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

During the diagnostic investigation of 750 acute leukemias, nine cases were morphologically, cytochemically, and phenotypically undifferentiated. In seven of these cases the blasts were class II+, CD34+ and TdT+, in one were class II+, TdT+, CD7+ while in the remaining leukemia blasts expressed class II only. Cytoplasmic and membrane CD22, CD3, CD13, and Ig as well as membrane CD19, CD10, CD37, CD2, CD33, CD14, glycophorin C, and CD61 were absent. The further characterization of these rare leukemias yielded the following results. The TCR-beta, -gamma and -delta genes were in germline configuration in seven cases studied while IgH genes were rearranged on both alleles in two cases and germline in the other five. By ultrastructural analysis peroxidase activity was detected on unfixed cells in a minority of blasts from four of seven cases. In two of the peroxidase-positive cases a small proportion of blasts also reacted with an anti-myeloperoxidase monoclonal antibody. In one of the peroxidase-negative cases, 7% of blasts were labeled by the antibody, suggesting the presence of peroxidase in its proenzyme form. Importantly, the two cases with Ig gene rearrangements did not have cytochemically or immunologically detectable peroxidase. Three of the nine patients were treated as ALL while six received AML chemotherapy. In five patients complete remission was achieved while the other four died from infections during remission induction. Four patients are still in remission 7, 12, 24, and 30 months after diagnosis while one patient relapsed after 12 months. In conclusion, we have characterized the genotypic and ultrastructural features of subtype of acute leukemia in which blasts expressed immaturity markers and lacked lineage associated antigens. In contrast to previously reported "unclassifiable" cases, the leukemias were phenotypically homogeneous and showed a good response to chemotherapy.
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PMID:Phenotypic, genotypic, cytochemical, and ultrastructural characterization of acute undifferentiated leukemia. 239 82

Deficient responses by NK cells may contribute to the susceptibility of human newborns to severe HSV infections. Furthermore, HSV disseminates widely during neonatal infection and may also infect and interfere with the function of blood mononuclear cells (MNC). To determine whether the function of newborn NK cells would be affected by contact with HSV, and whether newborn NK cells might be permissive for HSV replication, newborn MNC were cultured with HSV in vitro for 3 days. Before culture, the intracellular calcium mobilization in newborn NK cells induced by mAb to CD2 and CD16 did not differ from that of adult NK cells. This result argues against immaturity of an early NK cell activation event in human newborns. After culture with HSV the Ca2+ flux response was unaffected by lysis of K562 targets by newborn NK cells and NK-dependent suppression of HSV replication in fibroblasts were preserved or increased. Incorporation of thymidine by NKH-1 cells following stimulation with PHA and IL-2 was not suppressed. NK cells recovered from these cultures did not contain infectious HSV and synthesis of HSV-specific proteins was not detected by immunoprecipitation although HSV genome was detected by DNA hybridization. Our results extend the in vitro model stimulation systems in which newborn NK cells respond positively to include triggering through the CD2 Ag, cross-linking of cell surface CD 16 Ag and response to a pathogen, HSV.
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PMID:Human newborn natural killer cell responses to activation by monoclonal antibodies. Effect of culture with herpes simplex virus. 253 66

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.
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PMID:Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule. 256 56

It is still uncertain whether cell cultures attain the functional maturity of corresponding in vivo cells. The degree of differentiation of cultured collecting-duct (CD) epithelium cells was therefore examined using immunohistochemical procedures. Three monoclonal antibodies (mabs CD1, CD2, and CD3) were raised against proteins (PCD) isolated from the renal papilla. At Western-blot analysis, each of these antibodies reacted with a specific protein that was distinguishable according to its molecular weight [PCD1, 190 kilodaltons (kDa); PCD2, 210 kDa; PCD3, 50 kDa]. Using immunofluorescence, these proteins were found to be localized exclusively in the renal CD system. Other renal structures, such as the proximal or distal tubular portions, the glomeruli and the interstitial network, were not reactive. The mabs, CD2 and CD3, labeled both the cortical and medullary CD in a uniform way, whereas mab CD1 produced heterogeneous immunolabeling along the length of the cortical, medullary, and papillary CD. As revealed by immunohistochemistry, the mabs revealed differences with respect to the expression of the specific renal proteins in cultured CD cells. In polar-differentiated epithelium cultured for 5 days on a specific renal support, mab CD1 was unreactive, whereas mabs CD2 and CD3 were positive. This demonstrated the biochemical immaturity of this cultured epithelium with respect to CD1 reactivity. In morphologically dedifferentiated CD monolayer cells grown on the bottom of a culture dish, only a weak reaction for mab CD3 was observed. The loss of epithelial polarization in CD monolayer cells obviously coincides with the absence of the renal proteins PCD1 and PCD2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The expression of specific proteins in cultured renal collecting duct cells. 328 51

The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3 delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase for T- and myeloid-lineage commitment during immature stages of differentiation. This helps understand the conversion of some T-ALL/LBL cases to acute myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lineage determination of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoblasts: studies on phenotype, genotype, and gene expression of myeloperoxidase, CD3 epsilon, and CD3 delta. 751 45

Glucocorticoids (GC) are known to inhibit the proliferative response of leukocytes after mitogenic activation. Until now, the effects of GC on the immune system have been studied predominantly in adults. However, GC are frequently administered to human fetuses and newborns for the prevention and treatment of respiratory distress syndrome. The immune system of human newborns is still a functionally immature system. Therefore, we wondered whether the immaturity is also reflected by altered responses to hormonal signals such as glucocorticoids. We studied the effects of the GC dexamethasone (DEX) on the proliferation of peripheral blood mononuclear cells and T cells in vitro after stimulation with phytohemagglutinin, anti-CD3, anti-CD3/anti-CD28 or anti-CD2/anti-CD28. Our data demonstrate that neonatal cells are much more sensitive to inhibition of the proliferative response by DEX than adult cells (ED50 1 +/- 0.8 nM vs. 221 +/- 135 nM). This difference in sensitivity is not related to differences in affinity and capacity of binding of [3H] DEX. Moreover, we show that the mechanisms of GC inhibition differ between adult and neonatal cells. In adult cells, addition of interleukin (IL)-2 does not restore DEX inhibition of the proliferative response. In contrast, the proliferative response of neonatal cells can be restored completely by the addition of IL-2. These data suggest that the primary target of GC in neonatal cells is inhibition of IL-2 production. In adult cells, other mechanisms are responsible for inhibition of T cell proliferation.
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PMID:Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells. 777 38

Patients who have undergone allogeneic bone marrow transplantation (allo-BMT) are susceptible to a variety of opportunistic infectious complications in the months to years after engraftment. Impaired in vitro T-cell functions have been documented in these patients, and these T-cell dysfunctions contribute to the prolonged immune deficiency after allo-BMT. In the present study, we examined the expression of CD26 as well as the reconstitution of CD26-mediated T-cell costimulation via the CD3 and CD2 pathways at various times in patients aged greater than 18 years after CD6-positive, T-cell depleted allo-BMT. We found that the percentage of CD26- and CD3-positive cells, as well as the levels of expression of both antigens, was lower than in normal controls during the first 4 months after CD6-depleted allo-BMT. Subsequently, the amount of lymphocytes expressing CD3 and CD26 and the quantitative surface expression of CD3 and CD26 were not significantly different in patients and normal controls. Functional studies showed that CD26-mediated T-cell proliferation via the CD3 pathway was considerably improved and almost reached normal levels by 1 year, whereas recovery of CD26-mediated T-cell proliferation via the CD2 pathway was delayed for at least 2 years after CD6-depleted allo-BMT. As CD26 involvement in the regulation of human thymocyte activation is restricted preferentially to the CD3 pathway--unlike its involvement with both CD3 and CD2 pathways of peripheral T cells--our results suggest that the different effects of CD26-mediated costimulation via the CD3 and CD2 pathways after CD6-depleted allo-BMT may be a reflection of peripheral T-cell immaturity in those individuals, similar to that seen in mature medullary thymocytes or cord T lymphocytes.
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PMID:Differential CD26-mediated activation of the CD3 and CD2 pathways after CD6-depleted allogeneic bone marrow transplantation. 784 1

Clinical and cytologic characteristics were correlated to immunologic markers in 154 patients with newly diagnosed acute myeloid leukemia (AML). The panel of monoclonal antibodies (MoAbs) was selected to identify differentiation-associated antigens of both the myeloid and the lymphoid lineages (CD13, CD33, CD14, CD15, CD7, CD34, CD10, HLA-DR, CD19, CD2, CD5, TdT). The expression of multidrug resistance P-glycoprotein (P-170) was also evaluated in 117 patients. Differences in antigenic expression was observed among the various French-American-British (FAB) subgroups. HLA-DR was poorly expressed on the blasts of acute promyelocytic leukemia (M3), and was always found in FAB M5. CD34 was detectable in all M0 cases and only in one M3 (p < 0.001). Lymphoid-associated antigens were positive in 74 cases (48.1%). In particular, CD7 was found in 49 patients (31.8%), and TdT in 30 (21.3%), 15 samples displaying coexpression of these two antigens. The incidence of CD7+ cases was particularly elevated in M0 and M5 AML (p = 0.005). It significantly correlated with the expression of CD34, HLA-DR, P-170 (p < 0.001, p = 0.018 and p = 0.034 respectively), and with a leukocyte count > 50 x 10(9)/l (p = 0.038). Sixty-nine (59%) samples demonstrated P-170 positivity. Again, this phenotype was particularly expressed in the poorly differentiated forms (M5, M0 and M1) and showed significant correlation with the immaturity markers CD34, CD7 and HLA-DR (p = 0.013, p = 0.022 and p = 0.001, respectively). Expression of individual antigens correlated with prognosis. Refractoriness to first line therapy was associated with CD7 expression (p = 0.002) and P-170 (p = 0.001). The CD7 marker was also significantly associated with a very low overall survival (p < 0.001) and continuous complete remission (p < 0.001). CD14 expression also significantly predicted lower survival rates (p = 0.033). The combination (CD7+ CD14+) identified a subset of patients with a particularly adverse outcome. The prognostic value of CD7 expression, alone or in combination with other markers, was confirmed in multivariate analysis.
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PMID:Prognostic value of cell marker analysis in de novo acute myeloid leukemia. 790 93

The purpose of this study was to phenotype and assay immunological function on cord blood from 70 samples. Immunophenotyping indicated similar numbers of CD2, 3, and 8-positive cells as in adult bone marrow. CD4-positive cells were increased and CD19, 20, and CD56-positive cells were decreased in numbers. Proliferative responses to nonspecific mitogens were lower in cord blood cells than in adult cells, as was NK activity and spontaneous secretion of IL-6 and TNF-alpha. This study confirms the relative immaturity of cord blood cells even when some functional assays appear normal.
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PMID:Immunological characteristics of umbilical cord blood cells: phenotypic and functional analysis. 792 84

The physiologically low or absent IgG2 responses of infants have been attributed to T or B cell functional immaturity. We have analyzed the capacity of adult and neonatal T lymphocytes to secrete IgG2 switch factor (IgG2-SF) and the capacity of neonatal B cells to respond to such factors. The IgG2-SF capacity was assessed on CD40-activated naive B cells, measuring IgG2 by ELISA in supernatants of cultures performed in the presence of IL-10. T cells secreted IgG2-SF together with IL-2 and IFN-gamma, after activation with a combination of anti-CD2, anti-CD28 and phorbol myristate acetate (Th1-like activation). In contrast, activation with anti-CD3 and anti-CD28, which yielded IL-4 and IL-10 but neither IL-2 nor IFN-gamma (Th2-like activation), did not result in the secretion of IgG2-SF. The supernatant of activated neonatal T cells contained IgG2-SF. Neonates' B cells produced almost as much IgG2 as did naive adult B cells. The effect of IgG2-SF was further demonstrated by its ability to induce 3-15% of CD40-activated naive B cells to express cytoplasmic IgG2 regardless of the presence of IL-10. This study demonstrates that: (i) IgG2 switch can be T cell dependent in humans, (ii) IgG2-SF is produced with Th1-like cytokines and (iii) low IgG2 responses in infants do not result from either an inability of T cells to produce IgG2-SF or an inability of B cells to undergo IgG2 switch in vitro.
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PMID:Delayed IgG2 humoral response in infants is not due to intrinsic T or B cell defects. 892 28


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