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1.
J Immunol ; 212(6): 951-961, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38315039

RESUMO

Signal-transducing adaptor protein (STAP)-1 is an adaptor protein that is widely expressed in T cells. In this article, we show that STAP-1 upregulates TCR-mediated T cell activation and T cell-mediated airway inflammation. Using STAP-1 knockout mice and STAP-1-overexpressing Jurkat cells, we found that STAP-1 enhanced TCR signaling, resulting in increased calcium mobilization, NFAT activity, and IL-2 production. Upon TCR engagement, STAP-1 binding to ITK promoted formation of ITK-LCK and ITK-phospholipase Cγ1 complexes to induce downstream signaling. Consistent with the results, STAP-1 deficiency reduced the severity of symptoms in experimental autoimmune encephalomyelitis. Single-cell RNA-sequencing analysis revealed that STAP-1 is essential for accumulation of T cells and Ifng and Il17 expression in spinal cords after experimental autoimmune encephalomyelitis induction. Th1 and Th17 development was also attenuated in STAP-1 knockout naive T cells. Taken together, STAP-1 enhances TCR signaling and plays a role in T cell-mediated immune disorders.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Encefalomielite Autoimune Experimental , Inflamação , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Inflamação/metabolismo , Inflamação/patologia , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T , Transdução de Sinais
2.
Rinsho Ketsueki ; 64(4): 260-264, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37121769

RESUMO

A 75-year-old man developed multiple head masses as well as a compression fracture. His blood test revealed elevated immunoglobulin G (IgG) protein levels, and immunofixation electrophoresis revealed the presence of monoclonal IgGκ. Furthermore, positron emission tomography/computed tomography revealed multiple bone lesions, although bone marrow examination revealed only 1.2% of plasma cells. Biopsy of a head mass led to the diagnosis of plasmablastic lymphoma (PBL), an aggressive B-cell lymphoma with plasma cell phenotypes but no B-cell antigen expression. Because the tumor cells have plasmablastic morphologies, it is difficult to distinguish PBL from plasmablastic myeloma, which is a subtype of multiple myeloma. Both diseases have similar immunophenotypes and clinical courses. In this case, PBL was finally diagnosed based on Epstein-Barr virus positivity, and the patient made a complete recovery after treatment with DA-EPOCH.


Assuntos
Infecções por Vírus Epstein-Barr , Mieloma Múltiplo , Linfoma Plasmablástico , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4
3.
Rinsho Ketsueki ; 64(1): 35-41, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-36775305

RESUMO

Acquired hemophilia A (AHA) is a rare disease characteized by bleeding symptoms caused by decreased factor VIII activity due to the appearance of inhibitors to factor VIII triggered by malignancy or collagen disease. An 86-year-old woman developed purpura on her extremities after the first dose of the BNT162b2 mRNA COVID-19 vaccine. This symptom subsided after a few days. After the second dose of the BNT162b2 mRNA COVID-19 vaccine, purpura appeared again, and the patient was referred to our hospital Her APTT was remarkably prolonged to 110 seconds, and a cross-mixing test revealed an inhibitor pattern. Since FVIII activity was <1% and FVIII inhibitor was 51.6 BU, she was diagnosed with AHA. Prednisolone therapy was started, and coagulative complete remission was achieved. Because acquired hemophilia can develop after mRNA COVID-19 vaccination, as in this case, it is critical to monitor the appearance of bleeding symptom.


Assuntos
Vacina BNT162 , COVID-19 , Hemofilia A , Idoso de 80 Anos ou mais , Feminino , Humanos , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , COVID-19/complicações , Hemofilia A/induzido quimicamente , Hemofilia A/terapia , Hemorragia
4.
Leuk Res Rep ; 17: 100294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242526

RESUMO

To overcome the unfavorable outcome of refractory/relapsed (R/R) Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) and conduct allogeneic stem cell transplantation (allo-SCT) safely, we designed a sequential therapy involving a single cycle of Inotuzumab ozogamicin (InO) and Blinatumomab (Blina). Two heavily treated and aged patients with R/R Ph+ALL were treated with the therapy. Both of them achieved complete molecular remission without cytokine release syndrome and underwent allo-SCT without veno-occlusive disease/sinusoidal obstruction syndrome. Although appropriate central nervous system prophylaxis should be added, the InO-Blina sequential therapy is a promising strategy for treating R/R Ph+ALL as a bridging regimen before allo-SCT.

5.
Clin Case Rep ; 10(2): e05384, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35140970

RESUMO

FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation-positive acute myeloid leukemia (AML) has a poor prognosis. We report the first case of successful bridge therapy of novel FLT3 inhibitor, quizartinib, to umbilical cord blood stem cell transplantation for FLT3-ITD-positive AML-primary induction failure patients with central nervous system involvement.

6.
Int J Hematol ; 115(3): 322-328, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35037230

RESUMO

Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia. ITP is generally characterized by an increased percentage of RP, and a normal or slightly increased plasma TPO level. We now report three cases of thrombocytopenia after allo-HSCT. RP% was elevated in these patients, as it is in primary ITP. However, in contrast to primary ITP, plasma TPO levels were high in two of three patients. Anti-αIIbß3 and anti-GPIb/IX-specific direct IgG antibodies were detected as well, suggesting occurrence of immune-mediated platelet destruction in addition to bone marrow suppression in two patients. All three patients were successfully treated with corticosteroids and/or thrombopoietin receptor agonists (TPO-RAs). These results suggest that increased RP% and detection of glycoprotein-specific platelet autoantibodies are useful for the diagnosis of ITP after HSCT.


Assuntos
Autoanticorpos/sangue , Plaquetas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Contagem de Plaquetas , Glicoproteínas da Membrana de Plaquetas/imunologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/etiologia , Transplante Homólogo/efeitos adversos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Biomarcadores/sangue , Plaquetas/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico
7.
Exp Hematol ; 105: 10-17, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34780812

RESUMO

Inflammatory and immune signals are involved in stressed hematopoiesis under myeloablation, infection, chronic inflammation, and aging. These signals also affect malignant pathogenesis, and the dysregulated immune environment which causes the resistance to treatment. On activation, various types of protein tyrosine kinases in the cytoplasm mediate the cascade, leading to the transcription of target genes in the nucleus. Adaptor molecules are commonly defined as proteins that lack enzymatic activity, DNA-binding or receptor functions and possess protein-protein or protein-lipid interaction domains. By binding to specific domains of signaling molecules, adaptor proteins adjust the signaling responses after the ligation of receptors of soluble factors, including cytokines, chemokines, and growth factors, as well as pattern recognition receptors such as toll-like receptors. The signal-transducing adaptor protein (STAP) family regulates various intracellular signaling pathways. These proteins have a pleckstrin homology domain in the N-terminal region and an SRC-homology 2-like domain in the central region, representing typical binding structures as adapter proteins. Following the elucidation of the effects of STAPs on terminally differentiated immune cells, such as macrophages, T cells, mast cells, and basophils, recent findings have indicated the critical roles of STAP-2 in B-cell progenitor cells in marrow under hematopoietic stress and STAP-1 and -2 in BCR-ABL-transduced leukemogenesis. In this review, we focus on the role of STAPs in the bone marrow.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Hematológicas/metabolismo , Hematopoese , Fosfoproteínas/metabolismo , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Neoplasias Hematológicas/patologia , Humanos , Transdução de Sinais
8.
Biochem Biophys Res Commun ; 556: 185-191, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33845308

RESUMO

Chronic myeloid leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia chromosome and its oncogenic product, BCR-ABL, which activates multiple pathways involved in cell survival, growth promotion, and disease progression. We recently reported that signal-transducing adaptor protein 1 (STAP-1) is upregulated in CML stem cells (LSCs) and functions to reduce the apoptosis of CML LSCs by upregulating the STAT5-downstream anti-apoptotic genes. In this study, we demonstrate the detailed molecular interactions among BCR-ABL, STAP-1, and signal transducer and activator of transcription 5 (STAT5). Studies with deletion mutants have revealed that STAP-1 interacts with BCR-ABL and STAT5a through its SH2 and PH domains, respectively, suggesting the possible role of STAP-1 as a scaffold protein. Furthermore, the binding of STAP-1 to BCR-ABL stabilizes the BCR-ABL protein in CML cells. Since STAP-1 is highly expressed in CML cells, we also analyzed the STAP-1 promoter activity using a luciferase reporter construct and found that NFATc1 is involved in activating the STAP-1 promoter and inducing STAP-1 mRNA expression. Our results demonstrate that STAP-1 contributes to the BCR-ABL/STAT5 and BCR-ABL/Ca2+/NFAT signals to induce proliferation and STAP-1 mRNA expression in CML cells, respectively.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proliferação de Células , Proteínas de Fusão bcr-abl/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Proteínas de Fusão bcr-abl/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição NFATC/metabolismo , Ligação Proteica , Domínios Proteicos , Estabilidade Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
9.
Int J Hematol ; 114(1): 53-64, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33765256

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation. In addition to reactivation of Epstein-Barr virus in immunocompromised patients, impaired tumor immunity is suggested to be a risk factor for PTLD. However, it remains unclear whether immune suppressive tumor-infiltrating lymphocytes (TILs) correlate with the occurrence or prognosis of PTLD. We analyzed TILs in 26 patients with PTLD to elucidate the clinicopathological significance of the expression of PD-1 and FoxP3, which are associated with exhausted T-cells and regulatory T-cells (Tregs), respectively. Numbers of PD-1+ TILs in the PTLD specimens were significantly higher in patients who developed PTLD early after transplantation (P = 0.0040), while numbers of FoxP3+ TILs were not (P = 0.184). There was no difference in overall response rate regardless of the expression of PD-1 or FoxP3. FoxP3high patients tended to have a shorter time to progression compared with FoxP3low patients, especially in the case of FoxP3high patients with diffuse large B-cell lymphoma-subtype PTLD (P = 0.011), while PD-1high patients did not. These results suggest that T-cell exhaustion may be mainly associated with PTLD development, while immune suppression by Tregs may be dominant in enhanced progression of PTLD following disease occurrence.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos do Interstício Tumoral/patologia , Transtornos Linfoproliferativos/etiologia , Transplante de Órgãos/efeitos adversos , Receptor de Morte Celular Programada 1/análise , Adulto , Idoso , Feminino , Fatores de Transcrição Forkhead/análise , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Biochem Biophys Res Commun ; 537: 118-124, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33388414

RESUMO

Graft-versus-host disease (GVHD) is the most frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT), and is one of the major causes of non-relapse mortality. Transferred mature lymphocytes are thought to be responsible for GVHD based on the findings that mice transplanted with lymphocyte-depleted bone marrow (BM) cells from MHC-mismatched donors do not develop GVHD. However, we found that overexpression of signal-transducing adaptor protein (STAP)-2 in lymphoid cells could induce GVHD after lymphocyte-depleted BM transplantation. To examine the function of STAP-2, which has been shown to play an important role in development and function of lymphocytes, in GVHD, we transplanted BM cells from STAP-2 deficient, or Lck promoter/IgH enhancer-driven STAP-2 transgenic (Tg) mice into MHC-mismatched recipients. Unexpectedly, mice transplanted with lymphocyte-depleted BM cells from STAP-2 Tg mice developed severe acute GVHD with extensive colitis and atrophy of thymus, while no obvious GVHD developed in mice transplanted with the wild type or STAP-2 deficient graft. Furthermore, mice transplanted with lymphocyte-depleted BM cells from the syngeneic STAP-2 Tg mice developed modest GVHD with colitis and atrophy of thymus. These results suggest that STAP-2 overexpression may enhance survival of allo-, and even auto-, reactive lymphocytes derived from engrafted hematopoietic progenitor cells in lethally irradiated mice, and that clarification of the mechanism may help understanding induction of immune tolerance after HSCT.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células da Medula Óssea/imunologia , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/imunologia , Depleção Linfocítica , Doença Aguda , Animais , Contagem de Linfócitos , Complexo Principal de Histocompatibilidade , Camundongos Transgênicos , Linfócitos T Reguladores/imunologia , Transplante Homólogo
11.
Haematologica ; 106(2): 424-436, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31974192

RESUMO

Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and IκB kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia, however, none have been reported concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematological parameters were observed to be normal once recovery from transplantation was complete. Furthermore, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late-stage B cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7, however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-Seq analyses indicated multiple signaling pathways in B progenitors as STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Transplante de Células-Tronco Hematopoéticas , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linfócitos B/metabolismo , Macrófagos/metabolismo , Camundongos , Transdução de Sinais
12.
Oncogene ; 39(34): 5601-5615, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32661325

RESUMO

The family of signal-transducing adapter proteins (STAPs) has been reported to be involved in a variety of intracellular signaling pathways and implicated as transcriptional factors. We previously cloned STAP-2 as a c-Fms interacting protein and explored its effects on chronic myeloid leukemia (CML) leukemogenesis. STAP-2 binds to BCR-ABL, upregulates BCR-ABL phosphorylation, and activates its downstream molecules. In this study, we evaluated the role of STAP-1, another member of the STAP family, in CML pathogenesis. We found that the expression of STAP-1 is aberrantly upregulated in CML stem cells (LSCs) in patients' bone marrow. Using experimental model mice, deletion of STAP-1 prolonged the survival of CML mice with inducing apoptosis of LSCs. The impaired phosphorylation status of STAT5 by STAP-1 ablation leads to downregulation of antiapoptotic genes, Bcl-2 and Bcl-xL. Interestingly, transcriptome analyses indicated that STAP-1 affects several signaling pathways related to BCR-ABL, JAK2, and PPARγ. This adapter protein directly binds to not only BCR-ABL, but also STAT5 proteins, showing synergistic effects of STAP-1 inhibition and BCR-ABL or JAK2 tyrosine kinase inhibition. Our results identified STAP-1 as a regulator of CML LSCs and suggested it to be a potential therapeutic target for CML.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/genética , Modelos Animais de Doenças , Regulação Leucêmica da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Células K562 , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Neoplásicas/patologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/genética
13.
Int J Hematol ; 112(2): 254-257, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32200528

RESUMO

Various central nervous system (CNS) complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in severe clinical problems. Diagnosis is often difficult, as distinctive clinical symptoms may be absent and different neurological disorders may exhibit similar symptoms. Despite the fact that antibodies responding to brain cell surface antigens have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report on a patient who developed encephalitis associated with antibodies against N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against NMDA-type GluR in post-transplantation encephalitis. Autoimmunity to NMDA-type GluR may have contributed to neurological complications after transplantation in unresolved cases.


Assuntos
Autoanticorpos/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Encefalite Límbica/etiologia , Encefalite Límbica/imunologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/imunologia , Receptores de Glutamato/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Autoimunidade , Feminino , Humanos , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos
14.
Exp Clin Transplant ; 16(5): 628-630, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-27938314

RESUMO

Here, we describe a case of sequential varicella-zoster virus encephalomeningitis and progressive multifocal leukoencephalopathy following an allogeneic hematopoietic stem cell transplant procedure. A 37-year-old male patient presented with fever, incomplete paralysis of bilateral legs, and bullous eruptions 8 months after allogeneic transplant. Polymerase chain reaction assays of cerebrospinal fluid samples for varicella-zoster virus were positive. Bullous eruptions and incomplete paralysis of bilateral legs improved after administration of acyclovir. However, higher brain dysfunction was present and getting worse. We detected no herpes simplex virus, varicella-zoster virus, Cytomegalovirus, human herpes virus 6, Epstein-Barr virus, or JC virus in cerebrospinal fluid samples with polymerase chain reaction assays. Pathologic findings and polymerase chain reaction assays with brain biopsy samples revealed that the patient had progressive multifocal leukoencephalopathy. This is the first report of a case showing dual central nervous system infections due to varicella-zoster virus and JC virus after allogeneic stem cell transplant.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 3/patogenicidade , Vírus JC/patogenicidade , Leucoencefalopatia Multifocal Progressiva/virologia , Meningoencefalite/virologia , Infecções Oportunistas/virologia , Infecção pelo Vírus da Varicela-Zoster/virologia , Adulto , Antivirais/uso terapêutico , Biópsia , Progressão da Doença , Evolução Fatal , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Vírus JC/efeitos dos fármacos , Vírus JC/imunologia , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/imunologia , Imageamento por Ressonância Magnética , Masculino , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/imunologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/imunologia , Transplante Homólogo , Resultado do Tratamento , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Infecção pelo Vírus da Varicela-Zoster/imunologia , Ativação Viral
15.
Rinsho Ketsueki ; 56(11): 2351-6, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26666724

RESUMO

The rare central nervous system (CNS) infiltration of Waldenström macroglobulinemia (WM) is known as Bing-Neel syndrome (BNS). Furthermore, the transformation of WM into diffuse large B-cell lymphoma (DLBCL) is also unusual. Herein, we report a 69-year-old male with DLBCL transformed from BNS. In November 2008, the patient visited a prior hospital because of anemia and was diagnosed with WM. After receiving chemotherapy (R-CHOP), his serum immunoglobulin M (IgM) level decreased and then remained at approximately 2000 mg/dl for 3 years. In November 2011, he complained of visual impairment and photophobia in his left eye. Magnetic resonance imaging showed enlargement of the left optic nerve and cerebrospinal fluid examination indicated CNS infiltration of WM cells. Consequently, he was diagnosed with BNS. He thus received CNS targeted chemotherapy (R-MPV) and achieved a partial response. In May 2014, IgM was elevated and swelling of systemic lymph nodes was detected. Inguinal lymph node biopsy yielded a pathological diagnosis of DLBCL and the clonality of tumor cells between WM and DLBCL was confirmed by the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR).


Assuntos
Sistema Nervoso Central/patologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Macroglobulinemia de Waldenstrom/etiologia , Idoso , Rearranjo Gênico , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Macroglobulinemia de Waldenstrom/genética
16.
Int J Hematol ; 99(1): 95-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24264833

RESUMO

We report a case of a 40-year-old female who developed progressive multifocal leukoencephalopathy (PML), which is associated with JC virus reactivation, after allogeneic hematopoietic cell transplantation. As she had been suffering from graft-versus-host disease and lung damage after pneumocystis pneumonia, the administration of calcineurin inhibitor and steroid could not be discontinued. However, she showed a favorable improvement in clinical symptoms and imaging findings after treatment with the anti-malarial drug, mefloquine and a serotonin receptor blocker, mirtazapine. Continuation of the treatment for eight months finally led to the clearance of the JC virus from her cerebrospinal fluid. She currently shows no neurological disturbance and has resumed her daily activities. PML due to the severe immunosuppressive condition has been reported as a fatal complication after allo-SCT. Our case suggests that combination treatment with mefloquine and mirtazapine may be of great value for the treatment for PML patients in the post allo-SCT setting, although it is difficult to say whether the combination treatment alone led to improvement. Further clinical study is needed to clarify the efficacy of these drugs for the treatment of PML.


Assuntos
Antivirais/uso terapêutico , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Mefloquina/uso terapêutico , Mianserina/análogos & derivados , Adulto , Encéfalo/patologia , Quimioterapia Combinada , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/etiologia , Imageamento por Ressonância Magnética , Mianserina/uso terapêutico , Mirtazapina , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante Homólogo , Resultado do Tratamento
17.
Brain Res ; 960(1-2): 282-5, 2003 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-12505685

RESUMO

1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ) and TIQ are endogenous substances inducing bradykinesia, one of the symptoms of parkinsonism, in rodents and primates, and 2-methyl-TIQ is postulated to be an active form of TIQ. We investigated the effect of 1-BnTIQ-, TIQ- or 2-methyl-TIQ-treatment on the binding of 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-[N-methyl-11C]tropane to striatal dopamine transporters (DATs) in mice. Neither 1-BnTIQ (80 mg/kg, i.p., twice per day for 10 days) nor 2-methyl-TIQ (40 mg/kg, i.p., twice per day for 10 days) affected the radioligand-DAT binding, while TIQ (80 mg/kg, i.p., twice per day for 10 days) induced a 14% decrease. These results indicate that 1-BnTIQ does not affect the density of DATs on dopaminergic neurons, and that it is not clear whether or not 2-methyl-TIQ is an active form of TIQ.


Assuntos
Isoquinolinas/farmacologia , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras/metabolismo , Proteínas do Tecido Nervoso , Tetra-Hidroisoquinolinas , Animais , Sítios de Ligação/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina , Masculino , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Camundongos , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ensaio Radioligante
18.
J Texture Stud ; 2(2): 207-219, 1971 May.
Artigo em Inglês | MEDLINE | ID: mdl-28371975

RESUMO

In order to clarify the relationship between different texture measurements, a principal component analysis was applied to the analysis of instrumental and sensory texture descriptions obtained on 72 samples of boiled plant protein representing hard gels, soft gels, and pastes. Twelve objective parameters were quantified using the Texturometer, the OKADA Gelometer, and the Curd Meter. Over 80% of the total variance could be explained by the first three components. The first component corresponded to parameters measuring breaking stress or 'hardness', the second to parameters measuring 'springiness', and the third to parameters measuring 'adhesion'. Hard gel samples were characterized by high values for the first component. Soft gel and paste samples could be distinguished from each other on the basis of the third component, with pastes being generally more adhesive.

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