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

Peripheral blood progenitor cells (PBPC) were mobilised by recombinant human G-CSF (rhG-CSF) and cyclophosphamide, harvested by apheresis from 9 patients with NHL and stored at 4 degrees C without further manipulation. They were then reinfused after high-dose chemotherapy. We monitored the change in colony-forming units-granulocyte, macrophage (CFU-GM) proliferation as well as plasma glucose, lactate and pH levels over the period of the study. In an attempt to maintain CFU-GM numbers, rhG-CSF was added to storage bags at collection and 48 h later. Our observations suggest that cell viability is well maintained and that CFU-GM numbers rise over the first 48 h of storage before falling rapidly. Metabolic changes cause a fall in the pH and glucose levels with a reciprocal rise in plasma lactate. The addition of rhG-CSF at a concentration of 10 ng/ml to cells in storage showed no detectable benefit. Following storage for 96 h, 77% (SEM +/- 8%) of the initial CFU-GM remained.
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PMID:Liquid storage of peripheral blood progenitor cells for transplantation. 753 74

Anemia of prematurity (AOP) has been conventionally treated with erythrocyte transfusions. Recent investigations have reported the use of recombinant human erythropoietin (rHuEPO) as an alternative for treating AOP. The potential of rHuEPO in increasing erythropoiesis implies its clinical usefulness. The effect of rHuEPO on reticulocyte count as well as other parameters of blood cells was examined in 14 premature babies with AOP. The average birth body weight and gestational age of these premature babies were 1533.71 +/- 61.66 g (Mean +/- SEM) and 31.36 +/- 0.49 weeks respectively. They received the first dose of rHuEPO at age 26.14 +/- 2.03 days with a hemoglobin level by 9.40 +/- 0.27 g/dL and hematocrit level of 28.20 +/- 0.81%. They were given rHuEPO 200 U/kg subcutaneously every other day for 10 doses, and iron 3 mg/kg and vitamin E 25 IU/kg per os every day. Average erythropoietin level of the patients on entry into this study was low (7.66 +/- 1.10 mu/mL). After treatment with rHuEPO for 20 days, the corrected reticulocyte count increased from 0.64 +/- 0.10% to 1.68 +/- 0.42% on Day 5 (P < 0.05), 1.96 +/- 0.41% on Day 12 (P < 0.05), 1.77 +/- 0.43% on Day 20 (P < 0.05), and hematocrit increased from 28.2 +/- 0.81% to 29.58 +/- 1.02% (p < 0.05) on Day 20. Bone marrow aspirates on Day 10 for 9 infants revealed moderate to high cellularity, mostly with erythroblasts (47.89 +/- 1.78%); the M/E ratio was low (0.57 +/- 0.05). The granulocyte series and megakaryocyte could be well visualised.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of recombinant human erythropoietin in treating the anemia of prematurity. 779 77

The number of colony-forming units of granulocytes/monocytes (CFU-GM) in the peripheral blood of 7 patients with chronic myeloid leukemia (CML) in chronic phase (CP) receiving standard doses of busulfan (BSF, 0.1-0.2 mg/kg/day p.o.) was compared to that found in 8 patients with CML in CP not previously treated in order to establish if non-myeloablative chemotherapy mobilizes committed granulomonocytic progenitor cells into the circulation. The number (mean +/- SEM) of spontaneous CFU-GM in untreated patients was similar to that recorded in 10 sex- and age-matched controls, 2.6 +/- 1.9 and 3.5 +/- 2.1, respectively. BSF-treated patients showed significantly more spontaneous CFU-GM (13.9 +/- 7.5) than controls and untreated patients. Addition of recombinant human granulocyte/monocyte colony-stimulating factor to cultures promoted colony growth in controls but not in untreated and BSF-treated patients. These data seemingly indicate that: 1) administration of standard non-myeloablative doses of BSF to patients with CML in CP mobilizes CFU-GM into the circulation and 2) BSF therapy selects a granulomonocytic colony-forming progenitor cell population with increased autonomous growth potential. These findings may contribute to the understanding of the therapeutic role of BSF in CML.
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PMID:Circulating colony-forming units of granulocytes/monocytes in patients with chronic myeloid leukemia before and during busulfan treatment. 853 25

Recombinant human colony stimulating factors (CSFs) as single agents are increasingly used for mobilizing peripheral blood progenitor cells (PBPCs) for stem cell transplantation. We have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment markedly potentiated the increase in PBPC numbers of subsequent administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect of IL-3 pretreatment on GM-CSF-induced mobilization of PB progenitors in patients who were potential candidates for autologous stem cell transplantation (n = 16). Patients were treated with GM-CSF at a dose of 5 micrograms/kg/d for 5 d and after a treatment free interval received another cycle of GM-CSF immediately following pretreatment with IL-3 at different doses and duration: 2.5 micrograms/kg/d (n = 4), 5 micrograms/kg/d (n = 3) and 10 micrograms/kg/d (n = 3) for 3 d, 5 micrograms/kg/d for 7 d (n = 4) and 5 micrograms/kg/d for 14 d (n = 2), respectively. Only 7 d pretreatment with IL-3 showed consistent effects. Although IL-3 did not mobilize by itself, pretreatment with 5 micrograms/kg/d of IL-3 for 7 d significantly potentiated GM-CSF-induced mobilization of PB CFU-GM numbers, leading to a mean increase in PB CFU-GM numbers over baseline by 18.5 +/- 5.2 (SEM) fold by IL-3/GM-CSF as compared to a 4.7 +/- 1.7-fold increase by GM-CSF alone. A significant enhancement by the 7 d IL-3 pretreatment was also observed for erythroid (BFU-E) and multipotential progenitor cells (CFU-mix) which were 3.3 +/- 1.3- and 3.4 +/- 0.9-fold, respectively, mobilized by GM-CSF alone, as compared to 8.5 +/- 2.3- and 19.2 +/- 3.4-fold, respectively, by the IL-3/GM-CSF combination. Our results suggest that 7 d pretreatment with IL-3 may be a useful mean to augment mobilization of circulating progenitors by more lineage-restricted CSFs. These findings may be important for the design of mobilization strategies that use growth factors without preceding chemotherapy.
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PMID:Effect of interleukin-3 pretreatment on granulocyte/macrophage colony-stimulating factor induced mobilization of circulating haemopoietic progenitor cells. 854 65

Although granulocyte-colony stimulating factor (G-CSF) is commonly used in the field of supportive therapy for cancer treatment, the serum concentration of endogenous G-CSF in healthy women is still obscure due to the low sensitivity (30 pg mL-1) of the usual enzyme immunoassay. With the development of a highly sensitive (1.0 pg mL-1) chemiluminescent immunoassay by Kiriyama et al., we have clarified the changes of serum G-CSF levels in healthy women during the menstrual cycle and pregnancy. The G-CSF concentration showed a peak value of 27.3 +/- 2.5 pg mL-1 (mean +/- SEM) at the ovulatory phase during the menstrual cycle, which is significantly higher than in all other phases (P < 0.0001, unpaired t-test). A significantly higher value compared to the menstrual cycle, except during the ovulatory phase, was also revealed throughout pregnancy (P < 0.0001, unpaired t-test). These results suggest that G-CSF plays an important role in ovulation and the maintenance of pregnancy.
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PMID:Serum concentration of endogenous G-CSF in women during the menstrual cycle and pregnancy. 858 55

We recently described the development in vitro of cells with granules characteristic of eosinophils and basophils (hybrid granulocytes) from normal human cord blood mononuclear cells cultured for 14 days with recombinant human (rh) interleukin (IL)-3, rhIL-5, and a soluble basement membrane, Matrigel. Hybrid granulocytes constitutively produced granulocyte/macrophage colony-stimulating factor (GM-CSF) and rapidly developed into eosinophils after the exogenous cytokines and Matrigel were removed. To characterize the developmental progression of hybrid granulocytes, cells were maintained for an additional 14 days in medium containing rhIL-3, rhIL-5, and Matrigel. After 28 days, 73% +/- 1% (mean +/- SEM; n = 6) of the nonadherent cells were mononuclear eosinophils, 13% +/- 3% were eosinophils with two or more nuclear lobes, 13% +/- 4% were hybrid granulocytes, and 0.2% +/- 0.1% were basophils. More than 90% of the mononuclear eosinophils were hypodense as determined by centrifugation through metrizamide gradients. After an additional 5 days of culture in medium without exogenous cytokines, 65% +/- 3% (n = 5) of the 28-day cells excluded trypan blue. In contrast, 2% +/- 1% of freshly isolated peripheral blood eosinophils survived 5 days of culture without exogenous cytokines (n = 5). Fifty percent conditioned medium from in vitro derived 28-day mononuclear eosinophils and 14-day hybrid granulocytes maintained the survival of 60% +/- 7% and 77% +/- 7%, respectively, of freshly isolated peripheral blood eosinophils for 72 h, compared with 20% +/- 8% survival in medium alone (n = 3). The eosinophil viability-sustaining activity of 50% mononuclear eosinophil-conditioned medium was neutralized with a GM-CSF antibody. A total of 88% of the 28-day cells exhibited immunochemical staining for GM-CSF. Thus, during eosinophilopoiesis, both hybrid eosinophil/basophil intermediates and immature mononuclear eosinophils exhibit autocrine regulation of viability due to constitutive production of GM-CSF.
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PMID:Constitutive production of granulocyte/macrophage colony-stimulating factor by hypodense mononuclear eosinophils developed in vitro from hybrid eosinophil/basophil granulocytes. 863 92

Thrombocytopenia is common in sick preterm babies. Despite this, platelet production in thrombocytopenic preterm babies has rarely been assessed. To address this problem we have developed miniaturized assays to study circulating megakaryocyte (MK) progenitors [burst-forming unit (BFU)-MK and colony-forming unit (CFU)-MK], total cultured MK precursors and mature MK, by culturing mononuclear cells purified from 0.5-1 mL of preterm peripheral blood. MK lineage colonies and cells are identified by an anti-IIb/IIIa antibody (CD61). We prospectively studied circulating BFU-MK/CFU-MK, total cultured MK precursors and mature MK in 63 preterm babies (gestational age 24-34 wk). Twenty-six developed early thrombocytopenia (platelets < 150 x 10(9)/L by 48 h), whereas the remaining 37 babies maintained normal platelet counts. Twenty-one of the 26 thrombocytopenic babies were born to mothers with pregnancy-induced hypertension or were growth retarded. At birth, thrombocytopenic babies had severely reduced numbers of all MK precursors compared with nonthrombocytopenic babies: BFU-MK 82 +/- 50 versus 663 +/- 174 colonies/mL, mean +/- SEM; CFU-MK 596 +/- 196 versus 3267 +/- 530 colonies/mL; total MK precursors 97 +/- 30 versus 301 +/- 49 x 10(3) cells/mL and mature MK 8 +/- 2 versus 37 +/- 8 x 10(3) cells/mL, respectively. Thrombocytopenia resolved by d 10 in all babies accompanied or preceded by a recovery to normal numbers of circulating MK progenitors. Eighteen (69%) of the thrombocytopenic babies were also neutropenic (neutrophils < 2 x 10(9)/L); in these babies neutrophil progenitor cells (CFU-granulocyte/monocyte) were also severely reduced compared with the nonthrombocytopenic babies (539 +/- 280 versus 1937 +/- 348 colonies/mL, mean +/- SEM). This indicates that the principal cause of the thrombocytopenia and neutropenia is reduced platelet and neutrophil production occurring as a consequence of reduced numbers of MK and CFU-granulocyte/monocyte progenitors, respectively. Taken together these data suggest the hematologic abnormalities characteristic of newborns born to mothers with pregnancy-induced hypertension or with intrauterine growth retardation are a consequence of dysregulation of fetal hemopoiesis occurring proximal to committed MK and neutrophil progenitors, most likely at the level of the primitive multipotent hemopoietic stem cell.
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PMID:Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates. 879 56

During cardiopulmonary bypass (CPB) oxygen free radicals (OFR) are formed, which can mediate reactions damaging tissue components. Blood contact with artificial surfaces during CPB leads to an activation of leukocytes, which are one of the sources of the OFR. Heparin coating of the CPB circuit reduces granulocyte activation. In the present study, the heparin-coated circuits with noncoated cardiotomy reservoirs (Group HC) were compared with noncoated, otherwise similar CPB sets (Group C). In each group, 8 patients were operated on for coronary revascularization. The release of granulocyte granule proteins myeloperoxidase (MPO) and lactoferrin (LF) was evaluated. Production of OFR in the whole blood and in the granulocyte suspension were measured by chemiluminescence (CL). In both groups the whole blood CL declined during CPB. The whole blood CL induced by serum-opsonized zymosan, when enhanced by luminol, was significantly lower in Group HC at 45 min after CPB start (68 +/- 6% of initial values in Group HC vs. 87 +/- 6% in Group C, mean +/- SEM) and 30 min after protaminization (54 +/- 6% of initial values in Group HC vs. 72 +/- 6% in Group C, mean +/- SEM), and CL was significantly higher in Group HC at CPB end (83 +/- 5% of initial values in Group HC vs. 67 +/- 5% in Group C, mean +/- SEM) when enhanced by lucigenin. CL of isolated granulocytes showed no significant differences between the groups. Release of MPO at CPB end and of LF 45 min after start of CPB and at CPB end were significantly lower in the heparin-coated CPB circuits.
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PMID:Effects of heparin coating of cardiopulmonary bypass circuits on in vitro oxygen free radical production during coronary bypass surgery. 886 22

Plasma endothelin (ET) is increased in association with myocardial infarction. The aim of the present study was to get insight into the mechanisms behind this ischemia-induced increase in plasma ET. Since granulocytes increase ET production in vitro, we examined to what extent inhibition of granulocyte-derived proteases could reduce the increase in plasma ET observed in association with myocardial ischemia. We infused Eglin C, a selective inhibitor of the granulocyte-derived proteases elastase, cathepsin G, and chymotrypsin, in pigs subjected to 90 min left anterior descending coronary artery occlusion followed by 210 min reperfusion (n = 7). Arterial plasma ET increased in an untreated control group (n = 7) from 5.0 +/- 0.6 (mean +/- SEM) fmol . ml-1 before myocardial ischemia to 6.1 +/- 0.6 fmol . ml. at 90 min ischemia and reached a maximum of 6.8 +/- 0.9 fmol . ml-1 at 90 min reperfusion. The increase in plasma ET associated with myocardial ischemia was almost completely abolished in the Eglin C treated group (p = 0.005). Plasma ET in the Eglin C treated animals was 4.7 +/- 0.4, 4.7 +/- 0.4, and 4.6 +/- 0.4 fmol . ml-1 before myocardial ischemia, at 90 min ischemia, and at 90 min reperfusion, respectively. Our study suggests a role for granulocyte-derived proteases in the increase in plasma ET associated with myocardial ischemia. We have shown that the increase in plasma ET associated with myocardial ischemia was reduced by inhibition of granulocyte-derived proteases using the selective protease inhibitor Eglin C.
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PMID:Inhibition of granulocyte-derived proteases reduces the increase in plasma endothelin associated with myocardial ischemia in the pig. 887 78

To help establish an effective gene therapy protocol for patients with congenital metabolic diseases, we evaluated retrovirus-mediated transduction and long-term (LT) expression of the NeoR gene in cryopreserved and thawed CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) of infant and cord blood (CB). The results were compared with those in bone marrow (BM) CD34+ cells. The final purity of the CD34+-enriched fraction from PB, CB, and BM, based on FACS analysis, was 88 +/- 14%, 73 +/- 13%, and 68 +/- 19% (mean +/- SEM), respectively. Cells were then cultured for 96 hours with supernatant containing the vector in the presence of interleukin (IL)-3, IL-6, and stem cell factor (SCF). The average efficiency of gene transfer into mobilized PB (n = 5) or CB CD34+ cells (n = 6) was significantly higher than that into BM CD34+ cells, as measured by G418-resistant colony-forming units for granulocyte/macrophage (CFU-GM; 59% or 58% vs. 39%; p < 0.05) and PCR-positive CFU-GM (83% or 79% vs. 53%; p < 0.05). When the evaluation was made in an LT culture system with irradiated allogeneic marrow stroma, these efficiencies were, respectively, 74% or 61% vs. 34% (p < 0.005 or < 0.02) for G418-resistant CFU-GM at week 5 of long-term culture, and 88% or 83% vs. 63% (p < 0.05) for PCR-positive CFU-GM. Fluorometric examination was performed for cell-cycle analysis before and after culture, and the results showed that the fraction of cycling cells was largest in freshly prepared BM (18%), whereas only a small portion of PB (4.6%) and CB (2%) was cycling. However, this value was 17% in BM, 22% in PB, and 13% in CB after culture. These results suggest that mobilized PB from small children and CB cells are suitable and realistic targets for clinical gene therapy and that tandem transduction procedures can be achieved by combining CB and PB.
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PMID:Transduction of retrovirus-mediated NeoR gene into CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized infant and cord blood. 950 13


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