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Biomedical subjects

G Bloomberg

Publications and source records attributed to G Bloomberg.

10 recordsLinked to original sources
PubMed2001

Risk factors for asthma morbidity and mortality in a large metropolitan city.

Morbidity and mortality due to asthma continues to increase despite advances in understanding the pathophysiology and treatment of the disease. We evaluated the potential risk factors for asthma morbidity and mortality in a large metropolitan city (St. Louis, MO) using small area geographic analysis. We found that the risk of hospitalization for children with asthma was 8.4 times greater (95% confidence interval [CI] 7.0-9.9) in lower socioeconomic zip code areas and 5.3 times greater (95% CI 4.7-5.9) in those zip codes with a higher percentage of African Americans. Similarly, the risk of death due to asthma was 6.4 times greater in the lower socioeconomic zip code areas (95% CI3.4-12.1). Lower socioeconomic status and African American race are strong risk factors for hospitalization and mortality from asthma. Public policy and healthcare resources need to be organized and directed more efficiently to this population.

Adult↗
PubMed2000

Structural basis for recognition of the translocated intimin receptor (Tir) by intimin from enteropathogenic Escherichia coli.

Intimin is a bacterial adhesion molecule involved in intimate attachment of enteropathogenic and enterohaemorrhagic Escherichia coli to mammalian host cells. Intimin targets the translocated intimin receptor (Tir), which is exported by the bacteria and integrated into the host cell plasma membrane. In this study we localized the Tir-binding region of intimin to the C-terminal 190 amino acids (Int190). We have also determined the region's high-resolution solution structure, which comprises an immunoglobulin domain that is intimately coupled to a novel C-type lectin domain. This fragment, which is necessary and sufficient for Tir interaction, defines a new super domain in intimin that exhibits striking structural similarity to the integrin-binding domain of the Yersinia invasin and C-type lectin families. The extracellular portion of intimin comprises an articulated rod of immunoglobulin domains extending from the bacterium surface, conveying a highly accessible 'adhesive tip' to the target cell. The interpretation of NMR-titration and mutagenesis data has enabled us to identify, for the first time, the binding site for Tir, which is located at the extremity of the Int190 moiety.

Adhesins, Bacterial↗
PubMed1997

Solution structure of the ATF-2 recognition site and its interaction with the ATF-2 peptide.

The effect of leucine zipper proteins binding to the DNA recognition site is controversial. Results from crystallography, gel and solution methods have led to opposite conclusions about the conformation of the DNA in the complex. The role of the DNA binding site in the recognition process and in the gene induction mediated by transcription factors needs to be investigated further. In this article the self-complementary 16 bp oligodeoxynucleotide (CATGTGACGTCACATG)2, which contains the cAMP response element recognised by numerous transcription factors of the leucine zipper family, has been examined free from proteins and in its interaction with the mammalian activating transcription factor 2. The recognition process has been investigated by circular dichroism analysis, which has revealed conformational changes in both DNA and protein upon binding. The solution structure of the 16mer, important in order to define the effects induced by binding of leucine zipper proteins and the intrisic bending properties of DNA, has been determined from NMR data using direct refinement against NOE intensities, analysis of scalar coupling constants and restrained molecular dynamics calculations. Final structures starting from the A and B forms of DNA agreed to a pairwise root mean square deviation (r.m.s.d.) of 1.04 +/- 0.3 A (0.7 +/- 0.2 A to the average) for all atoms. The terminal base pairs were less well determined, and the pairwise deviation of the 12 core bp was 0.83 +/- 0.27 A (0.55 +/- 0.19 A to the average). The final structures are within the B-family with an average helical twist of 36+/-2 degrees. No significant intrinsic DNA bend is shown in the activating transcription factor regulatory site. However, there are substantial deviations from the canonical B-DNA (r.m.s.d. = 3.6 A) in the core of the molecule, associated with relatively large base inclinations.

Activating Transcription Factor 2↗
PubMed1995

Cutaneous presentation of juvenile chronic myelogenous leukemia: a diagnostic and therapeutic dilemma.

Annular, erythematous, circinate plaques were the first manifestation of juvenile chronic myelogenous leukemia (JCML) in an otherwise healthy 2.5-year-old boy who had had these lesions since 6 months of age. The lesions showed an atypical hematopoietic infiltrate on biopsy. Biopsy of a bone marrow specimen and peripheral blood smear were normal six months before leukemic transformation. At 3 years of age the boy developed splenomegaly, thrombocytopenia, and petechiae, and a bone marrow aspirate and cell marker studies were regarded as consistent with, if not diagnostic of, JCML. Four previous cases of cutaneous leukemic infiltrate associated with JCML have been published. Our patient had recurring urticarial-like plaques for two years before the initial bone marrow finding of JCML. Given the poor prognosis and progressively evolving course of JCML, it may be appropriate to consider therapy before bone marrow changes, based on the presence of the cutaneous eruption with the appropriate findings on skin biopsy and an elevated fetal hemoglobin.

Child, Preschool↗
PubMed1994

Identification of novel phosphorylation sites in the beta-subunit of translation initiation factor eIF-2.

Initiation factor eIF-2 (a trimer of subunits alpha, beta and gamma) attaches the initiator Met-tRNA to the ribosome during the initiation of translation in eukaryotic cells. Both the alpha and beta subunits can be phosphorylated although the sites in the beta-subunit have not previously been fully identified. Here we identify the sites at which eIF-2 beta is phosphorylated in vitro by three well-characterised protein kinases, casein kinase-2 (which phosphorylates serine residues-2 and -67), protein kinase C (serine-13) and cAMP-dependent protein kinase (serine-218). This constitutes an essential prerequisite for studying the phosphorylation of eIF-2 beta in vivo. Indeed, we present evidence that at least one of these sites (serine-67) is phosphorylated in reticulocytes. The major kinase activity against eIF-2 beta in reticulocyte lysates appears in CK-2 and protein phosphatase-2A is the principal enzyme responsible for dephosphorylation of eIF-2 beta phosphorylated by this kinase.

Amino Acid Sequence↗
PubMed1994

Lactoferricin, a new antimicrobial peptide.

Lactoferricin B (LF-B) is a peptide derived from acid-pepsin digestion of bovine lactoferrin, which has antimicrobial properties. In order to assess the antimicrobial spectrum of LF-B and its possible in vivo uses, the minimum inhibitory and microbicidal concentrations of pure lactoferricin B were determined for a range of bacterial species and under varying conditions of growth including growth phase and size of the inoculum, pH and ionic strength of the medium. Lactoferricin B was bactericidal against a wide range of bacteria and Candida albicans. Proteus spp., Pseudomonas cepacia and Serratia spp. were resistant. The bactericidal activity of LF-B was inhibited by increasing ionic strength and bacterial inoculum and at acid pH. The activity of lactoferricin B was completely inhibited by the addition of 5% whole cow's milk and was reduced in the presence of increasing concentrations of mucin. These results indicate the potential of LF-B to reduce the numbers of organisms in a simple medium, but raise doubts about its role in vivo because of its sensitivity to changes in physical variables. It may be that lactoferricin exerts a transient antimicrobial effect at mucosal surfaces.

Animals↗