Biomedical subjects

Matthew A Saxonhouse

Publications and source records attributed to Matthew A Saxonhouse.

9 recordsLinked to original sources

PubMed2005

Effects of hypoxia on megakaryocyte progenitors obtained from the umbilical cord blood of term and preterm neonates.

BACKGROUND: Placental insufficiency is associated with early-onset thrombocytopenia in preterm neonates. Prior studies demonstrated a reduction in circulating megakaryocyte (Mk) progenitors, suggesting decreased platelet production. We hypothesized that decreased Mk production is the result of a direct inhibitory effect of hypoxia on the proliferation of Mk progenitors, or a hypoxia-induced change in the fetal hematopoietic environment. OBJECTIVE: To test the effects of hypoxia on the clonogenic maturation of Mk progenitors obtained from term and preterm cord blood CD34(pos) cells, either cultured alone or in conjunction with CD34(neg) light density mononuclear cells (LDMCs). METHODS: CD34(pos) cells and CD34(neg) LDMCs were isolated from the cord blood of term and preterm deliveries, and mobilized peripheral blood CD34(pos) cells were obtained from healthy adults. CD34(pos) cells were then cultured alone or co-cultured with CD34(neg) LDMCs in a semisolid, serum-free media containing rTpo, IL-3, and IL-6. Cultures were exposed to 20%, 5%, or 1% oxygen for 10-12 days. Mk colonies were then quantified following immunohistochemical staining. RESULTS: Pure CD34(pos) cells from preterm (n = 5) and term (n = 5) neonates and from adults (n = 4) generated similar numbers of Mk colonies in all three oxygen concentrations. However, the number of Mk colonies in preterm co-cultures was progressively lower with decreasing O(2) concentrations. CONCLUSIONS: Hypoxia did not appear to directly inhibit colony formation of Mk progenitors from preterm and term cord blood CD34(pos) cells. However, co-culture studies showed a decrease in Mk colony formation with hypoxia, suggesting an indirect inhibitory effect of hypoxia on Mk clonogenic maturation mediated by non-progenitor cells in the hematopoietic microenvironment.

Antigens, CD34↗

PubMed2005

Neonatal neutrophils with prolonged survival exhibit enhanced inflammatory and cytotoxic responsiveness.

Apoptosis is critical to the resolution of inflammation, as it promotes the removal of neutrophils (PMN) by the reticuloendothelial system. In contrast, PMN persistence characterizes the early stages of chronic inflammation. Adult PMN with delayed senescence retain some functionality, although this has not been described for neonatal PMN. We hypothesized that neonatal PMN with prolonged survival retain cytotoxic and inflammatory function. To test one aspect of inflammatory function, we determined surface CD11b expression on 0-h and 24-h PMN after chemotactic formyl-methionine-leucine-phenylalanine (fMLP) stimulation. Although fMLP induced a greater percentage up-regulation of CD11b on 0-h adult PMN, this was similar between nonapoptotic cord blood and adult PMN at 24 h. Furthermore, percentage up-regulation of CD11b was more robust for 24-h than for 0-h cord blood PMN. In contrast, there was no difference in responsiveness between 0-h and 24-h adult PMN. In studies of cytotoxic potential, we determined the expression of reactive oxygen intermediates (ROI) in phorbol 12-myristate 13-acetate-stimulated cord blood and adult PMN at 0 h and in 24-h nonapoptotic PMN, using the dihydrorhodamine 123 assay. Stimulated cord blood PMN generated more ROI than did adult PMN at both 0 h and 24 h; in addition, ROI levels in 24-h cord blood PMN were similar to those of 0-h adult PMN. We conclude that PMN with prolonged survival retain specific cytotoxic and inflammatory functions, and these are enhanced in cord blood PMN. We speculate that neonatal PMN with prolonged survival have the functional capacity to contribute to the pathogenesis of inflammatory disorders.

Adult↗

PubMed2005

Neonatal hypothalamic hamartoma: a differentiating nonlethal hamartoblastoma.

The authors report on a patient with a large hypothalamic hamartoma with a cleft lip and palate and seizures. Neuroimaging revealed a large extraaxial, intradural mass in the prepontine and interpeduncular cisterns with significant distortion of the brainstem. A stereotactic transfontanel needle biopsy revealed a cellular lesion that contained immature-appearing neuroepithelial cells consistent with prior descriptions of hypothalamic hamartoblastoma. While having a low level of proliferation by Ki67 (MIB-1) labeling, the lesion also contained evidence of neuronal maturation, with many cells expressing neuronal nuclear antigen as observed during immunohistochemical analysis. Further clinical evaluation revealed no other significant congenital abnormalities, and the patient was discharged home. Outpatient follow up has continued for 2 years and the patient has been doing well, requiring no further treatment. This case illustrates that, despite its immature and proliferative histological appearance, this rare neonatal mass can be regarded as a "differentiating" hypothalamic hamartoma and can have a favorable prognosis.

Abnormalities, Multiple↗

PubMed2004

Benign B-cell precursors (hematogones) are the predominant lymphoid population in the bone marrow of preterm infants.

Bone marrow (BM) findings in 3rd-trimester stillborns and full-term living neonates have been previously described. However, there is no information regarding BM composition in living preterm infants. Specifically, it is unknown whether the BM lymphocytosis seen in full-term infants at 1-4 weeks of age also occurs in preterm infants. Furthermore, the lineage of these cells has never been investigated. We used a panel of immunohistochemical stains to characterize the BM composition in 11 neonates (8 living and 3 deceased). Unlike in the other age groups, immature B cells (hematogones) were the most common lymphoid population, accounting for 10-60% (mean 34%) of all cells. In two additional cases (both living patients), flow cytometry revealed a level of 3.8% of immature B cells in a <1-week-old neonate and 25.7% in a 19-week-old infant. Immature B cells were not identified in 6 peripheral blood samples from preterm neonates. These findings are pertinent for the interpretation of BM and peripheral blood samples in this age group as survival improves and diagnostic samples become more common.

Antigens, CD↗

PubMed2004

Platelet function in term and preterm neonates.

Platelet dysfunction likely contributes to the pathophysiology of catastrophic hemorrhages in preterm neonates. In vitro studies have demonstrated that platelets of both term and preterm neonates are hyporesponsive to a variety of agonists. In contrast,template bleeding times of term neonates are shorter than those from adults. Very little is known about this and other tests of primary hemostasis in premature and sick neonates in the neonatal intensive care unit (NICU). This article covers the current knowledge of platelet function in preterm and term neonates and review show new agents (such as recombinant thrombopoietin and recombinant factor VIIa) may enhance neonatal platelet function.

Blood Platelets↗

PubMed2004

The concentration of circulating megakaryocyte progenitors in preterm neonates is a function of post-conceptional age.

Circulating megakaryocyte (Mk) progenitors have been used as a measure of megakaryocytopoiesis in neonates. Prior studies have shown a gestational age-dependent decrease in their concentration, but it is unclear how this process continues after birth in preterm neonates. To answer this question, we quantified the Mk progenitors in the blood of 42 neonates of varying post-conceptional ages (gestational age+days of life). We found an inverse relationship between concentration of circulating Mk progenitors and post-conceptional age (r=-0.54, p=0.0002).

Blood Cell Count↗

PubMed2004

Reticulated platelet percentages in term and preterm neonates.

OBJECTIVES: The authors aimed to determine whether their reticulated platelet percentage (RP%) analysis technique was suitable for use in term and preterm neonates and to characterize RP% values among nonthrombocytopenic neonates. METHODS: The authors modified a whole blood method that uses dual-color CD41 staining for platelet gating and thiazole orange for RNA content, combined with RNase treatment of half the sample to subtract non-RNA fluorescence. The RP% was measured in samples from 10 healthy adults and then a longitudinal study was performed in 15 nonthrombocytopenic preterm neonates on days of life 0 to 1, 2 to 5, 6 to 10, and then weekly until day 28. The authors also performed a cross-sectional study of RP% in 22 nonthrombocytopenic neonates of different gestational age (GA) and postconceptional age (PCA). RESULTS: Overall, neonates had a higher RP% (2.7 +/- 1.6%) than adults (1.1 +/- 0.5%; P < 0.01). In preterm neonates, an increase in the RP% occurred between days 0 and 1 (3.3 +/- 1.3%) and days 2 and 5 (5.1 +/- 1.8%; P = 0.003). By days 6 to 10, the RP% decreased to 3.2 +/- 1.1% and remained unchanged throughout the rest of the study period. In neonates less than 7 days old, an inverse relationship was observed between RP% and GA (n = 20, r = -0.70; P = 0.0005). A correlation between RP% and PCA was not seen in neonates 7 days of age or older. CONCLUSIONS: This method for determining RP% is suitable for use in term and preterm neonates. In preterm infants, the RP% significantly increases over the first 2 to 5 days of life and then decreases to a stable level over the first 28 days. RP% is generally higher in neonates than in adults. Among preterm infants in the first week of life, the RP% is inversely related to GA.

Adult↗

PubMed2003

Effects of anoxia on megakaryocyte progenitors derived from cord blood CD34pos cells.

BACKGROUND: Severe hypoxic insults to the fetus and neonate are associated with the development of thrombocytopenia. The thrombocytopenia in some cases is the result of disseminated intravascular coagulation, but that mechanism fails to account for all, perhaps the majority, of cases. OBJECTIVE: We hypothesized that human fetal megakaryocyte (Mk) progenitors are directly adversely affected by transient anoxia. DESIGN AND METHODS: To test this, we isolated CD34pos cells from the umbilical cord blood of 10 healthy term neonates, and exposed these to 0% or 20% O2 for 24 h, with or without recombinant thrombopoietin (rTpo, 50 ng/mL). After 24 h, a portion of the CD34pos cells were harvested for flow cytometric evaluation of apoptosis. The remaining cells were cultured for an additional 10-12 days, under normoxic conditions, in a collagen-based serum-free system containing rTpo, IL-3, and IL-6. In this way, we sought to determine the effect of transient anoxia on clonogenic capacity of Mk progenitors. RESULTS: Contrary to our hypothesis, anoxia did not increase either apoptosis or cell death of the CD34pos cells. The addition of rTpo was protective, with a significant decrease in apoptosis and cell death (P < 0.0001), and an increase in the number of Mk colonies cultured (P = 0.04). There was no difference between the normoxic and anoxic groups in proliferative potential of the Mk progenitor cells. CONCLUSIONS: The thrombocytopenia observed in neonates following an acute hypoxic event is not likely due to a direct deleterious effect of hypoxia on Mk progenitors.

Antigens, CD34↗

PubMed2002

Primary antiphospholipid syndrome presenting with a branch retinal artery occlusion in a 15-year-old boy.

Acute vascular events are rare in the pediatric population, but there is an association with the presence of antiphospholipid antibodies. When there is no other underlying medical disorder, this is referred to as primary antiphospholipid syndrome. We present a case of a 15-year-old boy who developed an acute superior branch retinal artery occlusion. Complete evaluation revealed significant elevations in antiphospholipid antibodies. To our knowledge, there are no cases in children of primary antiphospholipid syndrome presenting with this clinical manifestation.

Adolescent↗