E. A. Mirand

Hormones in Renal Cancer

Plasma renin, erythropoietin and chorionic gonadotropin levels were evaluated in 57 patients with renal adenocarcinoma. Renin elevation, found in 37 per cent, was unrelated to blood pressure levels but was associated with high grade, high stage lesions of mixed histologic cell type and predicted a poor prognosis. Erythropoietin was raised in 63 per cent of patients and was more sensitive than renin in indicating the presence of renal adenocarcinoma. However, it was less specific and did not correlate directly with tumor grade, stage, histologic type, prognosis or hematocrit and hemoglobin levels. None of the patients had elevated chorionic gonadotropin levels. Therefore, we believe that renin and erythropoietin determinations may be of value as biochemical tumor markers in renal adenocarcinoma.

Virus-induced polycythemia in mice: erythropoiesis without erythropoietin.

Summary An experimental model system of virus-induced polycythemia in Ha/ICR Swiss mice is shown to represent an example of erythropoietin-independent erythropoiesis. This conclusion is based on the following findings: (i) No ESF activity was detected in the plasma or urine of mice at any time after virus infection, nor was there an increased level of REF, and (ii) multiple injections of antierythropoietin did not inhibit the re-initiation of erythropoiesis in plethorized, infected mice or the formation of macroscopic spleen foci in nonplethorized infected mice.

Spleen Focus Formation by Polycythemic Strains of Friend Leukemia Virus

Summary Several strains of Friend virus were tested for their ability to initiate focus formation in the spleens of susceptible mice. Strains which induce polycythemia had high focus-forming activity, while strains which induce anemia had little or no focus-forming activity. A positive correlation was also demonstrated between virus strains with focus-forming activity and those which initiate the resumption of erythropoiesis in plethorized mice. It is concluded that most Friend virus preparations contain at least 2 viruses: one which has spleen focus-forming activity (SFFV) and which probably is responsible for inducing polycythemia when present in high titers, and another which, when active in the presence of little or no SFFV, induces anemia. The role of either virus in initiating leukemia remains to be determined.

Erythropoietin levels in patients with renal tumors or cysts

Increased erythropoietin (ESF) values have been observed in 49 plasma samples and in 14 cyst fluids of 92 patients with renal cell carcinomas or renal cyst. High levels of ESF and, sometimes, erythrocytosis were observed in patients with renal carcinoma. Patients with renal cysts frequently had highly elevated ESF levels but not erythrocytosis. The elevated levels of ESF and erythrocytosis subsided upon the removal of the renal carcinomas. Elevated ESF levels fell following cyst excision. The highest levels of ESF were observed in patients developing metastasis after the removal of renal carcinoma. Moreover, androgen therapy in these patients with metastasis produced further substantial elevations of ESF levels. These studies provide evidence that renal neoplasms and renal cysts serve as aberrant sites of ESF production and/or storage of ESF. Also, the erythrocytosis seen in some of these patients with renal disorders is ESF‐dependent. This is unlike the erythrocytosis of polycythemia vera, which is not ESF‐dependent.

Erythropoietin-Like Effect of a Polycythemic Virus.∗

Summary Like erythropoictin, a murine polycythemic virus can initiate erythropoiesis in a hypertransfused-polycythemic state. The mechanism by which this virus is able to do this is not known.

Extra-renal Erythropoietin Production in the Baboon

Summary Erythropoietin activity has been studied in eight intact and renoprival baboons. These studies demonstrate that renoprival baboons revealed elevations of plasma ESF activity in response to bleeding stimulus as intact baboons subjected to similar repeated bleeding stimuli. It appears that humoral regulation of erythropoiesis persists in anephric baboons.

Erythropoietic responses to acute and chronic ureteral occlusions in dogs

Abstract Arterial and renal vein plasmas obtained from 58 nonanemic, nonuremic dogs subjected to unilateral ureteral occlusions acutely or for a period up to 5 weeks were assayed for ESF in the plethoric mouse. Despite the wide range of renal blood flows, resistances, and pO 2 levels, detectable elevations of ESF were not frequently observed. Complete or incomplete ureteral occlusions, infusion of vasoconstrictive agents, or the absence of the contralateral intact kidneys did not influence the ESF values. Elevation of arterial and renal vein ESF levels occurred only in animals subjected to acute ureteral occlusions at the level of the renal pelvis. These findings are discussed in the light of recent evidence for extrarenal control and release of ESF.

Erythropoietin Release in Baboons after Renal Allotransplantation

Summary The level of plasma erythropoietin (ESF) from untreated baboon renal allotransplants, compatibly or incompatibly matched in terms of their major human ABO blood groups, was assayed in polycythemic mice. Postoperative rises in ESF occur within 7 days if graft thrombosis ensues. Other grafts exhibit progressive elevations in ESF activity, which correlate directly with the reduction in measured renal blood flow due to renal rejection. Azotemia does not evidently influence this response in this species. Compatibly matched animals demonstrate continued ESF responses despite restoration of peripheral hematocrit values to preoperative ranges.

INHIBITION OF MOUSE TUMOR TRANSPLANTS BY POLYOMA VIRUS INOCULATION.

Abstract Polyoma virus inoculation of adult DBA 1 mice conferred resistance against two nonpolyoma-induced transplantable isologous tumors as well as a polyoma-induced parotid tumor. The basis for this cross resistance was not established.

Effect of Pituitary and Gonadal Hormones on Friend Virus Disease in Mice.

Summary The effect of pituitary and gonadal hormones on Friend Virus Disease in mice has been studied. Estradiol inhibited the virus-induced hypervolemic polycythemia, hepatomegaly, and splenomegaly. The effect was most evident during the second week following injection. Progesterone, adrenocor-ticotropic hormone, and testosterone did not influence significantly the hematologic and organ changes characterizing the disease. A possible mechanism of action of estrogen-induced suppressions of erythropoiesis in this disease is discussed. We extend thanks to Dr. P. Trudel, and to Edmund Dywinksi, Andres Bulba, Joyce Jividen, Ruth Deck-ert, Basilius Sywenkyj, A. G. Miramd, and W. Trudel.