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1.
Chin Med J (Engl) ; 129(9): 1072-7, 2016 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-27098793

RESUMO

BACKGROUND: Gaucher's disease (GD) is an autosomal recessive disorder caused by a deficiency of acid ß-glucosidase (glucocerebrosidase [GBA]) that results in the accumulation of glucocerebroside within macrophages. Many mutations have been reported to be associated with this disorder. This study aimed to discover more mutations and provide data for the genetic pattern of the gene, which will help the development of quick and accurate genetic diagnostic tools for this disease. METHODS: Genomic DNA was obtained from peripheral blood leukocytes of the patient and Sanger sequencing is used to sequence GBA gene. Sequence alignments of mammalian ß-GBA (GCase) and three-dimensional protein structure prediction of the mutation were made. A construct of this mutant and its compound heterozygous counterpart were used to measure GCase in vitro. RESULTS: GCase is relatively conserved at p.T219A. This novel mutation differs from its wild-type in structure. Moreover, it also causes a reduction in GCase enzyme activity. CONCLUSION: This novel mutation (c.655A>G, p.T219A) is a pathogenic missense mutation, which contributes to GD.


Assuntos
Doença de Gaucher/genética , Glucosilceramidase/genética , Mutação de Sentido Incorreto , Pré-Escolar , Glucosilceramidase/química , Humanos , Masculino , Modelos Moleculares , Estrutura Terciária de Proteína , Análise de Sequência de DNA
2.
J Med Virol ; 88(5): 871-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26455510

RESUMO

In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis.


Assuntos
Herpesvirus Humano 4/genética , Mononucleose Infecciosa/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Adulto , Criança , Pré-Escolar , DNA Viral/análise , DNA Viral/genética , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Lactente , Masculino , Sensibilidade e Especificidade , Carga Viral/métodos , Adulto Jovem
3.
Pediatr Hematol Oncol ; 31(1): 11-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24308692

RESUMO

BACKGROUND: Our previous experiments with gene chip suggested that basic fibroblastic growth factor (FGF2) levels were lower in mesenchymal stem cell (MSC) from aplastic anemia patients. The purpose of this study was to determine the expression of FGF2 in MSC and in bone marrow of children with aplastic anemia to better understand the role of low FGF2 expression in the pathogenesis of aplastic anemia. PROCEDURE: MSCs from the bone marrow of aplastic anemia children and control group were cultured in vitro. Growth curves of primary and passage MSC were plotted. FGF2 gene expression in MSCs was detected using quantitative real-time polymerase chain reaction (RT-PCR). FGF2 protein expression in mononuclear cells and FGF2 protein level in extracellular fluid of bone marrow were also investigated. RESULT: Decreased growth of MSCs from aplastic anemia children was observed after passage 8 in serial subcultivation, and FGF2 gene expression was downregulated. Within the patients' bone marrow, low FGF2 expression was validated both in mononuclear cells and in the extracellular fluid. CONCLUSION: Low FGF2 gene expression in MSCs and low FGF2 protein level in bone marrow of aplastic anemia may involve to pathogenesis of aplastic anemia.


Assuntos
Anemia Aplástica/metabolismo , Células da Medula Óssea/metabolismo , Fator 2 de Crescimento de Fibroblastos/biossíntese , Células-Tronco Mesenquimais/metabolismo , Adipócitos/metabolismo , Anemia Aplástica/genética , Células da Medula Óssea/patologia , Diferenciação Celular , Células Cultivadas , Criança , Ensaio de Unidades Formadoras de Colônias , Regulação para Baixo , Líquido Extracelular/química , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Células-Tronco Mesenquimais/patologia , Osteoblastos/metabolismo , RNA Mensageiro/biossíntese
4.
Zhonghua Er Ke Za Zhi ; 49(3): 226-30, 2011 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21575376

RESUMO

OBJECTIVE: To evaluate the efficacy of antithymocyte globulin (ATG) based immunosuppression therapy for childhood aplastic anemia, to reduce the adverse effects and to observe the long-term outcome. METHOD: Thirty-five children with aplastic anemia (AA) were enrolled in this study. Six of the cases had very severe AA (VSAA), 11 had severe AA (SAA)-I, 8 had SAA-II and 10 had moderate AA (MAA). All these patients were treated with ATG plus Cyclosporin A (CSA). The following measures were taken during the ATG therapy: infection of the patients had been controlled before ATG treatment. Comprehensive anti-allergic measures were implemented. Close attention was paid to the hemorrhage related with platelet reduction caused by ATG and severe infection of the patients. RESULT: Shortly after the ATG usage, all the patients had a significant decrease of absolute peripheral lymphoblast count by more than 60 percent. With a mean follow-up time of 28 months, the total effective rate was 77.14% (27/35), significant response rate was 57.14%(20/35). There was no significant difference among VSAA, SAA and MAA groups in the response rate. Adverse reactions included the following: (1) 48.6% (17/35) patients presented mild anaphylactoid reaction during the first day of ATG treatment; (2) 42.9%(15/35) cases presented serum sickness 5 - 11 days after the last dose of ATG with a mean duration of 3.6 days, all the patients were cured effectively with methylprednisolone; (3) 25.7% (9/35) patient's peripheral blood platelet count was reduced, might be caused by ATG, to below 10 × 10(9)/L, but no patient had severe hemorrhagic complication after platelet transfusion was performed; (4) 22.9%(8/35)of patients got infection within a month after ATG therapy, including 3 cases with clinical septicemia, all the 3 cases recovered after antibiotics treatment. There was no ATG treatment-related death in this series. CONCLUSION: ATG is a very effective therapy for children with SAA and MAA. Comprehensive measures are needed to prevent and handle the side effects to avoid treatment-related death. Long-term supportive therapy and proper follow up contribute to the favourable outcomes of the patients.


Assuntos
Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Resultado do Tratamento
6.
Zhonghua Er Ke Za Zhi ; 46(4): 276-80, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-19099730

RESUMO

OBJECTIVE: It has been reported that high-dose cytarabine (HD-AraC) was very effective for childhood hematological malignancies, especially for improving the long-term survival of high-risk acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and T-cell lymphoid malignancies (T-ALL, T-cell non-Hodgkin's lymphoma). This study aimed to evaluate the pharmacokinetics of HD-AraC for childhood hematological malignancies, and the relationship between the expression of the genes coding the key enzymes for Ara-C metabolism with the outcome of the patients. METHODS: The drug levels of Ara-C in plasma and cerebrospinal fluid were detected with HPLC while HD-AraC was used, the expression of deoxycytidine kinase (dCK) and cytidine deaminase (CDA) mRNA in human leukemia cell lines and the bone marrow cells were investigated in 48 cases of childhood hematological malignancies with RT-PCR methods, and the relationship between the expression of these enzymes mRNA and the outcome of the patients was analyzed. RESULTS: (1) When HD-AraC was used, the plasma levels of Ara-C and Ara-U could be respectively about 50 times and 25 times higher than those obtained when the patients were treated with regular dose of Ara-C treatment, and the level of Ara-C in cerebrospinal fluid could reach about 10% of plasma level of Ara-C. (2) There were significantly different expressions of dCK mRNA in different childhood acute leukemia (AL) patients, which were markedly related to the chemotherapy results. The expression of dCK in ALL was much higher than that in AML and relapsed AL cases. There were no significant differences in expressions of dCK in T-ALL and B lineage ALL. (3) In vitro study found that the expressions of dCK and CDA mRNA did not change in leukemia cell lines incubated at different doses and times of Ara-C. CONCLUSIONS: HD-AraC was a very effective protocol for childhood hematological malignancies for it could significantly elevate the plasma and cerebrospinal fluid drug levels. The expression of dCK may be an important factor in predicting the long-term outcomes of children with hematological malignancies. Good long-term outcomes of the childhood T-ALL could be achieved as the B lineage ALL had been treated with HD-AraC regimen. As the expression levels of dCK were much lower, it may be necessary for the treatment of AML with HD-AraC for consecutive three days.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Citarabina/farmacocinética , Leucemia/genética , Leucemia/metabolismo , Criança , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Citidina Desaminase/genética , Desoxicitidina Quinase/genética , Expressão Gênica , Humanos , Leucemia/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo
8.
Zhonghua Er Ke Za Zhi ; 46(12): 909-13, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19134253

RESUMO

OBJECTIVE: In contrast to severe aplastic anemia (SAA), the appropriate management of patients with moderate aplastic anemia (MAA) is unclear. Recently, it was reported that when childhood MAA was treated with supportive care alone, 2/3 of patients progressed to SAA, and therefore patients with MAA should be treated with immunosuppressive (IS) therapy in time. The present study aimed to review the natural history, the rate of progression to SAA and outcome of children with MAA seen at our institution over the past 12 years and to explore the relationship between the effectiveness of IS therapy and the immune mediated pathological mechanism. METHODS: Seventy-one MAA patients were included in this study. At the first stage, thirty-six children with MAA were given IS therapy (IS group, antithymocyte globulin, ATG or cyclosporin-A, CSA). The therapeutic effects were evaluated and compared with those of 35 children with MAA who received the treatment of supportive care alone (androgens, control group). At the second stage, the patients with MAA progressed to SAA were given combined immunosuppressive (CIS) therapy (CIS group, a combination of ATG, CSA and high-dose immunoglobulin). Peripheral blood lymphocyte subsets levels were measured with a flow cytometer. RESULTS: At the first stage, in the IS group, the percentage of overall and complete responders was 83.3% and 69.4%, respectively, which was significantly higher than that of the control group (34.3% and 17.1%). Twenty-three patients with MAA progressed to SAA. In the control group, 18 patients with MAA progressed to SAA. In the IS group, five patients with MAA progressed to SAA. The 17 patients with MAA who progressed to SAA were given combined immunosuppressive therapy. The percentage of overall and complete responders was 70.6% and 41.2%, respectively. The level of CD4(+), NK cell ratio decreased but the level of CD8(+) cell increased in MAA children before the treatment. The level of NK and CD4(+) cell was significantly higher in the IS group with the treatment than in the control group. CONCLUSION: When childhood MAA is treated with supportive care alone, more than 50% of patients may progress to SAA. Immune mediated pathological mechanism of MAA might be the base of IS therapy. IS therapy is effective and safe for childhood MAA.CIS therapy given to patients with MAA that was progressed to SAA may also be effective.


Assuntos
Anemia Aplástica/terapia , Imunossupressão , Imunossupressores/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento
10.
Zhonghua Er Ke Za Zhi ; 41(7): 525-7, 2003 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-14746680

RESUMO

OBJECTIVE: Some recent studies revealed that phenthiazine might be able to reverse tumor cell drug-resistance. Chlorderazin belongs to the phenthiazine compounds. The study aimed to investigate the reversing effect and mechanism of chlorderazin on multidrug resistance of leukemic cell line K562/AO2. METHODS: (1) The cytotoxicities of chlorderazin were assayed with the tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. (2) The reverse effect of chlorderazin on K562/AO2 cells was analyzed with MTT method. The multidrug resistance reversal index (RI) was equal to the ratio of control group IC(50)/test group half inhibition concentration IC(50). (3) The intracellular daunorubicin (DNR) concentrations were measured by the flow cytometry. (4) Mdr1 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). The ratio of mdr-1/beta-actin density was calculated. RESULTS: (1) Chlorderazin 3 micro g/ml showed little toxicity to K562/AO2 cells and the suppression rate was less than 5%, so the concentration of 3 micro g/ml chlorderazin was selected as the experiment concentration. (2) The cytotoxicities of DNR to K562/AO2 were enhanced by 3 micro g/ml of chlorderazin (P < 0.05) and RI was 1.901. (3) Chlorderazin of 3 micro g/ml could increase the intracellular DNR accumulation significantly (P < 0.05), and the fluorescence staining by the flow cytometry was higher (250.95 +/- 18.96) than the control group (112.75 +/- 15.78) and shift right in K562/AO2 cells treated with chlorderazin, and the difference was significant (P < 0.05). (4) Chlorderazin has no significant influence to the expression level of mdr-1 mRNA. Both test group and control group showed a clear mdr-1 mRNA band located at the position of 157 kb. The ratios of mdr-1/beta-actin density were 0.414 +/- 0.012 in the test group and 0.447 +/- 0.027 in the control group, respectively, and the difference was not significant (P > 0.05). CONCLUSION: Chlorderazin could reverse the multidrug resistance by increasing the intracellular DNR accumulation in K562/AO2 cells. The effects had no correlation to the mdr-1 gene. Further study is needed.


Assuntos
Antieméticos/farmacologia , Clorpromazina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Divisão Celular/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Citometria de Fluxo , Humanos , Células K562 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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