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  • 1
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1709-1709
    Abstract: Abstract 1709 The outcome of myelodysplastic syndromes (MDS) still remains unsatisfactory, with a low complete remission (CR) rate and a poor overall survival rate. Decitabine improved the overall responses of MDS as a hypomethylating agent, but CR rates remain low and prolonged pancytopenia. Our recently study showed that infusion of G-CSF mobilized HLA-mismatched peripheral blood stem cells (G-PBSC) can improve the outcome of chemotherapy for acute myeloid leukemia in elderly patients. However, whether G-PBSC combining decitabine and cytarabine chemotherapy will improve outcomes in MDS patients is unknown. Material and methods: Total of 72 patients with MDS, from 16 to 82 years of age, were assigned to receive decitabine 25–30 mg/m2daily for 4 days with cytarabine 150 mg/m2 daily for 7 days by intravenous followed to infusion of G-PBSC on 24 hours after each completion of the cytarabine therapy (Microtransplantation-group, n=28) or decitabine 20 mg/m2 daily for 5days (Decitabine group, n=27) or 15 mg/m2 daily for 5days (low decitabine group, n=17). The infused cells of mononuclear cells and CD34+ cells with HLA-mismatched in 3 loci (n=22) and 2 loci (n=5) and 1 loci (n=1) were 3.33(3.04–10.8)108/kg, 2.26(0.68–5.25)106/kg and no any GVHD prophylactic treatment was used in the Microtransplantation-group. Results: Total CR rate of was 42.9%#x2610;#x0025; A14.8% and 29.4% in the three groups, respectively. That of MST-group is significantly higher than that of B group (P=0.02). The CR rate after first course in MST group is 21.5% which was higher the other two groups (10% and 0%, P=0.14#x2610;#x0025; GP=0.04). The complete cytogenetic response rate in the Microtransplantation-group was 90.9% which is highest than the other two groups (10% and 11%, P 〈 0.001,P 〈 0.001). The progress free survival(PFS) of Microtransplantation-group in 12 months is 50.1% which is higher than other two group (9.9%,9.6%, P=0.01#x2610;#x0025; GP=0.008). Median times of neutrophil recovering over 1×109/L in three groups after 1 course therapy was 17,19 and 13 days and median times of platelet recovering over 50×109/L was 17,26 and 28days, respectively. These of MST group recovered more fastly than those of the other groups. The severe infection rate and early phase mortality rate in three groups had no differences. No donor chimerism, no graft-versus-host disease were observed in all of the patients in the MST group. Conclusion: Our clinical results suggested that decitabine with cytarabine and microtransplantation may improve clinical response CR rate early, especially on complete cytogenetic response and PFS, no increase infection rate and early phase mortality rate. The MST may provide an new method for MDS treatment. Further studies with much more patients and long-term follow-up should be conducted. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Physical Review B, American Physical Society (APS), Vol. 100, No. 1 ( 2019-7-3)
    Type of Medium: Online Resource
    ISSN: 2469-9950 , 2469-9969
    RVK:
    Language: English
    Publisher: American Physical Society (APS)
    Publication Date: 2019
    detail.hit.zdb_id: 2844160-6
    detail.hit.zdb_id: 209770-9
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  • 3
    In: npj Parkinson's Disease, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2023-02-09)
    Abstract: Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson’s disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 ( P combined  = 1.47 × 10 −9 ) with low allele frequency, four previously reported risk variants ( NUCKS1/RAB29 -rs11557080, SNCA -rs356182, FYN -rs997368, and VPS13C -rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance ( P   〈  5 × 10 −8 ) for PD in Chinese population. Moreover, of the reported genome-wide significant risk variants found mostly in European ancestry populations, the correlation coefficient ( r b ) of effect size accounting for sampling errors was 0.91 between datasets and 63.6% attained P   〈  0.05 in Chinese population. Accordingly, we estimated a heritability of 0.14–0.18 for PD, and a moderate genetic correlation between European ancestry and Chinese populations ( r g  = 0.47, se = 0.21). Polygenic risk score (PRS) analysis revealed that individuals with PRS values in the highest quartile had a 3.9-fold higher risk of developing PD than the lowest quartile. In conclusion, the present GWAS identified PD-associated variants in Chinese population, as well as genetic factors shared among distant populations. Our findings shed light on the genetic homogeneity and heterogeneity of PD in different ethnic groups and suggested WGS might continue to improve our understanding of the genetic architecture of PD.
    Type of Medium: Online Resource
    ISSN: 2373-8057
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2819218-7
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  • 4
    In: Ceramics International, Elsevier BV, ( 2024-4)
    Type of Medium: Online Resource
    ISSN: 0272-8842
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2018052-4
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Aging Neuroscience Vol. 15 ( 2023-7-31)
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 15 ( 2023-7-31)
    Abstract: There is controversial evidence that FMR1 premutation or “gray zone” (GZ) allele (small CGG expansion, 45–54 repeats) was associated with Parkinson’s disease (PD). We aimed to explore further the association between FMR1 CGG repeat expansions and PD in a large sample of Chinese origin. Methods We included a cohort of 2,362 PD patients and 1,072 controls from the Parkinson’s Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) in this study and conducted repeat-primed polymerase chain reaction (RP-PCR) for the size of FMR1 CGG repeat expansions. Results Two PD patients were detected with FMR1 premutation (61 and 56 repeats), and the other eleven PD patients were detected with the GZ allele of FMR1 CGG repeat expansions. Those thirteen PD patients responded well to levodopa and were diagnosed with clinically established PD. Specifically, one female PD patient with GZ allele was also found with premature ovarian failure. However, compared to healthy controls, we found no significant enrichment of GZ allele carriers in PD patients or other subgroups of PD cases, including the subgroups of female, male, early-onset, and late-onset PD patients. Furthermore, we did not find any correlation between the FMR1 gene CGG repeat sizes and age at onset of PD. Conclusion It suggested that FMR1 premutation was related to PD, but the GZ allele of FMR1 CGG repeat expansions was not significantly enriched in PD cases of Chinese origin. Further larger multiple ethnic studies are needed to determine further the role of the FMR1 GZ allele in PD.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2558898-9
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  • 6
    In: Biomaterials, Elsevier BV, Vol. 112 ( 2017-01), p. 336-345
    Type of Medium: Online Resource
    ISSN: 0142-9612
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2004010-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 4099-4099
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4099-4099
    Abstract: Objective: To explore mechanism of human marrow mesenchymal stem cells (MSCs) in treating patients with aplastic anemia(AA). Methods: MSCs in patients with aplastic anemia(AA) and the control group were separated with Percoll(1.073g/m L) and cultured in low glucose DMEM. Then, observed their morphologies,checked their molecule surface antigen by flow cytometry and examined the process of adipogenic differention. The mononuclear cells (MNC)of marrow in patients with AA were enriched based 1.077g/L density centrifuge and cultured in the 1640 medium. (1)MSC in control group and MNC in AA group were co-cultured with or without cytokines. The function of supporting hematopoiesis for MSC was to be observed in single confluence layer after plating by counting the total cells and the clones in every well every week. Then analyzed the dynamics of proliferation. T cells were harvested by using nylon column. MSC in control group and T cells in AA group were co-cultured. The proliferation of T cell was measured by MTT method. The CD25,CD69,CD4,CD8,Annexin-V expression rates of CD3+T cells were analyzed by flow cytometry .The gene and protein of IL-2, IL-4,IL-10,TNF-α,IFN-γ,TGF-β1 were examined by RT-PCR and ELISA respectively. MSC treated to the model of AA, by the examination of peripheral hemogram, bone marrow biopsy, pathological section of spleen. Results: There was no significant difference between control group MSC and AA-MSC in morphologies but adipogenic differentiation in AA patients is earlier than controls. The clones of CFU-GM in group(MSC)(78.46±3.58)/2×105 cells, after 14 days cultured was significantly higher than(9.21±4.32)/2×105 cells in group(CK + DMEM medium), while lower than (99.32±4.34)/2×105 cells in group(MSC+CK). (1)the Treg cells (TCD4+CD25+) in AA group (2.01±1.21)/ 2×105 was significantly lower than (4.43±1.67)/2×105 cells in control group, while(5.43±2.31) / 2×105 in group (MSC+AAT) was no more than (4.43±1.67)/2×105 cells in control group. (2) MSCs significantly inhibited T cell proliferation (P 〈 0. O5)by MTT. (3) RT-PCR and ELISA analysis showed that MSCs induced the expression of IL-4, IL-10, TGF-β1 and decreased significantly the expression of IL-2, TNF-α, IFN -γ in T cells of AA. the model of AA treated by MSCs showed improvements in 3 blood components greatly(p 〈 0.05), Bone marrow proliferated and restored to the normal level, hematopoietic cell increased obviously (hematopoietic cell capacity was more than 40%), and atrophied spleen restore to normality. Conclusions: morphologies of AA’MSC had no evident different with the control but was more easy adipogenic differention. aplastic anemia belongs to autoimmune diseases in which T cells effect organ-specific destruction. The fundamental mechanism of MSC in treating AA should be potential to promote hematopoietic cell proliferation by adjusting immunity.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 5182-5182
    Abstract: Abstract 5182 Objective To study the immune regulatory effects of human bone marrow Mesenchymal stem cells(MSCs) on active T lymphocytes in vitro and to explore the new strategy to prevent Graft-Versus-Host Disease(GVHD) in allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods 1. Mononuclear cells from human peripheral blood cells were isolated and cultured in the presence of phytohemagglutinin (PHA) (final concentration was 10μ g/ml) for different time (24hours, 36hours, 48hours, 72hours). 2. The ability of T lymphocyte proliferation and activation was measured by 3H-Thydimine incorporation. 3. MSCs from human bone marrow cells were isolated and cultured.The purity of MSCs were identified with morphological characterization by microphotograph and the phenotypes were tested by flow cytometry (FCM). 4.MSCs were planted in 6-well plates (2×104/well for group B,4×104/well for group C and 8×104/well for group D) and cocultured for 72 hours with T cells activated as the control group (group A). CD3+CD4+, CD3+CD8+, CD4+CD25+ and CD4+CD152+ expressed on T cells were analyzed by FCM after coculture with MSCs for 72 hours respectively.T lymphocyte proliferation after cocultured with MSCs was evaluated by 3H-Thydimine incorporation. The expressions of IL-2, sIL-2R and TGF-β1 proteins in these four groups was detected by ELISA. Results 1. The ability of T lymphocyte proliferation in the same PHA concentration increased with the time changing. Its ability was strongest when culturing for 48 hours (P 〈 0.01)and had no difference between 48 hours and 72 hours (P 〉 0.05). 2. The phenotypes of MSCs were measured by FCM:they were positive on the expression of CD44, CD105, CD29 and FIK1 and negtive on the expression of CD33, CD34, CD45 and HLA-DR. 3. MSCs inhibited T lymphocyte proliferation and the inhibitory effect depended on the amount of MSCs:CD3+CD8+, CD4+CD25+ and CD4+CD152+ T cells cocultured with bone marrow MSCs (group B, group C, group D) increased obviously and a significant decrease of CD3+CD4+ T cell proliferation as compared with control group (T lymphocytes uncocultured with MSCs) (P 〈 0.01), and there were no difference between group C and group D (P 〉 0.05). In group B, C and D, IL-2 and sIL-2R levels were lower than control group (P 〈 0.01) and TGF-β1 level was higher obviously than group A (P 〈 0.01). Every of IL-2, sIL-2R and TGF-β1 expressions has difference during group B, C and D (P 〈 0.05). Conclusions 1. Mitogen PHA could increase proliferation function of T lymphocytes and this function was strongest when cultured for 48 hours in same concentration of PHA. 2. MSCs inhibit T lymphocyte proliferation and perform their immunosuppressive function by up-regulation of CD3+CD8+ T cells, CD4+CD25+ Tcells and CD4+CD152+ Tcells. MSCs decreased IL-2 and sIL-2R levels and increased TGF-β1 level in PHA-stimulated peripheral blood lymphocytes. 3. MSCs play a critical immune negative regulatory effect on preventing GVHD. MSCs pretreatment may be useful in the prevention of GVHD in allo-HSCT and provides a new strategy to induce transplantation tolerance. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4427-4427
    Abstract: Abstract 4427 FLT3 Internal Tandem Duplication is a kinase mutation frequently observed in cases of adult acute myeloid leukemia (AML). This study was aimed to investigate the expression of FLT3 internal tandem duplication (FLT3-ITD) in pediatric patients with acute myeloid leukemia (AML) and to analyse the clinical features of patients with mutations and the relation of FLT3-ITD with multidrug resistance gene 1 (mdr1). Samples were analysised from eighty-one new diagnosed pediatric patients with AML. The diagnosis was based on French-American-British (FAB) criteria. Immunophenotyping was done by flow cytometry. For each patient, several clinical and biological characteristics were analyzed (age, WHO performance status, WBC count at diagnosis, bone marrow blasts, FAB subtypes, immunologic phenotype, and cytogenetics). The expressions of FIT3-ITD and mdr1 gene in bone marrow samples was determined by RT-PCR. patients were treated with uniform chemotherapy. Statistical analysis were carried by SAS. The results indicated that the FLT3-ITDs were detected in 8 out of 81 pediatric patients (9.88%) and all mutations detected were hybrid, while less frequently this mutation was detected in adult patients. Although they were irrelevant with sex and immunophenotypes, the mutations seemed predominant in older pediatric patients. The average age is 14-year-old in the patients with mutations, but 9-year-old in those without mutation (P=0.039). The leukocyte counts and bone marrow blast cell counts in pediatric patients with FLT3-ITD at diagnosis were higher than those in pediatric patients without FLT3-ITD (median of 58.4×10∧9/L versus 19.49 ×10∧9/L, p = 0.001 and median of 78.5% versus 54.4%,p = 0.041 respectively). The normal chromosomes were found in most pediatric patients with FLT3-ITD, although no significane in the stastistics. The patients with FLT3-ITD had lower induction remission rate (only 25%), but the patients without FLT3-ITD had higher remission rate (76.1%). According results detected by RT-PCR, the mdr1 gene was found in 27 pediatric patients, but only 3 out of 8 pediatric patients with FLT3-ITD were detected to express both FLT3-ITD and mdr1. It is concluded that the FLT3-ITD is a frequent mutation in pediatric patients with AML, especially in the elder pediatric patients. It is related with higher leukocyte counts and bone marrow blast cell counts, which may due to the continual activation of Flt3 tyrosine kinase. The prognosis of these patients with mutations is worse and the induction remission rate is lowe. But the FLT3-ITD not relates with the mdr1, which suggests that the low induction rate is not resulted from the multidrug resistance, at least not from the P-glycoprotein (Pgp) activity. So the common MDR modulators may be uneffective for therapy of the patients with FLT3-ITD. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 3855-3855
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 3855-3855
    Abstract: Objective: The human umbilical vein endothelial cells (hUVECs) were taken as experimental cells after successfully sub-cultured in vitro. Whether the HSPGs can express stably on the cultured hUVECs was determined firstly. The contents of HSPGs on the surface of endothelial cells were measured under the exterior intervening factors action, and the effect of exterior intervening factors on HSPGs were evaluated. The cell adhesion models, in which the mononuclear apart from circulate blood in normal human body can adhere to hUVECs, were used to evaluate the relation between the HSPGs contents and cell adhesion. The aim of the study was to explore the new ideas or methods on preventing or treatment for extramedullary infiltration in leukaemia patients. Methods: Enzyme-digestion method was used to obtain hUVECs, and cell number can up to scratch for experiment study by sub-cultured in vitro. RT-PCR was performed to half-determine the expression of Syndecan-1, Glypican-1 on the surface of ECs. NaClO3, 4-methylumbelliferyl-7-β-D-xyloside (4-β-DX), heparin, tumor necrosis factor α (TNFα), heparinaseIII and leukaemia serum were taken as intervening factors to work on the ECs. The RT-PCR method was used to determine the expression of Syndecan-1 and Glypican-1 on the surface of ECs, and biocolor measure method was used to evaluate the PGs contents in the ECs. The normal human mononuclear cell aparted from peripheral blood by density centrifugation were co-cultured with ECs, on which the HSPGs contents have been modified by intervening factors. Methyl thiazolyl tetrazolium (MTT) colorimetry method was used to determine the mononuclear-endothelial cell adhesion, inverted microscopy and scanning electron microscopy were used to observe the cell adhesion. The flow cytometry method was used to determine the ECs activated by exterior TNFα and leukaemia serum, the expression for CD62E antigen was evaluated to determine the effect of traditional adhesion molecular and confirm the function of HSPGs. Results: The cultured human umbilical endothelial cells can passage stable. Syndecan-1 and Glypican-1 are two HSPGs families representations on the surface of cell, can be used to judge the expression level of HSPGs on the EC surface. The exterior intervening factor, such as TNFα, 4-methylumbelliferyl-7-β-D -xyloside, NaClO3, heparin, heparanase and leukaemia serum, can work on the HSPGs expression on ECs in transcription and cell level. Affected by these intervening factors, mononuclear cells showed different exhibition on adhesion to cultured endothelial cells. Conclusion: The traditional adhesion molecules can dominate the cell adhesion, the HSPGs expressed on the endothelial cells can participate in the process of cell adhesion. For the more, HSPGs can promote the cell adhesion progression. ALL serum can up-regulate the expression of Syndecan-1 on the hUVECs, and result in contents of HSPGs increasing, which is coincident with the phenomenon that more extramedullary infiltration can be found in ALL patients in clinic. The above-mentioned can indicated that the HSPGs on the surface of ECs may participate the leukemia cell adhesion process, and the research aimed on the cell surface HSPGs maybe represent an important direction to control the pathological cell adhesion.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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