A B S T R A C T Inhibitors of erythropoiesis have been found in the blood of uremic patients but their nature has not been identified. These patients have excess blood levels of parathyroid hormone (PTH) and it is possible that PTH inhibits erythropoiesis. The present study was undertaken to examine the effect of intact PTH molecules and some of its fragments on human peripheral blood and mouse bone marrow burst-forming units-erythroid (BFU-E), on mouse bone marrow erythroid colony-forming unit (CFU-E), and granulocyte macrophage progenitors (CFU-GM), and evaluate the interaction between PTH and erythropoietin (Ep) on human BFU-E. Intact PTH (1-84 bPTH) in concentrations (7.5-30 U/ml) comparable to those found in blood of uremic patients produced marked and significant (P < 0.01) inhibition of BFU-E and mouse marrow GFU-GM, but not of mouse marrow CFU-E. Inactivation of 1-84 bPTH abolished its action on erythropoiesis. Increasing the concentration of Ep in the media from 0.67 to 1.9 U/ml overcame the inhibitory effect of 1-84 bPTH on BFU-E. The N-terminal fragment of PTH (1-34 bPTH) and 53-84 hPTH had no effect on BFU-E.The results deomonstrate that (a) either the intact PTH molecule or a C-terminal fragment(s) bigger than 53-84 moiety exerts the inhibitory effect on erythropoiesis, and (b) adequate amounts of Ep can overcome this action of PTH. The data provide one possible pathway for the participation of excess PTH in the genesis of the anemia of uremia.

Both natural and synthetic estrogens have been found to rapidly depress erythropoiesis in male rats. The doses employed and the time relationships obtained in these experiments suggest that estrogens are part of the regulatory mechanism governing red cell production.T HE administration of estrogens has been known to impair erythropoiesis in different animal species, when studied over rather long periods of time. Large doses of estrogens cause severe anemia in dogs (1,2) and mice (3) but in the monkey the effect of similar doses is only slight (4). The regeneration of red cells was studied extensively in the rat (5, 6) and it was found that males recover from bleeding more rapidly than females. If bled female rats are given estradiol continuously they completely fail to restore their original red cell levels.The conclusions drawn from these experiments, which utilized the usual indices of the peripheral blood (red cell count, hemoglobin concentration and hematocrit) in addition to studies of the morphology of the marrow was that the anemia resulting from estrogen administration is caused by the replacement of the marrow erythropoietic tissue by edema fluid or by bone.By using a short method for determination of the rate of erythropoiesis (7, 8) Ave were able to study the mechanism of the inhibition of red cell formation by estrogens in more detail than had previously been possible. The results of the experiments reported here indicate that there is a rapid effect of estrogens on the marrow, which we suggest may compete with the effect of erythropoietin (9) in the maintenance of the steady state of erythropoiesis. A preliminary report of this work has already appeared (10). MATERIALS AND METHODSMale, Sprague-Dawley rats weighing 160 to 200 gm. (6 to 8 weeks old) were used in all experiments in groups of five or more. The animals received food (Purina rat chow) and water ad libitum. Test substances were injected subcutaneous^, dissolved in peanut oil containing 3 mg. of benzjd alcohol per ml. However, erythropoietin and inorganic compounds were dissolved in saline. Erythropoiesis was measured by injecting 1 /xc. of

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We have obtained 5 specific DNA probes for African trypanosomes of the subgenera Trypanozoon and Nannomonas. Each probe consists of one repeat unit of the major repetitive DNA (satellite DNA) of each species or intra-specific group. One probe hybridized with all members of subgenus Trypanozoon (except T. equiperdum which was not tested). In subgenus Nannomonas, one probe recognized T. simiae, but 3 probes were needed to identify all stocks of T. congolense available. Each of the 3 latter probes recognized trypanosomes from one of the 3 major groups of T. congolense previously defined by isoenzyme characterization, i.e. savannah, forest and Kenya coast types. As few as 100 trypanosomes could be unequivocally identified by dot blot hybridization and individual trypanosomes could be identified by in situ hybridization. We show how this simple methodology can be used in the field for the identification of immature and mature trypanosome infections in tsetse.

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