The impact of opioid exposure during pregnancy on the human neonatal immune profile.

Background: The increasing magnitude of the opioid crisis and rising rates of neonatal abstinence syndrome (NAS) diagnoses highlight the need for increased research into how maternal substance use during pregnancy can impact the neonatal immune profile and its functionality. We hypothesized that neonates with opioid exposure would have reduced proportions of some immune cells, an anti-inflammatory cytokine profile, reduced T cell proliferation, and monocyte bacterial killing activity compared to the control population.

Methods: The present study compares immune cell populations, inflammatory and anti-inflammatory cytokine and chemokine levels in the serum, and monocyte and T cell functional activity using umbilical cord samples from neonates with known opioid exposure during gestation and from control neonates without known exposure.

Neonatal low-density granulocytes internalize and kill bacteria but suppress monocyte function using extracellular DNA.

Low-density granulocytes (LDGs) are found abundantly in neonatal blood; however, there is limited mechanistic understanding of LDG interactions with bacteria and innate immune cells during acute infection. We aimed to determine how human neonatal LDGs may influence control of the bacterial burden at sites of infection, both individually and in the presence of mononuclear phagocytes. LDGs from human umbilical cord blood do phagocytose O1:K1:H7 and traffic bacteria into acidic compartments.

Clearance of Persistent Bacteremia in a Preterm Neonate With the Use of Combination Cefazolin and Ertapenem.

Late-onset sepsis caused by is a serious and relatively common complication encountered by preterm neonates in NICUs. Typical treatment regimens for invasive methicillin-sensitive (MSSA) include semisynthetic beta lactam antibiotics, such as nafcillin. This report describes the first use of a combination of cefazolin and ertapenem to successfully treat persistent MSSA bacteremia in a preterm neonate who failed traditional first-line therapy.

Bone marrow osteoblast damage by chemotherapeutic agents.

Hematopoietic reconstitution, following bone marrow or stem cell transplantation, requires a microenvironment niche capable of supporting both immature progenitors and stem cells with the capacity to differentiate and expand. Osteoblasts comprise one important component of this niche. We determined that treatment of human primary osteoblasts (HOB) with melphalan or VP-16 resulted in increased phospho-Smad2, consistent with increased TGF-β1 activity.

Cellular elements of the subarachnoid space promote ALL survival during chemotherapy.

CNS infiltration by leukemic cells remains a problematic disease manifestation of acute lymphoblastic leukemia (ALL). Prophylactic regimens for CNS leukemia including intrathecal chemotherapeutics have decreased CNS involvement in ALL, but are not without toxicities. Using co-culture models, we show that astrocytes, choroid plexus epithelial cells, and meningeal cells protect ALL cells from chemotherapy-induced cell death using drugs included in prophylactic regimens-cytarabine, dexamethasone, and methotrexate.

VE-cadherin Regulates Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Sensitivity to Apoptosis.

The mechanisms by which the bone marrow microenvironment regulates tumor cell survival are diverse. This study describes the novel observation that in addition to Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) cell lines, primary patient cells also express Hypoxia Inducible Factor-2α (HIF-2α) and Vascular Endothelial Cadherin (VE-cadherin), which are regulated by Abl kinase. Tumor expression of the classical endothelial protein, VE-cadherin, has been associated with aggressive phenotype and poor prognosis in other models, but has not been investigated in hematopoietic malignancies.

VE-cadherin and PECAM-1 enhance ALL migration across brain microvascular endothelial cell monolayers.

Objective: Infiltration of the central nervous system (CNS) by leukemia is a problematic disease manifestation of acute lymphoblastic leukemia (ALL). The mechanisms by which leukocytes interact with human brain-derived microvasculature endothelial cells (HBMEC) and enter the CNS are largely derived from models of inflammation. However, our data indicate that ALL cells do not elicit an inflammatory phenotype by HBMEC.

Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway.

Background: The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC). As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development.