of our knowledge, only eight such cases have been documented. We must be aware of the possible combination of CC in the follow-up of the patients with DA associated with AP.


Assuntos
Cisto do Colédoco/complicações , Duodeno/anormalidades , Atresia Intestinal/complicações , Pré-Escolar , Cisto do Colédoco/diagnóstico , Feminino , Humanos , Atresia Intestinal/diagnóstico
3.
Cell Death Differ ; 16(12): 1615-21, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19644511

RESUMO

Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, a process known as anoikis. We have shown that DAP3 is critical for anoikis induction. However, the mechanism for anoikis induction mediated by DAP3 is still unclear. Here, we show that interferon-beta promoter stimulator 1 (IPS-1) binds DAP3 and induces anoikis by caspase activation. Recently, IPS-1 has been shown to be critical for antiviral immune responses, although there has been no report of its function in apoptosis induction. We show that overexpression of IPS-1 induces apoptosis by activation of caspase-3, -8, and -9. In addition, IPS-1 knockout mouse embryonic fibroblasts were shown to be resistant to anoikis. Interestingly, IPS-1 expression, recruitment of caspase-8 to IPS-1, and caspase-8 activation were induced after cell detachment. Furthermore, DAP3-mediated anoikis induction was inhibited by knockdown of IPS-1 expression. Therefore, we elucidated a novel function of IPS-1 for anoikis induction by caspase-8 activation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Anoikis , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 8/metabolismo , Proteínas Ribossômicas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular , Ativação Enzimática , Humanos , Camundongos , Ligação Proteica , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA , Proteínas Ribossômicas/genética
4.
Transpl Infect Dis ; 11(1): 49-53, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18713137

RESUMO

We report a case of a mycotic aneurysm of the internal carotid artery and cerebral hemorrhagic infarction resulting from Aspergillus middle ear infection in a patient with severe aplastic anemia who received unrelated bone marrow transplantation. Although a mycotic aneurysm is a rare complication, and most often fatal, the patient was successfully treated with catheter coil embolization of the internal carotid artery and long-term systemic antifungal therapy. This case emphasizes the need for the rapid diagnosis of potential fungal involvement of the vascular system and suggests the necessity for aggressive treatment, such as with the modality illustrated in this case.


Assuntos
Aneurisma Infectado/microbiologia , Aspergilose/complicações , Transplante de Medula Óssea/efeitos adversos , Doenças das Artérias Carótidas/microbiologia , Infarto Cerebral/microbiologia , Transplante Homólogo/efeitos adversos , Adolescente , Aneurisma Infectado/diagnóstico , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Doenças das Artérias Carótidas/diagnóstico , Artéria Carótida Interna/microbiologia , Infarto Cerebral/diagnóstico , Embolização Terapêutica , Humanos , Masculino , Resultado do Tratamento
5.
Oncogene ; 27(46): 6002-11, 2008 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-18574468

RESUMO

The parkin was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism. Deregulation of the parkin gene, however, has been observed in various human cancers, suggesting that the parkin gene may be important in tumorigenesis. To gain insight into the physiologic role of parkin, we generated parkin-/- mice lacking exon 3 of the parkin gene. We demonstrated here that parkin-/- mice had enhanced hepatocyte proliferation and developed macroscopic hepatic tumors with the characteristics of hepatocellular carcinoma. Microarray analyses revealed that parkin deficiency caused the alteration of gene expression profiles in the liver. Among them, endogenous follistatin is commonly upregulated in both nontumorous and tumorous liver tissues of parkin-deficient mice. Parkin deficiency resulted in suppression of caspase activation and rendered hepatocytes resistant to apoptosis in a follistatin-dependent manner. These results suggested that parkin deficiency caused enhanced hepatocyte proliferation and resistance to apoptosis, resulting in hepatic tumor development, partially through the upregulation of endogenous follistatin. The finding that parkin-deficient mice are susceptible to hepatocarcinogenesis provided the first evidence showing that parkin is indeed a tumor suppressor gene.


Assuntos
Carcinoma Hepatocelular/genética , Genes Supressores de Tumor , Neoplasias Hepáticas/genética , Ubiquitina-Proteína Ligases/fisiologia , Animais , Células Cultivadas , Folistatina/genética , Folistatina/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor/fisiologia , Predisposição Genética para Doença , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células NIH 3T3 , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima
6.
Oncogene ; 27(11): 1520-6, 2008 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-17873903

RESUMO

Aberrant accumulation of beta-catenin is closely related to carcinogenesis. Mutations in the p53 gene are reported to induce the aberrant accumulation of beta-catenin in the absence of dysfunction in the glycogen synthase kinase 3beta (GSK3beta)-mediated degradation pathway, but the mechanism remains incompletely understood. Here, we show that human coiled-coil domain containing 85B (CCDC85B) is induced by p53 and regulates beta-catenin activity via interaction with the T-cell factor 4 in the nucleus. Moreover, CCDC85B enhances the degradation of beta-catenin and suppresses tumor cell growth. In conclusion, we revealed that CCDC85B-induced degradation of beta-catenin is independent of GSK3beta and other p53-inducible products, Siah-1L, suggesting that CCDC85B constitutes the one of the frameworks of p53-induced multiple regulatory pathways for beta-catenin activity.


Assuntos
Proteínas de Transporte/fisiologia , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Núcleo Celular/metabolismo , Células Cultivadas , Inibidores de Cisteína Proteinase/farmacologia , Imunofluorescência , Perfilação da Expressão Gênica , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Fator 1-alfa Nuclear de Hepatócito/antagonistas & inibidores , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Immunoblotting , Imunoprecipitação , Leupeptinas/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Repressoras , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição TCF/genética , Fatores de Transcrição TCF/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição , Transfecção , Ubiquitina/metabolismo
7.
J Viral Hepat ; 13(8): 523-31, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16901282

RESUMO

Patients with recurrent hepatitis C after liver transplantation usually have a high viral load and are generally resistant to interferon (IFN)-alpha2b plus ribavirin (RBV) therapy. However, it remains unclear whether pretreatment viral titre determines the effectiveness of combination therapy, especially in patients with a high viral load. The aim of this study was to identify the viral factors associated with a sustained virological response (SVR) to antiviral therapy in patients with recurrent hepatitis C after living-donor liver transplantation. Twenty-three patients with recurrent hepatitis C received combination therapy of IFN-alpha2b plus RBV. SVR was achieved in 7 of the 23 patients (30.4%). Predictive factors for SVR included a 2 log10 decline in Hepatitis C virus (HCV) RNA at 2 weeks after the start of therapy and disappearance of HCV RNA at 4 or 24 weeks after the start of therapy. As the pretreatment high viral load showed no association with SVR, we asked whether other viral factor was associated with the response to the combination therapy in transplant recipients. We found the several novel defective HCV clones in 4 of 12 recipients' sera. All defective HCV clones had deletions in the envelope region. Interestingly, no patients with defective clones showed a prompt decrease in HCV RNA after the start of IFN-alpha2b plus RBV therapy. Thus, early decline in serum HCV RNA after treatment was closely associated with SVR. The circulating defective HCV clones are present and might be associated with the response to the combination therapy in patients with recurrent hepatitis after liver transplantation.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Transplante de Fígado , Ribavirina/administração & dosagem , Adulto , Idoso , Sequência de Bases , Células Clonais , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/sangue , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Viral/sangue , RNA Viral/genética , Proteínas Recombinantes , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga Viral
8.
Aktuelle Urol ; 34(4): 270-2, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-14566683

RESUMO

Our previous study demonstrated the clear detection of MN/CA9 mRNA in peripheral blood samples from RCC patients. However, approximately 30 % of control blood samples from healthy volunteers showed MN/CA9 expression. We have developed a new primer set and optimized the PCR conditions, now resulting in a specificity of 100 %. In tissue samples, all clear cell type carcinomas but none of the spindle cell type and pleomorphic cell type tumors expressed the MN/CA9 message. Analysis of MN/CA9 messages in peripheral blood samples from RCC patients gave positive results for 0/2, 1/9, 0/4 and 4/12 of stage I, II, III and IV cases, respectively. RT-PCR analysis using preoperative renal venous blood samples resulted in clear detection of MN/CA9 positive cells in 2/4, 3/13, 2/6 and 1/1 of stage I, II, III and IV cases, respectively. Our results suggest that assessment of MN/CA9 expression by RT-PCR is a promising method for detecting cancer cells in the circulation of patients with RCC.


Assuntos
Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Anidrases Carbônicas/genética , Carcinoma de Células Renais/sangue , Neoplasias Renais/sangue , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes , Adulto , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Anidrase Carbônica IX , Anidrases Carbônicas/sangue , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/cirurgia , DNA Complementar , Eletroforese em Gel de Ágar , Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , RNA Mensageiro , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade
10.
Clin Exp Immunol ; 126(2): 259-65, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11703369

RESUMO

Although increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) has been demonstrated in inflammatory sites of various diseases, its role in colitis remains unknown. In this study, we examined whether MAdCAM-1 is involved in the pathogenesis of granulomatous colitis induced by peptidoglycan-polysaccharide (PG-PS). Experimental colitis was induced by intramural injection of PG-PS to rat colon. After 3 weeks the colon was removed and the mucosal inflammation was assessed. The area of MAdCAM-1-positive venules and the subsets of infiltrating cells were determined in colonic mucosa by immunohistochemistry. In another experiment, monoclonal antibody against MAdCAM-1 was administered intraperitoneally to examine its attenuating effect on colitis. The intramural injection of PG-PS induced significant colonic inflammation with granuloma formation. The submucosa was drastically thickened with the infiltration of CD4 positive lymphocytes and ED-1 positive macrophages. Intense MAdCAM-1 expression was observed on endothelium of the submucosal venules in inflamed mucosa. Administration of anti-MAdCAM-1 antibody significantly attenuated the PG-PS-induced colonic damage and cell infiltration. Enhanced expression of MAdCAM-1 was demonstrated in venular endothelium of the inflamed colon in PG-PS-induced colitis. The attenuating effect of anti-MAdCAM-1 suggests the importance of the MAdCAM-1-dependent process in the formation of chronic granulomatous colitis.


Assuntos
Moléculas de Adesão Celular/fisiologia , Doença de Crohn/etiologia , Doença de Crohn/imunologia , Imunoglobulinas/fisiologia , Mucosa Intestinal/imunologia , Mucoproteínas/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Moléculas de Adesão Celular/antagonistas & inibidores , Movimento Celular , Doença Crônica , Doença de Crohn/induzido quimicamente , Doença de Crohn/patologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Feminino , Imuno-Histoquímica , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/patologia , Mucoproteínas/antagonistas & inibidores , Peptidoglicano/toxicidade , Polissacarídeos/toxicidade , Ratos , Ratos Endogâmicos Lew
11.
Leuk Lymphoma ; 42(3): 393-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11699404

RESUMO

To evaluate the clinical implications of CD45 expression in acute childhood lymphoblastic leukemia (ALL), we measured the CD45 expression of blast cells from 133 untreated patients with childhood B-precursor ALL (n = 118) or T-ALL (n = 15). CD45 expression (> or = 20%) was detected in all 15 cases (100%) of T-ALL, and 101 cases (86%) of B-precursor ALL. In 122 cases, the fluorescence intensity of the CD45 expression was measured as a relative value; the ratio of average linear values (RALV) of CD45 on the blasts to that on CD3-positive T-lymphocytes from the same specimen. The expression was more intense in the T-ALL cases than in the B-precursor ALL cases (RALV, mean +/- SE: T-ALL 0.230 +/- 0.04 vs. pro-B ALL 0.150 +/- 0.012/pre-B ALL 0.153 +/- 0.019, p < 0.05). However, the intensity of the CD10, CD19, CD20 and CD34 antigen immunoreactivity did not correlate with the CD45 expression. Patients with hyperdiploidy (chromosome number > 50) showed significantly lower levels of CD45 expression than patients with t(1;19) or normal karyotypes (RALV, mean +/- SE: 0.081 +/- 0.022 vs. 0.133 +/- 0.03/0.143 +/- 0.019, p < 0.05). Other clinical features such as age, gender and WBC count did not correlate with CD45 expression. The prognostic implications of CD45 expression were studied in non-high-risk (low-risk + intermediate-risk) (n = 60) and high-risk patients (n = 52) with B-precursor ALL who had been treated with the risk-directed protocol of ALL-941 trial. Although CD45 expression did not correlate with the event-free survival (EFS) of the non-high-risk patients, there was a significant correlation between the expression levels and the EFS of the high-risk patients: the 3-year EFS rate of the CD45low group (n = 26, RALV = 0.017-0.132) was 88 +/- 7% versus the CD45high group (n = 26, RALV = 0.133-0.450) at 34 +/- 24% (p < 0.05). These results show that the levels of expression of the CD45 antigen on leukemic lymphoblasts are significantly correlated with the clinical features and prognosis of childhood ALL.


Assuntos
Antígenos CD/análise , Linfócitos B/imunologia , Antígenos Comuns de Leucócito/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Criança , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Humanos , Imunofenotipagem , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisolona/administração & dosagem , Prognóstico , Indução de Remissão , Fatores de Tempo , Vincristina/administração & dosagem
12.
Pathol Int ; 51(8): 643-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11564221

RESUMO

Here we report the case of a 50-year-old woman with adenocarcinoma of the colon, showing heterotopic ossification. The patient was referred to our hospital for investigation of anemia secondary to occult gastrointestinal blood loss. By colonoscopy, an irregular polypoid mass was found in the ascending colon. A biopsy of the lesion revealed moderately to poorly differentiated adenocarcinoma with heterotopic ossification. A right hemicolectomy was done and revealed areas of heterotopic bone within the tumor, but no ossification was evident in the metastatic lesions within the mesenteric lymph nodes. The formation of heterotopic bone in gastrointestinal tumors is rare and its exact mechanism is unknown. Immunohistochemical localization of bone morphogenetic proteins (BMP), known to be primary inducers of new bone formation, was determined. BMP-5 and -6 were prominent in the cytoplasm of tumor cells, and they stained weakly in osteoblast-like cells adjacent to newly formed bone. Cytoplasmic staining for BMP-2 and -4 was weak in tumor cells, osteoblast-like cells, and stromal fibroblast cells. BMP may play an important role in heterotopic ossification in colon adenocarcinoma.


Assuntos
Adenocarcinoma/patologia , Proteínas Morfogenéticas Ósseas/análise , Neoplasias do Colo/patologia , Ossificação Heterotópica/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
13.
Free Radic Biol Med ; 31(2): 153-63, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11440827

RESUMO

BACKGROUND: Overproduction of nitric oxide by the inducible form of nitric oxide synthase (iNOS) has been implicated in colitis. Different authors have postulated both toxic and protective effects of nitric oxide (NO) in the pathophysiology of active inflammation. The objective of this study was to examine the role of iNOS in experimental chronic colitis using iNOS-deficient mice. METHODS: For induction of colitis, mice received three cycles of 2% of dextran sodium sulfate (DSS) (M.W. 40,000) treatment in drinking water. The degree of colonic inflammation, leukocyte infiltration, and the expression of cell adhesion molecules were determined. INOS expression and nitrotyrosine were also determined by immunohistochemistry. RESULTS: After DSS treatment, a moderate colitis with marked cell infiltration was observed. Intense expression of iNOS was observed on infiltrating cells as well as on the colonic mucosal epithelium in these animals. In the iNOS-deficient mice, tissue damage was significantly diminished. No iNOS or nitrotyrosine staining was found in iNOS-deficient mice. The number of infiltrating cells and the expression of mucosal adressin cell adhesion molecule-1 were significantly attenuated in the DSS-treated colon of iNOS-deficient mice. CONCLUSION: Induction of iNOS seems to act as a critical toxic effector molecule in the pathogenesis of chronic colonic inflammation.


Assuntos
Colite/etiologia , Óxido Nítrico Sintase/deficiência , Tirosina/análogos & derivados , Animais , Moléculas de Adesão Celular , Doença Crônica , Colite/enzimologia , Colite/genética , Colite/patologia , Sulfato de Dextrana/toxicidade , Imunoglobulinas/metabolismo , Imuno-Histoquímica , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucoproteínas/metabolismo , Óxido Nítrico/fisiologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Tirosina/metabolismo
14.
Neuroscience ; 104(2): 299-310, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11377835

RESUMO

A transgenic mouse expressing the human beta-amyloid precursor protein with the "Swedish" mutation, Tg2576, was used to investigate the mechanism of amyloid-beta peptide (Abeta) deposition. We characterized Abeta deposits in the cerebral cortex biochemically and pathologically. A surface-enhanced laser desorption/ionization affinity mass spectrometric study using the 6E10 monoclonal antibody demonstrated that the major species of Abeta in a formic acid-extracted fraction of the cortex were Abeta(1-38), Abeta(1-40) and Abeta(1-42). Immunohistochemistry using antibodies to the carboxy-terminal epitopes of Abeta(1-40) and Abeta(1-42), as well as 6E10, showed that plaques containing Abeta(1-42) were more numerous than those containing Abeta(1-40) throughout the cortex. Laser confocal analysis of the immunoreactivities in the plaques demonstrated that Abeta(1-40) was preferentially located in the central part of the Abeta(1-42) positive plaques. Enzyme-linked immunosorbent assay measurements of Abeta(1-40) and Abeta(1-42) showed that Abeta(1-40) was several-fold more abundant than Abeta(1-42). From these data we suggest that Abeta(1-42) deposition may precede Abeta(1-40) deposition, while Abeta(1-40) begins to deposit in the central part of the plaques and accumulates there. Furthermore, localization of Abeta(1-40) corresponded almost exactly to congophilic structures, which were associated with aberrant swollen synapses detected with antibodies to synaptophysin and alpha-synuclein. Thus, Abeta deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Córtex Cerebral/metabolismo , Camundongos Transgênicos/metabolismo , Neurônios/metabolismo , Placa Amiloide/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/imunologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/imunologia , Animais , Especificidade de Anticorpos/imunologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Humanos , Masculino , Espectrometria de Massas , Camundongos , Camundongos Transgênicos/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/patologia , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/patologia , Sinaptofisina/metabolismo , Sinucleínas , alfa-Sinucleína
15.
Brain Res ; 900(1): 48-56, 2001 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-11325345

RESUMO

A transgenic mouse expressing the human beta-amyloid precursor protein with the 'Swedish' mutation, Tg2576, was used to investigate the mechanism of beta-amyloid (Abeta) deposition. Previously, we have reported that the major species of Abeta in the amyloid plaques of Tg2576 mice are Abeta1-40 and Abeta1-42. Moreover, Abeta1-42 deposition precedes Abeta1-40 deposition, while Abeta1-40 accumulates in the central part of the plaques later in the pathogenic process. Those data indicate that Abeta deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease. In the present study, to understand more fully the amyloid deposition mechanism implicating Alzheimer's disease pathogenesis, we examined immunohistochemically the distributions of apolipoprotein E (apoE) and Abeta in amyloid plaques of aged Tg2576 mouse brains. Our findings suggest that Abeta1-42 deposition precedes apoE deposition, and that Abeta1-40 deposition follows apoE deposition during plaque maturation. We next examined the relationship between apoE and astrogliosis associated with amyloid plaques using a double-immunofluorescence method. Extracellular apoE deposits were always associated with reactive astrocytes whose processes showed enhancement of apoE-immunoreactivity. Taken together, the characteristics of amyloid plaques in Tg2576 mice are similar to those in Alzheimer's disease with respect to apoE and astrogliosis. Furthermore, apoE deposition and astrogliosis may be necessary for amyloid plaque maturation.


Assuntos
Doença de Alzheimer/etiologia , Substituição de Aminoácidos , Precursor de Proteína beta-Amiloide/metabolismo , Apolipoproteínas E/metabolismo , Córtex Cerebral/metabolismo , Gliose/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Placa Amiloide/metabolismo , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Astrócitos/patologia , Córtex Cerebral/patologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética
16.
Biochem Biophys Res Commun ; 281(5): 1321-4, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11243880

RESUMO

The anti-glutathione antibody scFv 20C9, which we previously isolated from a human synthetic phage antibody scFv library [Hirose, M., Hayano, T., Shirai, H., Nakamura, H., and Kikuchi, M. (1998) Protein Eng. 11, 243-248], was expressed in the E. coli pET system and purified by sequential chromatography on Ni and glutathione-conjugated affinity resins. The purified scFv 20C9 antibody was characterized for its binding affinity for several glutathione derivatives by the BIACORE system. Although GSH, GSSG, and gamma-Glu-Cys could bind to the immobilized antibody, this was not the case for Cys-Gly, l-Glu, l-Cys, l-Gly, or several other glutathione derivatives such as gamma-Glu-Ser-Gly. The results suggest that a gamma-glutamic acid and sulfur atom are important for scFv 20C9 antibody recognition of glutathione. This is the first report to indicate that an scFv antibody can recognize a region as small as a dipeptide.


Assuntos
Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Dipeptídeos/imunologia , Glutationa/imunologia , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , Técnicas Biossensoriais , Escherichia coli , Glutationa/análogos & derivados , Humanos , Fragmentos de Imunoglobulinas/genética , Fragmentos de Imunoglobulinas/imunologia , Fragmentos de Imunoglobulinas/metabolismo , Cinética , Transfecção
18.
Gan To Kagaku Ryoho ; 27(11): 1695-702, 2000 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-11057320

RESUMO

To address the issue of salvageability in relapsed children with NHL who had all received the same frontline therapy, we retrospectively studied the treatment response and the outcome of 27 children who relapsed following the CCLSG-NHL890 protocol. The reinduction rates and 3-year survival rates (mean +/- SD) were as follows: lymphoblastic lymphoma (LB, n = 9), 44% & 17 +/- 14%; leukemia lymphoma syndrome (LLS, n = 8), 25% & 0%; large cell lymphoma (LC, n = 3) 100% & 67 +/- 27%; Burkitt's lymphoma (B, n = 7) 0% & 0%. Thus, the salvageability of LC lymphoma was good, but the outcome of Burkitt's lymphoma was very poor. CCLSG-NHL960 protocol for LB lymphomas and intensive multiagent regimens for LC lymphomas produced favorable response rates, but the effect of the high-dose Ara-C regimen for Burkitt's lymphoma was not determined. The initial stages of the disease seemed to be associated with the patient outcome: the outcome of the patients in stage IV was inferior to that of patients in stages II or III. Other clinical variables, such as relapse sites, relapse time and BM rescue did not affect the patients' outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Esquema de Medicação , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Prednisolona/administração & dosagem , Prognóstico , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Vincristina/administração & dosagem
19.
Jpn J Clin Oncol ; 30(9): 389-96, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11095136

RESUMO

BACKGROUND: A randomized multicenter study was conducted to investigate the efficacy of total androgen blockade (TAB) for patients with previously untreated prostate cancer using the steroidal anti-androgen chlormadinone acetate (CMA) and the non-steroidal anti-androgen flutamide. We also compared the liver dysfunction in these two arms. METHODS: From November 1995 to October 1997, 71 patients were registered into this study and 70 of them were eligible. RESULTS: There was no significant difference in the efficacy of TAB between CMA and flutamide at 24 weeks. The testosterone and prostate-specific antigen (PSA) levels in patients administered flutamide (Group II) increased significantly 3 days after the first dose of LH-RH analog, whereas no such increase was observed in patients administered CMA (Group I), indicating that CMA prevented the flare-up. Parameters of liver function, serum GOT and GPT levels, which were normal at the baseline, became abnormal in 30.0% and 35.3%, respectively, of patients in Group II. These figures were significantly higher than the corresponding figures of 6.3% and 12.5%, respectively, in Group I. When the degree of change in each of these parameters was analyzed, both GOT and GPT levels showed a significantly greater increase in Group II than in Group I. CONCLUSION: These results indicate that attention must be paid to changes in liver function during the administration of flutamide in patients with prostate cancer even if their baseline liver function is normal. It is also suggested that CMA may be better tolerated from the viewpoint of the drug effects on liver function.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Acetato de Clormadinona/análogos & derivados , Acetato de Clormadinona/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Flutamida/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/fisiopatologia , Idoso , Humanos , Fígado/fisiopatologia , Masculino , Estudos Prospectivos , Neoplasias da Próstata/fisiopatologia
20.
J Pharmacol Exp Ther ; 295(1): 183-9, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10991977

RESUMO

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is an adhesion molecule that mediates recruitment of lymphocytes into the gut mucosa. Attenuation of excessive expression of MAdCAM-1 in the inflamed mucosa could be useful for treatment of inflammatory bowel diseases. The aim of this study was to investigate whether anti-MAdCAM-1 antibody has a prophylactic effect on experimental colitis induced by dextran sulfate sodium (DSS). Colitis was induced by orally feeding BALB/c mice 5% DSS (mol. wt. 5000). Mice were sacrificed at intervals up to 21 days after administration to evaluate the changes over time in intestinal damage. The infiltrating lymphocytes and their subpopulations, and the expression of cell adhesion molecules were determined by immunohistochemistry. In another set of experiments, the attenuating effect of i.p.-injected anti-MAdCAM-1 antibody on colonic lesions was evaluated on day 14. Significant histological damage with shortening of crypts was observed on day 14 in colonic mucosa of DSS-treated mice. Before mucosal inflammation had become significant, expression of MAdCAM-1 was already increased in the microvessels of lamina propria on day 7. Significant infiltration of beta7-integrin-positive T and B cells in the mucosa was then noted on day 14. Administration of anti-MAdCAM-1 antibody significantly reduced colonic injury as well as the infiltration of beta7-integrin-positive lymphocytes in the colonic mucosa. This antibody also was effective when given 7 days after the start of DSS treatment. In the present study, we demonstrated that anti-MAdCAM-1 antibody significantly ameliorates DSS-induced colitis, suggesting that MAdCAM-1 may be useful for control of inflammatory bowel diseases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Colite/prevenção & controle , Imunoglobulinas/fisiologia , Cadeias beta de Integrinas , Mucoproteínas/fisiologia , Animais , Moléculas de Adesão Celular , Colite/etiologia , Sulfato de Dextrana/toxicidade , Feminino , Integrinas/análise , Molécula 1 de Adesão Intercelular/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Molécula 1 de Adesão de Célula Vascular/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...