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Biomedical subjects

E Goldwasser

Publications and source records attributed to E Goldwasser.

At least 109 records · Page 6Linked to original sources
PubMed1983

Characterization of human megakaryocyte colony-stimulating factor in the urinary extracts from patients with aplastic anemia and idiopathic thrombocytopenic purpura.

Using procedures that were effective in the purification of human urinary erythropoietin (Epo), we attempted initial purification of megakaryocyte colony-stimulating factors (CSF) in urinary extracts from patients with aplastic anemia (AA) and idiopathic thrombocytopenic purpura (ITP). Comparison of colony stimulation by purified human Epo and crude urinary extracts revealed: (1) that the pure Epo augments megakaryocyte colony formation in culture and (2) MEG-CSF activity is also present in materials other than Epo in the crude urinary extracts from the two types of patients. Similar to purification of Epo, ethanol precipitation and sulfopropyl-Sephadex chromatography provided twofold and threefold increases in the specific activity of MEG-CSF, respectively. In contrast to Epo, however, significant inactivation of MEG-CSF activity was seen with phenol treatment. The elution profile of MEG-CSF seen on hydroxylapatite chromatography of urinary extracts was different from that of Epo. These data provided a basis for initial steps for purification of MEG-CSF and support the notion that MEG-CSF is distinct from Epo.

Aminosalicylic Acids↗
PubMed1983

The effect of erythropoietin and other factors on DNA synthesis by mouse spleen cells.

The effects of pure and crude human urinary erythropoietin, crude sheep plasma erythropoietin and other growth factors on the incorporation of labeled thymidine were studied using spleen cells from mice previously treated with phenylhydrazine hydrochloride. Erythropoietin at 400 mU/ml caused a 40-80 fold increase in the incorporation of the labeled nucleoside. The slope of the dose-response curve found for pure erythropoietin was not significantly different from that found for a crude urinary erythropoietin preparation or for crude sheep plasma erythropoietin. Colony-stimulating factor, interleukin 2, interleukin 3 and the lectin, concanavalin A were also stimulatory but at concentrations from one hundred to one million times higher than that found for erythropoietin.

Animals↗
PubMed1982

Characterization of a monoclonal antibody to human erythropoietin.

Hybrid cells that synthesize a monospecific antibody directed toward erythropoietin have been produced by the fusion of mouse plasmacytoma cells with spleen cells from rats immunized against human erythropoietin. The antibody binds the alpha and beta forms and the asialo alpha form of erythropoietin to the same extent. It is an immunoglobulin of the IgG class and binds only erythropoietin in an impure preparation of the hormone. Biologically active unlabeled erythropoietin competes with biologically inactive radiolabeled hormone for monoclonal antibody binding sites. In addition, the biological activity of erythropoietin measured in vitro is not inactivated when it is bound by the monoclonal antibody.

Animals↗
PubMed1982

Erythrocytosis in patients on long-term hemodialysis.

Erythrocytosis was seen in two men during maintenance hemodialysis therapy for end-stage renal disease secondary to apparent chronic glomerulonephritis. Nonrenal causes of erythrocytosis such as polycythemia vera, chronic hypoxemia, high-oxygen affinity hemoglobin, and hepatoma were excluded by appropriate clinical studies. A computed tomographic scan of the abdomen showed numerous renal cysts in each patient consistent with acquired cystic disease of end-stage kidneys. Peripheral serum erythropoietin levels were elevated as measured by sensitive radioimmunoassay. The findings suggest that the erythrocytosis is caused by an erythropoietic mechanism related to the diseased kidneys. A review of the literature failed to show previous reports of this clinical association.

Erythropoietin↗
PubMed1982

Alloreactive cloned T cell lines. VI. Multiple lymphokine activities secreted by helper and cytolytic cloned T lymphocytes.

Culture supernatants generated by alloantigenic or lectin stimulation of a cloned helper T lymphocyte, designated L2, contain interleukin 2 (IL 2), granulocyte/macrophage colony-stimulating factor (CSF), B cell stimulating factor (BCSF), macrophage (Ia+)-recruiting factor (MIRF), (Ia+)-inducing activity, gamma-interferon, Fc receptor-enhancing activity, macrophage migration inhibitory factor (MIF), macrophage activation factor (MAF), interleukin 3 (IL 3), and a factor responsible for prolonging the synthesis and secretion of the fourth and second components of complement by guinea pig peritoneal macrophages. Erythropoietin was not detected. A spontaneously arising variant of L2, designated L2V, produces much lower quantities of macrophage-stimulating activities, IL 2, and interferon. However, when compared to L2, L2V produces much higher levels of BCSF, equivalent amounts of IL 3, and slightly smaller amounts of CSF. Unlike L2V, a cytolytic clone, designated L3, secretes lymphokines that primarily affect macrophage function. The time course of lymphokine production by L2 cells indicates that for the six lymphokine activities studied there are three different times at which maximal or near maximal levels are reached, as follows: 1) IL 2, 12 to 24 hr; 2) IL 3 and CSF, 24 to 48 hr; and 3) (Ia+)-inducing activity, MAF, and interferon, 48 hr or later. Only IL 2 activity disappears during the 8-day culture cycle. The time course data and the differential production of activities by the three types of lymphocyte clones suggest that at least four terminal effector lymphokine molecules account for the ten biologic activities tested.

Animals↗
PubMed1982

The regeneration of stem cells after a bone marrow depression induced by thiamphenicol.

Thiamphenicol (TAP) administered subcutaneously for 4 days via a dialysis bag to bled mice, caused a total inhibition of the differentiation of BFUE into CFUE. The femoral BFUE numbers remained constant whereas the CFUE compartment was virtually absent. The proliferation of CFUs and BFUE was inhibited as well. The granuloid cell line was hardly affected. Shortly after removal of the drug, proliferation of CFUs and BFUE was resumed and a specific time sequence in the regeneration of erythropoiesis in marrow and spleen was observed. A decline in the number in BFUE in the femoral marrow was followed by an increase in the total CFUE in the marrow and an increase in the number of BFUE in the femoral marrow was followed by an increase in the total CFUE in the marrow and an increase in the number of BFUE in the spleen. Maximal erythropoiesis in the spleen occurred 1-2 days later than in marrow. The first wave of erythropoiesis in marrow was followed by a second one leading to high normal values of femoral stem cells. Spleen erythropoiesis consisted of one wave of proliferation and differentiation. The experimental system offers a valuable model for studying certain aspects of erythropoiesis and provides good starting material for CFUE isolation.

Anemia↗
PubMed1981

The formation of erythrocyte membrane proteins during erythropoietin-induced differentiation.

The effect of erythropoietin on the synthesis of the proteins characteristic of mature erythrocyte membranes was studied in cultures of bone marrow cells from adult, polycythemic rats. Stimulated synthesis of the major glycoprotein, glycophorin, was maximal at 30 h and fell to control level by 66 h. Stimulated synthesis of the major integral membrane protein, band 3, occurred at about 18 h was maximal at 66 h, and fell to control level by 114 h. In contrast, stimulated hemoglobin synthesis did not start until after 24 h, was maximal at 96 h, and was at control level at 114 h. Erythropoietin had, in addition, a transient effect on the synthesis of some membrane proteins found in marrow cells but not in mature red cells.

Animals↗
PubMed1981

The biological properties of endotoxin-free human erythropoietin.

The biological effects formerly attributed to erythropoietin were generally observed using impure preparations of the hormone containing, among the impurities, bacterial endotoxin, a contaminant that has recently been shown to affect the haemopoietic system. Erythropoietin, purified to apparent homogeneity and freed of trace contamination by endotoxin (1) promotes erythroid burst formation from mouse marrow cells in semi-solid culture medium, (2) stimulates haemoglobin synthesis in rat marrow cell cultures, (3) stimulates transcription in mouse and rat bone marrow cell cultures and (4) causes the formation of the cytoplasmic mediator protein in rat marrow cells, which enhances transcription in isolated nuclei.

Animals↗
PubMed1981

Erythropoietin radioimmunoassay in evaluating patients with polycythemia.

We measured serum concentrations of erythropoietin in 59 patients with polycythemia using a sensitive and specific radioimmunoassay. The mean concentration was 17.5 +/- 8.4 mU/mL (+/- SD) in 26 patients with polycythemia vera and 14.9 +/- 4.2 mU/mL in 26 normal persons. In contrast, the average concentration was 94.3 +/- 101.2 mU/mL in 33 patients with secondary polycythemia, representing a highly significant elevation (p < 0.0001) compared to both normal and polycythemia vera groups. The average hematocrit value did not differ between the polycythemia vera and the secondary polycythemia patients, and both groups had higher values (median, 55%) than the normal donors (median, 41%). Erythropoietin concentrations ascertained by radioimmunoassay helped discriminate between polycythemia vera and secondary polycythemia. Ninety-two percent of polycythemia vera patients had concentrations less than 30 mU/mL (the concentration used as a cut off point), and 94% of secondary polycythemia patients had concentrations greater than 30 mU/mL. This represents an overall correct classification of 93% of the patients. Serum erythropoietin levels as ascertained by radioimmunoassay can distinguish between most polycythemia vera and secondary polycythemia patients and should prove useful in the differential diagnosis of polycythemia.

Adult↗
PubMed1981

Alloreactive cloned T cell lines. V. Differential kinetics of IL 2, CSF, and BCSF release by a cloned T amplifier cell and its variant.

A noncytolytic, Thy-1+, MIs-responsive cloned T amplifier cell, designated L2, derived from secondary C57BL/6 anti-DBA/2 mixed leukocyte culture was found to produce IL 2 (Interleukin 2), granulocyte/macrophage colony-stimulating factor (CSF), and a polyclonal B cell-stimulating factor (BCSF) after alloantigenic stimulation. IL 2 activity was present transiently, with maximal levels observed 12 to 24 hr after exposure to alloantigen. Only trace amounts were present 96 hr after initiation of culture. CSF and BCSF activities were present at high levels by 24 hr and remained elevated throughout an 8-day culture period. Further evidence that the lymphokine(s) having IL 2 activity is different from those having CSF and BCSF activities was provided by L2V, a variant of L2 that did not produce IL 2. The time course of CSF and BCSF production by L2V after stimulation with alloantigen was similar to that found with L2, although IL 2 activity was not detected at any time. Since the release of lymphokines from both L2 and L2V cells could be induced by Con A in the absence of stimulating alloantigen, it is likely that the biologically active factors were produced by the cloned T cell.

Animals↗
PubMed1981

Autosomal Dominant familial erythrocytosis due to autonomous erythropoietin production.

A family is described in which four members spanning three consecutive generations have erythrocytosis associated with a normal hemoglobin oxygen affinity. When bone marrow from one affected family member was cultured in vitro, erythroid colonies formed only when erythropoietin was added to the culture. Serum erythropoietin, measured by radioimmunoassay, was significantly elevated above normal in each of the affected family members. Bioassayable erythropoietin was detected in the urine of two of the three affected family members. In two of the affected family members, erythropoietin was measured in serum by radioimmunoassay and in urine by bioassay before and for 4 days following an isovolemic phlebotomy, which reduced the red cell mass by 20%. Neither serum nor urinary erythropoietin levels changes following phlebotomy. The erythrocytosis in this family appears to be secondary to inappropriately increased erythropoietin production unassociated with a decrease in the blood oxygen-carrying capacity. This is the first instance in which autonomous erythropoietin production appears to be inherited on an autosomal dominant basis.

Adolescent↗
PubMed1980

Effect of burst-promoting activity (BPA) and erythropoietin on hemoglobin biosynthesis in culture.

The influence of erythropoietin (Ep) and burst-promoting activity (BPA) on the relative rates of synthesis of fetal and adult hemoglobins (HbF and HbA) were investigated in clonal cell culture. In the case of crude Ep, a positive dose-response relationship between the concentration and the relative rate of HbF biosynthesis by circulating erythropoietic precursors was clearly observed. In contrast, increasing the concentration of purified Ep enhanced the synthesis of HbF and HbA equally. BPA from bone marrow conditioned media and T-cell conditioned media enhanced the relative rate of HbF biosynthesis and burst number at limiting serum concentrations (10%-15%). We, therefore, conclude that BPA is important in the modulation of HbF biosynthesis in culture.

Animals↗
PubMed1980

Evidence for cellular cooperativity in hemoglobin synthesis by erythroid bursts.

We have studied hemoglobin synthesis associated with erythroid bursts under various conditions. The slope of the curve relating log cell number to log hemoglobin synthesis is consistently greater than the slope of the curve relating log cell number to log bursts, suggesting that cellular interactions may be involved in maximal hemoglobin synthesis by the cells comprising the bursts. This suggestion if strengthened by experiments which show that gentle disruption of burst structure is accompanied by a decline in hemoglobin synthesis.

Animals↗
PubMed1979

The relationship of hemoglobin synthesis to erythroid colony and burst formation.

We have demonstrated that the cyclohexanone method for the extraction of hematin can be used to measure hemoglobin synthesis induced by erythropoietin (epo) in mouse bone marrow cells cultured in medium containing methyl cellulose. The time course of hemoglobin synthesis by mouse marrow cells showed two effects due to epo: an increase in hemoglobin synthesis at day 2, which corresponded to the formation of small erythroid colonies resulting from the CFU-E (colony-forming unit, erythroid), and a very large increase in hemoglobin synthesis, which was maximal at days 7-8 and corresponded to the formation of large erythroid colonies (bursts) resulting from the BFU-E (burst-forming unit, erythroid). The epo dose-response curves for CFU-E colony counts and day-2 hemoglobin synthesis were similar, and the cell-number-response curves for these two paramaters were parallel. The epo dose-response curve for BFU-E colony counts reached a plateau at an epo concentration between 3 and 5 units/ml, whereas the dose-response curve for 6-8-day hemoglobin synthesis did not reach a plateau even at an epo dose of 10 units/ml.

Animals↗