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1.
Eur J Clin Microbiol Infect Dis ; 39(2): 339-343, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901114

RESUMO

The roll-out of molecular diagnostic tools continues to be the most important shift in the tuberculosis diagnostic landscape. The aim of this study was to develop a novel external quality assessment (EQA) panels for molecular TB diagnostics. In addition, we also assessed the performance of the laboratories with the EQA panels in China. Dried Mycobacterium tuberculosis (MTB) DNA in the chelex resin was designed as part of an EQA program. The storage of genomic DNA in the chelex resin layer had no effect on the stability of genomic DNA, even after 12 weeks of storage. Seventy-one laboratories have participated in EQA of molecular diagnostics for TB diagnosis in 2018. GeneXpert (74.6%, 53/71) was the most predominant molecular method, followed by GeneChip (32.3%, 23/71), MeltPro (22.5%, 16/71), and TB-LAMP (7.0%, 5/71). Out of 105 EQA panels, 103 EQA results (98.1%) achieved perfect scores, whereas the other two (1.9%) had satisfactory scores. There were a total of two false-negative results reported from two laboratories with local LAMP, respectively. In conclusion, we firstly develop feasible EQA panels for molecular diagnostics for tuberculosis in China. Our data demonstrate that a majority of participating laboratories are able to produce perfect results with molecular diagnostics in China, giving us important hints for the implementation of molecular diagnostics.

2.
Biomed Res Int ; 2019: 9310917, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531372

RESUMO

Design: A national tuberculosis- (TB-) designated hospital survey was conducted in 2015 to identify significant changes since 2009 in implementation of TB-testing services within hospitals of various types and administrative levels in various regions in China. Methods: In 2015, all TB-designated hospitals were required to complete questionnaires designed by the National Clinical Center for TB. Community hospitals also completed simplified questionnaires as part of the study. Results: Overall, in 2015 there were 1685 TB-designated hospitals in China, consisting of 1335 (79.2%) county-level hospitals and 350 (20.8%) hospitals at the prefecture level and above. The percentage of counties with TB-designated hospitals in the western region (57.4%) was significantly lower than corresponding percentages for eastern and middle regions (70.3% and 96.5, respectively). Based on data recorded on hospital surveys in both 2009 and 2015, significant differences were noted between years in proportions of general hospitals with TB wards and of specialized infectious disease hospitals (P < 0.01). Of 1256 county-level laboratories conducting smear microscopy, only 979 (79%) performed external quality control evaluations of test results in 2015. For prefecture-level hospitals, 70% (234/334), 76% (155/203), and 67% (66/98) of hospitals obtained external quality control validations of smear microscopy, phenotypic DST, and molecular test results, respectively. Conclusions: Although China's health reform efforts have resulted in improved TB patient access to quality health care, more attention should be paid to balancing the distribution of medical facilities across different regions. In addition, laboratory capabilities and quality control systems should be strengthened to ensure delivery of high-quality laboratory services by TB-designated hospitals throughout China.


Assuntos
Hospitais Gerais/estatística & dados numéricos , Tuberculose/diagnóstico , China , Doenças Transmissíveis/diagnóstico , Infecção Hospitalar/diagnóstico , Reforma dos Serviços de Saúde/estatística & dados numéricos , Humanos , Laboratórios/estatística & dados numéricos , Estudos Longitudinais , Qualidade da Assistência à Saúde , Inquéritos e Questionários
3.
Eur J Clin Microbiol Infect Dis ; 38(10): 1961-1968, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342215

RESUMO

Mycobacterial culture remains the gold standard for detection of Mycobacterium tuberculosis (MTB) in clinical samples. However, no external quality assessment (EQA) tools exist to validate results obtained using this sophisticated method. Therefore, we developed EQA panels to assess the quality of mycobacterial culture results produced by designated TB hospitals in China. Artificial sputum containing methylcellulose was used to supplement quantified mycobacterial solutions to simulate culture-negative and culture-positive clinical sputum samples of low or high mycobacterial concentration, respectively. After storage of the quantified simulated EQA panels for 4 weeks at 4 °C, experimental bacterial quantification of the panels was again conducted, with no impact of artificial sputum on mycobacterial culture results observed. Next, 47 tuberculosis (TB) hospitals were recruited for evaluation of the EQA panels. Overall, 29 hospitals (61.7%) produced mycobacterial culture test results matching expected results for the EQA panels, while the remaining 18 (38.3%) hospitals did not. False-negative results for the low mycobacterial concentration panel sample accounted for 33 (73.3%) diagnostic errors. Compared with hospitals using solid culture methods as a control group, hospitals using the liquid culture method were less likely to produce uncertified results (aOR 0.064, 95% CI 0.005-0.770). In conclusion, we first developed then evaluated EQA panels for validation of mycobacterial culture testing in China. Our data demonstrate that approximately one-third of TB hospitals failed to produce results that met criteria for classification as certified mycobacterial culture testing providers, emphasizing the importance of quality control and quality assurance in TB diagnostics.


Assuntos
Técnicas Bacteriológicas/métodos , Testes Diagnósticos de Rotina/métodos , Ensaio de Proficiência Laboratorial/métodos , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose/diagnóstico , Técnicas Bacteriológicas/normas , China , Testes Diagnósticos de Rotina/normas , Hospitais , Humanos
4.
J Pathol ; 249(2): 193-205, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31090071

RESUMO

Cancer-associated fibroblasts (CAFs) are known to promote tumourigenesis through various mechanisms. Fibroblast growth factor (FGF)/FGF receptor (FGFR)-dependent lung cancers have been described. We have developed a mouse model of lung adenocarcinoma that was constructed through the induction of Fgf9 overexpression in type 2 alveolar cells. The expression of Fgf9 in adult lungs resulted in the rapid development of multiple adenocarcinoma-like tumour nodules. Here, we have characterised the contribution of CAFs and the Fgf/Fgfr signalling pathway in maintaining the lung tumours initiated by Fgf9 overexpression. We found that CAF-secreted Fgf2 contributes to tumour cell growth. CAFs overexpressed Tgfb, Mmp7, Fgf9, and Fgf2; synthesised more collagen, and secreted inflammatory cell-recruiting cytokines. CAFs also enhanced the conversion of tumour-associated macrophages (TAMs) to the tumour-supportive M2 phenotype but did not influence angiogenesis. In vivo inhibition of Fgfrs during early lung tumour development resulted in significantly smaller and fewer tumour nodules, whereas inhibition in established lung tumours caused a significant reduction in tumour size and number. Fgfr inhibition also influenced tumour stromal cells, as it significantly abolished TAM recruitment and reduced tumour vascularity. However, the withdrawal of the inhibitor caused a significant recurrence/regrowth of Fgf/Fgfr-independent lung tumours. These recurrent tumours did not possess a higher proliferative or propagative potential. Our results provide evidence that fibroblasts associated with the Fgf9-induced lung adenocarcinoma provide multiple means of support to the tumour. Although the Fgfr blocker significantly suppressed the tumour and its stromal cells, it was not sufficient to completely eliminate the tumour, probably due to the emergence of alternative (resistance/maintenance) mechanism(s). This model represents an excellent tool to further study the complex interactions between CAFs, their related chemokines, and the progression of lung adenocarcinoma; it also provides further evidence to support the need for a combinatorial strategy to treat lung cancer. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

5.
BMC Infect Dis ; 17(1): 435, 2017 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-28629333

RESUMO

BACKGROUND: Shortening the standard 6-month treatment for drug-susceptible pulmonary tuberculosis (DS-PTB) would be a major improvement for TB case management and disease control. METHODS: We are conducting a randomized, open-label, controlled, non-inferiority trial involving patients with smear-positive, newly diagnosed DS-PTB cases nationwide to assess the efficacy and safety of two 4.5- month regimens in comparison to the standard 6-month WHO recommended regimen. The regimen used in one experiment group is a 4.5-month fluoroquinolone-containing regimen, which consists of full course of levofloxacin, isoniazid (H), rifampin (R), parazinamid (Z) and ethambutol (E). Regimen used in the second experiment group includes 4.5-month full course of H, R, Z, E with levofloxacin removed. Patients in the control group, receive H, R, Z and E for 2 months, followed by 4 months of H and R. The primary endpoint is treatment failure or relapse within 24 month after treatment completion. DISCUSSION: Results from this trial along with other studies will contribute to the science of constructing a shorter, effective and safe regiment for TB patients. TRIAL REGISTRATION: The protocol has been registered on ClinicalTrials.gov on 2 September,2016 with identifier NCT02901288 .


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/uso terapêutico , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico
6.
BMC Pulm Med ; 16: 26, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26846562

RESUMO

BACKGROUNDS: The failure of current Standard Short-Course Chemotherapy (SCC) in new and previously treated cases with tuberculosis (TB) was mainly due to drug resistance development. But little is known on the characteristics of acquired drug resistant TB during SCC and its correlation with SCC failure. The objective of the study is to explore the traits of acquired drug resistant TB emergence and evaluate their impacts on treatment outcomes. METHODS: A prospective observational study was performed on newly admitted smear positive pulmonary TB (PTB) cases without drug resistance pretreatment treated with SCC under China's National TB Control Program (NTP) condition from 2008 to 2010. Enrolled cases were followed up through sputum smear, culture and drug susceptibility testing (DST) at the end of 1, 2, and 5 months after treatment initiation. The effect factors of early or late emergence of acquired drug resistant TB , such as acquired drug resistance patterns, the number of acquired resistant drugs and previous treatment history were investigated by multivariate logistic regression; and the impact of acquired drug resistant TB emergence on treatment failure were further evaluated. RESULTS: Among 1671 enrolled new and previously treated cases with SCC, 62 (3.7%) acquired different patterns of drug resistant TB at early period within 2 months or later around 3-5 months of treatment. Previously treated cases were more likely to develop acquired multi-drug resistant TB (MDR-TB) (OR, 3.8; 95%CI, 1.4-10.4; P = 0.015). Additionally, acquired MDR-TB cases were more likely to emerge at later period around 3-5 months after treatment starting than that of non-MDR-TB mainly appeared within 2 months (OR, 8.3; 95%CI, 1.7-39.9; P = 0.008). Treatment failure was associated with late acquired drug resistant TB emergence (OR, 25.7; 95%CI, 4.3-153.4; P < 0.001) with the reference of early acquired drug resistant TB emergence. CONCLUSIONS: This study demonstrates that later development of acquired drug resistant TB during SCC is liable to suffer treatment failure and acquired MDR-TB pattern may be one of the possible causes.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , China/epidemiologia , Estudos de Coortes , Quimioterapia Combinada , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Estreptomicina/uso terapêutico , Falha de Tratamento , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
7.
Stem Cell Res ; 15(1): 109-21, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26042794

RESUMO

The niche surrounding stem cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study stem cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive cells. We established an assay to study both lung and trachea stem cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that lung epithelial (but not tracheal basal) stem cells require co-culture with stromal cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial cells in offering this support and the pattern of support varied based on the tissue origin of the stromal cells. Treating distal lung epithelial or basal stem cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of lung stem cell niche components and factors that can manipulate lung stem cell behavior.


Assuntos
Células Epiteliais/citologia , Pulmão/citologia , Nicho de Células-Tronco , Células-Tronco/citologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Camundongos Endogâmicos C57BL , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Nicho de Células-Tronco/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(4): 1043-7, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21867641

RESUMO

Tn order to set up a mouse model of myelofibrosis (MF) induced with high dose recombinant human erythropoietin (rhEPO). 60 mice were collected and divided into EPO and control groups, the former was injected with rhEPO and the latter with normal saline intraperitoneally. 5 mice from each group were executed on day 6, 30, 60, 90, 120 and 150 respectively. Their WBC count, Hb level, MCV, RDW and platelet amount were measured by automatic blood cell analyzer; CD34(+) cell ratio in bone marrow were analyzed by flow cytometry; liver and spleen coefficients were measured; pathological changes of liver, spleen, femur were observed by HE staining and reticular fibers staining; cortex thickness, femoral canal diameter and lumbar spine density were determined by computerized tomography (CT). The results indicated that as compared with normal control group in EPO induced group, WBC count was increased slightly in whole period, but without statistic significance (p > 0.05), Hb level and RDW increased at day 6 and 30 significantly (p < 0.05), MCV increased at day 6 significantly (p < 0.05), but platelet amount decreased significantly at all time points (p < 0.05). Most mice in EPO-induced group had hepatomegalia and their liver and spleen coefficient increased significantly at day 60 (p < 0.05), while most mice had splenomegaly and its coefficient was increased significantly at all time-points (p < 0.05). CD43(+) cell ratio of EPO group increased significantly in whole period (p < 0.05). CT scanning displayed femoral cortical thickening, medulla canal narrowing and lumbar spine density increasing at day 150, meanwhile, HE staining and reticular fiber staining showed the fatty degeneration or vacuolization in liver, splenomegaly with megakaryocytic proliferation, femur bone marrow fibrosis and osteosclerosis. It is concluded that the mouse induced by high dose of rhEPO displays the myelofibrosis associated with splenic extramedullary hemopoiesis, and this study is useful to establish a practical MF model, and to explore its pathological mechanism.


Assuntos
Modelos Animais de Doenças , Eritropoetina/efeitos adversos , Mielofibrose Primária/induzido quimicamente , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos , Proteínas Recombinantes/efeitos adversos
9.
Zhonghua Jie He He Hu Xi Za Zhi ; 34(10): 762-5, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22321711

RESUMO

OBJECTIVE: To compare the antimycobacterial activities of rifampicin (RFP) and rifabutin (RBT), and to evaluate the correlation between RBT resistance and genetic alterations in the rpoB gene. METHODS: The microplate-based alamar blue assay (MABA) method was performed to detect the antimycobacterial activities of RFP and RBT in 168 strains of Mycobacterium tuberculosis (M. tuberculosis). Meanwhile, we also analyzed the 81 bp core region of rpoB gene by DNA sequencing. The rate of gene mutations was analyzed by chi-square test. RESULTS: RBT was sensitive for all of the 66 RFP-sensitive strains with no mutations in 81 bp core region of rpoB gene. But of the 102 RFP-resistant strains, 76 strains were also resistant to RBT. Cross resistance between RFP and RBT was 74.5% (76/102). Alterations at codons 516, 526, 531 in the rpoB gene correlated with resistance to both RFP and RBT. While point mutations at codons 511 and 533 possibly influenced the susceptibility to RFP but not to RBT. The mutation rate (92.1%, 70/76) of rpoB gene of RBT-resistant strains was significantly higher than that (23.9%, 22/92) of RBT-sensitive strains (χ(2) = 78.12, P < 0.05). CONCLUSIONS: RBT was more active against M. tuberculosis as compared to RFP. The RFP-resistant strains with MIC ≤ 4 mg/L were still susceptible to RBT. Our results suggest that analysis of genetic alterations in the rpoB gene is useful for predicting RFP-resistance, and may have implications for evaluating RBT-resistance.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Mycobacterium tuberculosis/genética , Rifabutina/farmacologia , Rifampina/farmacologia , Análise Mutacional de DNA , RNA Polimerases Dirigidas por DNA , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Análise de Sequência de DNA
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(4): 1010-5, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19698249

RESUMO

The purpose of this study was to explore the effect of intra-bone marrow infusion (iBMI) of cord blood (CB)-derived hematopoietic stem/progenitor cells (HS/PCs) on human hematopoietic reconstitution in xenotransplanted NOD-SCID mouse model. Aliquots containing 5 x 10(5) CB CD34(+) cells were transplanted into sublethally irradiated NOD-SCID mouse via intravenous infusion (iVI) or iBMI routes. 64 female NOD-SCID mice were divided randomly into 3 groups: iBMI group, iVI group and negative control group. The engraftment levels of human hematopoietic cells at 3, 5 and 8 weeks after xenotransplantation were detected by fluorescence-activated cell sorter (FACS), polymerase chain reaction (PCR), immunohistochemistry and HPC colony formation assay, and long-term hematopoietic reconstitution capacity of HSC was tested by secondary transplantation. The results showed that the percentages of human CD45(+) cells in bone marrow, peripheral blood and spleen of recipient in iBMI group at 8 weeks after xenotransplantation were significantly higher than those in iVI group (p < 0.05). HS/PCs given through both iVI and iBMI methods had the ability of multilineage differentiation, the percentages of CD45(+)CD19(+) cells, CD45(+)CD33(+) cells, CD45(+)CD56(+) cells and CD45(+)CD34(+) cells of recipient bone marrow in iBMI group at 8 weeks after xenotransplantation were significantly higher than those in iVI group (p < 0.05), while other lineages in iBMI group were also higher than that in iVI group (p > 0.05). alpha-satellite-specific fragment of human chromosome 17 could be detected by PCR in liver, spleen, lung, peripheral blood and bone marrow cells of long-term survival recipients in both iVI and iBMI groups. Human CD45 antigen could be detected by immunohistochemical method in spleen, liver and lung of recipients in iBMI group at 8 weeks after xenotransplantation. Total colony count in iBMI group at 8 weeks after xenotransplantation was significantly higher than that in iVI group (p < 0.05). alpha-satellite-specific fragment of human chromosome 17 could be detected in all above organs of both group recipients at 6 weeks after secondary xenotransplantation. It is concluded that iBMI of CB CD34(+) cells improves hematopoietic reconstitution in xenotransplanted NOD-SCID mouse model.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Sistema Hematopoético , Transplante Heterólogo , Animais , Antígenos CD34 , Medula Óssea , Diferenciação Celular , Feminino , Sobrevivência de Enxerto , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Recuperação de Função Fisiológica
11.
Zhonghua Xue Ye Xue Za Zhi ; 30(2): 97-102, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19563019

RESUMO

OBJECTIVE: To investigate the role of tumor necrosis factor (TNF) alpha on the homing efficiency of hematopoietic stem/progenitor cells (HS/PC) into bone marrow and its mechanism. METHODS: CFSE-labeled umbilical cord blood (UCB) CD34+ cells were transplanted into irradiated (control group) or combined with TNF alpha prepared (experimental group) BALB/c recipient mice. The distribution in peripheral blood, liver, lung and homing characteristics in bone marrow and spleen of UCB CD34+ cells, in BALB/c recipient mice were determined 20 hours after xenotransplantation by flow cytometry (FACS) and their homing efficiency was calculated. ELISA was used to measure serum SDF-1 alpha level. CXCR4 expression levels of on UCB CD34+ cells were assessed by FACS pre-/post-manipulation with TNF alpha. SDF-1 alpha expression level in bone marrow and spleen was tested by immunohistochemistry. RESULTS: UCB CD34+ cells mainly home into recipient mice bone marrow and spleen; The homing efficiency in experimental group bone marrow [(0.65 +/- 0.13)%] was significantly higher than that in control ones [(0.30 +/- 0.09)%, P < 0.01], whereas the homing efficiency in experimental group spleen was dramatically lower than that in control ones (P < 0.01); Treatment with TNF alpha did not affect recipient serum SDF-1 alpha level; After 18 hours co-cultured with TNF alpha, the CXCR4e expression level on UCB CD34+ cells was similar to that on fresh ones; TNF alpha treatment induced significantly higher SDF-1 alpha expression on osteoblastic and stromal cells in bone marrow, and reversed spleen SDF-1 alpha gradient that was originally favorable for CD34+ cells homing. CONCLUSION: TNF alpha enhances the homing efficiency of HS/PC via up-regulating SDF-1 alpha gradient in bone marrow, and might be an useful enhancer for HS/PC homing in clinical practice.


Assuntos
Medula Óssea , Movimento Celular , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/imunologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Antígenos CD34 , Separação Celular , Quimiocina CXCL12/metabolismo , Feminino , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Receptores CXCR4/metabolismo , Condicionamento Pré-Transplante , Transplante Heterólogo
12.
Exp Hematol ; 37(8): 990-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19481136

RESUMO

OBJECTIVE: This study was designed to investigate the dynamics of transmigration and engraftment of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) introduced via intra-bone marrow transplantation (IBMT), which is reserved as a novel strategy for possible clinical transplantation. MATERIALS AND METHODS: The early distribution pattern and engraftment level of human HS/PCs introduced via traditional intravenous transplantation (IVT) and IBMT routes were compared in the xenotransplanted nonobese diabetic/severe combined immunodeficient mouse model by means of flow cytometric analysis and an optical imaging system. RESULTS: It was obvious that a good deal of IVT-introduced donor cells were entrapped in the liver and lung, 0.06% +/- 0.01% and 0.07% +/- 0.02%, respectively. Meanwhile three to six times fewer IBMT-introduced donor cells were entrapped in recipients' liver and lung (p<0.05 and p<0.05, respectively). Superior 8-week engraftment of human cells was observed in IBMT recipients (54.019% +/- 31.338%) than in IVT recipients (12.197% +/- 10.350%) when given transplants of 1.0 x 10(4) UCB CD34(+) cells and, furthermore, human hematopoietic cell engraftment was observed in IBMT, but not in IVT recipients when given transplants of 1.0 x 10(3) UCB CD34(+) cells. CONCLUSION: Our results demonstrated that higher levels of human hematopoietic cell engraftment in nonobese diabetic/severe combined immunodeficient recipients achieved by IBMT might be due to the superior in vivo motility potential of IBMT-introduced HS/PCs. Clinical transplantation using transplants of UCB containing limited numbers of HS/PCs might benefit from the efficient IBMT strategy.


Assuntos
Medula Óssea , Movimento Celular , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Células-Tronco Hematopoéticas/citologia , Animais , Sobrevivência de Enxerto , Humanos , Fígado/citologia , Pulmão/citologia , Camundongos , Camundongos Endogâmicos NOD , Transplante Heterólogo
13.
Zhonghua Xue Ye Xue Za Zhi ; 29(6): 361-5, 2008 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19031735

RESUMO

OBJECTIVE: To explore whether intra-bone marrow injection strategy could promote the engraftment of human umbilical cord blood derived hematopoietic stem/progenitor cells (HS/PC) in xenotransplanted NOD/SCID mouse model. METHODS: Aliquots containing 1 x 10(3), 1 x 10(4), 0.5 x 10(5), 1 x 10(5) and 5 x 10(5) human umbilical cord blood (hUCB) CD34+ cells were transplanted into sublethally irradiated NOD/SCID mice via intra-venous (i.v.) and intra-bone marrow (iBM) injection. The homing and long-term engraftment capabilities of hUCB CD34+ cells from right tibia, right femur, left tibia, left femur and spleen were detected by PCR 24h after xenotransplantation and by FACS 8-week after xenotransplantation. RESULTS: Tissues of liver, spleen, lungs, or cells from peripheral blood, right tibia, right femur, left tibia and left femur 24 hours after xenotransplantation in iBM injecting 5 x 10(5) CD34+ cells recipients expressed human chromosome 17 specific alpha-satellite fragment. 8-week engraftment of human cells was observed and engraftment level indicated dose-dependent effect in injected bone (right tibia) as well as non-injected bones (including right femur, left tibia and left femur), spleen and peripheral blood in all iBM recipients. 8-week engraftment levels of human cells were (44.063 +/- 20.095)% and (45.881 +/- 22.316)% for i.v. and iBM groups respectively, when transplanted with 1 x 10(5) hUCB CD34+ cells, being no statistical difference (P >0.05). More superior 8-week engraftment levels of human cells were observed in iBM recipients [(54.019 +/- 31.338)%] than in i.v. recipients [(12.197 +/- 10.350)%] when transplanted with 1.0 x 10(4) CD34 cells (P<0.01). Human cell engraftment was observed in iBM but not in i.v. recipients when transplanted with 1.0 x 10(3) CD34+ cells, and was usually observed in non-injected bones. CONCLUSION: Intra-bone marrow strategy can efficiently increase the engraftment of umbilical cord blood derived hematopoietic stem/progenitor cells in xenotransplanted NOD/SCID mouse model.


Assuntos
Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Células-Tronco Hematopoéticas/citologia , Animais , Antígenos CD34 , Feminino , Sangue Fetal/citologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Condicionamento Pré-Transplante , Transplante Heterólogo
14.
Ultrastruct Pathol ; 32(3): 81-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18570152

RESUMO

The objective of this study was to investigate the ultrastructural characteristics of nucleated cells in the bone marrow of patients with aplastic anemia (AA). This was done by observing the morphology of nucleated cells in bone marrow aspirates from 20 patients with AA by transmission electron microscopy. Erythroblasts were decreased in all cases and not observed in 6 cases. Nuclear abnormalities, such as pyknosis, karyolysis, karyorrhexis, apoptosis, and "Swiss cheese"-like changes, were found in 10 cases. Focal cytoplasmic necrotic changes and cytolysis were found in 3 cases. There were more megaloblasts in 4 cases. Abnormalities of granulocytes were found in 12 out of 18 cases. Megakaryocytes showed focal cytoplasmic necrotic changes. Most monocytes had dendritic features, including excessive cytoplasm, processes, and large round nuclei in all cases. Other monocytes illustrated typical monocytic features with twisted nuclei, plentiful RER, vacuoles, lysosomes, and prominent Golgi apparatus. Macrophages and hemophagocytes occurred in all cases. The incidence of lymphocytes was high in 17 out of 20 cases and occasionally lymphocytes were enlarged in 8 cases. More plasmacytes and plasmacytoid lymphocytes were found in 5 and 3 cases, respectively. The observations suggest that (1) the universal nuclear injury of erythroblasts may be related to the pathogenetic pathway of AA development; (2) the dendritic cells and hemophagocytes from the mononuclear phagocyte system may play a more critical role in hematopoietic failure of AA, directly and/or indirectly; and (3) besides T lymphocytes, increasing numbers of plasmacytes or plasmacytoid lymphocytes are associated with AA in some cases.


Assuntos
Anemia Aplástica/patologia , Células da Medula Óssea/ultraestrutura , Núcleo Celular/ultraestrutura , Adolescente , Adulto , Exame de Medula Óssea , Criança , Pré-Escolar , Eritroblastos/ultraestrutura , Feminino , Humanos , Linfócitos/ultraestrutura , Macrófagos/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Fagócitos/ultraestrutura
15.
Ann Hematol ; 87(9): 751-4, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18575862

RESUMO

Congenital dyserythropoietic anemia I (CDA I) is a well-defined entity within the heterogeneous group of the CDAs. So far, most CDA cases were reported from Europe and Israel. A homozygous mutation of the CDAN1-gene was identified from a founder population observed in Bedouin tribes in Israel, and many different mutations in additional cases from Europe were reported. Few cases of CDA I were presented from Asian regions so far, mostly without convincing data and only one case in which a mutation of the CDAN1-gene was detected. Here, the first Chinese family with the typical hematological phenotype, osseous syndactyly and with a compound heterozygous CDAN1-gene mutation is described. Prevalence data of CDA I from Asian countries are not known, but experiences from Europe suggest that in many families the disorder remains undiagnosed.


Assuntos
Anemia Diseritropoética Congênita/genética , Glicoproteínas/genética , Mutação , Anemia Diseritropoética Congênita/patologia , Células da Medula Óssea/patologia , China , Eritroblastos/patologia , Eritroblastos/ultraestrutura , Feminino , Humanos , Masculino , Núcleo Familiar , Proteínas Nucleares
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