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Biomedical subjects

R K Silver

Publications and source records attributed to R K Silver.

62 records · Page 4Linked to original sources
PubMed1968

Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype.

This investigation is concerned with the kinetics of the reciprocal relationship between sheep hemoglobin (Hb) A and Hb C formation in response to anemia. The relative synthesis of the hemoglobin types was assessed at various times in bone marrow erythroid cells incubated in vitro with (59)Fe. The changeover from Hb A to Hb C formation lagged by about 3 days behind the development of anemia and was complete within about 11 days. After recovery from anemia the reciprocal change back to preanemic conditions proceeded at a much slower rate, Hb C formation gradually declining to unmeasurable levels over about 25 days. Infusions of plasma with high erythropoietin titre induced the formation of relatively large quantities of Hb C in erythroid cells of nonanemic sheep, demonstrating the central importance of a humoral mechanism in the change of expression of the hemoglobin genes. THE FOLLOWING CONCLUSIONS WERE DRAWN: hemoglobin phenotype is determined at a stem cell level. Erythroid stem cells appear to undergo gradual renewal. The identity of the plasma factor which induces Hb C formation is not yet known; it is not present in plasma from nonanemic sheep, and its production is not dependent upon hemoglobin genotype. If the plasma factor turns out to be erythropoietin, then this hormone must have an important influence on the pool of erythroid stem cells.

Anemia, Hemolytic↗
PubMedDate not supplied

Endothelin-1-induced placental and fetal growth restriction in the rat.

The objective of this study was to evaluate the effect of increased circulating endothelin on fetal and placental growth in the rat. Indwelling arterial and venous catheters were placed on day 14 of a 22-day gestation in timed-pregnant Sprague-Dawley rats. Saline, 0.2 nmol/kg/h endothelin, or 0.5 nmol/kg/h endothelin was continuously infused from day 15 through 21 in randomly assigned animals (n = 12 in each group). Maternal arterial blood pressure and serum endothelin levels were evaluated on days 15, 18, and 21 of gestation. On day 21, pregnancy outcome data including fetal and placental weights, litter size, and the occurrence of stillbirths were ascertained, and fetal blood was obtained for serum endothelin levels. All data were compared among the three groups, and statistical significance was determined by analysis of variance. Endothelin infusion resulted in a dose-dependent decrease in fetal and placental weights when compared to saline-treated pregnancies. A significant increase in maternal arterial blood pressure was noted only in the 0.5 nmol/kg/h endothelin group. Fetal and placental growth restriction occurred in the absence of maternal hypertension in the 0.2 nmol/kg/h group. These results demonstrate that endothelin infusion causes restriction of fetal and placental growth, even in the absence of maternal hypertension.

Analysis of Variance↗
PubMedDate not supplied

Serum from patients with severe preeclampsia is not cytotoxic to endothelial cells.

OBJECTIVE: We evaluated the hypothesis that circulating factors in preeclampsia promote direct endothelial cell injury using an in vitro index of cytotoxicity. METHODS: Subconfluent umbilical vein endothelial cell monolayers were established and radiolabeled with chromium (51Cr), then randomly exposed for 24 hours in triplicate to 20% sera from nonlaboring patients with severe preeclampsia (n = 5) or mild preeclampsia and normotensive controls (n = 5). Additional experiments were performed by exposing endothelial monolayers to sera for 3 and 48 hours, and under hypoxic conditions (1% oxygen). Cytotoxicity was defined by the percentage of 51Cr release, expressed as the ratio of radioactivity in the supernatant to the maximum cell-associated radioactivity. RESULTS: Mean 51Cr release was similar in all experiments comparing preeclamptic and normal sera. Although consistently greater 51Cr release was noted in hypoxic as compared with normoxic incubations, no differences in cytotoxicity were identified among severe preeclampsia, mild preeclampsia, and normal sera in hypoxia. CONCLUSION: Sera from patients with preeclampsia do not appear to be cytotoxic to vascular endothelium in this in vitro model.

Adult↗
PubMedDate not supplied

Comparison of active phase labor between triplet, twin, and singleton gestations.

OBJECTIVE: To characterize the active phase of labor in triplet pregnancies and compare it with gestational age-matched twins and singletons. METHODS: Active phase rates were calculated beginning at 5 cm of dilation for women with triplet gestations longer than 24 weeks who labored and reached the second stage. Twin and singleton cohorts that also completed the first stage of labor were matched for gestational age at delivery (+/-1 week), parity, and epidural use. Intrapartum variables included oxytocin use (induction or augmentation, duration of infusion, and maximum dosage), cervical dilation at membrane rupture, and active phase dilation rate. RESULTS: Thirty-two triplet pregnancies met inclusion criteria between January 1994 and September 1998 and were each compared with twin and singleton cases in a 1:2 ratio. Triplet and twin active phase rates, while similar (1.8 versus 1.7 cm/hour, respectively), were significantly lower than the mean singleton dilation rate (2.3 cm/hour, P =.02). No other intrapartum variables differed between the three groups. Despite controlling for gestational age at delivery, mean birth weights were significantly higher in singletons and correspondingly lower in twins and triplets (2,493 versus 2,112 and 1,968 g, respectively; P =.001). An analysis of active phase dilation rates as a function of the cumulative birth weight per pregnancy demonstrated an inverse correlation, with slower progress in active labor associated with increasing total fetal weight (R = -.24; P =.002). CONCLUSIONS: Triplet and twin active phase dilation proceeds at a slower rate than that observed in singleton pregnancies. The rate of active phase dilation is inversely correlated to total fetal weight.

Birth Weight↗
PubMedDate not supplied

Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats.

OBJECTIVE: To determine the role of endothelin (ET) in fetal and placental growth in rats with and without long-term nitric oxide synthase (NOS) inhibition. METHODS: Pregnant rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline and with one of three ET receptor antagonists or vehicle. The antagonists included A-182086 (nonselective) as well as A-127722 and FR-139317 (both ET(A) selective). Treatment was begun on day 14 of gestation. On gestational day 21, a hysterotomy was done. Litter size was recorded, and viability and fetal and placental weights were determined. Results were analyzed by analysis of variance or by a Kruskal-Wallis nonparametric analysis. RESULTS: In the absence of L-NAME, fetal and placental weights were not affected by ET(A)-selective antagonism but were significantly decreased by nonselective receptor antagonism (P <.001 and P <.05 for fetal and placental weights, respectively). Infusion of L-NAME resulted in fetal and placental growth restriction (P <.001). In the setting of L-NAME infusion, fetal and placental weights were increased by the ET(A)-selective antagonists (P <.01) but not by the nonselective antagonist, compared with weights from animals treated with L-NAME alone. There were more fetal deaths with L-NAME treatment (P <.05), but their occurrence was not significantly affected by any of the ET receptor antagonists. CONCLUSIONS: Endothelin-A antagonism alone did not affect fetal or placental growth, whereas combined ET(A) plus ET(B) antagonism produced fetal and placental growth restriction. In the setting of long-term NOS inhibition, ET(A)-selective antagonism improved fetal and placental growth, whereas antagonism of both ET(A) and ET(B) receptors did not. Endothelin contributes to NOS inhibition-induced growth restriction acting through the ET(A) receptor.

Animals↗