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Biomedical subjects

R D Christensen

Publications and source records attributed to R D Christensen.

At least 109 records · Page 6Linked to original sources
PubMed1990

Effects of interleukin-6 on fetal hematopoietic progenitors.

Effects of interleukin-6 (IL-6) on cycling status and clonogenic maturation of human fetal (cord blood) and adult hematopoietic progenitors were compared. Adult marrow cells were incubated for various lengths of time with various concentrations of IL-6, in a serum-free system, after which tritiated thymidine suicide studies were performed. After incubation of 2 to 5 x 10(6) cells/mL for 4 hours in 5.0 ng IL-6/mL, increased thymidine suicide rates were observed for multipotent progenitors (CFU-Mix), granulocyte-macrophage progenitors (CFU-GM), and erythroid burst-forming units (BFU-E). Similar incubations of fetal cells in IL-6 resulted in similar increases in tritiated thymidine suicide rates. In other studies, IL-6 used alone did not support colony formation from adult progenitors. However, it did support colony formation from fetal CFU-Mix (P less than .05), CFU-GM (P less than .001), and BFU-E (P less than .05). In cultures of adult progenitors, IL-6 acted synergistically with IL-3 to support CFU-Mix colony formation (P less than .001), but synergistic actions on CFU-GM and BFU-E were not seen. In contrast, IL-6 acted synergistically with IL-3 and with GM-CSF to support colony formation by fetal CFU-Mix, CFU-GM, and BFU-E. Thus, IL-6 appears to have a wider spectrum of action on fetal progenitors from cord blood than on adult progenitors; including not only the induction of cycling, but also the support of clonogenic maturation of CFU-Mix, CFU-GM, and BFU-E.

Aging↗
PubMed1990

Congenital hypoplastic (Diamond-Blackfan) anemia in seven members of one kindred.

Congenital hypoplastic (Diamond-Blackfan) anemia is a rare macrocytic anemia, generally presenting during infancy or childhood. The condition usually occurs sporadically or in a pattern consistent with autosomal recessive inheritance, although autosomal dominant transmission has been proposed in some kindreds. We report the largest known kindred of congenital hypoplastic anemia, with at least 7 affected individuals over 3 generations, and propose that studies of this kindred may be useful for identifying the mechanism by which their genetic abnormality results in congenital hypoplastic anemia. Erythropoietic investigations on relatives show no inhibitors of erythropoiesis in serum, T-lymphocytes, or macrophages. Their erythroid progenitor cells (CFU-E and BFU-E) were generally quantitatively normal, and were capable of rapid proliferation, as judged by cell-cycle shortening. However, their erythroid progenitors displayed a relative insensitivity to recombinant erythropoietin, and produced relatively few normoblasts per erythroid progenitor cell. We propose that these and subsequent studies may be helpful in selecting candidate genes responsible for the molecular defect in this kindred.

Adolescent↗
PubMed1990

Effect of erythropoietin on granulocytopoiesis: in vitro and in vivo studies in weanling rats.

In clonogenic assays, high concentrations of erythropoietin (epo) result in reduced generation of neutrophils from progenitors. Fetal progenitors appear to be more sensitive to this effect than are those of adults. Neutropenia has not been observed, however, as a complication of epo administration to anemic adults. Nevertheless, we remained concerned that diminutions in the neutrophil proliferative or storage pools might occur in epo-treated neonates. Therefore, after establishing that epo induces down-modulation of neutrophil generation in vitro from progenitors of weanling rats, we administered high doses of epo and subsequently performed neutrophil kinetic studies. Six pairs of 8-9-d-old rats were given three daily injections of 2000 IU/kg of either epo or a control Forty-eight h later, the epo recipients had elevations in reticulocytes, circulating normoblasts, and hematocrits, as well as in splenic and femoral normoblasts and mature erythroid progenitors. However, no changes were observed in concentrations of circulating neutrophils, monocytes, or lymphocytes. In addition, no changes were observed in the splenic or marrow neutrophil storage or proliferative pools, or the pools of granulocyte-macrophage progenitors or multipotent progenitors. Thus, although in vitro high concentrations of epo resulted in diminished generation of neutrophils from progenitors, no reductions were observed in vivo using epo doses 4- to 40-fold higher than those generally administered to humans.

Animals↗
PubMed1990

In vivo effect of interleukin-6 on cycling status of hematopoietic progenitors from adults and neonates.

In vitro, IL-6 can induce hematopoietic progenitors to progress from G0 into cycle, but a role for IL-6 in regulating cycling status of progenitors in vivo has not been established. In our studies, groups of five to six adult and newborn rats received i.v. injections of either IL-6 (1 ng/g body wt) or the vehicle (control), after which cycling of hematopoietic progenitors was evaluated by tritiated thymidine suicide. Progenitors from adult rats injected with the control had thymidine suicide rates of 7 +/- 1% (mean +/- SEM), compared with 23 +/- 7% in the IL-6 recipients (p less than 0.02). Progenitors from newborn rats injected with the control had thymidine suicide rates of 19 +/- 2%, compared with 29 +/- 1% in the IL-6 recipients (p less than 0.003). In addition, IL-6 administration resulted in release of cells from the neutrophil storage pool into the circulation, as evidenced by fewer polymorphonuclear cells flushed from the long bones (neonates, p less than 0.001; adults, p less than 0.003), a rise in blood neutrophil concentration (neonates, p less than 0.001; adults, p less than 0.05), and a leukocyte "left shift" (neonates, p less than 0.001; adults, p less than 0.01). Thus, the effects of IL-6 in vivo in newborn and adult rats include cycle induction of hematopoietic progenitors and release of neutrophils from the storage pool into the circulation.

Aging↗
PubMed1990

Complement C3 deposition onto bacteria by neonatal serum is not enhanced after the infusion of intravenous immunoglobulin.

To determine the effect of intravenous immunoglobulin (IVIG) on the capacity of serum from septic neonates to deposit complement C3 and IgG onto the bacteria isolated from their blood, 500 mg/kg of IVIG was administered to 18 neonates suspected of being septic. Blood was obtained just before the infusion, and again 15 minutes after its completion. Group B streptococcus type II, group B streptococcus type III, Staphylococcus aureus, and Staphylococcus epidermidis were isolated from the pre-infusion blood of four neonates. Bacteria were incubated with the appropriate serum, washed, and the amount of C3 and IgG subsequently bound to the organisms was quantified by radioimmunobinding assay. Sera from the four septic neonates and sera from four neonates of similar gestational age but whose blood cultures were negative were compared with pooled sera from healthy adults. Before the administration of IVIG, C3 deposition onto the bacteria by sera from five of the seven neonates tested was significantly less than that observed for adult sera. Following the infusion, no increase in C3 deposition was observed for any of the seven sera assayed, and in two cases C3 deposition fell significantly. In contrast, in seven of eight cases, IVIG enhanced the IgG deposition to levels greater than or equal to those observed for adult sera. Therefore, following the infusion of IVIG into neonates with proven or suspected sepsis, the deposition of C3 onto invasive bacteria by their serum was not enhanced even though IgG deposition was increased.

Antibodies, Viral↗
PubMed1989

Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension.

Neutropenia occurs often among the newborns of women with hypertension, but its cause, mechanism, and clinical consequences have not been adequately studied. Of 72 infants whose mothers had hypertension during pregnancy, 35 (49 percent) had neutropenia, which persisted from 1 hour to 30 days. The disorder was more prevalent among newborns whose growth had been retarded in utero (P less than 0.01), those who had been delivered prematurely (P less than 0.001), and those whose mothers had had severe hypertension (P less than 0.002) or hypertension and the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) (P less than 0.01). Kinetic investigations of circulating, marginated, storage, and proliferative neutrophils and their progenitors suggested that the neutropenia was the result of diminished neutrophil production. Noscomial infections occurred during the first 2 1/2 weeks of life in eight (23 percent) of the newborns with neutropenia, but in only one (3 percent) of those without this disorder (P less than 0.01). We conclude that the neonatal neutropenia associated with maternal hypertension is due to transiently reduced neutrophil production and is associated with an increased risk of noscomial infection. Its basic cause remains unknown.

Adult↗
PubMed1989

Down-modulation of neutrophil production by erythropoietin in human hematopoietic clones.

In clonogenic assays of hematopoietic progenitors, high concentrations (4 U/mL) of erythropoietin (epo) reduced the formation of granulocyte-macrophage (GM) colonies and diminished the number of granulocytes formed per culture plate. Fetal progenitors were more sensitive to these effects of epo than were progenitors from adults, displaying these reductions at greater than or equal to 1 U epo/mL. The mechanism was investigated by growing fetal progenitors stimulated by recombinant GM-CSF, in the absence of epo, and when eight-cell clones first appeared, mapping their location, then adding epo, and assessing its effect on the subsequent differentiation of the clones. In the absence of epo, the clones developed exclusively into GM colonies. However, if developing clones were presented with epo, 85% matured into GM colonies, but 15% became multilineage or normoblast colonies. In addition, developing clones that were presented with epo produced colonies that contained fewer neutrophils. These effects of epo on neutrophil generation were observed with each of three varieties of recombinant epo, and also with purified human epo, but were not observed using epo that had been neutralized with rabbit anti-epo antiserum.

Adult↗
PubMed1989

Interstitial deletion of chromosome 5, del(5q), in a newborn with Down syndrome and an unusual hematologic disorder.

A newborn with Down syndrome was noted on the 1st day of life to have an elevated white blood cell count of 79,900/mm3 with 62% lymphoblasts and a platelet count of 61,000/mm3, consistent with either transient myeloproliferative disorder of Down syndrome (TMD) or acute leukemia. Karyotype analysis of a bone marrow aspirate revealed that 20% of the cells had a 47,XY, +21 karyotype, and 80% had a 47,XY, +21, del(5)(q13q31) complement. Cytochemical and immunophenotyping of the peripheral blasts were consistent with the presence of an acute undifferentiated precursor blast clone. Results of clonogenic assays of hematopoietic progenitors from this patient's bone marrow were similar to those of patients with TMD. This patient's hematologic abnormalities resolved spontaneously without treatment by week 10 of life. This is the first report of an interstitial deletion of 5q associated with a hematologic abnormality present in an infant at birth.

Adult↗
PubMed1989

Intravenous immune globulin use in newborns.

Newborn infants, and especially premature ones, are uniquely susceptible to severe and overwhelming bacterial infections. The reasons for this are not completely understood. A number of defects in the neonate's host defense system have been described, including deficiency of opsonic antibodies, abnormalities in the number and function of polymorphonuclear leukocytes, and depressed levels of the major complement components. Experimental animal studies in our laboratory have indicated that many of these defects can be overcome through the administration of intravenous immune globulin. Recently several investigators have attempted to treat or prevent bacterial infections in human neonates with intravenous immune globulin. We have found that doses as high as 750 mg/kg can be administered to premature infants without detectable side effects. This results in IgG levels comparable with those in term infants and adults. Limited studies in the literature suggest that intravenous immune globulin therapy may decrease morbidity and mortality from infection in premature human infants. Furthermore, prophylactic treatment of preterm infants may serve to prevent the development of infection in some instances. Optimal management of preterm and some term human infants may involve immunotherapy with intravenous immune globulin.

Animals↗
PubMed1989

Neutropenia and thrombocytopenia in infants with Rh hemolytic disease.

To assess the incidence and mechanisms of thrombocytopenia and neutropenia in neonates with Rh hemolytic disease, we studied 20 consecutive patients with this condition who were born at our hospital. All five patients with severe disease (hydrops) had neutropenia and thrombocytopenia before and after exchange transfusions. Two of six patients with moderately severe disease (not hydropic but requiring exchange transfusion) had neutropenia; all six had thrombocytopenia. Of nine patients with mild disease (not treated with exchange transfusions), two had neutropenia but none had thrombocytopenia. The mean platelet volume was low or normal (7.5 +/- 0.2 ft) in the patients with thrombocytopenia, and the neutropenia was not accompanied by a "left shift" (ratio of immature to total neutrophils 0.26 +/- 0.03, mean +/- SEM). In two severely affected patients, erythroid progenitor levels were elevated and their proliferative rates (tritiated thymidine suicide) were increased, whereas their granulocyte-macrophage progenitor levels and the proliferative rates of those progenitors were diminished. In a severely affected patient, the in vitro maturation of multipotent progenitors was altered, with production of a greater than normal proportion of normoblasts (p less than 0.01) but fewer neutrophils (p less than 0.02) and megakaryocytes (p less than 0.03). It appears that the marked increase in erythropoiesis in fetuses with Rh hemolytic disease can be accompanied by a down-modulation of neutrophil and platelet production.

Agranulocytosis↗