Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the differentiation and proliferation of erythroid cells. To determine the cellular mechanism of action of these growth factors, we measured changes in intracellular free calcium concentration (jCaJ) in single human erythroid precursors in response to recombinant erythropoietin and GM-CSF. [CaJ in immature erythroblasts derived from cultured human cord blood erythroid progenitors was measured with fluorescence microscopy digital video imaging.When stimulated with erythropoietin, [CaJ in the majority of erythroblasts increased within 3 min, peaked at 5 min, and returned toward baseline at 10 min. The percentage of cells that responded to erythropoietin stimulation increased in a dose-dependent manner. Additional stimulation with GM-CSF in cells previously exposed to erythropoietin resulted in a second [Ca¢J increase. Immature erythroblasts treated with GM-CSF followed by erythropoietin responded similarly to each factor with a rise in [Ck]. The source of transient calcium is intracellular since erythroblasts were incubated in medium devoid of extracellular calcium. Our observations suggest that changes in [CaJ may be an intracellular signal that mediates the proliferative/differentiating effect of hematopoietic growth factors.
Gastric dysrhythmias have been recorded from patients with a variety of nausea syndromes. The aim of this study was to measure gastric myoelectric activity in women with and without nausea during the first trimester of pregnancy. In 32 pregnant women gastric myoeletric activity was recorded for 30-45 min with cutaneous electrodes that yielded electrogastrograms (EGGs). Frequencies of the EGG waves were analyzed visually and by computer. Subjects rated their nausea at the time of EGG recording on a visual analog scale with 0 representing no nausea and 300 mm severe nausea. Gastric dysrhythmias were found in 26 pregnant subject: Seventeen had tachygastrias (EGG frequencies of 4-9 cpm), five had 1- to 2-cpm EGG waves, and four had flat-line patterns Mean nausea scores of the subjects with tachygastrias, 1- to 2-cpm, and flat-line patterns were 64.8 +/- 13, 93.4 +/- 23, and 77.2 +/- 36, respectively. Six pregnant subjects had normal 3-cpm EGG patterns, and their nausea scores averaged 2.8 +/- 1.1 (P less than 0.05 compared with nausea scores in subjects with tachygastrias, 1- to 2-cpm, and flat-line rhythms). Six subjects with gastric dysrhythmias during pregnancy were restudied after delivery; each of these subjects had normal 3-cpm EGG patterns and none had nausea. Thus, gastric dysrhythmias are objective pathophysiologic events associated with symptoms of nausea reported during the first trimester of pregnancy.
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