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2.
Malays J Pathol ; 45(3): 405-416, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38155382

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis and cytopenia. Studies have reported differences in MDS between Asian and Western countries, but data from Taiwan are scarce. MATERIALS AND METHODS: In this study we analysed the clinical and pathological features of 32 Taiwanese MDS patients with del(5q) (ie, del(5q) alone [Group A, n = 11], del(5q) with one additional cytogenetic abnormality other than monosomy 7 or del(7q) [Group B, del(5q)+1; n = 6], and del(5q) with ≥2 additional cytogenetic abnormalities [Group C, n = 15]). RESULTS: Progression-free survival (PFS) and overall survival (OS) were more favourable for Group A than for Groups B (p < 0.05) and C (p ≤ 0.001). Multivariate analysis showed that age >70 years, thrombocytopenia, and karyotype other than del(5q) alone were poor prognostic factors. Among the patients that had World Health Organization (WHO)-defined MDS with isolated del(5q), one patient (9%) had a typical marrow morphology of 5q minus syndrome with erythroid hypoplasia and four patients (36%) had hypolobated megakaryocytes. In addition, PFS and OS were significantly more favorable for the patients with del(5q) alone than for those with del(5q)+1 (p < 0.05). CONCLUSION: The bone marrow morphology, clinical features, and prognosis of Taiwanese MDS patients with del(5q) were different from those associated with MDS with isolated del(5q) as defined in the current WHO classification. Researchers should compare different geographic regions and racial populations to determine whether geographic and racial differences exist with respect to MDS with del(5q).


Assuntos
Síndromes Mielodisplásicas , Humanos , Idoso , Taiwan , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Deleção Cromossômica , Medula Óssea , Cariotipagem
3.
Malays J Pathol ; 44(1): 61-66, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35484887

RESUMO

Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour affecting mainly elderly patients and is more common in the West than in Asia. It is associated with Merkel cell polyomavirus (MCPyV), immunosuppression, and ultraviolet light. In this study, we retrospectively investigated the first series of MCC from Taiwan and identified 19 cases from three tertiary centres. All patients were males with a median age of 67.5. Twelve (63%) cases occurred in the extremities, with one unique case presenting initially as nodal metastasis of unknown primary. Immunohistochemically, the great majority of tumours expressed CK20 (89%), synaptophysin (89%), and INSM1 (84%), with none positive for TTF1. Eleven (58%) cases were positive for MCPyV by immunohistochemistry (clone CM2B4). All patients were treated with excision, including four with additional radiotherapy and one with radiotherapy and chemotherapy. Nodal status and treatment modalities significantly affected survival. The median survival time of MCPyV-positive cases was much longer than the negative cases (median 40 vs. 10 months). In summary, we presented the first report on the clinicopathological features of MCC in Taiwan, with 58% cases associated with MCPyV. The prognosis of patients with MCPyV-positive tumours was better than those negative for MCPyV.


Assuntos
Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Neoplasias Cutâneas , Idoso , Carcinoma de Célula de Merkel/patologia , Feminino , Humanos , Masculino , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/patologia , Prognóstico , Proteínas Repressoras , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Taiwan
4.
Malays J Pathol ; 42(2): 237-243, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32860376

RESUMO

INTRODUCTION: Follicular lymphoma (FL) is usually a nodal lymphoma expressing CD10, rarely with leukaemic presentation (FL-LP). MATERIALS AND METHODS: We searched for FL-LP in our institution from 2000 to 2018 and characterised the neoplastic cells by flow cytometry, immunohistochemistry and fluorescence in situ hybridization. Thirteen (6.1%) of 212 FL cases were FL-LP, all de novo neoplasms. The leukaemic cells were small in 12 cases and large in one. All had concurrent FL, mostly (92%; 12/13) low-grade. The single case with large leukaemic cells had a concurrent primary splenic low-grade FL and a double-hit large B-cell lymphoma in the marrow. RESULTS: CD10 was expressed in the leukaemic cells in 38% (5/13) cases by flow cytometry and in 77% (10/13) cases in tumours (p= 0.0471). IGH/BCL2 reciprocal translocation was identified in 85% (11/13) cases. Most patients were treated with chemotherapy. In a median follow-up time of 36 months, nine patients were in complete remission. The 2- and 5-year survival rates were at 100% and 83%, respectively. In this study, we characterised a series of de novo FL-LP in Taiwan. All patients had concurrent nodal and/or tissue tumours, which might suggest that these patients seek medical help too late. CONCLUSION: The lower CD10 expression rate by flow cytometry than by immunohistochemistry might be due to different epitopes for these assays. Alternatively, loss of CD10 expression might play a role in the pathogenesis of leukaemic change. The clinical course of FL-LP could be aggressive, but a significant proportion of the patients obtained complete remission with chemotherapy.


Assuntos
Leucemia de Células B , Linfoma Folicular , Neprilisina/metabolismo , Adulto , Idoso , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Leucemia de Células B/metabolismo , Leucemia de Células B/patologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
5.
Ann Oncol ; 29(1): 256-263, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29077846

RESUMO

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/radioterapia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Quimiorradioterapia , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Linfoma Extranodal de Células T-NK/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
6.
J Eur Acad Dermatol Venereol ; 27(5): 628-33, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22452516

RESUMO

BACKGROUND: Toxic epidermal necrolysis syndrome (TEN) is a rare, life-threatening, drug-related skin reaction with a high mortality rate. To date, only a few studies with insufficient sample sizes have been conducted to analyse SCORTEN in Asian populations with TEN. OBJECTIVE: To analyse SCORTEN and other related factors that affect TEN patients in Taiwan. METHODS: A retrospective review of medical records of 101 patients with TEN from 1992 to 2009. RESULTS: There were 62 cases of adverse reactions to a single medication and 39 cases of idiopathic reaction, from multiple medications, or infectious pathogens, of 101 TEN patients. Of the seven individual SCORTEN parameters, only associate malignancy, detached or compromised body surface area >10%, serum urea and bicarbonate were statistically significant in the multivariate analysis. Factors such as 1.5 times baseline serum creatinine levels, urine output of less than 0.5 mL/kg for 6 h and acute renal failure were connected with subsequent mortality. CONCLUSION: The SCORTEN score is effective in predicting the outcome in Taiwanese TEN patients. A number of factors are predictors of mortality. In our study, we determine renal insufficiency and failure to be a marker for predicting a poor outcome.


Assuntos
Rim/fisiopatologia , Síndrome de Stevens-Johnson/mortalidade , Adulto , Idoso , Povo Asiático , Humanos , Auditoria Médica , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Stevens-Johnson/fisiopatologia
7.
Ann Oncol ; 23(10): 2703-2707, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22547542

RESUMO

BACKGROUND: Clinical features and outcomes of extranodal natural killer/T-cell lymphoma (ENKL) arising from extranasal sites are not fully understood. The purpose of this study was to study the prognosis and treatment outcome of skin/soft tissue primary ENKL. PATIENTS AND METHODS: This multicenter retrospective study included 48 patients with skin/soft tissue primary ENKL diagnosed from 1993 to 2010. RESULTS: Patients with Ann Arbor stage I, T1-2N0M0 by International Society for Cutaneous Lymphomas-European Organization of Research and Treatment of Cancer TNM (tumour-node-metastasis) stage, International prognostic index score of 0-1, and a Korean prognostic index (KPI) score of 0-1 were associated with better survival. Four of five patients with T1-2N0M0 disease achieved complete response with radiation alone. In disseminated disease, only 6 of 13 patients responded to anthracycline-containing chemotherapy, and all the two patients receiving SMILE showed response. CONCLUSION: In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.


Assuntos
Células Matadoras Naturais/imunologia , Linfoma de Células T/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias de Tecidos Moles/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma de Células T/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/terapia , Neoplasias de Tecidos Moles/terapia , Adulto Jovem
8.
Ann Oncol ; 22(5): 1170-1180, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21115603

RESUMO

BACKGROUND: Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined. METHODS: We completed a comprehensive literature search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed. RESULTS: One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0-12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R [proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9-34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4-31.1]. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01-16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ(2) = 2.12, P = 0.5473). CONCLUSIONS: The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.


Assuntos
Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/efeitos adversos , Vírus da Hepatite B , Hepatite B/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite B/complicações , Humanos , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Recidiva , Rituximab , Estados Unidos , United States Food and Drug Administration , Adulto Jovem
9.
Histopathology ; 53(4): 432-40, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18983608

RESUMO

AIMS: To elucidate the clinicopathological features and prognostic factors of primary intestinal diffuse large B-cell lymphoma (PI-DLBL). METHODS AND RESULTS: Archival tissues from 30 tumours were used for tissue microarray construction, immunohistochemistry and interphase fluorescence in situ hybridization for chromosomal translocation. The M:F ratio was 1.7:1, with a median age of 60 years. The ileum and ileocaecum were most frequently involved (40% each). Fourteen (47%) were at stage I(E) disease, 15 (50%) at stage II(E). Five (17%) tumours were perforated at presentation. The tumours expressed Bcl-6 (73%), MUM1 (70%), Bcl-2 (67%) and CD10 (23%). Nine (30%) were classified as germinal centre B-cell (GCB) phenotype and 21 non-GCB. Eight of 30 (27%), 7/30 (23%) and 2/29 (7%) cases were positive for rearrangements involving IGH, BCL6, and C-MYC loci, respectively, whereas all cases were negative for BCL2 and CCND1 translocation. Perforation was a poor prognostic indicator, with a hazard ratio of tumour-related death at 8.75 (P = 0.001). The differentiation antigens, GCB versus non-GCB phenotype, or lymphoma-associated translocations were of no prognostic significance. CONCLUSIONS: We found a higher rate of perforation and lower frequency of GCB phenotype in PI-DLBL in Taiwan compared with other geographical areas; perforation is a poor prognostic indicator.


Assuntos
Neoplasias Intestinais/patologia , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Centro Germinativo/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/mortalidade , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Análise de Sobrevida , Translocação Genética
10.
Histopathology ; 52(4): 427-35, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18315595

RESUMO

AIMS: To characterize the clinicopathological features of sporadic Burkitt lymphoma (BL). METHODS AND RESULTS: A retrospective study of 17 paediatric and 14 adult BLs with history and histopathology review, immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization (EBER) and fluorescence in situ hybridization. There was no statistically significant difference in gender, frequency of central nervous system (CNS) involvement and leukaemic change at presentation, or frequency of CD10+/Bcl-2-/Bcl-6+ (88% versus 86%), Ki67 labelling index, EBER (24% versus 21%), or C-MYC translocation (100% versus 92%) between paediatric and adult tumours. Correct pretreatment diagnoses were made in 13/17 (76%) paediatric and in 9/14 (64%) adult tumours. Twenty-eight patients received chemotherapy including 13/16 (81%) paediatric and 3/12 (25%) adult patients with appropriate regimens; 16 (57%) received CNS prophylaxis. The 1- and 5-year overall survival (OS) rates for paediatric patients were 80% and 50%, respectively, whereas 1-year OS for adults was 15%. CONCLUSIONS: Sporadic paediatric and adult BLs were phenotypically and genotypically similar. The significant prognosticators were age (P = 0.001), with or without CNS prophylaxis (P = 0.004), and CNS involvement (P = 0.008) and leukaemic change (P = 0.019) in disease course. The poor outcome in adult patients might be related to incorrect diagnosis and inappropriate treatment.


Assuntos
Linfoma de Burkitt/patologia , Neoplasias do Sistema Nervoso Central/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/genética , Linfoma de Burkitt/mortalidade , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/mortalidade , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Genótipo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Viral/análise , Proteínas de Ligação a RNA/análise , Estudos Retrospectivos , Proteínas Ribossômicas/análise , Taxa de Sobrevida , Taiwan/epidemiologia
11.
Mol Cell Biol ; 12(7): 3183-91, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1620125

RESUMO

Apolipoprotein B100 (apoB), the only protein of low-density lipoprotein, is produced primarily in the liver and serves as a ligand for the low-density lipoprotein receptor. Hepatic cell-specific expression of the human apoB gene is controlled by at least two cis-acting positive elements located between positions-128 and -70 (H. K. Das, T. Leff, and J.L. Breslow, J. Biol. Chem. 263:11452-11458, 1988). The distal element (-128 to -85) appears to be liver specific since it shows positive activity in HepG2 cells and negative activity in HeLa cells. The proximal element (-84 to -70) acts as a positive element in both these cell lines, and two rat liver nuclear proteins, BRF-1 and C/EBP, bind to two overlapping sites (-84 to -60 and -70 to -50, respectively). By gel mobility shift assay, we have identified a rat liver nuclear protein (BRF-2) which binds to the distal element (-128 to -85) of the apoB gene. This putative trans-acting factor has been purified to apparent homogeneity by DEAE-cellulose, heparin-agarose, and DNA-specific affinity chromatography. The purified BRF-2 has an apparent molecular mass of 120 kDa and was found to specifically recognize sequence -128 to -85; BRF-2 also produced a strong hypersensitive site at nucleotide position -95 with copper-orthophenanthroline reagent. A double-stranded oligonucleotide (-128 to -85) containing a 3-nucleotide (TTC) insertion between position -95 and -94 was found to abolish DNA binding by BRF-2. This result suggests that the region surrounding the hypersensitive site -95 is important for protein-DNA interaction. By using apoB promoter fragments containing various internal deletions as templates for gel mobility shift assay, the region between -104 and -85 was identified to be crucial for binding by BRF-2. We propose that BRF-2 may play an important role in the tissue-specific regulation of apoB gene transcription.


Assuntos
Apolipoproteínas B/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Sequências Reguladoras de Ácido Nucleico/genética , Animais , Apolipoproteínas B/isolamento & purificação , Sequência de Bases , Núcleo Celular/química , Mapeamento Cromossômico , Proteínas de Ligação a DNA/isolamento & purificação , Células HeLa/química , Humanos , Fígado/química , Dados de Sequência Molecular , Fenantrolinas/metabolismo , Regiões Promotoras Genéticas/genética , Ratos , Transcrição Gênica , Ativação Transcricional
12.
Leukemia ; 30(6): 1311-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26854024

RESUMO

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.


Assuntos
Linfoma de Células T Associado a Enteropatia/metabolismo , Janus Quinases/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Linfoma de Células T Associado a Enteropatia/patologia , Feminino , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Humanos , Janus Quinase 3/genética , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT5/genética , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
13.
Biochim Biophys Acta ; 1436(3): 600-5, 1999 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-9989290

RESUMO

Hepatic cell-specific expression of the human apolipoprotein B (apoB) gene is controlled by at least four cis-acting elements located within the -128 to +122 promoter region (S.S. Chuang, H.K. Das, Identification of trans-acting factors that interact with cis-acting elements present in the first non-translated exon of the human apolipoprotein B gene, Biochem. Biophys. Res. Commun. 220 (1996) 553-562). Two cis-acting positive elements (-104 to -85; -84 to -60) are located upstream from the start of transcription. A negative element (+20 to +40) and a strong positive element (+43 to +53) are located in the first non-translated exon of the human apolipoprotein B gene. Trans-acting factors BRF-2, BRF-1, BRF-3, and BRF-4 interact with the above four cis-acting elements respectively. In this study, we examine the roles of the upstream positive elements -104 to -85 and -84 to -60 in modulating transcriptional regulation of the apoB gene by downstream elements +20 to +40 and +43 to +53. Using in vitro mutagenesis and transient transfection experiments in HepG2 cells, the cis-acting element -84 to -60 has been found to be absolutely necessary for the function of the upstream element -104 to -85 and downstream elements +20 to +40 and +43 to +53. In vitro mutagenesis of the downstream positive element +43 to +53 and transfection of the mutant promoter constructs in HepG2 cells reveal that nucleotide G at position +51 is essential for the strong positive activity of the element +43 to +53. A single substitution point mutation of nucleotide G to either A or T at position +51 reduces apolipoprotein B gene transcription substantially in HepG2 cells. These results suggest that a single substitution mutation in vivo, of nucleotide G to either A or T at position +51 in the downstream positive promoter element +43 to +53 may potentially cause hypobetalipoproteinemia, a heterozygous from of an autosomal-dominant disorder.


Assuntos
Apolipoproteínas B/genética , Mutação Puntual , Sequência de Bases , Linhagem Celular , Cloranfenicol O-Acetiltransferase/genética , DNA/genética , Éxons , Regulação da Expressão Gênica , Genes Reporter , Humanos , Hipobetalipoproteinemias/genética , Fígado/metabolismo , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , Transcrição Gênica , Transfecção
14.
Biochim Biophys Acta ; 1447(2-3): 244-50, 1999 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-10542322

RESUMO

Natural killer (NK) cells are bone marrow-derived lymphocytes that have the ability to kill certain tumor cells and virally infected cells. The activation of NK cells is mediated by a balance of negative and positive signals from cell-cell interactions and from responses to cytokines. However, the molecular basis of NK cell activation and recognition of target cells is poorly understood. We have previously identified, cloned and characterized a receptor, 2B4, expressed on murine NK cells. 2B4 is not only expressed on all NK cells, but also on a subset of T-cells which have NK-like killing properties. Structural analysis indicated that 2B4 belongs to the CD2 subset of immunoglobulin superfamily. We have also shown 2B4 to interact with CD48 with nine times more affinity than that of CD2-CD48 interaction. In order to understand the transcriptional regulation as well as the mechanisms controlling the restricted expression of the 2B4 gene, we obtained a genomic 2B4 clone including the sequence of the 5'-flanking region. To define the start site of transcription, we performed primer extension and 5'-RACE assays and found that the 2B4 gene may be initiated at multiple start sites and driven by a TATA-less promoter. Transient transfections of nested 5'-fragments of the 2B4 promoter to drive CAT expression revealed tissue specific expression in CTLL-2 cells, a mouse T-cell line. A promoter fragment of 348 bases upstream from the first base of the mouse 2B4 cDNA clone p2B4.8 produced maximal CAT activity in CTLL-2 cells. The presence of the region -653 to -540 on the other hand, drastically reduced transcription. Sequence analysis of this promoter region has identified potential recognition motifs for a number of lymphocyte-restricted in addition to ubiquitous transcription factors, which may play a role in the transcriptional regulation of the mouse 2B4 gene.


Assuntos
Antígenos CD , Células Matadoras Naturais , Glicoproteínas de Membrana/genética , Regiões Promotoras Genéticas/genética , Receptores Imunológicos/genética , Animais , Sequência de Bases , Clonagem Molecular , Genoma , Camundongos , Dados de Sequência Molecular , Família de Moléculas de Sinalização da Ativação Linfocitária
15.
Mol Immunol ; 37(12-13): 735-44, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11275258

RESUMO

2B4 (CD244) is a cell surface glycoprotein of the immunoglobulin superfamily involved in the regulation of natural killer and T lymphocyte function. It is the high affinity counter-receptor for CD48. In mouse and human NK cells, crosslinking of 2B4 with a specific monoclonal antibody or with CD48 can trigger cell-mediated cytotoxicity, IFN-gamma secretion, phosphoinositol turnover and NK cell invasiveness. Recent reports of defective 2B4 signaling and NK cell function in X-linked lymphoproliferative syndrome suggest that this may contribute to the progression of this human disease. Here we describe the molecular characterization of the rat 2B4 gene. The cDNA encodes a protein of 395 amino acid residues that contain two Ig domains in the extracellular region and three unique tyrosine motifs (TxYxxV/I/A) in the cytoplasmic region. The predicted protein has 81 and 68% similarity with mouse 2B4 and human 2B4, respectively. Additionally, it has 94 and 89% similarity at the protein level with the recently reported rat 2B4 related genes, r2B4R-tm and r2B4R-se respectively. Northern blot analysis indicated the presence of multiple transcripts in rat LAK cells and RNK-16 cells. Immunoprecipitation and deglycosylation studies showed that rat 2B4 is glycosylated to similar extent as that of mouse and human 2B4. The cloning of r2B4 in the light of the availability of rat NK cell lines should facilitate in vitro and in vivo experiments to decipher the functional role of 2B4 in NK cell biology.


Assuntos
Antígenos CD , Células Matadoras Naturais/imunologia , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Biblioteca Gênica , Glicoproteínas de Membrana/imunologia , Dados de Sequência Molecular , RNA Mensageiro/genética , Ratos , Receptores Imunológicos/imunologia , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Família de Moléculas de Sinalização da Ativação Linfocitária , Especificidade da Espécie
16.
Am J Clin Pathol ; 107(4): 410-8, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9124209

RESUMO

To evaluate the feasibility of acute leukemia typing on routinely processed bone marrow biopsy specimens, 72 cases of previously established acute leukemia covering the spectrum of 17 known subtypes were studied immunohistochemically. Most leukemic myeloblasts were positive for myeloperoxidase in 16 (84%) of 19 cases of acute myeloid leukemia, M1-M4, and M6. Most leukemic cells in 11 of 12 M4 and M5 cases were positive for CD68 (PG-M1). All six M6 cases stained with hemoglobin. Leukemic megakaryoblasts in three of four M7 cases were positive for factor VIII-related antigen. Almost all leukemic cells of 8 T-lineage acute lymphoblastic leukemia (ALL) and 19 B-lineage ALL cases were positive for CD3 and CD79a (HM57), respectively. Staining with CD20 (L26) was positive in the more differentiated B-lineage ALL cases and strongest in L3. Immunohistochemical typing of acute leukemia is possible for most types using this panel of cell lineage-specific antibodies.


Assuntos
Anticorpos , Medula Óssea/patologia , Imuno-Histoquímica/métodos , Leucemia/classificação , Trepanação/métodos , Doença Aguda , Anticorpos/análise , Anticorpos/imunologia , Antígenos CD/análise , Antígenos CD/imunologia , Antígenos CD20/análise , Antígenos CD20/imunologia , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Diferenciação Mielomonocítica/imunologia , Medula Óssea/química , Complexo CD3/análise , Complexo CD3/imunologia , Hemoglobinas/análise , Hemoglobinas/imunologia , Humanos , Imuno-Histoquímica/normas , Leucemia/diagnóstico , Leucemia/patologia , Leucemia Mieloide/classificação , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/patologia , Peroxidase/análise , Peroxidase/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Sensibilidade e Especificidade , Trepanação/normas , Fator de von Willebrand/análise , Fator de von Willebrand/imunologia
17.
Am J Clin Pathol ; 113(4): 506-11, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10761451

RESUMO

To find the best immunohistochemical marker for megakaryocytes in normal marrow, myelodysplastic syndrome (MDS), and chronic myeloproliferative disorders (CMPD), 57 marrow biopsy specimens were studied semiquantitatively with immunohistochemical methods using a panel of 7 antibodies. The staining intensity was graded 0 to 3 for scoring 100 consecutive megakaryocytes in each stained section. The final score for each stain was the sum of these 100 megakaryocytes individually multiplied by their corresponding grade. In normal marrow (11 cases), the average scores for antivon Willebrand factor (vWF) and Ulex europaeus agglutinin-1 (UEA-1) were 177.1 and 195.1, respectively. The scores for the other 5 markers, including anti-platelet-derived growth factor-BB, 2 anti-transforming growth factor-beta 3, anti-CD61, and anti-CD79a ranged from 96.1 to 124.1. In MDS (27 cases), the scores were 200.8 (vWF), 152.6 (UEA-1), and 28.7 to 98.5 (others). In CMPD (19 cases), the scores were 220.5 (vWF), 179.2 (UAE-1), and 64.8 to 101.2 (others). These results show that vWF and UEA-1 are good immunohistochemical markers for megakaryocytes in normal marrow, and vWF is the best marker in MDS and CMPD. For routine practice, vWF is the most reliable marker for identifying atypical megakaryocytes, especially in the cases of 5q-syndrome and agnogenic myeloid metaplasia.


Assuntos
Medula Óssea/metabolismo , Megacariócitos/metabolismo , Síndromes Mielodisplásicas/metabolismo , Transtornos Mieloproliferativos/metabolismo , Fator de von Willebrand/metabolismo , Biomarcadores/análise , Medula Óssea/patologia , Doença Crônica , Estudos de Avaliação como Assunto , Humanos , Imuno-Histoquímica/métodos , Síndromes Mielodisplásicas/patologia , Transtornos Mieloproliferativos/patologia , Variações Dependentes do Observador
18.
Pathol Oncol Res ; 5(3): 235-8, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10491025

RESUMO

Two Taiwanese patients with gallbladder small cell carcinoma are reported. One is a 79 year-old male, the other, a 86 year-old female. They both presented with the symptom/signs of acute cholecystitis and underwent cholecystectomy. An intramural mass in the gallbladder neck region was found in the first patient, while the second patient had a transmural indurated tumor in the gallbladder body with extension to the neck region. Characteristic histological and immunohistochemical features of small cell carcinoma were present in both, and electron dense neurosecretory granules were identified in the second. To our knowledge, the second patient is the oldest ever reported. The first patient received chemotherapy directed toward the initial erroneous diagnosis of non-Hodgkin s lymphoma and developed liver metastasis in two months. The second patient did not receive chemotherapy due to her poor general condition and local recurrence occurred in six weeks. Both passed away three and five months after surgery, respectively.


Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias da Vesícula Biliar/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/diagnóstico , Colecistite/patologia , Cromogranina A , Cromograninas/metabolismo , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Humanos , Masculino , Microscopia Eletrônica , Necrose
19.
Br J Radiol ; 77(921): 780-1, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15447967

RESUMO

Malignant mesothelioma of the tunica vaginalis is rare, and is usually not diagnosed until surgery is undertaken. Reports on the ultrasound features of this tumour are limited. We present an unusual case with ultrasound features mimicking an adenomatoid tumour.


Assuntos
Tumor Adenomatoide/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Neoplasias Testiculares/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Ultrassonografia Doppler em Cores
20.
Pathol Res Pract ; 197(2): 135-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11261818

RESUMO

Uterine leiomyoma with massive lymphoid infiltration is very rare and may simulate malignant lymphoma. To the best of our knowledge, this is the first description of such a lesion occurring in an Oriental, and the ninth case in the English literature. A 50-year-old Taiwanese woman had urinary frequency and nocturia because of a uterine myoma. The myomectomy specimen was identified as a well-defined tumor, 6.5-cm in diameter, the cut surface of which was pale, white and whorled. A massive lymphocytic infiltration accompanied by plasma cells and histiocytes was noted in the leiomyoma but not in the surrounding non-neoplastic myometrial fibers. Most infiltrating lymphocytes were positive for CD3 and T cell intracellular antigen-1, a cytotoxic marker. The postoperative course was uneventful, and the urinary symptoms improved within a 6-month follow-up period.


Assuntos
Leiomioma/patologia , Infiltração Leucêmica/patologia , Linfoma/patologia , Linfócitos T Citotóxicos/patologia , Neoplasias Uterinas/patologia , Útero/patologia , Adulto , Complexo CD3/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Leiomioma/cirurgia , Infiltração Leucêmica/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Linfócitos T Citotóxicos/metabolismo , Neoplasias Uterinas/cirurgia , Útero/cirurgia
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