C.-S. Wright

A comparison of four preparations of erythropoiesis regulatory factors

Abstract A comparison was made of two erythropoietin preparations distributed by the National Heart and Lung Institute with two preparations from our laboratory. One NIH preparation contained a mixture of at least two erythropoiesis regulatory factors, an erythropoietin-generating factor and erythropoietin. A second NIH preparation contained erythropoietin but had no detectable generating factor.

Potentiation of Purified Erythropoietin with Serum Proteins

1 Non‐neutralizing antiserum, normal rabbit, human and mouse sera potentiate the erythropoietic activity of anaemic human urinary Fraction II + III. This substantiates the concepts introduced by Kuratowska, Lewartowski and Lipinski. 2 Orosomucoid (alpha‐1 acidic‐glycoprotein) similarly potentiates the erythropoietic activity of anaemic human urinary Fraction II + III. 3 The erythropoietic activity of Standard B was not enhanced by the addition of serum proteins. 4 The erythropoietic activity of human urinary concentrates was enhanced by the addition of normal serum proteins and suggestive enhancement of anaemic human serum and plasma was noted.

The Isolation of Erythropoiesis Regulatory Factors by an Electrofractionation Technique Combined with Selective Membrane Permeability

Summary A urine concentrate from a patient with paroxysmal nocturnal hemoglobinuria contained four regulators of erythro-poiesis that could be isolated by an electro-fractionation technique combined with selective membrane permeability. An erythropoie-sis-stimulating factor (ESF) passed toward the anode through a membrane with a cutoff at a molecular weight of 30,000, but was retained by a membrane with a cutoff at 20,000, while another ESF was retained by a membrane with a cutoff at 50,000. An ESF-generating factor passed toward the cathode through a membrane with a cutoff at 50,000 but was retained by a membrane with a cutoff at 30,000. An inhibitor of erythropoiesis (EIF) passed toward the cathode through a membrane with a cutoff at a mol wt of 30,000 but was retained by a membrane with a cutoff at 10,000. The EIF brought about maximal depression of erythropoiesis 6 days after the first of four daily injections, but erythropoiesis gradually returned to normal 3 days later, though the EIF injections were continued. The EIF appeared to be mostly lipid and about 7.5% protein. The authors express their appreciation to members of the engineering departments at the Veterans Administration Hospitals in Augusta, GA and St. Louis, MO for their assistance in the construction of the electrofractionation apparatus used in this work.

Multiple myeloma associated with a 9S IgG paraprotein and carcinoma of the prostate

A case of multiple myeloma associated with a 9S IgG complex. kappa‐type light chains, and adenocarcinoma of the prostate is described. The relative amount of 9S globulin was independent of total protein concentration; it was the predominant M‐component in both highly diluted serum and also in whole serum. At low pH, it was dissociated to the 7S monomer. The presence of moderately high concentrations of the 9S species in the patients serum did not cause symptoms of the hyperviscosity syndrome. A review of the literature suggests that the association of myeloma with nonreticular neoplasms may occur more often than previously supposed.

The Selective Inactivation of an ESF-Generating Factor (EGF) in the Presence of Erythropoietin (ESF)

Summary An ESF-generating factor (EGF), erythropoietin (ESF) and a mixture of both were incubated with dithiothreitol (DTT, a protective reagent for sulfhydryl groups). Ten μM DTT completely prevented the production of 0.26 ± 0.01 IU of ESF by EGF but did not inactivate ESF. DTT was used to indicate the relative amounts of EGF and ESF activity in a mixture of both.

The Selective Membrane Filtration of an ESF-generating Factor (EGF) in the Presence of Erythropoietin (ESF)

Summary A mixture of an erythropoiesis stimulating factor (ESF) and an ESF-generating factor (EGF), isolated from the urine of a patient with paroxysmal nocturnal hemoglobinuria (PNH), was separated by selective membrane filtration. The optimum pH for activity of the EGF fraction from the urine of the PNH patient was about 7.4, the same as that previously found for the EGF from the urine of a patient with an anemia secondary to multiple myeloma (MM). The urine from the PNH patient contained an ESF that appeared larger than EGF, whereas the urine from the MM patient did not; the urine from both patients, however, contained an ESF that appeared smaller than EGF as previously noted.