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Biomedical subjects

Stuart M Brown

Publications and source records attributed to Stuart M Brown.

8 recordsLinked to original sources
PubMed2003

Atopic dermatitis: a new treatment paradigm using pimecrolimus.

Atopic dermatitis (AD), often called eczema, is a disease characterized by intense pruritus, erythema, dry skin, and inflammation. Pimecrolimus is a novel steroid-free treatment for AD. Consistently positive results have been found with pimecrolimus treatment in infants, children/adolescents, and adults. Its safety record is excellent, and studies have found no clinically relevant drug-related systemic adverse events. In this article, we first review atopic dermatitis and conventional treatment strategies. We then discuss various aspects of pimecrolimus, including pharmacologic properties, toxicology, short- and long-term studies, and safety and adverse events. Finally, we propose a new steroid-sparing treatment strategy for AD.

Animals↗
PubMed2002

Infectivity-associated changes in the transcriptional repertoire of the malaria parasite sporozoite stage.

Injection of Plasmodium salivary gland sporozoites into the vertebrate host by Anopheles mosquitoes initiates malaria infection. Sporozoites develop within oocysts in the mosquito midgut and then enter and mature in the salivary glands. Although morphologically similar, oocyst sporozoites and salivary gland sporozoites differ strikingly in their infectivity to the mammalian host, ability to elicit protective immune responses, and cell motility. Here, we show that differential gene expression coincides with these dramatic phenotypic differences. Using suppression subtractive cDNA hybridization we identified highly up-regulated mRNAs transcribed from 30 distinct genes in salivary gland sporozoites. Of those genes, 29 are not significantly expressed in the parasite's blood stages. The most frequently recovered transcript encodes a protein kinase. Developmental up-regulation of specific mRNAs in the infectious transmission stage of Plasmodium indicates that their translation products may have unique roles in hepatocyte infection and/or development of liver stages.

Animals↗
PubMed2002

Rare, structurally homologous self-peptides promote thymocyte positive selection.

Although it is clear that positive selection of T cells involves recognition of specific self-peptide/MHC complexes, the nature of these self-ligands and their relationship to the cognate antigen are controversial. Here we used two complementary strategies to identify naturally occurring self-peptides able to induce positive selection of T cells bearing a specific T cell receptor, OT-I. Both the bioassay- and bioinformatics-based strategies identified the same self-peptides, derived from F-actin capping protein and beta-catenin. These peptides displayed charge conservation at two key TCR contact residues. The biological activity of 43 other self-peptides and of complex peptide libraries directly correlated to the extent of conservation at TCR contact residues. These results demonstrate that selecting self-peptides are rare and can be identified by homology-based search strategies.

Actin Depolymerizing Factors↗
PubMed2002

Genomics-based identification of self-ligands with T cell receptor-specific biological activity.

Self-peptide/major histocompatibility complex (MHC) complexes profoundly influence the biology of T lymphocytes. They promote the selection of the T cell receptor (TCR) repertoire in the thymus, maintain the homeostasis of peripheral T cells prior to encounter with antigen, and modify the responsiveness of T cells to foreign antigens. In addition, they can serve as antigens for autoaggressive T cells that induce autoimmune diseases. The complete sequencing of the genomes of human, mouse, and many pathogenic organisms now provides us with a comprehensive list of all possible proteins that may be the source of foreign antigenic and self-peptides. A computational approach using profile-based similarity searches on potential self-MHC-binding peptides can be used to efficiently predict self-peptides with biological activities. The common feature of the identified peptides is similarity to antigen. Thus, self-peptides may form 'hazy' images of the universe of antigens that are used as templates to create and maintain the TCR repertoire.

Amino Acid Motifs↗