Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report summarizes our results of sequential treatment with IL-3 and GM-CSF following high-dose chemotherapy with respect to the yield and composition of peripheral blood stem cells (PBSC). Eight patients with high-grade non-Hodgkin's lymphoma were included in the study. Starting 24 h after high-dose cytosine arabinoside (Ara C)/mitoxantrone, IL-3 was given for 6 days, followed by GM-CSF. The increase of circulating hematopoietic progenitor cells during leukocyte recovery varied substantially from patient to patient. Up to a 22-fold interindividual difference was observed for the peak levels of CD34+ cells. A special focus of our study was the antigenic profile of the CD34+ PBSC. On analysis of the antigenic profile of the CD34+ cells, the proportion of CD34+/HLA-DR- and CD34+/CD38- cells representing non-committed hematopoietic stem cells was consistently < 5%. The vast majority of CD34+ cells was found to coexpress CD33 (86.3 +/- 2.1%, mean +/- SEM), reflecting myeloid lineage commitment. CD71 antigen was present on 47.4 +/- 3.0% CD34+ cells with two populations (CD71dim/bright), while the percentage of early B lymphoid (CD34+/CD19+) progenitor cells was extremely low (0.38 +/- 0.13%). We therefore conclude that the cytokines currently available such as G-CSF, GM-CSF or IL-3 facilitate an ontogenetic phenomenon supporting the redistribution of hematopoietic progenitor cells after cytotoxic treatment. Six patients were autografted with the IL-3/GM-CSF-exposed blood stem cells following high-dose conditioning therapy. It is worth noting that no additional BM or hematopoietic growth factors were given post-transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Autografting with peripheral blood stem cells mobilized by sequential interleukin-3/granulocyte-macrophage colony-stimulating factor following high-dose chemotherapy in non-Hodgkin's lymphoma. 751 Oct 17

We assessed the expression of the adhesion molecules leukocyte function antigen-1 (LFA-1, CD11a), intercellular adhesion molecule-1 (ICAM-1, CD54), homing-associated cell adhesion molecule (H-CAM, CD44), and c-kit (stem cell factor receptor) on the CD34+ progenitor population from the leukapheresis products of 23 patients (LP CD34+). For blood stem cell collection granulocyte colony-stimulating factor (G-CSF) or interleukin-3/granulocyte-macrophage colony-stimulating factor (IL-3/GM-CSF) was administered after cytotoxic chemotherapy. Furthermore, bone marrow- and blood-derived CD34+ progenitor cells from 6 normal volunteers (BM and PB CD34+) were analyzed. LFA-1 expression was higher on PB CD34+ (88.2 +/- 2.5%, mean +/- SEM) than on BM CD34+ (75.3 +/- 4.3%). Following cytokine administration, LFA-1 was expressed on only 59.7 +/- 3.7% of LP CD34+ at a low fluorescence intensity, suggesting that down-regulation of LFA-1 may facilitate the egress of cells from the bone marrow and prolong their circulation. In contrast, ICAM-1 was weakly positive on CD34+ cells from all sources. CD44 was expressed on the vast majority of CD34+ cells (> 95%) in all samples studied. The highest proportion of CD34+ cells costaining for c-kit was found in normal bone marrow (32.2 +/- 3.3%). In normal peripheral blood and after cytokine mobilization, fewer of the CD34+ cells weakly expressed c-kit (< 15%). The low percentage and level of c-kit expression may indicate that the majority of cytokine-mobilized CD34+ cells are lineage-committed progenitor cells, as reflected by the coexpression pattern for CD38, HLA-DR, and CD33.
 ...
PMID:Expression of adhesion molecules and c-kit on CD34+ hematopoietic progenitor cells: comparison of cytokine-mobilized blood stem cells with normal bone marrow and peripheral blood. 752 8

T lymphocyte activation after leukocyte membrane interaction may play a role in immune dysfunction associated with hemodialysis (HD). Studies of T-lymphocyte activation markers in HD have yielded conflicting results, perhaps due to the use of a limited number of markers and different measurement techniques. We studied the lymphocyte activation markers CD25 (interleukin-2 receptor), CD38, CDw49b (VLA-2), CD71 (transferrin receptor), and HLA-DR, as well as the surface antigens CD3, CD4, CD7, and CD8 by two-color flow cytometry in 23 chronic HD patients before and after a single dialysis session; we also studied 30 normal controls. There was no increase in the percentage of activated T cells in the controls and in the patients pre- and post-HD. Conversely, the percentage of CD3+/CD71+ (transferrin receptor) cells was significantly decreased in the patients pre-HD compared with the controls (3.6% +/- 0.5% [mean +/- SEM] v 5.9% +/- 0.5%; P < 0.005). A single dialysis session did not alter the percentage of activated subsets, but led to significant depletion in the number (x 10(9)/L) of cells that were CD3+ (1.10 +/- 0.10 v 0.97 +/- 0.09; P < 0.05), CD7+ (1.0 +/- 0.09 v 0.85 +/- 0.08; P < 0.0001), and CD8+ (0.50 +/- 0.06 v 0.37 +/- 0.04; P < 0.001), but not CD4+ cells (0.73 +/- 0.08 v 0.69 +/- 0.07; P = NS). These data indicate that the chronic HD patients at baseline "predialysis" do not appear to have an increased percentage of circulating activated T lymphocyte subsets and that the CD3+/CD71+ subset is in fact decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activated and regulatory T lymphocyte populations in chronic hemodialysis patients. 791 75

It was the aim of our study to determine the collection efficiency and yield of CD34+ cells in 88 cancer patients (pts, 44 males/44 females) who underwent 154 large-volume leukaphereses (LV-LPs). The diagnoses were as follows: 18 patients had Non-Hodgkin's lymphoma, 9 Hodgkin's disease, 24 multiple myeloma, 6 acute leukemia, 27 breast cancer, and 4 patients had solid tumors of different types. During the course of LV-LPs, 20 liters (1) of blood were processed at a median flow-rate of 85 ml/min (CS 3000 Baxter) and 130 ml/min (COBE Spectra), respectively. Peripheral blood stem cells (PBSC) were collected following granulocyte colony-stimulating factor (G-CSF)-supported cytotoxic chemotherapy. A 31% and 21% mean decrease in the platelet and white blood count was noted at the end of the LV-LPs when compared with the pre-leukapheresis values. The aphereses were well tolerated without adverse effects. The level of circulating CD34+ cells was closely related to the number of CD34+ cells contained in the respective leukapheresis product (R = 0.89, P < 0.001). Compared with 270 patients who underwent 838 regular 10 1 LPs, the yield of CD34+ cells/kg was almost two-fold greater (4.84 +/- 0.63 x 10(6) [Mean +/- SEM] vs. 2.60 +/- 0.16 x 10(6), P < 0.001). The antigenic profile of CD34+ cells was assessed in 54 separate products collected on the occasion of 27 LV-LPs following the processing of 10 1 and 20 1, respectively. The intra-individual comparison included differentiation- as well as lineage-associated markers (CD38, Thy-1, c-kit, CD33, CD45RA). No difference in the subset composition was observed between the first and second product, arguing against a preferential release of particular CD34+ cell subsets during the procedure. As shown by molecular biological or immunocytochemical examination, the likelihood of harvesting malignant cells using large-volume aphereses was not increased in comparison with regular leukaphereses. Single harvests of > or = 2.5 x 10(6) CD34+ cells/kg could be obtained in 74% of the patients, compared with 52% in case of regular LPs. As the majority of patients were autografted with more than 2.5 x 10(6) CD34+ cells/kg following high-dose therapy, hematological recovery in general was rapid and not related to the type of apheresis product used. Considering patient comfort and savings in resource utilization, large-volume leukaphereses have become the standard procedure for PBSC collection in our center.
 ...
PMID:Successful collection and transplantation of peripheral blood stem cells in cancer patients using large-volume leukaphereses. 898 64

Retinoids, especially all-trans-retinoic acid (ATRA), are well known for their differentiating activity on HL-60 cells. Moreover ATRA induces CD38 antigen overexpression on these cells. In this study we examined the effects of ATRA on purified normal CD34+ cells from adult human marrows incubated with ATRA (1 microM) or stem cell factor (SCF) after 7 d liquid cultures in serum-deprived medium. Before and after the incubation, CD34+ cells were studied by flow cytometry to evaluate the cell-surface expression of CD38 and c-Kit antigens and the cycle status of these cells using high-resolution analysis (DNA content v Ki-67 antigen expression) to clarify the functional meaning of antigenic variations. When compared with control cultures, ATRA-treated cells displayed changes in their immunophenotypic profile. Particularly relevant was the up-regulation of CD38 antigen with a mean (+/-SEM) fold increase of 21 +/- 0.1 (P=0.028) for geometric mean fluorescence intensity (GMFI), without modulation of c-Kit expression. SCF only down-regulated expression of c-Kit with a fold decrease of 4.6 +/- 0.9 for GMFI (P=0.043). Unlike SCF, ATRA did not induce CD34+ cells to entry into cell cycle despite increased levels of surface CD38 antigen. Moreover morphological and functional assays did not argue for an ATRA-induced maturation process. Contrary to steady-state cells, CD34+ cells treated with pharmacological doses of ATRA alone displayed CD38 over-expression without change in c-Kit levels and cycle status, suggesting an absence of maturation pressure.
 ...
PMID:All-trans-retinoic acid up-regulates CD38 but not c-Kit antigens on human marrow CD34+ cells without recruitment into cell cycle. 982 3

The ability of ex-vivo expanded peripheral blood stem cells (PBSC) to engraft non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice has not been evaluated to date. We investigated the maintenance of primitive SCID-repopulating cells (SRC) and long-term culture-initiating cells (LTCIC) in PBSC expanded with early-acting cytokines, thrombopoietin (TPO), stem cell factor (SCF) and FlT3-ligand (FL) with or without interleukin 3 (IL-3) and IL-6 in short-term (6 d) stroma-free serum-free cultures. TPO + SCF + FL and TPO + SCF + FL + IL-3 + IL-6 produced 5.9 +/- 1.97 and 18.25 +/- 4.49 (mean +/- SEM)-fold increase of CD34+ cells respectively. We tracked cellular division with PKH26 and sorted post-mitotic CD34+ PKH26(low) cells to assess their primitive functional properties. After culture with TPO + SCF + FL, LTCICs among post-mitotic cells increased 12.08 +/- 3.4 times, and 4.3 +/- 1.6 times when IL-3 + IL-6 were added. CD34+ PKH26(low) cells cultured with TPO + SCF + FL provided human multilineage (CD34, CD33 and CD19) engraftment in NOD/SCID mice, whereas no human cells were detected in mice injected with cells cultured with TPO + SCF + FL + IL-3 + IL-6. Percentages of CD34+/CD38-, CD34+/CD33-, CD34+/DR- and cells in G(0)/G(1) phase were similar among cells cultured with both cytokine combinations, indicating that the deleterious impact of IL-3 + IL-6 on the ability to engraft is not translated into phenotypic or cycling features. In conclusion, TPO + SCF + FL-expanded PBSC maintain multilineage engraftment ability in NOD/SCID mice, which is abrogated by the addition of IL-3 + IL-6.
 ...
PMID:Early-acting cytokine-driven ex vivo expansion of mobilized peripheral blood CD34+ cells generates post-mitotic offspring with preserved engraftment ability in non-obese diabetic/severe combined immunodeficient mice. 1156 87

Antiretroviral therapy in human immunodeficiency virus infection is occasionally associated with poor immunologic responses despite full suppression of viral replication. As some combinations of nucleoside analogues (NA) have been associated with paradoxical depletion of CD4(+) T- cells, we postulated that depleting the antiretroviral regimen of NAs would improve quantitative immunological parameters. In a longitudinal prospective study we quantified CD4(+) T-cells after removing NAs from antiretroviral therapy. The NA for regimen consisted of atazanavir (300 mg qd), saquinavir (1000 mg bid), and ritonavir (100mg qd) in 14 patients with immunologic failure despite undetectable plasma HIV-RNA (CD4(+) T-cells < 250 cells/microL (<17%) HIV RNA, <= 50 copies/mL). Additionally, we assessed the state of immunologic activation markers (CD38(+)HLA-DR(+) on CD4(+) and CD8(+) T-cells) by flow cytometry. The regimen was well tolerated. During the 48 week study CD4(+) T-cell counts improved significantly (mean and +/- SEM [standard error of mean], baseline: 174/microL (12.4%) [15, 5.8%], week 24: 232/microL (14%) [26, 5.3%], week 48: 267/microL (15.4%) [34, 4.3%]) with preservation of full viral suppression (p<0.05). Activation parameters of CD4(+) T-cells, but not of CD8(+) T-cells, decreased significantly. This treatment strategy may represent an option for patients with poor immunologic responses to antiretroviral therapy despite undetectable viremia.
 ...
PMID:Nucleoside-free boosted double PI regimen: significant CD4+ T-cell recovery in patients with poor immunologic response despite virologic suppression. 1899 21