Human granulocyte-macrophage colony-stimulating factor enhancer function is associated with cooperative interactions between AP-1 and NFATp/c.

The promoter of the human granulocyte-macrophage colony-stimulating factor gene is regulated by an inducible upstream enhancer. The enhancer encompasses three previously defined binding sites for the transcription factor NFAT (GM170, GM330, and GM550) and a novel NFAT site defined here as the GM420 element. While there was considerable redundancy within the enhancer, the GM330, GM420, and GM550 motifs each functioned efficiently in isolation as enhancer elements and bound NFATp and AP-1 in a highly cooperative fashion.

Clinical toxicology for the pediatrician.

The pediatrician has at his or her disposal a highly accurate and reliable system of drug testing to provide additional information relevant to substance abuse in children and adolescents. As always, the judgments engendered in questions such as when it is ethical to order such tests, the confidentiality of the results, and how to integrate such findings into the overall management of the patient and his or her family are much more important and problematic than the technical aspects of testing. In selected clinical situations, however, drug testing can provide reliable and useful information and is indicated in the diagnosis and management of substance abuse in adolescents.

Ethanol-related visits by adolescents to a pediatric emergency department.

The objectives of this study were to determine if the presence of ethanol (ETOH) in patients 10 to 20 years of age is associated with injury and if the patient's mental status reliably predicts their blood ethanol concentration. The study was designed as a retrospective, case-controlled report from a children's hospital emergency department. The data are from 45 patients 10 to 20 years old in whom ETOH was detected on toxic screen and 37 patients (N-ETOH) 10 to 20 years old in whom a toxic screen did not reveal ETOH.

A multifactorial approach to understanding anesthesia selection.

A full hospital cost accounting model to track the total costs of surgery and anesthesia for inpatients, from the perspective of a hospital CFO, utilizing time-allocation methodology is presented. This model was tested in a prospective multicenter economic clinical trial in three settings.

A sequence-specific single-strand DNA binding protein that contacts repressor sequences in the human GM-CSF promoter.

NF-GMb is a nuclear factor that binds to the proximal promoter of the human granulocyte-macrophage colony stimulating factor (GM-CSF) gene. NF-GMb has a subunit molecular weight of 22 kDa, is constitutively expressed in embryonic fibroblasts and binds to sequences within the adjacent CK-1 and CK-2 elements (CK-1/CK-2 region), located at approximately -100 in the GM-CSF gene promoter. These elements are conserved in haemopoietic growth factor (HGF) genes.

Efficacy of magnesium citrate cathartic in pediatric toxic ingestions.

Study Objective: To investigate the efficacy of magnesium citrate in reducing gastrointestinal transit time of activated charcoal in children.

Design: A prospective, randomized, clinical comparison of four magnesium doses.

Setting: Urban children's hospital emergency department.

T-cell functional regions of the human IL-3 proximal promoter.

The human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells. Its expression is regulated at both the transcriptional and post-transcriptional level. We have previously shown that treatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene.

Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6.

Transcriptional activation of the IL-8 gene by several inflammatory mediators, including the cytokines IL-1 and TNF-alpha, is mediated through sequences located between nucleotide -94 and -71 of the IL-8 promoter. Because adjacent binding sites for the inducible transcription factors NF-kappa B and NF-IL-6 are located within this region, we examined the functional interaction of these two transcription factor families in IL-8 gene regulation. Maximal transcriptional activation by PMA in Jurkat T lymphocytes was shown to require intact binding sites for both NF-kappa B and NF-IL-6.

Specific human granulocyte-macrophage colony-stimulating factor antagonists.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic hemopoietic growth factor and activator of mature myeloid cell function. We have previously shown that residue 21 in the first helix of GM-CSF plays a critical role in both biological activity and high-affinity receptor binding. We have now generated analogues of GM-CSF mutated at residue 21, expressed them in Escherichia coli, and examined them for binding, agonistic, and antagonistic activities.

Identification of residues in the first and fourth helices of human granulocyte-macrophage colony-stimulating factor involved in biologic activity and in binding to the alpha- and beta-chains of its receptor.

Residues within the first and fourth helices of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) were analyzed for their role in biologic activity and interaction with the alpha- and beta-chains of the hGM-CSF receptor. Within the first helix substitution of the surface residues Glu14, Asn17, Gln20, Arg23, Arg24, and Asn27 or the buried residues Ala18, Leu25, and Leu28 did not significantly impair bioactivity or receptor binding. Substitutions at the buried residues Ala22 and Leu26 had intermediate bioactivity.

Requirement for nuclear factor (NF)-kappa B p65 and NF-interleukin-6 binding elements in the tumor necrosis factor response region of the granulocyte colony-stimulating factor promoter.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor produced by mesenchymal and myeloid cells following activation by inflammatory stimuli. It has previously been shown that a region of the G-CSF promoter, (-200 to -165) containing the decanucleotide CK-1 element and two repeated sequences that resemble nuclear factor (NF)-interleukin-6 (IL-6) binding sites, is required for activation of the G-CSF gene by tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta. We now show that the NF-kappa B p65 protein can bind to and activate this TNF response region.

Two contiguous residues in human interleukin-3, Asp21 and Glu22, selectively interact with the alpha- and beta-chains of its receptor and participate in function.

We have previously reported that the predicted first helix of human interleukin (IL)-3 contains a hydrophilic region encompassing residues Asp21, Glu22, and Thr25 that is crucial for biological activity and IL-3 receptor binding. Using single amino acid substitution mutagenesis, we have now determined that Asp21 and Glu22, but not Thr25, were crucial for full IL-3 activity. Mutant D21R was 30-fold less potent than wild type IL-3 in the stimulation of biological activity.

Clinical issues and therapeutic interventions in the care of pregnant women infected with the human immunodeficiency virus.

As the incidence of human immunodeficiency virus (HIV) infection increases in women of reproductive age in the United States, clinical issues and therapeutic interventions specifically addressing the needs of HIV-positive pregnant women will continue to evolve and be incorporated into their obstetric care. This article provides perinatal nurse clinicians with an overview to the epidemiology and clinical manifestations of HIV infection in pregnant women, as well as the therapeutic modalities and psychosocial components included in their plan of care. Data regarding perinatal transmission rates and maternal factors possibly facilitating vertical transmission are also presented.

Efficacy of oral meso-2,3-dimercaptosuccinic acid therapy for low-level childhood plumbism.

Objective: To compare the response to oral meso-2,3-dimercaptosuccinic acid (DMSA) treatment in children with an initial blood lead (BPb) concentration less than versus more than 2.17 mumol/L (45 micrograms/dl).

Design: Retrospective cohort study.

Hypokalemia, hyperglycemia and plasma catecholamine activity after severe theophylline intoxication.

To determine if differences in the rate of hypokalemia and hyperglycemia between victims of acute versus chronic theophylline intoxication relate to alterations in plasma catecholamine activity, we evaluated plasma catechols in three groups of patients: victims of acute theophylline intoxication (n = 10), chronic theophylline overmedication (n = 3), and healthy controls (n = 6). There were no differences in peak serum theophylline concentration between acute and chronic groups (86.6 vs 73.

Children exposed to disaster: II. Risk factors for the development of post-traumatic symptomatology.

Objective: To examine the influence of subject and exposure variables on the development of post-traumatic stress disorder (PTSD) symptoms and syndrome in children exposed to disaster.

Method: Three months after Hurricane Hugo, 5,687 school-aged children were surveyed about their experiences and reactions to the hurricane. Self-reports of PTSD symptoms were obtained by use of a PTSD Reaction Index.

Children exposed to disaster: I. Epidemiology of post-traumatic symptoms and symptom profiles.

Objective: To determine the range and severity of post-traumatic stress disorder (PTSD) symptoms exhibited by children after exposure to a natural disaster.

Method: Three months after Hurricane Hugo struck Berkeley County, South Carolina, 5,687 school-aged children were surveyed about their experiences and reactions related to the storm. Self-reports of PTSD symptoms were obtained by use of a PTSD Reaction Index.

Predictors of major toxicity after theophylline overdose.

Objective: To identify patients at high risk for major toxicity after theophylline intoxication who might benefit from early charcoal hemoperfusion.

Design: A 67-month prospective study.

Setting: Massachusetts Poison Control System.

HTLV-1 tax activation of the GM-CSF and G-CSF promoters requires the interaction of NF-kB with other transcription factor families.

The trans-activator protein, tax, from the human T leukemia virus type 1 (HTLV-1) trans-activates both viral and cellular genes. It has previously been shown that granulocyte macrophage-colony stimulating factor (GM-CSF) is constitutively expressed in HTLV-1 infected cells and in cells artificially expressing tax. We show here that the GM-CSF promoter is tax responsive in fibroblasts and T cells, whereas the granulocyte (G)-CSF promoter is tax responsive only in fibroblasts.