Dr. Robert Christensen and coworkers recently reported that neutropenia occurred in 49 percent of neonates delivered to women with pregnancy-induced-hypertension, that the neutropenia is the result of decreased neutrophil production, and that these neonates have a high rate of nosocomial infections (NEJM 32: 557, 1989). They now propose to employ studies of the production of hematopoietic growth factors and cultured hematopoietic progenitors to determine the mechanisms of the reduced neutrophil production. In other experiments, they found that high concentrations of erythropoietin (epo) down-modulate the production of neutrophils from progenitors, and that fetal progenitors are more sensitive to this effect than are those of adults (Blood 74: 817, 1989). They postulate that this mechanism underlies several different transient neonatal hyporegenerative neutropenias. They now propose to test this hypothesis using human and animal studies which evaluate the effect of high concentrations of epo on neutrophil storage, proliferative, and progenitor pools, and neutrophil production. Other experiments focus upon their observation that complete depletion of the neutrophil reserve is common in infected neonate and predicts a poor outcome (J Peds 98: 101, 1981). They now propose to define the molecular mechanisms used by normal adults to increase neutrophil production during bacterial infection, and to define the defect(s) that limit such increases in infected neonates. Finally, they recently described a unique kindred, containing seven individuals over three generations, affected with a neonatal hyporegenerative anemia (Am J Med Genetics, 1989). Using clonogenic marrow cell studies, they demonstrated that their defect involves impairment of the generation of normoblasts from erythroid progenitors. They postulate that study of the defective gene in this kindred will contribute to an understanding of the regulation of normal erythropoiesis, as well as identifying the defect in this family. They propose to begin such studies by determining the map-site location of the gene responsible for the anemia in this kindred, using DNA-linkage analysis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL044951-01A1
Application #
3363772
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1991-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Lu, Wenge; Gersting, Jason A; Maheshwari, Akhil et al. (2005) Developmental expression of chemokine receptor genes in the human fetus. Early Hum Dev 81:489-96
Dame, J Benjamin; Chegini, Nasser; Christensen, Robert D et al. (2002) The effect of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) on granulocyte macrophage-colony stimulating factor (GM-CSF) production by neuronal precursor cells. Eur Cytokine Netw 13:128-33
Sullivan, Sandra E; Staba, Susan L; Gersting, Jason A et al. (2002) Circulating concentrations of chemokines in cord blood, neonates, and adults. Pediatr Res 51:653-7
Calhoun, D A; Gersting, J A; Lunoe, M et al. (2001) Transfer of recombinant human granulocyte colony stimulating factor (rhG-CSF) from the maternal to the fetal circulation is not dependent upon a functional G-CSF-receptor. Placenta 22:609-12
Christensen, R D (2001) Origins of the discipline 'neonatal haematology', 1925-75. Br J Haematol 113:853-60
Sola, M C; del Vecchio, A; Edwards, T J et al. (2001) The relationship between hematocrit and bleeding time in very low birth weight infants during the first week of life. J Perinatol 21:368-71
Del Vecchio, A; Sola, M C; Theriaque, D W et al. (2001) Platelet transfusions in the neonatal intensive care unit:factors predicting which patients will require multiple transfusions. Transfusion 41:803-8
Papoff, P; Christensen, R D; Calhoun, D A et al. (2001) Granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor and neutrophils in the bronchoalveolar lavage fluid of premature infants with respiratory distress syndrome. Biol Neonate 80:133-41
Koenig, J M; Luttge, B; Benson, N A et al. (2001) Cell cycle status of CD34+ cells in human fetal bone marrow. Early Hum Dev 65:159-63
Calhoun, D A; Chegini, N; Polliotti, B M et al. (2001) Granulocyte colony-stimulating factor in preterm and term pregnancy, parturition, and intra-amniotic infection. Obstet Gynecol 97:229-34

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