Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cord blood (CB) cells are a useful source of hematopoietic cells for transplantation. The hematopoietic activities of CB cells are different from those of bone marrow and peripheral blood (PB) cells. Platelet recovery is significantly slower after transplantation with CB cells than with cells from other sources. However, the cellular mechanisms underlying these differences have not been elucidated. We compared the surface marker expression profiles of PB and CB hematopoietic cells. We focused on two surface markers of hematopoietic cell immaturity, i.e., CD34 and AC133. In addition to differences in surface marker expression, the PB and CB cells showed nonidentical differentiation pathways from AC133(+)CD34(+) (immature) hematopoietic cells to terminally differentiated cells. The majority of the AC133(+)CD34(+) PB cells initially lost AC133 expression and eventually became AC133(-)CD34(-) cells. In contrast, the AC133(+)CD34(+) CB cells did not go through the intermediate AC133(-)CD34(+) stage and lost both markers simultaneously. Meanwhile, the vast majority of megakaryocyte progenitors were of the AC133(-)CD34(+) phenotype. We conclude that the delayed recovery of platelets after CB transplantation is due to both subpopulation distribution and the process of differentiation from AC133(+)CD34(+) cells.
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PMID:Differences between peripheral blood and cord blood in the kinetics of lineage-restricted hematopoietic cells: implications for delayed platelet recovery following cord blood transplantation. 1263 10

Epidermal Langerhans cells (LCs) are a subset of immature dendritic cells (DCs) and play a key role in the initiation and regulation of T cell responses. Upon antigenic stimulation, LCs differentiate into mature DCs undergoing profound morphologic and functional changes. Studies of the biological details of this conversion process have been hampered by difficulties in generating immature dendritic cells of a defined lineage. We propose a new method of purifying homogenous immature DCs in large numbers by sorting for CLA (Langerhans-like cells) from cord-blood-derived haematopoietic progenitor cells (HPCs). Established protocols describe the generation of LCs from CD34(+) HPCs by sorting for CD1a after 5 days of culture in the presence of GM-CSF and TNF-alpha. However, the numbers of LCs obtained by this method remain within the low range. Furthermore, CD1a is also expressed on interstitial DCs. LCs but not interstitial DCs express the cutaneous leukocyte antigen (CLA). The expression of CLA by cells stimulated with TNF-alpha and GM-CSF peaks on day 10. This expression can be raised further by stimulating the cells with TGF-beta1 and omitting TNF-alpha from day 6 onwards. CLA(+) cells were isolated on day 10 by AutoMACS. Their LC phenotype was established by the presence CD207. The immaturity of Langerhans-like cells was shown by the lack of CD83 and CD208 expression as well as their lower ability to activate allogeneic naive T cells as compared to maturing dendritic cells. However, CLA(+) cells cannot be termed Langerhans cells as they do not express Birbeck granules. Compared to sorting for CD1a (on day 6), sorting for CLA (on day 10) results in isolates of higher purity (80% vs. 50%) and a yield eight times higher (4.9x10(6) vs. 6.5x10(5) cells) when using identical numbers of input cells (5x10(5) cells). This novel method guarantees large numbers of pure and functionally active immature dendritic cells.
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PMID:Large-scale isolation of immature dendritic cells with features of Langerhans cells by sorting CD34+ cord blood stem cells cultured in the presence of TGF-beta1 for cutaneous leukocyte antigen (CLA). 1266 78

The present study compares immune reconstitution after allogeneic cord blood transplantation (CBT) and CD34+ stem cell transplantation (CD34-SCT) with that after bone marrow transplantation (BMT). Eighty-eight children who underwent CBT (20 patients), BMT (58), and CD34-SCT (10) were enrolled, and lymphocytes and T-, B-, and natural killer-lymphocyte subsets were monitored for more than 5 years after transplantation. CBT recipients showed significant ircreases in (1) total lymphocyte counts (P < .001), (2) CD4+/CD8+ cell ratios (P < .01), (3) CD4+ and CD4+CD45RA+ cells (P < .001), (4) CD8+CD11b+ cells (P < .001), and (5) CD19+ and CD19+CD5+ cells (P < .0001) and marked decreases in the frequencies of CD8+ and CD8+CD11b- cells (P < .0001). CD34-SCT recipients showed lower lymphocyte counts in the first 6 months and an emergence of lymphocyte and CD4+CD45RA+ cells at approximately 9 months and 1 year. Both CBT and CD34-SCT recipients showed increased frequencies of CD56+ cells at 1 month (CD34-SCT versus BMT, P < .001) but decreased frequencies after 6 months (CBT versus BMT, P < .001). Lymphoproliferative responses to exogenous interleukin 2 were constantly lower in CBT and CD34-SCT recipients than in BMT recipients. These results suggest that the delay in immune reconstitution after CBT in the early phase was mainly qualitative and related to the immaturity of cells, whereas the delay in CD34-SCT was mainly quantitative in the first several months.
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PMID:The kinetics of immune reconstitution after cord blood transplantation and selected CD34+ stem cell transplantation in children: comparison with bone marrow transplantation. 1277 32

Adult stem cells are finding increased therapeutic potential not least in tissue regeneration protocols. The cell sources being proposed for such protocols include embryonic, umbilical cord blood (CB) and adult bone marrow (BM). Although embryonic sources are controversial, CB and marrow are available immediately. The appropriate cells of use in these sources are considered to be extremely rare and a characterisation of the starting cell source is important for the development of adult stem cell protocols and ex vivo expansion. Umbilical CB and BM mononuclear cells were labelled for the antigens CD34, CD133, CD117, CD164, Thy-1 or CD38, and additional intracellular CD34 antigen. Three dimensional flow-cytometric analyses were carried out together with dual laser confocal microscope analysis for antigen profile expression. Variable levels of immaturity were detected on CB and BM populations using internal and external CD34 antigen. For CB and BM cells, internal CD34 (intCD34+) could be detected on co-expressing CD133+ cells before expression of external CD34 antigen (extCD34+). CD38 co-expression analysis also showed that a small but distinct group of cells expressing low CD38 and no external CD34 antigen could be detected. Additional phenotyping of these cells using CD117, Thy-1, CD164 and CD133 demonstrated variable primitive status detectable within the external CD34- population. Newly harvested primary CB and BM populations were shown to contain not only cellular populations of known standard sequential maturity but also populations of more extreme rarity. The presence of cells which lacked extracellular CD34 antigen, in both CB and BM, but which possessed CD133, has important implications for purification of human stem cells in clinical applications.
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PMID:Multiparametric analysis of immature cell populations in umbilical cord blood and bone marrow. 1466 97

DNA methylation plays important roles in a wide range of biological phenomena, especially in the embryonic development and tumorigenesis. However, correlations between differentiation and DNA methylation have not been clarified well in each differentiation system. In this study, we focused our attention on regulatory roles of DNA methylation in normal hematopoietic differentiation using a demethylating reagent, 5-azacytidine (5-AzaC). As a source of hematopoietic progenitor cells, we used CD34(+) cells prepared from human umbilical cord blood and examined the effects of 5-AzaC on the colony-forming activity and the long-term culture-initiating (LTC-IC) activity of these cells. 5-AzaC treatment increased LTC-IC frequency 1.57- to 2.50-fold as compared to the nontreated control. In parallel to this, immunoblotting analysis showed that the intensity of overall DNA methylation decreased after 5-AzaC treatment. These results indicated the involvement of DNA methylation and demethylation in controlling immaturity of hematopoietic progenitor cells and the usefulness of 5-AzaC for regulating this immaturity.
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PMID:5-Azacytidine supports the long-term repopulating activity of cord blood CD34(+) cells. 1549 41

The diagnosis of pediatric tumors relies heavily on immunohistochemical staining of small tissue biopsies, since many entities share a "small blue cell" phenotype. More recently, molecular genetic analysis for detection of specific gene fusion products has become available. With the increased use of such molecular techniques, the authors have noted that tumors with proven molecular diagnoses can exhibit unusual patterns of immunohistochemical staining. This study examines pediatric tumors with a "small blue cell" phenotype in which molecular diagnoses were available where applicable. A panel of immunohistochemical stains was performed (S100, CD56, NB84, CD99 [MIC2], Bcl-2, CD117, CD34, desmin, MNF116, and WT1). In the 370 sections from 37 cases, all primitive neuroectodermal tumors, with and without the presence of t(11;22), demonstrated uniform membranous membrane staining with CD99 (MIC2) and focal staining with CD56, NB84, MNF116, and WT1. All rhabdomyosarcomas, both alveolar and embryonal, demonstrated uniform desmin, CD56, and cytoplasmic WT1 immunostaining. Desmoplastic small round cell tumors showed positive cytokeratin staining, with half having "dot-like" cytoplasmic desmin and WT1 positivity; some showed focal positivity for NB84, CD99, and Bcl-2. The "undifferentiated" sarcomas showed the widest range of staining, with no marker staining all cases. Neuroblastomas exhibited uniform strong staining for CD56 and NB84 and marked cytoplasmic Bcl-2 positivity, and some cases showed cytoplasmic WT1 expression. Blastematous Wilms' tumors showed uniform strong membranous staining for CD56, uniform cytoplasmic staining for Bcl-2, and nuclear expression of WT1. Embryonal pediatric malignancies can demonstrate apparently nonspecific expression patterns for several antigens, which may reflect developmental immaturity rather than specific differentiation pathways.
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PMID:Immunohistochemical findings in embryonal small round cell tumors with molecular diagnostic confirmation. 1572 86

Although neuroepithelial tubules (NET) often are a component of immature teratoma (IT), they are not always required for diagnosis. Other somatic elements are sufficient and often verified with immunohistochemical stain. This study was designed to determine the definition of immaturity versus fetal ontogeny, using several molecular markers in IT. It is our contention that IT is equivalent to an embryonic stage less than a fertilization age (FA) of 8 weeks, and a mature teratoma (MT) to a fetal stage later than a FA of 8 weeks, whereas an embryonal carcinoma (Eca) matches a pre-embryonic stage earlier than a FA of 2 weeks. The teratomatous components used as a roadmap to evaluate maturity included: a lobular structure of primitive endodermal tubules (FA 4 to 6 weeks), a ventricle-lined cortical plate (FA 9 weeks), a complex papillary choroid plexus (FA 10 weeks), melanin deposition in hair follicles (FA 15 weeks), and the bell stage of odontogenesis (FA 19 weeks). The teratomatous components of 25 resected ovarian solid teratoma samples were compared with fetal ontogeny. For an immunohistochemical analysis, the CD30, CD34, CD99, bcl-2, alpha-fetoprotein (AFP), and placenta-like alkaline phosphatase (PLAP) were assessed. The AFP and Ki-1 were positive in the embryoid body, which was identified at a FA less than 4 weeks in Eca. The AFP was positive in the primitive endodermal components and some of the squamous epithelium in IT. The CD99 and bcl-2 were selectively stained in the primitive NET, which was detected no later than a FA of 6 weeks. The CD34 and bcl-2 were positive in the immature-looking precartilage blastomatous components, which proved useful for detecting immature cartilage, corresponding to a FA of 5 to 6 weeks. The ontogeny of IT was found to correspond to the embryonic stage at a FA of 2 to 8 weeks, and CD99, CD34, bcl-2, AFP, CD30, and PLAP could be used as supportive tools to define IT. This new grading system could be more scientific and more reproducible in any spectra of teratoma.
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PMID:Diagnostic challenge of fetal ontogeny and its application on the ovarian teratomas. 1578 74

Spleen is a common site of extramedullary hematopoiesis. Extramedullary hematopoiesis seen in non-neoplastic conditions can occasionally be extensive and raise concerns for a myeloid neoplasm. We compared the morphologic and immunohistochemical features of splenic hematopoietic proliferations seen in neoplastic myeloid disorders (eg chronic myeloproliferative disorders, myelodysplastic/myeloproliferative disorders and acute myeloid leukemias) to extramedullary hematopoiesis seen in a variety of reactive conditions. In all, 80 spleen specimens were reviewed. The presence of each marrow-derived lineage, dysplasia and immunohistochemical results were evaluated (CD34, CD117, myeloperoxidase, CD68, p53, TdT, CD42b and hemoglobin). Neoplastic hematopoietic proliferations in chronic myeloproliferative disorders are characterized by trilineage hematopoiesis with significant dysplasia in all cell lineages. Acute myeloid leukemia showed an increase in immature forms, which were highlighted by immunohistochemistry. Reactive extramedullary hematopoiesis showed variability in histologic features. Post-bone marrow transplant and thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome spleens showed extramedullary hematopoiesis with some morphologic features of immaturity, which could simulate chronic myeloproliferative disorder. However, they lacked characteristic immunohistochemical features of neoplastic myeloid disorders such as positivity for CD34 or CD117.
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PMID:Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders. 1611 26

This study was aimed at exploring the immunophenotypic features of blasts in patients with myelodysplastic syndromes (MDS). Four-color flow cytometry using conventional and secondary gating strategies was used to immunophenotype blasts and the CD34 positive cells in bone marrow nucleated cells of 29 patients with MDS. The results showed: (1) with progression of MDS from RA/RAS, RAEB to RAEB-T, the proportion of CD34(+) cells were gradually increased from 8.0%, 46.4% to 76.8% (P < 0.05); (2) using CD45 vs SSC gating strategy, with the transformation of RA/RAS, RAEB to RAEB-T, the expression of HLA-DR, CD13, CD33, CD117 were also gradually increased (P < 0.05), and the expression of CD15 was gradually decreased (P < 0.05); (3) using CD45 vs CD34 gating strategy, the expression of HLA-DR, CD13, CD33, CD117 on blasts were higher by secondary gating method than those by conventional gating (P < 0.05). However, there were no significant difference (P > 0.05) in the expression of above-mentioned antigens on CD34(+) cells among different MDS subtypes. It is concluded that conventional gating method can reflect MDS progression from RA/RAS, RAEB to RAEB-T, and secondary gating strategy may accurately reflect the biological features of blasts in MDS. Abnormal expression of CD34 is related to the immaturity level and heterogeneity of blast cells, which is beneficial to the diagnosis of clinically suspected MDS incapable of diagnosing with morphology and cytogenetics.
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PMID:[Four-color flow cytometric immunophenotypic features of blasts in myelodysplastic syndromes]. 1658 91

Dendritic cells (DCs) have been characterized as having an immature phenotype in infants when compared with adults; but it is unclear whether the phenotype or function of these populations changes during human intrauterine development. Three-colour flow cytometry was used to phenotype fetal/neonatal circulating DCs during the second half (>20-wk gestation) of pregnancy, (n = 34) and adults (n = 9). DCs were identified from peripheral blood mononuclear cells (PBMCs) or cord blood mononuclear cells (CBMCs) as staining brightly for HLA-DR but negative for T cell, B cell, monocyte, and NK cell lineage markers. The surface molecule of interest was detected in a third colour. During gestation CD34, a marker of immaturity was significantly higher, and CD4, a differentiation marker, was significantly lower than adult levels. The percentage of CD11c+ cells did not differ significantly at any age, although a trend to reduced intensity of expression at earlier stages of gestation was observed. Significantly fewer DCs expressed the IgG receptors CD32 and CD64 at all gestations. The percentage of HLA-DR+/lin- cells expressing CD40 was lowest at 20-23 wks and was always significantly lower on DCs from cord blood vs. adult blood. Similarly, the percentage of CD86+ and CD54+ DCs was significantly lower than adults throughout gestation. Thus, immaturity of cord blood DCs is likely to arise as a consequence of decreased ability to take up antigen (at least via IgG-mediated mechanisms) and reduced provision of co-stimulation.
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PMID:Phenotypic analysis of circulating dendritic cells during the second half of human gestation. 1879 98


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