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1.
Phys Rev Lett ; 130(17): 176301, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37172228

RESUMO

The phonon magnetochiral effect (MChE) is the nonreciprocal acoustic and thermal transports of phonons caused by the simultaneous breaking of the mirror and time-reversal symmetries. So far, the phonon MChE has been observed only in a ferrimagnetic insulator Cu_{2}OSeO_{3}, where the nonreciprocal response disappears above the Curie temperature of 58 K. Here, we study the nonreciprocal acoustic properties of a room-temperature ferromagnet Co_{9}Zn_{9}Mn_{2} for unveiling the phonon MChE close to room temperature. Surprisingly, the nonreciprocity in this metallic compound is enhanced at higher temperatures and observed up to 250 K. This clear contrast between insulating Cu_{2}OSeO_{3} and metallic Co_{9}Zn_{9}Mn_{2} suggests that metallic magnets have a mechanism to enhance the nonreciprocity at higher temperatures. From the ultrasound and microwave-spectroscopy experiments, we conclude that the magnitude of the phonon MChE of Co_{9}Zn_{9}Mn_{2} mostly depends on the Gilbert damping, which increases at low temperatures and hinders the magnon-phonon hybridization. Our results suggest that the phonon nonreciprocity could be further enhanced by engineering the magnon band of materials.

2.
Leukemia ; 32(3): 675-684, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28804123

RESUMO

Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. An in silico drug discovery analysis recognized 69 (46%) cases carrying at least one genomic alteration considered a potential target of drug response according to early clinical trials or preclinical assays in DLBCL or other lymphomas. In conclusion, this study identifies relevant pathways and mutated genes in DLBCL and recognizes potential targets for new intervention strategies.


Assuntos
Variação Genética , Genômica , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Transdução de Sinais , Adulto , Idoso , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA , Feminino , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Janus Quinases/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Receptores Notch/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Ann Oncol ; 28(11): 2799-2805, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29045517

RESUMO

BACKGROUND: The co-existence at diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a transformed lymphoma and accordingly treated although clinicobiological information on these patients is scarce. The aim of this study was to analyze the initial features and outcome of FL/DLBCL patients in the rituximab era. PATIENTS AND METHODS: All patients consecutively diagnosed at a single institution with FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n = 510) as controls. RESULTS: The proportion of the DLBCL component was highly variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these cases. The proportion of DLBCL component did not impact on overall survival (OS). Regarding initial characteristics, patients with FL/DLBCL were closer to FL in terms of primary nodal origin, good performance status and advanced stage, whereas the other features were intermediate between FL and DLBCL. FL/DLBCL patients were treated as DLBCL with no further intensification. Complete response and primary refractory rates were 65% and 20%, respectively, with these figures being similar to DLBCL and worse than FL. Progression-free survival and OS were intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic value for OS in the multivariate analyses. CONCLUSIONS: The outcome of FL/DLBCL patients is not worse than that of de novo DLBCL. These cases should be treated with immunochemotherapy as DLBCL, but intensification with ASCT may not be necessary. The biological insights of FL/DLBCL warrants further genetic and molecular studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Recidiva Local de Neoplasia/mortalidade , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Linfoma Folicular/complicações , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida
4.
Nat Mater ; 15(12): 1237-1242, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27643728

RESUMO

Skyrmions, topologically protected nanometric spin vortices, are being investigated extensively in various magnets. Among them, many structurally chiral cubic magnets host the triangular-lattice skyrmion crystal (SkX) as the thermodynamic equilibrium state. However, this state exists only in a narrow temperature and magnetic-field region just below the magnetic transition temperature Tc, while a helical or conical magnetic state prevails at lower temperatures. Here we describe that for a room-temperature skyrmion material, ß-Mn-type Co 8Zn 8Mn 4, a field-cooling via the equilibrium SkX state can suppress the transition to the helical or conical state, instead realizing robust metastable SkX states that survive over a very wide temperature and magnetic-field region. Furthermore, the lattice form of the metastable SkX is found to undergo reversible transitions between a conventional triangular lattice and a novel square lattice upon varying the temperature and magnetic field. These findings exemplify the topological robustness of the once-created skyrmions, and establish metastable skyrmion phases as a fertile ground for technological applications.

5.
Ann Oncol ; 20(4): 715-21, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19150954

RESUMO

BACKGROUND: The International Peripheral T-cell Lymphoma Project was organized to better understand the T-cell and natural killer (NK) cell lymphomas, and our task is to present the clinicopathologic correlations and therapeutic results for adult T-cell leukemia/lymphoma (ATL). PATIENTS AND METHODS: Among 1153 patients with T-cell or NK cell lymphomas, 126 patients (9.6%) with ATL were represented in this project. All were categorized as aggressive ATL, i.e. acute or lymphoma type, and 87% fell into the lymphoma type. RESULTS: The median age was 62 years and the male to female ratio was 1.2 : 1. Significant prognostic factors for overall survival (OS) by univariate analysis were the presence of B symptoms (P = 0.018), platelet count <150 x 10(9)/l (P = 0.065), and the International Prognostic Index (IPI; P = 0.019). However, multivariate analysis indicated that only the IPI was an independent predictor of OS. Combination chemotherapy including anthracyclines was given as the initial therapy in 109 of the 116 patients (94%) who received treatment, and the overall and complete response rates were 70% and 34%, respectively. However, there was no survival benefit for those receiving an anthracycline-containing regimen. CONCLUSION: Patients with aggressive ATL have a poor clinical outcome and the IPI is a useful model for predicting outcome in ATL of the lymphoma type.


Assuntos
Leucemia-Linfoma de Células T do Adulto/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
Leukemia ; 22(1): 87-95, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18033315

RESUMO

An acquired JAK2 V617F mutation is found in most patients with polycythemia vera (PV), and about half of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Mice transplanted with bone marrow cells in which JAK2 V617F was retrovirally expressed developed PV-like features, but not ET or PMF. To address the contribution of this mutation to the pathogenesis of these three MPDs, we generated two lines of JAK2 V617F transgenic mice. One line showed granulocytosis after 4 months of age. Among 43 mice, 8 (19%) showed polycythemia and 15 (35%) showed thrombocythemia. The second line showed extreme leukocytosis and thromobocytosis. They showed anemia that means Hb value from 9 to 10 g per 100 ml when 1 month old. Myeloid cells and megakaryocytes were predominant in the bone marrow of these animals, and splenomegaly was observed. The expression of JAK2 V617F mRNA in bone marrow cells was 0.45 and 1.35 that of endogenous wild-type JAK2 in the two lines, respectively. In vitro analysis of bone marrow cells from both lines showed constitutive activation of ERK1/2, STAT5 and AKT, and augmentation of their phosphorylations by cytokine stimulation. We conclude that in vivo expression of JAK2 V617F results in ET-, PMF- and PV-like disease.


Assuntos
Regulação da Expressão Gênica/fisiologia , Janus Quinase 2/genética , Policitemia Vera/genética , Mielofibrose Primária/genética , Trombocitemia Essencial/genética , Animais , Transplante de Medula Óssea , Citocinas/metabolismo , Feminino , Humanos , Leucocitose/patologia , Masculino , Megacariócitos/citologia , Megacariócitos/metabolismo , Camundongos , Camundongos Transgênicos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mutação/genética , Células Mieloides/citologia , Células Mieloides/metabolismo , Fosforilação , Policitemia Vera/metabolismo , Policitemia Vera/patologia , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Fator de Transcrição STAT5/metabolismo , Trombocitemia Essencial/metabolismo , Trombocitemia Essencial/patologia
8.
Br J Dermatol ; 154(5): 904-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16634894

RESUMO

BACKGROUND: Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. OBJECTIVES: To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES. METHODS: Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30. RESULTS: CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder. CONCLUSIONS: We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.


Assuntos
Quimiocinas/metabolismo , Linfoma Anaplásico de Células Grandes/imunologia , Papulose Linfomatoide/imunologia , Receptores de Quimiocinas/metabolismo , Neoplasias Cutâneas/imunologia , Adolescente , Adulto , Quimiocina CCL5/metabolismo , Quimiocina CXCL9 , Quimiocinas CXC/metabolismo , Criança , Feminino , Humanos , Antígeno Ki-1/análise , Ligantes , Linfoma Anaplásico de Células Grandes/patologia , Papulose Linfomatoide/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Receptores CCR3 , Receptores CXCR3 , Neoplasias Cutâneas/patologia
9.
J Clin Pathol ; 59(2): 160-5, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16443732

RESUMO

BACKGROUND: Malignant peripheral nerve sheath tumour (MPNST) is a highly aggressive malignancy that arises within peripheral nerves, and is associated with poor prognosis. Little is known about the underlying biology of MPNST, especially the mechanisms involved in cell proliferation, invasion, or escape from apoptosis. AIMS: To identify genes differentially expressed in MPNST compared with benign tumours, such as neurofibromas and schwannomas, by means of cDNA microarray analysis. METHODS: Six MPNST cases and five benign cases (three schwannomas and two neurofibromas) were analysed. RESULTS: Six genes (keratin 18, survivin, tenascin C, adenosine deaminase, collagen type VIa3, and collagen type VIIa1) were significantly upregulated in MPNST, whereas one gene, insulin-like growth factor binding protein 6, was downregulated in MPNST. Survivin and tenascin C expression was validated by reverse transcription polymerase chain reaction. Immunohistochemistry confirmed upregulation of survivin in MPNST at the protein level in six of eight cases compared with benign tumours. Tenascin C was also expressed at the invasive front and tumorous stroma in all MPNST cases. MPNST cells expressed tenascin C in four of nine cases. CONCLUSIONS: Survivin and tenascin C may be associated with the malignant potential of MPNST and could be considered as potential therapeutic targets.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Neoplasias de Bainha Neural/metabolismo , Neoplasias do Sistema Nervoso Periférico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Técnicas Imunoenzimáticas , Proteínas Inibidoras de Apoptose , Masculino , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Neoplasias de Bainha Neural/genética , Neoplasias de Bainha Neural/patologia , Neurilemoma/genética , Neurilemoma/metabolismo , Neurilemoma/patologia , Neurofibroma/genética , Neurofibroma/metabolismo , Neurofibroma/patologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Neoplasias do Sistema Nervoso Periférico/genética , Neoplasias do Sistema Nervoso Periférico/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Survivina , Tenascina/biossíntese , Tenascina/genética , Regulação para Cima
10.
Ann Oncol ; 17(1): 110-6, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16291580

RESUMO

We microdissected Hodgkin and Reed-Sternberg (HRS) cells from 14 Hodgkin's lymphoma tissue samples (nodular sclerosis = 5; mixed cellularity = 9), and after isolation and amplification of mRNA, analyzed the expression profile of 140 genes of chemokines, cytokines and their receptors by cDNA microarray methods. We also compared the profile with those of germinal center (GC) cells in reactive lymphadenitis. Unsupervised clustering revealed a relatively homogeneous expression profile in HRS cells. HRS cells tended to express mainly Th2 T cell-associated molecules rather than those of Th1, compared with GC cells. Interleukin-11 receptor alpha (IL-11Ralpha), a previously unknown HRS cell-specific gene, was detected in addition to known genes. Immunohistochemical staining confirmed the expression of IL-11Ralpha at the protein level. In contrast, only few cases were positive for IL-11Ralpha in B cell lymphoma, diffuse large cell lymphoma and follicular lymphoma. This is the first analysis report of tissue HRS cells with cDNA microarray technique.


Assuntos
Citocinas/genética , Perfilação da Expressão Gênica , Doença de Hodgkin/genética , Receptores de Interleucina/genética , Células de Reed-Sternberg/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiocinas/genética , Criança , Feminino , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Subunidade alfa de Receptor de Interleucina-11 , Masculino , Microdissecção , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Receptores de Interleucina-11 , Células de Reed-Sternberg/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/patologia , Células Th2/imunologia , Células Th2/metabolismo , Células Th2/patologia , Células Tumorais Cultivadas
11.
Histopathology ; 47(5): 467-78, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16241994

RESUMO

AIMS: Lymphomatous polyposis (LP) is considered to represent mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract. However, a few reports have suggested that some are follicular lymphoma (FL) or mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we analysed 35 patients and clarified the clinicopathological features of LP. METHODS AND RESULTS: Paraffin-embedded tissue samples were stained immunohistochemically and analysed by tissue-fluorescence in situ hybridization (T-FISH) for IGH/CCND1 (cyclin D1) and IGH/BCL2. The average age of the patients was 58.3 years. Over half of the cases showed gastric, duodenal, small intestinal, ileocaecal and sigmoid colonic lesions (15, 19, 15, 16 and 16 cases, respectively). Phenotypically, cases were classified into three types of MCL (cyclin D1+ CD5+ CD10-) (n=12), FL (cyclin D1- CD5- CD10+) (n=14) and MALT (cyclin D1- CD5- CD10-) (n=9). T-FISH identified 11 of the 11 examined cases with MCLs to have IGH/CCND1, while seven of 10 cases with FL had IGH/BCL2, and none of the MALT cases were positive for IGH/CCND1 or IGH/BCL2. At the study endpoint, five of 12 patients with MCL were dead, two of 14 with FL and one of nine with MALT were dead of other disease. Event-free survival analysis showed significantly poorest outcome in MCL, followed by FL, while MALT was associated with a favourable outcome (P=0.0040). CONCLUSIONS: Our study emphasizes the importance of differentiating MCL, FL and MALT of LP in evaluating prognosis and hence the most suitable therapeutic regimen.


Assuntos
Neoplasias Gastrointestinais/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma Folicular/diagnóstico , Linfoma de Célula do Manto/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Neoplasias Gastrointestinais/patologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Folicular/patologia , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade
12.
Clin Exp Rheumatol ; 23(2): 239-42, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15895897

RESUMO

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is upregulated and recruits and activates inflammatory cells in nephritis of MRL lpr mice. It has been shown that anti-MCP-1 gene therapy is specifically effective in nephritis, while it was apparent that an imbalance towards Th1 predominance accelerates nephritis in MRL/lpr mice. The aim of this study was to clarify whether blockade of the MCP-1 signal by anti-MCP-1 gene therapy influences the Th1/Th2 balance in MRL/lpr mice. METHOD: An NH2-terminal deletion mutant of the MCP-1 gene (7ND) was injected into the skeletal muscles of MRL/Ipr mice with advanced stage nephritis to suppress MCP-1 and its receptor (CCR2) signaling pathway. We evaluated the local tissue production of cytokines in splenocytes and microdissected infiltrating cells within the glomeruli or interstitium. RESULT: Although the production of cytokines in splenocytes was not influenced by anti-MCP-1 gene therapy, kidney glomeruli IL-12 mRNA production and interstitium-infiltrating cell production of IL-12 and IFN-gamma mRNA were significantly reduced. CONCLUSION: The blockade of MCP-1 gene therapy does not influence helper T cell polarization, but acts directly on the regional Th1 immunoreaction in MRL/lpr mice.


Assuntos
Quimiocina CCL2/genética , Terapia Genética , Nefrite Lúpica/terapia , Células Th1/metabolismo , Animais , Quimiocina CCL2/antagonistas & inibidores , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Terapia Genética/métodos , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-12/genética , Interleucina-12/metabolismo , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Camundongos , Camundongos Endogâmicos MRL lpr , RNA Mensageiro/biossíntese , Células Th1/imunologia , Células Th2/imunologia , Células Th2/metabolismo
13.
Leukemia ; 19(6): 1058-63, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15815725

RESUMO

Follicular lymphomas (FL) are morphologically classified into grades 1, 2, 3a and 3b by the World Health Organization. Bcl2, Bcl6 and CD10 are phenotypic markers of FL while the Bcl2 t(14;18) and Bcl6 t(3q27) gene translocations are common genetic changes. However, to date, there has been no integrated analysis based on phenotype, grade and genotype from large numbers of FL cases. We graded 261 cases of FL and determined their phenotypes and gene alterations. According to the antigen markers and gene alterations of 147 cases, we classified FL into typical and the others types. The typical group, which includes 69% cases of FL, is characterized by low histological grade (grade 1, 2), coexpression of BCL2 and CD10 and Bcl2 gene translocation. The rest comprises a small part of low-grade FL without Bcl2 gene translocation and high-grade (grade 3a, 3b) FL. These FLs include some heterogeneous disease entities. They are characterized by high histological grade (87%), no definite expression of BCL2 or CD10 and several kinds of gene aberrances including Bcl2 translocation, Bcl6 translocation, Bcl2 amplification or other unknown gene abnormality. Our findings indicate that typical FL presents a homogeneous disease entity whereas the rest comprises heterogeneous diseases entities.


Assuntos
Proteínas de Ligação a DNA/genética , Linfoma Folicular/genética , Linfoma Folicular/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Translocação Genética , Biomarcadores Tumorais , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Marcadores Genéticos , Genótipo , Humanos , Hibridização in Situ Fluorescente , Linfoma Folicular/classificação , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-6
14.
Br J Dermatol ; 152(1): 76-81, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15656804

RESUMO

BACKGROUND: Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). ATLL frequently involves the skin. OBJECTIVES: To correlate the clinicopathological features and prognosis in patients with ATLL and cutaneous lesions. METHODS: We examined the HTLV-I proviral state and the clinicopathological features of the cutaneous lesions in 80 patients with serum anti-ATL antibody, to clarify the correlation between macroscopic/histopathological findings and prognosis. Southern blot analysis was performed in all cases to detect monoclonal HTLV-I proviral DNA integration. RESULTS: The cutaneous lesions of 46 patients were positive for proviral DNA integration. The median survival time of patients with monoclonal proviral DNA integration in cutaneous lesions was 14 months, which was markedly shorter than that of patients negative for proviral DNA integration (72 months). Of the 46 patients with proviral DNA, 21 had solitary or multiple red nodules (including three with subcutaneous induration), eight had multiple red papules and 17 had erythema. Patients with papules and nodules had poorer prognosis than those with erythema. Histopathologically, the prognosis was poorer in patients with nodular or diffuse infiltration of medium-sized to large lymphoma cells, compared with those with perivascular infiltration of small to medium-sized lymphoma cells. CONCLUSIONS: Our results show a close correlation between clinicopathological features of HTLV-I-associated cutaneous lesions and prognosis.


Assuntos
Leucemia-Linfoma de Células T do Adulto/patologia , Infiltração Leucêmica , Pele/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Viral/análise , Feminino , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Provírus/isolamento & purificação , Pele/imunologia , Pele/virologia , Análise de Sobrevida , Integração Viral
15.
Br J Haematol ; 127(3): 305-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15491290

RESUMO

The expression and prognostic significance of hepatocyte growth factor (HGF) and its receptor c-MET (MET proto-oncogene) was analysed in 96 cases of diffuse large B-cell lymphoma (DLBCL). Tissue sections were immunohistochemically stained for HGF and c-Met. The prognosis of HGF-positive and c-Met-positive cases was significantly worse than negative cases (HGF: P = 0.0036; c-Met: P = 0.0002). In addition, in the low-risk international prognostic index group, HGF-negative and c-Met-negative cases had a significantly better prognosis than positive cases (HGF: P = 0.0009; c-Met: P < 0.0001). Our results suggest that HGF/c-MET is a useful clinical marker of prognosis for patients with DLBCL.


Assuntos
Fator de Crescimento de Hepatócito/análise , Linfoma Difuso de Grandes Células B/química , Proteínas Proto-Oncogênicas c-met/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica/métodos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proto-Oncogene Mas , Análise de Sobrevida
16.
Leuk Lymphoma ; 44(8): 1339-46, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12952227

RESUMO

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. The heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is involved in pre-mRNA processing and binds to telomeric cDNA repeats. The hnRNP B1 is a marker for early cancer. The aim of our study was to clarify the relationships between prognosis and apoptosis, telomerase activity (TA) and hnRNP expression in the bone marrow. The subjects were 51 patients with MDS, including patients with refractory anemia (RA) (n = 32), refractory anemia with ringed sideroblasts (RARS) (n = 1), refractory anemia with excess blasts (RAEB) (n = 7), refractory anemia with excess blasts in transformation (RAEB-t) (n = 8) and chronic myelomonocytic leukemia (CMMoL) (n = 3). We also studied 6 cases with acute myelogenous leukemia (AML) arising from MDS (AML-MDS) and 10 control subjects. Bone marrow biopsies were stained immunohistochemically for caspase-3 (marker of apoptotic activity) and human telomerase reverse transcriptase (hTERT), and hnRNP B1. Fatal pancytopenia was the cause of death in 19 of the 51 patients. The caspase-3 positive cell rate was higher in MDS (16.3%) than in controls (4.4%) and AML-MDS (0.5%). The percentage of hnRNP B1-positive cells was higher in MDS (15.3%) and AML-MDS (56.3%) than in controls (5.6%). In MDS, hnRNP B1 levels were higher in RAEB and RAEB-t subtypes than in RA and RARS. The percentage of hTERT-positive cells was higher in AML-MDS (50.0%) than in controls (20.2%) and MDS (23.6%). Our findings suggest that activation of apoptosis occurs in MDS in the absence of hTERT expression, implicating high apoptosis in the absence of high TA with ineffective hematopoiesis. Poor prognosis correlated with higher caspase-3 and lower hTERT rates. In MDS, hnRNP B1 activity may be associated with leukemic transformation.


Assuntos
Apoptose , Hematopoese , Síndromes Mielodisplásicas/enzimologia , Síndromes Mielodisplásicas/patologia , Telomerase/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Medula Óssea/patologia , Estudos de Casos e Controles , Caspase 3 , Caspases/análise , Feminino , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/análise , Humanos , Imuno-Histoquímica , Leucemia Mieloide , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Pancitopenia/etiologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
17.
J Biol Chem ; 264(29): 17606-12, 1989 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-2677012

RESUMO

We found an endogenous growth factor, referred to here as heart-derived growth factor (HDGF), that stimulates the proliferation of vascular endothelial cells. HDGF was purified from bovine myocardium using a procedure that involves denaturation of undesired proteins with methanol and chloroform. Soluble HDGF was purified essentially to homogeneity in a single step by heparin affinity chromatography. The purified HDGF was identified to be acidic fibroblast growth factor based on the following properties: molecular weight of 18,000, isoelectric point of 5.2, amino acid composition and sequence, its dissociation from a heparin affinity column at 0.9 M NaCl, potentiation of activity in the presence of heparin, and antigenicity. Our yield of HDGF was 500 micrograms/kg of tissue. Antiserum raised to HDGF localized HDGF in the cardiac myocytes in culture. These data indicate that a large amount of acidic fibroblast growth factor is present in the heart, and the cardiac myocytes are likely to be a major source of it.


Assuntos
Fatores de Crescimento de Fibroblastos/isolamento & purificação , Miocárdio/análise , Sequência de Aminoácidos , Aminoácidos/análise , Animais , Bovinos , Divisão Celular , Cromatografia de Afinidade , Sinergismo Farmacológico , Endotélio Vascular/citologia , Fatores de Crescimento de Fibroblastos/farmacologia , Heparina/farmacologia , Imunoensaio , Técnicas Imunoenzimáticas , Ponto Isoelétrico , Dados de Sequência Molecular , Peso Molecular , Fragmentos de Peptídeos
18.
Tohoku J Exp Med ; 134(1): 55-8, 1981 May.
Artigo em Inglês | MEDLINE | ID: mdl-6797099

RESUMO

The oral loading tests of lysine in 9 healthy men and the intravenous loading tests of lysine, ornithine and arginine in 3 healthy men were carried out. The results indicated that the membrane transport system of citrulline in the human kidney was clearly inhibited by dibasic amino acids, lysine, ornithine, and arginine.


Assuntos
Aminoácidos/metabolismo , Citrulina/metabolismo , Rim/metabolismo , Arginina/metabolismo , Transporte Biológico , Humanos , Lisina/metabolismo , Masculino , Ornitina/metabolismo
19.
Hum Genet ; 44(3): 287-93, 1978 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-103801

RESUMO

A prenatal diagnosis of GM1-gangliosidosis was made in a pregnancy at risk, on the basis of a deficiency of beta-galactosidase activity demonstrated in cultured amniotic fluid cells. Biochemical analyses were performed in the aborted fetus. GM1-ganglioside beta-galactosidase activity was reduced to 1% of the control value in both the brain and liver of the affected fetus. Lamellar bodies suggestive of membranous cytoplasmic bodies were found in cells of basal ganglions, while the accumulation of GM1-ganglioside in the brain was not remarkable.


Assuntos
Encéfalo/enzimologia , Feto/enzimologia , Galactosidases/metabolismo , Gangliosidoses/genética , beta-Galactosidase/metabolismo , Líquido Amniótico/citologia , Feminino , Gangliosidoses/diagnóstico , Glucuronidase/metabolismo , Humanos , Leucócitos/enzimologia , Fígado/enzimologia , Masculino , Manosidases/metabolismo , Gravidez , Diagnóstico Pré-Natal
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