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)

The fate of preexisting mRNA sequences was examined after infection by herpes simplex virus. Murine erythroid cells transformed by Friend leukemia virus were used as the host. Such cells, when exposed to 2% dimethyl sulfoxide, produce large amounts of globin and globin mRNA. The protein and its mRNA are easily recognized at 4 days by electrophoresis in high percentage acrylamide gels and by hybridization to cDNA, respectively. Herpes simplex virus replicates in these cells. By 2 hr after infection the rate of protein synthesis decreases to 30% of the level in mock-infected cells and only 49+/-8% (SEM) of the globin mRNA sequences present prior to infection could be detected by hybridization to cDNA. At 4 hr after infection, when the rate of protein synthesis in infected cells is at a maximum, only about 15% of the globin mRNA sequences remained. Control experiments support the hypothesis that globin mRNA sequences are degraded after infection by herpes simplex virus.
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PMID:Degradation of cellular mRNA during infection by herpes simplex virus. 19 89

Anaemia is a feature almost invariably complicating chronic renal failure. Its pathophysiology is multifactorial but the most important cause is erythropoietin (Epo) deficiency. However, either no relation or even a weakly positive relation generally exists between serum immunoreactive (i) Epo and haematocrit values in uraemic anaemia, whereas in anaemias of non-renal origin the correlation is most often strongly negative. Recent evidence indicates that growth hormone also stimulates erythropoiesis. Moreover, late erythroid progenitor cells (CFU-E) require insulin and/or insulin-like growth factor I (IGF-I) for development in vitro. IGF-I has been shown to have a synergistic action with Epo. We have measured serum iEpo and IGF-I levels in 17 haemodialysis patients with severe hyperparathyroidism (mean +/- SEM serum iPTH, 988 +/- 88 pg/ml). Mean age and duration of dialysis treatment were 46.1 +/- 3.4 and 8.8 +/- 1.0 years respectively. Mean haematocrit and haemoglobin values wer 28.1 +/- 1.7% and 9.39 +/- 0.54 g/dl respectively. Mean serum iEpo and IGF-I levels were 20.3 +/- 4.7 mU/ml and 320 +/- 20 ng/ml respectively (normal values for serum iEpo and IGF-I, 17.9 +/- 6 mU/ml and 91 +/- 23 ng/ml respectively). We found that serum IGF-I concentrations were well correlated with haematocrit values (r = 0.68, n = 15, P less than 0.004) whereas serum iEpo values were not (r = 0.41, n = 12, P = 0.18). IGF-I could therefore be an important factor regulating erythropoiesis in uraemic patients, at least when associated with severe hyperparathyroidism.
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PMID:Insulin-like growth factor I: a modulator of erythropoiesis in uraemic patients? 131 79

The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone-marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral-blood progenitor cells and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. 17 patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone-marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral-blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days after infusion of haemopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. This method may be widely applicable to aid both neutrophil and platelet recovery after high-dose chemotherapy; it will allow investigation of peripheral-blood progenitor-cell allotransplantation.
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PMID:Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. 137 71

The availability of an in vitro assay able to detect hematopoietic progenitor cells closely related to those responsible for marrow engraftment following autologous bone marrow transplantation (ABMT) prompted us to establish a procedure aimed at maximally increasing the concentration of the cyclophosphamide derivative mafosfamide used for marrow purging. It, therefore, was the aim of the present study to investigate in a group of patients with acute nonlymphoblastic leukemia (ANLL; n = 19) and acute lymphoblastic leukemia (ALL; n = 19) in complete remission the effect of mafosfamide at the level of adherent blast colony-forming units (blast colony-forming units, CFU-Blast), as well as multipotential (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM), erythroid (erythroid burst-forming units, BFU-E), and granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) progenitor cells. When nonadherent marrow mononuclear cells (MNCs) were incubated (30 min, 37 degrees C) with increasing doses of mafosfamide (30-120 micrograms/ml), a statistically significant (p less than or equal to 0.0005) dose-dependent suppression of CFU-Blast growth was observed. The mean (+/- 1 standard error of the mean [SEM]) values of 50% inhibition (ID50) of the CFU-Blast growth were not significantly different for ANLL (106 +/- 5) and ALL (107 +/- 5) patients. Analysis of CFU-Blast ID50 distribution demonstrated that ID50 ranged from 100 to 120 micrograms/ml in 17 cases (45%), whereas it ranged from 60 to 100 micrograms/ml in 12 cases and from 120 to 160 micrograms/ml in 9 cases. A statistically significant (p less than or equal to 0.05), dose-dependent suppression of colony growth from multi-potential and lineage-restricted progenitor cells was also observed. However, the value of CFU-Blast ID50 was significantly higher (p less than or equal to 0.05) than CFU-GEMM, BFU-E, and CFU-GM ID50 and ID95 values. In conclusion, our data demonstrate that: 1) the CFU-Blast assay allows to detect on an individual basis the doses of mafosfamide used for marrow purging, and 2) the concentrations of mafosfamide extrapolated by using the CFU-Blast assay are significantly higher than those obtained with the CFU-GM assay. The absence of any detrimental effect on marrow engraftment in vivo supports the safety of the CFU-Blast assay to evaluate the dose of mafosfamide used for marrow purging before ABMT.
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PMID:Differential sensitivity of adherent CFU-blast, CFU-mix, BFU-E, and CFU-GM to mafosfamide: implications for adjusted dose purging in autologous bone marrow transplantation. 156 48

Interferon-gamma (IFN-gamma) has been shown to influence globin gene expression in cord blood and normal adult progenitor-derived erythroblasts. To explore the influence of IFN-gamma on fetal hemoglobin (HbF) synthesis in the hemoglobinopathies, erythroid progenitors (BFU-E, burst forming unit-erythroid) from patients with sickle cell anemia (SCA) and thalassemia were co-cultured with or without IFN-gamma. Hemoglobin content in progenitor-derived erythroblasts was assessed by radioligand assay (RIA). Co-culture of erythroid progenitors from 12 SCA patients with 200-400 U/ml of IFN-gamma resulted in a significant decrease in picograms of HbF and percent HbF per BFU-E-derived erythroblast. The mean decrease (+/- SEM) of picograms of HbF per cell and percent of HbF was by 42 +/- 9% and 35 +/- 8% of control cultures, respectively. Co-culture of erythroid progenitors from 10 patients with thalassemia major or thalassemia variant (HPFH/thalassemia, sickle/beta 0-thalassemia) with 200 U/ml IFN-gamma also resulted in a significant decrease in picograms and percent of HbF per BFU-E-derived erythroblast. IFN-gamma treatment also inhibited the enhancement in gamma-globin synthesis induced in culture by butyric acid. Erythroid progenitors from 2 patients with SCA, 1 patient with sickle/beta 0-thalassemia, and 1 patient with HbE/beta 0-thalassemia were co-cultured with IFN-gamma, L-alpha-amino-n-butyric acid, or both. HbF content (expressed as picograms HbF/cell) was decreased in samples co-cultured with IFN, increased in cultures with L-alpha-amino-n-butyric acid, but remained at control values in cultures treated with IFN plus L-alpha-amino-n-butyric acid. These data demonstrate that IFN-gamma is an environmental factor that influences gamma-globin gene expression in the beta hemoglobinopathies in vitro.
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PMID:Interferon-gamma modulates fetal hemoglobin synthesis in sickle cell anemia and thalassemia. 170 29

Erythroid progenitors circulating in peripheral blood and their response to erythropoietin (EPO), interleukin-3 (IL3), and phytohemagglutinin-stimulated, lymphocyte-conditioned medium (PHALCM) were assessed in sickle cell anemia (SCA) patients and controls. SCA patients have significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E) compared with controls (mean +/- SEM, 940.27 +/- 129.11 per ml and 86.56 +/- 19.74 per ml, respectively; P less than 0.0001). At low doses of EPO, BFU-E-derived colonies were significantly increased in SCA patients compared with controls (each P less than 0.05). The EPO dose required to produce 50% of maximum colony numbers was 47 times greater in control subjects than in SCA patients. Moreover, in 11 of 17 patients with SCA, spontaneous BFU-E-derived colonies were formed without added erythropoietin. This phenomenon was not observed in control subjects (P = 0.035). PHALCM developed from mononuclear cells of SCA patients had significantly greater stimulatory effect than did that derived from controls regardless of the source of target cells (each P less than 0.05). A two-step study of IL3 sensitivity of erythroid progenitors was conducted. First, in a liquid culture system, circulating erythroid progenitors of SCA patients and controls were incubated in the presence of varying doses of IL3. During a second step, CFU-E-like colonies were observed in methylcellulose cultures of these cells. The mean numbers of colony-forming unit-erythroid (CFU-E)-like colonies was significantly higher in SCA patients compared with control subjects at low doses of IL3 (each P less than 0.02). The increased response of erythroid progenitors to IL3 and the increased production of hemopoietic growth factors (IL3 or non-IL3) contribute to the hemopoietic response in SCA patients. These mechanisms and increased sensitivity of the BFU-E to EPO may explain lower than expected EPO levels in SCA patients.
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PMID:Increased response of erythroid progenitors to interleukin-3 in sickle cell anemia: CFU-E-like behavior of circulating erythroid progenitors in liquid culture. 195 Dec 99

Effects of erythropoietin treatment on haem synthesis in peripheral blood were evaluated in 11 patients on haemodialysis. After 2 weeks of erythropoietin, mean (SEM) uroporphyrinogen-l synthase activity increased significantly from 88 (10) to 116 (9) pmol/h per mg protein. Haem synthase activity, thought to be the rate-limiting step in erythroid haem synthesis, also showed a significant increase from 4.5 (0.8) to 8.4 (1.8) pmol/h per 10(6) reticulocytes. 4 patients, who showed only a partial response to erythropoietin, had significantly higher serum aluminium concentrations than the 7 who responded fully (225 [44] vs 55 [23] micrograms/l); erythrocyte protoporphyrin concentrations in partial responders were also much higher than in responders (973 [120] vs 388 [29] nmol/l). Aluminium intoxication may cause resistance to erythropoietin by interference with haem synthesis, with accumulation of protoporphyrin.
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PMID:Erythropoietin, aluminium, and anaemia in patients on haemodialysis. 197 9

Glucose transport is decreased in skeletal muscle and adipose tissues of obese, hyperglycemic, insulin-resistant animals. Here we have characterized the glucose transporter(s) in muscle and adipose tissues from normal and obese mice, and we have studied the effect of a treatment with the thermogenic agent BRL 26830A. Glucose transporters were examined in crude tissue membrane fractions (microsomal + plasma membranes) by Western blot analysis using antipeptide antibodies specific for the erythroid (Glut 1) or muscle/fat (Glut 4) glucose transporters. In these insulin sensitive tissues, only Glut 4 was detected. In membranes from obese animals, the Glut 4 number was decreased by 40% +/- 4% in brown adipose tissue (mean +/- SEM of 9 preparations, P less than 0.001), whether the results were expressed per total tissue or per mg of protein. By contrast, Glut 4 number was unchanged in skeletal muscle. In white adipose tissue of obese animals, Glut 4 number per total fat pad was increased. However, due to the enlarged fat pad size, Glut 4 content was diminished when expressed per mg of white adipose tissue membrane protein in obese compared to lean animals. After a 18 day-treatment with BRL 26830A (1 or 2 mg/kg.day), glycemia of obese mice, which was slightly elevated compared to lean animals, was normalized, while insulinemia remained markedly above control values. In brown adipose tissue, the total number of Glut 4 returned to normal at 1 mg of the drug, or increased by 63% +/- 14% at 2 mg. Since membrane protein content was increased by the treatment, when results were expressed per mg of membrane protein, Glut 4 was similar in lean and BRL 26830A (1 or 2 mg) treated obese mice. BRL 26830A treatment did not modify Glut 4 in skeletal muscle, and it increased Glut 4 number in white adipose tissue in a dose-dependent manner. In conclusion, in obese mice, the glucose transporter number was reduced mainly in brown adipose tissue, a defect which could contribute to the hyperglycemic syndrome. Treatment with the thermogenic agent BRL 26830A normalized in parallel glycemia and glucose transporter number in brown adipose tissue, suggesting that this tissue could play a role in glucose homeostasis in rodents.
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PMID:Glucose transporter in insulin sensitive tissues of lean and obese mice. Effect of the thermogenic agent BRL 26830A. 224 21

A glycoprotein that regulates the deposition of C3b on the erythrocyte surface, called decay-accelerating factor or DAF, is absent from the red blood cells (RBC) of patients with paroxysmal nocturnal hemoglobinuria (PNH), explaining in part their abnormal sensitivity to complement. We used a specific antiserum to DAF, flow microfluorometry, and clonogenic assays for erythroid progenitor cells to study PNH erythropoiesis in vitro. By fluorescence-activated cell sorter analysis, all RBC from normal individuals are DAF+. In contrast, the RBC of six patients with PNH showed discrete populations of DAF- cells (10-44%; x +/- SEM = 31 +/- 6%). The DAF- RBC population was partly eliminated by prior acidified serum lysis. To determine whether erythropoietic progenitors expressed DAF, bone marrow cells were sorted by flow microfluorometry and the separated DAF+ and DAF- populations then cultured in vitro. In two normal individuals, but also in six patients with PNH, erythroid colonies formed only from cells in the DAF+ fraction. However, a variable proportion of the normoblast progeny of these DAF+ progenitor cells from patients with PNH was DAF-. Individual bursts removed from cultures of PNH bone marrow showed two discrete populations by fluorescence; the majority of normoblasts were DAF-, only 3 of 27 individual bursts had greater than 50% DAF+ cells, and in three patients, DAF- normoblasts averaged 79%. In contrast, the progeny of individual bursts from normal individuals comprised a unimodal DAF+ population. In each PNH patient, one normal burst (greater than 80% DAF+ normoblasts) was detected, possibly reflecting a normal residual population of erythroid progenitors. By the criterion of DAF expression, there was no evidence of separate populations of normal and PNH type progenitor cells. The phenotypically normal erythroid progenitors of PNH bone marrow acquire the PNH characteristics during differentiation in vitro.
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PMID:Decay-accelerating factor is present on paroxysmal nocturnal hemoglobinuria erythroid progenitors and lost during erythropoiesis in vitro. 241 53

Serum has been shown to have an inhibitory effect on the growth of human megakaryocyte colony-forming units (CFU-Meg), both in the methylcellulose and plasma clot systems. Charcoal-dextran (CD) treatment of fetal bovine serum (FBS), a method that is known to adsorb free hormones and various other substances from their protein-bound counterparts, has been used for the improvement of human erythroid colony growth. We now report a CD treatment of FBS to improve human CFU-Meg growth, using a modified plasma clot colony assay. We found 22.9 +/- 1.9 (SEM) colonies in cultures containing CD-treated FBS, as compared to 7.1 +/- 0.9 colonies with control FBS (different at p less than or equal to 0.0001). Serum treated with dextran alone produced 5.0 +/- 1.6 colonies, which did not differ from control FBS. Cultures containing CD-treated human AB serum, human AB plasma, and citrated bovine plasma yielded significantly (p less than 0.05) fewer colonies than those with CD-treated FBS. Endotoxin, cortisol, T3, T4, insulin, estradiol, testosterone, and erythropoietin levels were not changed in a consistent direction by the CD treatment. Our treatment of FBS with CD allows improved growth of human CFU-Meg colonies and likely represents the removal of an as-yet-undefined inhibitor(s) of CFU-Meg. This technique provides the ability to assay for stimulators or potentiators less hampered by the influence of an undefined inhibitor(s).
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PMID:Charcoal-dextran treatment of fetal bovine serum removes an inhibitor of human CFU-megakaryocytes. 243 53


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