PubMed Health⌕ Search

Biomedical subjects

J C Egrie

Publications and source records attributed to J C Egrie.

33 records · Page 2Linked to original sources
PubMed1988

The use of recombinant human erythropoietin (EPO) to correct the anemia of end-stage renal disease: a progress report.

End-stage renal disease (ESRD) typically is associated with severe anemia. The major contributor to the anemia appears to be the absolute or relative deficiency of erythropoietin (EPO) production by the kidney. A series of clinical trials have been conducted in the United States using recombinant human EPO (rh EPO) to treat anemic patients with ESRD. The encouraging results of the Phase I-II clinical trials have been confirmed in a multicenter trial in which over 250 patients have been treated. The results indicate that rh EPO can effectively correct the anemia of ESRD and the rate of correction is dependent upon the initial dose given. The rHuEpo was well tolerated, produced few or no direct side effects, and was effective in greater than 95 percent of the patients. rh EPO should have a major role in the correction of the anemia of ESRD and contribute significantly to the rehabilitation of such patients.

Anemia↗
PubMed1988

Recombinant human erythropoietin and autologous blood donation.

Risks of transfusion are minimized with autologous blood. However, autologous donation programs require 2 to 5 weeks to yield only 2.2 units per patient. Recombinant human erythropoietin (r-HuEPO) has been shown to increase erythropoiesis. This study evaluated the effects of r-HuEPO on an aggressive autologous donation program. Twelve adult male baboons were randomized into two groups of six. All animals were studied three times per week for 5 weeks. A unit of blood was donated when on any study day the hematocrit was greater than 30%. Animals received intravenously either 750 units/kg of r-HuEPO (n = 6) or placebo (n = 6) on each study day. Iron dextran was given intravenously to replace 150% of shed iron. The r-HuEPO group had an earlier onset of reticulocytosis (2.7 vs 5.5 days, p less than 0.01) and donated 35% more blood (13.5 vs 10.0 units, p = 0.01) than the control group. No adverse reactions to r-HuEPO were observed. The data show that an aggressive autologous donation program can yield 10 units of blood over a 5-week period. Further, r-HuEPO increases that yield by an additional 35%. This aggressive autologous donation program with r-HuEPO may significantly reduce the need for homologous transfusion and its attendant risks.

Animals↗
PubMed1987

Development of radioimmunoassays for human erythropoietin using recombinant erythropoietin as tracer and immunogen.

Since the estimation of erythropoietin (EPO) by radioimmunoassay (RIA) has been limited by the availability of highly purified urinary (U) human (Hu) EPO, we investigated the use of recombinant (R)-HuEPO as a replacement for U-HuEPO in the preparation of 125I-tracer and high affinity antisera. In each of two validated RIAs developed using U-HuEPO-derived reagents, dose-response lines and potency estimates for samples were compared when 125I-U-HuEPO and anti-U-HuEPO antisera were sequentially replaced to give assay variants using R-HuEPO-derived reagents. Two U-HuEPO preparations, the 2nd International Reference Preparation and CAT-1, and R-HuEPO were variously used as standards. The samples tested included clinically relevant human sera and partially purified preparations of U-HuEPO and R-HuEPO. In each RIA and for each assay variant tested, samples gave dose-response lines whose slopes did not differ significantly from that of the standard. For each of the two variant RIAs, potency estimates for any sample were consistent and, where examined, RIA potency estimates agreed with in vivo bioassay determinations. These results, obtained independently in two laboratories, indicate that RIAs having appropriate specificity and sensitivity for the estimation of EPO in clinical samples can be developed using reagents derived from R-HuEPO.

Biological Assay↗
PubMed1987

Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial.

We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis. The recombinant human erythropoietin was given intravenously three times weekly after dialysis, and transfusion requirements, hematocrit, ferrokinetics, and reticulocyte responses were monitored. Over a range of doses between 15 and 500 units per kilogram of body weight, dose-dependent increases in effective erythropoiesis were noted. At 500 units per kilogram, changes in the hematocrit of as much as 10 percentage points were seen within three weeks, and increases in ferrokinetics of three to four times basal values, as measured by erythron transferrin uptake, were observed. Of 18 patients receiving effective doses of recombinant human erythropoietin, 12 who had required transfusions no longer needed them, and in 11 the hematocrit increased to 35 percent or more. Along with the rise in hematocrit, four patients had an increase in blood pressure, and a majority had increases in serum creatinine and potassium levels. No organ dysfunction or other toxic effects were observed, and no antibodies to the recombinant hormone were formed. These results demonstrate that recombinant human erythropoietin is effective, can eliminate the need for transfusions with their risks of immunologic sensitization, infection, and iron overload, and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease.

Adult↗
PubMed1986

Monkey erythropoietin gene: cloning, expression and comparison with the human erythropoietin gene.

The erythropoietin (Epo) gene from Cynomolgus monkeys has been isolated from a kidney cDNA library using mixed 20-mer oligodeoxynucleotide probes. The gene encodes a 168 amino acid (aa) mature protein with a calculated Mr of 18,490 and a presumptive signal peptide of 24 aa. The Epo gene, when transfected into Chinese hamster ovary (CHO) cells, produces a glycosylated protein with an apparent Mr of 34,000. The expressed product is biologically active in vivo. The monkey gene exhibits 92% and 94% homology to the human gene at the aa and nucleotide sequence levels, respectively. When compared with the human Epo, monkey Epo has an additional 3-aa residue at the N terminus of the mature protein and a deletion of an internal lysine residue.

Amino Acid Sequence↗
PubMed1986

Characterization and biological effects of recombinant human erythropoietin.

Human recombinant erythropoietin (rHuEPO) has been purified to apparent homogeneity and compared to purified human urinary erythropoietin (EPO). Both the purified natural and recombinant EPO preparations were characterized in a competition radioimmunoassay (RIA), the exhypoxic polycythemic mouse bioassay, in vitro tissue culture bioassays using bone marrow cells, and by Western analysis. In the immunological and biological activity assays, the rHuEPO shows a dose response which parallels that of the natural hormone. By Western analysis, the recombinant and human urinary EPO migrate identically. Administration of rHuEPO increases the hematocrit of normal mice in a dose-dependent manner. Additionally, the rHuEPO is able to increase the hematocrit of rats made uremic as a result of subtotal nephrectomy. In summary, by all criteria examined, the rHuEPO is biologically active and equivalent to the natural hormone.

Animals↗
PubMed1985

Cloning and expression of the human erythropoietin gene.

The human erythropoietin gene has been isolated from a genomic phage library by using mixed 20-mer and 17-mer oligonucleotide probes. The entire coding region of the gene is contained in a 5.4-kilobase HindIII-BamHI fragment. The gene contains four intervening sequences (1562 base pairs) and five exons (582 base pairs). It encodes a 27-amino acid signal peptide and a 166-amino acid mature protein with a calculated Mr of 18,399. The erythropoietin gene, when introduced into Chinese hamster ovary cells, produces erythropoietin that is biologically active in vitro and in vivo.

Amino Acid Sequence↗
PubMed1985

Characterization of recombinant monkey and human erythropoietin.

We have isolated the human EPO gene from a human genomic lambda library and a monkey EPO cDNA from an anemic monkey kidney cDNA library. These sequences have been expressed in both COS1 and Chinese hamster ovary cells. The expressed EPO has been shown to be fully biologically active both in vitro and in vivo and immunologically identical to the native hormone. In addition, administration of recombinant EPO to animals causes a dramatic increase in their hematocrit.

Anemia↗