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1.
Intern Med ; 58(1): 109-113, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30146558

RESUMO

Werner syndrome (WS) confers a high risk of the development of neoplasias, including hematological malignancies, and curative treatment for these malignancies is difficult to achieve. A 44-year-old man with myelodysplastic syndrome was admitted to our hospital. He was diagnosed with mutation-proven WS. He underwent cord blood transplantation (CBT) following fludarabine, busulfan, and melphalan administration. A chimerism analysis of his marrow blood on day 62 showed a donor pattern >95%, which confirmed engraftment. The patient lived for 15 months while maintaining remission of MDS without treatment-related toxicity. Our case shows that CBT can be a treatment modality for WS patients with hematological malignancies.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Síndromes Mielodisplásicas/terapia , Síndrome de Werner/terapia , Adulto , Antineoplásicos/uso terapêutico , Humanos , Masculino , Síndromes Mielodisplásicas/etiologia , Transplante Homólogo , Resultado do Tratamento , Síndrome de Werner/complicações
2.
Int J Radiat Biol ; 94(4): 315-326, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29424599

RESUMO

PURPOSE: Chronic low-dose-rate (20 mGy/day) γ-irradiation increases the incidence of hepatocellular adenomas (HCA) in female B6C3F1 mice. The purpose of this study is to identify potential serum biomarkers for these HCAs by a new approach. MATERIAL AND METHODS: Microarray analysis were performed to compare the gene expression profiles of HCAs from mice exposed to low-dose-rate γ-rays with those of normal livers from non-irradiated mice. From the differentially expressed genes, those for possibly secretory proteins were selected. Then, the levels of the proteins in sera were analysed by ELISA. RESULTS: Microarray analysis identified 4181 genes differentially expressed in HCAs (>2.0-fold). From these genes, those for α-fetoprotein (Afp), α-1B-glycoprotein (A1bg) and serine peptidase inhibitor Kazal type-3 (Spink3) were selected as the genes for candidate proteins. ELISA revealed that the levels of Afp and A1bg proteins in sera significantly increased and decreased, respectively, in low-dose-rate irradiated mice with HCAs and also same tendency was observed in human patients with hepatocellular carcinomas. CONCLUSION: These results indicate that A1bg could be a new serum biomarker for liver tumor. This new approach of using microarray to select genes for secretory proteins is useful for prediction of novel tumor markers in sera.


Assuntos
Adenoma/diagnóstico , Biomarcadores Tumorais/sangue , Glicoproteínas/sangue , Imunoglobulinas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Induzidas por Radiação/diagnóstico , Adenoma/sangue , Adenoma/etiologia , Animais , Feminino , Raios gama , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etiologia , Camundongos , Neoplasias Induzidas por Radiação/sangue , Proteínas Secretadas pela Próstata/sangue , Doses de Radiação , Transcriptoma , Inibidor da Tripsina Pancreática de Kazal/sangue , alfa-Fetoproteínas/análise
3.
Int J Hematol ; 106(4): 533-540, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28612278

RESUMO

BACKGROUND: Primary testicular lymphoma (PTL) is a rare, extranodal lymphoma that often relapses in the contralateral testis. We evaluated outcomes in patients with any stage of PTL who had received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab chemotherapy and prophylactic radiotherapy to the contralateral testis. METHODS: We retrospectively identified 15 patients (median age 66 years; range 39-81) diagnosed with diffuse large B-cell PTL in the period 2000-2014. Characteristics and outcomes of these cases were evaluated. RESULTS: All patients received initial orchiectomy followed by CHOP with or without rituximab. Thirteen patients received prophylactic irradiation to the contralateral testis. During follow-up (median 67 months; range 8-190), one patient died of PTL, three died of other disease, and nine were free from relapse. For stage I-II disease, 5-year progression-free and overall survival rates were 80 and 100%, respectively. For stage III-IV PTL, 5-year progression-free and overall survival rates were 50 and 72%, respectively. Notably, no patient developed contralateral testicular involvement after prophylactic irradiation. CONCLUSIONS: The observed outcomes suggest that the combination of (i) CHOP plus rituximab and (ii) radiotherapy for local recurrence prophylaxis is promising for both stage I-II and stage III-IV PTL.


Assuntos
Linfoma/mortalidade , Linfoma/terapia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/prevenção & controle , Testículo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Radioterapia/métodos , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Vincristina/administração & dosagem
4.
Springerplus ; 5(1): 1146, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27504244

RESUMO

Calreticulin (CALR) and JAK2-V617F gene mutations, which are major genetic mutations in patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET), exert different effects on the clinical features and outcomes of these diseases. We analyzed 88 and 9 patients with ET and PMF, respectively, and determined the differences in the clinical characteristics of ET patients with JAK2-V617F compared with CALR mutations. The frequency of the JAK2-V617F and CALR mutations were 64 and 22 %, respectively. Patients with CALR mutations were younger, had a lower white blood cell count, and had a lower rate of thrombotic events than patients with the JAK2 mutation. The neutrophil alkaline phosphatase (NAP) score of 16 patients with CALR mutations was significantly lower than the normal controls, which was mainly due to the high proportion of NAP-negative neutrophils. This is the first report to show an association between CALR mutations in patients with myeloproliferative neoplasms (MPN) and the NAP score. Although the mechanism is unclear, the NAP score could be a useful and reliable biochemical marker to discriminate the mutational status of MPN patients. Further investigation is warranted to determine whether these characteristics contribute to the pathogenesis of MPN and the NAP score.

5.
Br J Haematol ; 174(2): 264-74, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27061580

RESUMO

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target.


Assuntos
Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/diagnóstico , Receptores de Lisoesfingolipídeo/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Centro Germinativo , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/química , Lisofosfolipídeos , Masculino , Pessoa de Meia-Idade , Fosforilação , Prognóstico , RNA Mensageiro/análise , Receptores de Lisoesfingolipídeo/genética , Fator de Transcrição STAT3/metabolismo , Esfingosina/análogos & derivados , Neoplasias Testiculares
6.
Rinsho Ketsueki ; 57(2): 165-70, 2016 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-26935634

RESUMO

In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 µmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.


Assuntos
Cardiomiopatias/terapia , Carnitina/deficiência , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal/transplante , Transplante de Células-Tronco Hematopoéticas , Hiperamonemia/terapia , Doenças Musculares/terapia , Neutrófilos/citologia , Doença Enxerto-Hospedeiro/terapia , Humanos
7.
Int J Hematol ; 104(1): 125-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26971963

RESUMO

Hereditary xerocytosis (HX) or dehydrated hereditary stomatocytosis (DHS) [OMIM 194380], in which PIEZO1 gene mutation has recently been identified, is difficult to diagnose. We report here the discovery of a PIEZO1 gene mutation in a Japanese family (father, daughter, and son) who were previously diagnosed with hereditary high phosphatidylcholine hemolytic anemia (HPCHA). All of the affected family members had non-spherocytic hemolytic anemia associated with severe hemochromatosis-related diabetes mellitus. Although the causative correlation between HPCHA and PIEZO1-gene mutated HX/DHS remains to be clarified, our findings raise an important question as to whether any of the HPCHA cases previously diagnosed in Japan may have in fact been the form of hemolytic anemia known as HX/DHS with PIEZO1 gene mutation.


Assuntos
Anemia Hemolítica Congênita não Esferocítica/genética , Anemia Hemolítica Congênita/diagnóstico , Anemia Hemolítica Congênita/genética , Diabetes Mellitus/etiologia , Canais Iônicos/genética , Mutação , Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Grupo com Ancestrais do Continente Asiático , Saúde da Família , Feminino , Hemocromatose/complicações , Humanos , Hidropisia Fetal/diagnóstico , Masculino , Linhagem , Fosfatidilcolinas
8.
Clin J Gastroenterol ; 9(2): 59-62, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27015999

RESUMO

A 16-year-old girl presented to our hospital with diarrhea and abdominal pain. The macroscopic findings of colonoscopy revealed multiple submucosal tumors and multiple ulcers, which were localized in the sigmoid colon, and diffuse granular mucosa which extended to the total colon. The pathological diagnosis was malignant lymphoma comprising both components of diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, because the large lymphoma cells were CD20+, CD10-, and CD5-. Furthermore, immunohistochemical analysis of colorectal biopsy samples from multiple ulcers revealed cytomegalovirus (CMV)-positive cells. The patient was diagnosed with primary colorectal lymphoma comprising both components of DLBCL and MALT lymphoma combined with CMV colitis. She received anti-viral medication and chemotherapy.


Assuntos
Colite/complicações , Neoplasias do Colo/complicações , Infecções por Citomegalovirus/complicações , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma Difuso de Grandes Células B/complicações , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Colite/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Ganciclovir/uso terapêutico , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico
10.
Biomed Res Int ; 2015: 451861, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26557672

RESUMO

Flow cytometric test for analyzing the eosin-5-maleimide (EMA) binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS). However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP) and Southeast Asian ovalocytosis (SAO), which are forms in the category of hereditary elliptocytosis (HE), show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF) cut-off value of 36.4 (sensitivity 0.97, specificity 0.95). Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells.


Assuntos
Eliptocitose Hereditária/metabolismo , Amarelo de Eosina-(YS)/análogos & derivados , Eritrócitos/metabolismo , Estudos de Casos e Controles , Amarelo de Eosina-(YS)/metabolismo , Citometria de Fluxo/métodos , Humanos , Sensibilidade e Especificidade
11.
Rinsho Ketsueki ; 56(7): 760-70, 2015 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-26251138

RESUMO

Red cell membrane disorders are the most common type of inherited hemolytic disorders in the Japanese population. In hereditary spherocytosis (HS), the primary presentation is a loss of membrane surface area, leading to reduced deformability because of defects in the membrane proteins ankyrin, band 3, ß-spectrin, α spectrin, or protein 4.2 (P4.2). Complete P4.2 deficiencies, which are inherited in an autosomal recessive manner, comprise a unique HS subgroup and are common in Japanese, but rare in other populations. In contrast, the principle presentation in hereditary elliptocytosis (HE) is mechanical weakness of the erythrocyte membrane skeleton due to defects in α-spectrin, ß-spectrin, or protein 4.1. Although α-spectrin mutations are the most frequent cause of HE in Caucasian, African, and Mediterranean populations, these mutations are rare in the Japanese population, in which P4.1 deficiencies are instead most common. Furthermore, hereditary stomatocytoses (HSt) are disorders of monovalent cation permeability in the red cell membrane.


Assuntos
Eliptocitose Hereditária/genética , Predisposição Genética para Doença , Eliptocitose Hereditária/metabolismo , Eliptocitose Hereditária/fisiopatologia , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Humanos , Japão , Modelos Biológicos , Mutação
12.
Rinsho Ketsueki ; 56(7): 837-45, 2015 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-26251147

RESUMO

Band 3 protein accounts for the largest percentage of whole erythrocyte membrane proteins. Abnormalities in this protein are closely associated with pathologies including hereditary spherocytosis (HS), Southeast Asian ovalocytosis and distant renal tubular acidosis. Currently, EMA binding capacity measurement in erythrocytes is the most useful screening test for diagnosing HS. We have also demonstrated reduced EMA binding capacity in patients with HS who have deficiencies of membrane proteins such as ankyrin not directly binding to EMA and who have as yet undetectable abnormalities of membrane proteins. However, even patients with hereditary elliptocytosis, who have a partial spectrin deficiency, were found to show reduced EMA binding capacity. Six of 7 had spherocytic elliptocytosis. Therefore, it is necessary to meticulously diagnose HS by ruling out all other possibilities.


Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/química , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Anquirinas/deficiência , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Esferocitose Hereditária/metabolismo , Proteína 1 de Troca de Ânion do Eritrócito/deficiência , Proteína 1 de Troca de Ânion do Eritrócito/genética , Anquirinas/química , Anquirinas/genética , Anquirinas/metabolismo , Humanos , Mutação , Ligação Proteica , Esferocitose Hereditária/genética
13.
Kansenshogaku Zasshi ; 89(6): 733-40, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26821522

RESUMO

Extremely early diagnosis of human immunodeficiency virus (HIV) infection has been considered highly important for its treatment. We conducted a performance assessment of a newly developed rapid diagnostic reagent for HIV by using a fourth-generation immunochromatographic assay (Alere HIV Combo). We used whole-blood, plasma, and serum samples obtained from 250 Japanese adults who visited the Kawasaki Medical School Hospital and underwent HIV screening tests. We also used 12 types of commercial HIV-1 sero- conversion panels and World Health Organization standard antigens. This method, which has a detection sensitivity of 100% and a specificity of 99.3%, was as accurate as the chemiluminescent immunoassay (CLIA) method. In a sensitivity test using seroconversion panels in the early phase of infection, the mean duration until positive conversion was 19.3 days. With this method having a high detection sensitivity for HIV-1p24 antigen, the results from whole-blood samples were the same as those from plasma and serum samples. Therefore, it can be considered as a useful rapid measurement method for general practice.


Assuntos
Cromatografia de Afinidade , Infecções por HIV/diagnóstico , HIV-1/imunologia , Adulto , Cromatografia de Afinidade/métodos , Anticorpos Anti-HIV/imunologia , Antígenos HIV/análise , HIV-1/isolamento & purificação , Humanos , Pessoa de Meia-Idade
14.
Virchows Arch ; 466(3): 343-50, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25503078

RESUMO

Genetic testing for mutations in the WRN gene is critical for the diagnosis of Werner syndrome (WS); however, these tests cannot be performed in a clinical setting. Nearly all of the WRN mutations result in expression of truncated WRN proteins that are missing the C-terminal nuclear localization signal. We evaluated the use of WRN protein immunohistochemistry for diagnosing WS using paraffin-embedded bone marrow sections. Using a well-defined commercially available polyclonal antibody against the C terminus of WRN, we found that of all the cell types tested, bone marrow erythroid precursors showed the strongest nuclear expression of WRN. Immunohistochemical analysis of bone marrow samples from 120 patients with non-WS hematological disorders (age range, 7 days-90 years) revealed WRN staining of the nuclei of CD71-positive early and late erythroid precursors. Erythroblasts negative for WRN immunostaining were only observed in two patients, both of whom were diagnosed with WS: one with concomitant myelodysplastic syndrome and the other with erythroleukemia with overexpression of TP53. Western blot analysis and immunocytochemistry indicated WRN was localized in the nuclei of the four positive control cell lines from non-WS patients but not in the five cell lines from WS patients, who had three different types of WRN mutations. Thus, immunohistochemical detection of WRN in erythroblasts from bone marrow paraffin sections could be useful in screening of WS cases and worthy of further molecular confirmation.


Assuntos
Eritroblastos/metabolismo , Exodesoxirribonucleases/metabolismo , RecQ Helicases/metabolismo , Síndrome de Werner/diagnóstico , Síndrome de Werner/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Linhagem Celular , Criança , Pré-Escolar , Eritroblastos/patologia , Exodesoxirribonucleases/genética , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Mutação/genética , RecQ Helicases/genética , Síndrome de Werner/patologia , Helicase da Síndrome de Werner , Adulto Jovem
15.
Intern Med ; 53(22): 2635-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25400189

RESUMO

We herein describe the case of a 60-year-old man with a history of Behçet's disease and myelodysplastic syndrome who received cord blood transplantation (CBT). The patient was given anti-thymocyte globulin conditioning and tacrolimus to prevent graft-versus-host disease. Two months after CBT, his blood Tac concentration measured by an antibody-conjugated magnetic immunoassay (ACMIA) was found to have increased >4-fold, even after the Tac treatment was stopped. This false response was caused by the interference of endogenous heterophilic antibodies with ACMIA. Therefore, physicians must be aware of possible false ACMIA results for patients with a history of autoimmune disease and/or treated by xenogeneic antibody therapy.


Assuntos
Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/administração & dosagem , Síndromes Mielodisplásicas/terapia , Tacrolimo/administração & dosagem , Síndrome de Behçet/epidemiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Reações Falso-Positivas , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia
16.
Case Rep Gastroenterol ; 8(2): 240-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25120415

RESUMO

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are members of the herpesvirus family and common causes of viral infection in humans. CMV infection of the gastrointestinal tract occurs mainly in immunocompromised individuals, on the other hand EBV infection and reactivation involving the gastrointestinal tract is very rare. A 56-year-old man was diagnosed with severe aplastic anemia and treated with antithymocyte globulin (ATG) and cyclosporine (CSP). After 2 years of ATG/CSP therapy, he suddenly started passing bloody diarrhea and developed a high fever despite CSP treatment. Endoscopic features included severe edema and multiple superficial ulcers; the patient was initially diagnosed with severe colitis resembling inflammatory bowel disease (IBD). However, his symptoms did not resolve with steroid treatment. Immunohistochemical analysis of samples obtained from a second colonoscopy showed cells positive for CMV, and in situ hybridization revealed EBV-encoded small RNA-1-positive cells. Additionally, the patient's serum was positive for C7-HRP, and both blood and colon tissues were positive for EBV DNA, which was detected using PCR analysis. We finally diagnosed the patient with colitis associated with reactivation of both CMV and EBV. The patient remains diarrhea-free after 1.5 years with scheduled globulin treatment and after cessation of immunosuppressive drug therapy. To our knowledge, this is the first reported case of an immunodeficient patient with severe hemorrhagic colitis that was associated with reactivation of both EBV and CMV, and whose endoscopic findings mimicked IBD.

17.
Springerplus ; 3: 177, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24790822

RESUMO

Central nervous system (CNS) relapse is a critical issue while treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). A 58-year-old woman with Ph-positive ALL who relapsed after bone marrow transplantation for meningeal leukemia was treated with high-dose methotrexate, which resulted in remission. She underwent allogeneic cord blood transplantation followed by reduced intensity conditioning chemotherapy with imatinib; however, she experienced CNS relapse and developed an extramedullary mass on the right side of the temporal region. We treated 40 mg of dasatinib once daily, which had to be temporarily discontinued because she developed grade 2 pleural effusion and grade 2 hematemesis. After reinitiation of dasatinib, the extramedullary mass disappeared and meningeal leukemia ameliorated almost immediately. With 40 mg dasatinib administered once daily, its trough level and cerebrospinal fluid (CSF) concentration were 32 ng/mL and below the sensitivity threshold of 1 ng/mL, respectively. Treatment was continued, and the patient remained in complete remission until she died of pneumonia 7 years after the initial diagnosis of ALL. Dasatinib can be an effective treatment for Ph-positive ALL with CNS relapse. Although the concentration in the CSF seems low, it may be sufficient to exert anti-leukemic effects in the human CNS.

18.
Opt Express ; 22(7): 8798-812, 2014 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24718249

RESUMO

In this paper, we examine the performance of several modulation formats in more than four dimensions for coherent optical communications systems. We compare two high-dimensional modulation design methodologies based on spherical cutting of lattices and block coding of a 'base constellation' of binary phase shift keying (BPSK) on each dimension. The performances of modulation formats generated with these methodologies is analyzed in the asymptotic signal-to-noise ratio regime and for an additive white Gaussian noise (AWGN) channel. We then study the application of both types of high-dimensional modulation formats to standard single-mode fiber (SSMF) transmission systems. For modulation with spectral efficiencies comparable to dual-polarization (DP-) BPSK, polarization-switched quaternary phase shift keying (PS-QPSK) and DP-QPSK, we demonstrate SNR gains of up to 3 dB, 0.9 dB and 1 dB respectively, at a BER of 10(-3).

19.
Thromb Haemost ; 109(4): 661-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23407795

RESUMO

Factor XIII (FXIII) is a fibrin-stabilising factor consisting of catalytic A subunits (FXIII-A) and carrier B subunits (FXIII-B). FXIII-B prevents the fast clearance of FXIII-A from the circulation. Congenital FXIII-A deficiency is a rare bleeding disorder, and congenital FXIII-B deficiency is even rarer. Through our recent nationwide survey on "acquired haemophilia-like disease due to anti-FXIII autoantibodies," we newly diagnosed severe congenital FXIII-B deficiency in a Japanese man. He developed thrombocytopenia and gingival bleedings at the age of 73, and his FXIII activity was as low as 10% of the normal. When he suddenly developed spontaneous intramuscular haematoma, the bleeding was arrested by infusing FXIII concentrates. However, his FXIII activity remained around 10% of the normal. At the age of 74, ELISA and western blotting assay unexpectedly revealed complete absence of FXIII-B in the patient's plasma. A dot blot assay detected anti-FXIII-B alloantibodies for the first time in this disease, which could be attributed to the infusion of exogenous FXIII. He was found to be homozygous for a Japanese founder-effect mutation of F13B. Repeated infusions of exogenous FXIII for hemostasis increased anti-FXIII-B alloantibodies that resisted FXIII substitution. To the best knowledge of the authors, none of the remaining 10 reported cases of congenital FXIII-B deficiency developed alloantibodies to exogenous FXIII-B of plasma FXIII. An originally mild bleeding phenotype of severe congenital FXIII-B deficiency can be exaggerated by additional acquired conditions. Physicians should consider congenital FXIII-B deficiency when they encounter cases of unexplained bleeding disorders.


Assuntos
Coagulação Sanguínea , Deficiência do Fator XIII/imunologia , Fator XIII/imunologia , Isoanticorpos/sangue , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , Testes de Coagulação Sanguínea , Coagulantes/administração & dosagem , Coagulantes/imunologia , Fator XIII/administração & dosagem , Fator XIII/genética , Deficiência do Fator XIII/sangue , Deficiência do Fator XIII/congênito , Deficiência do Fator XIII/diagnóstico , Deficiência do Fator XIII/tratamento farmacológico , Predisposição Genética para Doença , Humanos , Masculino , Mutação , Fenótipo , Fatores de Tempo , Resultado do Tratamento
20.
Radiat Res ; 179(2): 221-31, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23289387

RESUMO

The biological activities of molecules secreted into the serum of mice chronically irradiated with γ rays at low or medium dose rate (L/MDR) have not been well studied. In this work, the bioactive molecules found in the serum of chronically irradiated mice (dose rate: 0.0181 Gy/h) were characterized by a cell-based assay (CBA) using microarrays. This technique can predict changes in cytokine levels in serum by measuring gene expression profiles and analyzing molecular signaling pathways. Gene expression in cultured mouse embryo fibroblasts (MEFs) 1 day after addition of serum from nonirradiated or irradiated mice had different profiles. A high level of expression of lipocalin2 (Lcn2) was induced in MEFs upon addition of serum from MDR irradiated mice, and Lcn2 was used as a marker for identifying secreted molecules in serum. Based on microarray analysis of molecular pathways, we predicted that the enhanced gene expression of Lcn2 in MEFs might be caused by interleukin-1 (IL-1) in the serum of the irradiated mice, and that an IL-1α antibody could completely neutralize the enhanced gene expression of Lcn2 in MEFs. The increase in IL-1α levels in the serum from the irradiated mice was confirmed by ELISA experiments. However, an increase in IL-1ß could not be detected. These results indicated that IL-1α was released into the serum of mice chronically exposed to a high dose of γ-ray radiation at MDR. We therefore believe that the CBA method using microarrays will be applicable for the screening of bioactive molecules in serum, which will be useful for detecting various diseases and metabolic changes.


Assuntos
Efeito Espectador/efeitos da radiação , Raios gama/efeitos adversos , Proteínas da Fase Aguda/genética , Proteínas da Fase Aguda/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Especificidade de Anticorpos , Efeito Espectador/genética , Linhagem Celular , Citocinas/imunologia , Relação Dose-Resposta à Radiação , Feminino , Lipocalina-2 , Lipocalinas/genética , Lipocalinas/imunologia , Fígado/metabolismo , Fígado/efeitos da radiação , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/imunologia , Soro/metabolismo , Soro/efeitos da radiação , Fatores de Tempo , Transcriptoma/efeitos da radiação
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