Asunto(s)
Tejido Adiposo/patología , Imagen por Resonancia Magnética/métodos , Miastenia Gravis/diagnóstico , Timoma/diagnóstico , Timo/patología , Neoplasias del Timo/diagnóstico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/complicaciones , Estudios Retrospectivos , Timoma/complicaciones , Neoplasias del Timo/complicacionesRESUMEN
OBJECTIVE: To investigate the association of two glucocorticoid receptor (GR) polymorphisms (BclI, ER22/23EK) with Myasthenia Gravis (MG). METHODS: The genotypes of GR in 61 MG patients (MGG) and 57 age and gender-matched healthy controls (HCG) were determined by polymerase chain reaction and nucleotide sequence determination. RESULTS: The frequencies of three genotypes (GG, CG, CC) in BclIwere 3.3%, 34.4%, 62.3% in MGG and 3.5%, 38.6%, 57.9%in HCG respectively. The difference in the distribution of genotypes between MGG and HCG was statistically insignificant (P = 0.887). The frequencies of G and C allele were 20.5% vs 79.5 %in MGG, and 22.8% vs 77.2% in HCG. The difference in the distribution of alleles between MGG and HCG was statistically insignificant (P = 0.968). The genotype frequencies in two groups were both in Hardy-Weinberg equilibrium (P > 0.05). The genotypes of ER22/23EK in MGG and HCG were all GG and no mutation was detected. CONCLUSION: BclI and ER22/23EK polymorphisms of GR have no definite relationship with the risk of MG.
Asunto(s)
Miastenia Gravis/genética , Polimorfismo de Nucleótido Simple , Receptores de Glucocorticoides/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. METHODS: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). RESULTS: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. CONCLUSIONS: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
Asunto(s)
Crotonatos/uso terapéutico , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Toluidinas/uso terapéutico , China , Crotonatos/administración & dosificación , Crotonatos/efectos adversos , Método Doble Ciego , Esquema de Medicación , Humanos , Hidroxibutiratos , Inmunosupresores/administración & dosificación , Estudios Multicéntricos como Asunto , Esclerosis Múltiple/metabolismo , Nitrilos , Modelos de Riesgos Proporcionales , Toluidinas/administración & dosificación , Toluidinas/efectos adversosRESUMEN
OBJECTIVE: To investigate the characteristics of enhanced brain magnetic resonance imaging (MRI) with gadolinium-DTPA (GD) in patients with multiple sclerosis (MS). METHODS: Brain enhanced MRI were studied in 186 patients with clinically definite multiple sclerosis. 298 MRI enhanced lesions were followed every 4 weeks and the study lasted 3 months to 2 years. RESULTS: Of the 298 enhanced MRI lesions 207 (69.5%) lasted less than 4 weeks, 251 (84.2%) 8 weeks, and 272 (91.3%) 12 weeks. There were 3 lesions lasting more than 2 years. Round, oval, ring form, arcuate, spotty, or irregular MRI GD enhanced lesions were found in our MS data. CONCLUSIONS: Most of the MRI GD enhanced lesions disappear in 4 weeks. Very few can last more than 2 years. So it is necessary to perform the GD enhanced MRI in 4 weeks for studying MS intracranial GD enhanced lesions. The DA enhanced MRI lesions in MS may be round, oval, ring form, arcuate, spotty or irregular.
Asunto(s)
Medios de Contraste , Gadolinio DTPA , Esclerosis Múltiple/diagnóstico , Adolescente , Adulto , Anciano , Encéfalo/patología , Niño , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
This study was purposed to investigate the biological characteristics and immunogenicity changes of ex vivo expanded megakaryocyte progenitors from human umbilical cord blood CD34(+) cells in order to provide experimental basis for clinical application of ex vivo expanded umbilical cord blood megakaryocyte progenitor cells. Mononuclear cells (MNCs) were obtained from umbilical cord blood by Ficoll-Hyapaque density gradient separation. CD34(+) cells were enriched by magnetic cell sorting (MACS). The selected CD34(+) cells were seeded in serum-free medium stimulated with thrombopoietin (TPO, 50 ng/ml), interleukin 11 (IL-11, 50 ng/ml), and heparin (25 U/ml) for 14 days. The immunophenotyping (CD34(+), CD41a(+), CD61(+), CD34(+) CD41a(+) and CD34(+) CD61(+) cells) of amplificated products, matured megakaryocyte apoptosis, and expression of human leukocyte antigen (HLA) class I and class II molecules were measured by fluorescence-activated cell sorter (FACS). The number of colony-forming units-megakaryocyte (CFU-Mk) was also evaluated by CFU-Mk assay. The results showed that the umbilical cord blood CD34(+) mononuclear cells could be effectively differentiated into megakaryocytes. The peak expression ratios of CD41a(+) and CD61(+) cells were all at 14th days, while that of CD34(+) CD41(+) and CD34(+) CD61(+) cells were at 7th day [(3.41 +/- 2.80)% and (1.89 +/- 1.43)%, respectively]. The expansion times of large and small CFU-Mk reached peak at 7th day (20.66 +/- 32.79) and 10th day (435.62 +/- 482.65), respectively. The apoptotic rates of megakaryocytes at 7th, 10th, 14th day were (19.48 +/- 9.64)%, (26.87 +/- 9.03)%, and (52.46 +/- 11.74)%, respectively. The apoptotic rate of megakaryocytes had no significant difference in 7 and 10 days culture (p > 0.05), while that significantly increased in culture for 14 day culture, compared with culture for 7 and 10 days (p < 0.05, respectively). The expression of HLA class I and class II molecules on megakaryocytes decreased along with the prolongation of expansion time and sharply decreased in 0 to 10 days. It is concluded that the cytokines of TPO, IL-11, and heparin can promote the expansion of megakaryocyte progenitors from umbilical cord blood CD34(+) mononuclear cells effectively in vitro. The peaked expansion times of large CFU-Mk, the peaked expression ratios of CD34(+) CD41(+) and CD34(+) CD61(+) cells were all at 7th day. So the culture for 7 days appeared to be the optimal duration of expanding megakaryocyte progenitors.
Asunto(s)
Sangre Fetal/citología , Células Progenitoras de Megacariocitos/citología , Antígenos CD34/inmunología , Diferenciación Celular , División Celular , Separación Celular , Células Cultivadas , Sangre Fetal/inmunología , HumanosRESUMEN
The purpose of this study was to explore the differences in megakaryocyte progenitor ex vivo expansion between CD34+ cells derived from human umbilical cord blood (CB) and bone marrow (BM). Mononuclear cells (MNCs) were obtained from CB or BM by Ficoll-Hypaque density gradient separation. CD34+ cells were purified by magnetic cell sorting (MACS). The selected CD34+ cells were seeded in serum-free conditions stimulated with thrombopoietin (TPO), TPO+interleukin 11 (IL-11), or TPO+IL11+heparin for 14 days. Amplification product (CD34+, CD41a+, and CD34+ CD41a+ cells) immunophenotypes, megakaryocyte apoptosis rates and the DNA content were measured by fluorescence-activated cell sorting (FACS). The colony-forming units of granulocytes and monocytes (CFU-GM), burst-forming units of erythrocytes (BFU-E), and colony-forming units of megakaryocytes (CFU-Mk) were also evaluated by the colony-forming units (CFU) assay. The results indicated that CD34+ cells derived from CB showed higher expansion ability of total cell counts, CD41a+ and CD34+ CD41a+ cells than those derived from BM for all days 14 of culture (p<0.05, respectively). There were no significant differences in CFU-GM, BFU-E, and total CFU-Mk counts between CB and BM-derived CD34+ cells on day 0 (p>0.05, respectively), but CB-derived CFU-Mk seemed mainly large colonies, and the number of large colonies was higher than that from BM (p<0.05) on day 0. There were no significant differences in expansion ability of CFU-GM between CB and BM-derived cells on days 7, 10, and 14 of culture (p > 0.05, respectively), but the expansion ability of BFU-E and CFU-Mk derived from CB cells was higher than that from BM (p<0.05, respectively). There were no significant differences in apoptosis rates of megakaryocyte from two source cells for days 14 of culture. Megakaryocytes derived from CB mostly showed the 2N DNA content (>90%) for days 14 of culture, while those cells derived from BM showed the increased DNA content, and 4N, 8N or more ploidy cells gradually increased with prolonging of culture time. It is concluded that CB-derived CD34+ cells have a greater proliferation potential than that derived from BM, which is therefore proven to be a better cell source for megakaryocyte progenitor expansion in vitro.