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Biomedical subjects

Robert A Swerlick

Publications and source records attributed to Robert A Swerlick.

9 recordsLinked to original sources
PubMed2006

Azathioprine in dermatology: the past, the present, and the future.

For several decades, dermatologists have utilized azathioprine to treat numerous debilitating skin diseases. This synthetic purine analog is derived from 6-mercaptopurine. It is thought to act by disrupting nucleic acid synthesis and has recently been found to interfere with T-cell activation. The most recognized uses of azathioprine in dermatology are for immunobullous diseases, generalized eczematous disorders, and photodermatoses. In this comprehensive review, the authors present recent advancements in the understanding of azathioprine and address aspects not covered in prior reviews. They (1) summarize the history of azathioprine; (2) discuss metabolism, integrating information from recent publications; (3) review the mechanism of action with attention paid to the activities of azathioprine not mediated by its 6-mercaptopurine metabolites and review new data about inhibition by azathioprine of the CD28 signal transduction pathway; (4) thoroughly examine thiopurine s-methyltransferase genetics, its clinical relevance, and interethnic variations; (5) review prior uses of azathioprine in the field of dermatology and grade the level of evidence; (6) discuss the use of azathioprine in pregnancy and pediatrics; review (7) key drug interactions and (8) adverse effects; (9) suggest a dosing and monitoring approach different from prior recommendations; and (10) explore the future of azathioprine, focusing on laboratory considerations and therapeutic application.

Azathioprine↗
PubMed2003

Iron chelators inhibit VCAM-1 expression in human dermal microvascular endothelial cells.

Vascular cell adhesion molecule (VCAM)-1 expression may be coupled to redox-sensitive regulatory pathways, and iron may play a role in generation of reactive oxygen species that participate in these signaling pathways. To investigate the role of iron in TNF alpha-induced VCAM-1 gene expression, human dermal microvascular endothelial cells (HDMEC) were stimulated with TNF alpha in the presence of iron chelators and examined for expression of VCAM-1. The iron chelators dipyridyl (DP) and desferoxamine (DFO) inhibited VCAM-1 protein and mRNA induction in a concentration- and time-dependent manner. The induction of VCAM-1 was not inhibited by nonmetal binding reactive oxygen species (ROS) scavengers, implying a direct effect of iron in the expression of these adhesion molecules. The effect of iron was mediated at the level of gene transcription since pretreatment with DP abrogated the TNF alpha-mediated up-regulation of VCAM-1 heterogeneous nuclear RNA. Pretreatment of HDMEC with DP prior to TNFalpha treatment had no effect on p65 nuclear localization, DNA binding, or serine phosphorylation. DP pretreatment inhibited TNF alpha- and IFN gamma-mediated interferon regulatory factor 1 (IRF-1) protein expression, although restoration of IRF-1 expression failed to reconstitute VCAM-1 expression. DP treatment also blocked VCAM-1 induction in human umbilical vein endothelium and blocked induction of a host of NF-kB activated genes in HDMEC including ICAM-1, IL-8, and tissue factor. I kappa B alpha, an NF-kappa B inducible and constitutively accessible gene not requiring chromatin remodeling for transcription, was not affected by DP treatment. These data suggest that iron plays a critical role in TNF alpha mediated VCAM-1 induction in HDMEC, and the target for iron effects may be IRF-1, NF-kappa B, and potentially chromatin remodeling.

2,2'-Dipyridyl↗
PubMed2003

Induction of interferon regulatory factor 1 expression in human dermal endothelial cells by interferon-gamma and tumor necrosis factor-alpha is transcriptionally regulated and requires iron.

Interferon regulatory factor-1 is a transcription factor that is linked to the expression of genes important in the initiation of the inflammatory response and the control of cell cycle. In this study, we determined that the generation of interferon regulatory factor-1 expression in human dermal microvascular endothelial cells was transcriptionally mediated by tumor necrosis factor-alpha or interferon-gamma via iron-dependent pathways. The induction of interferon regulatory factor-1 protein and the up-regulation of interferon regulatory factor-1 mRNA levels was inhibited when cells were pretreated with the iron chelators 2-2-dipyridyl or deferoxamine. This inhibition of interferon regulatory factor-1 expression was associated with loss of interferon regulatory factor-1 binding to the interferon-stimulated response element as assessed by electrophoretic mobility shift assay. Addition of exogenous iron with the iron chelator resulted in reconstitution of cytokine responsiveness, thus demonstrating iron as the target for the chelator effect. Both tumor necrosis factor-alpha and interferon-gamma-induced interferon regulatory factor-1 gene transcription, as assessed by the measurement of unspliced, nascent, heterogeneous nuclear RNA, and treatment with iron chelators blocked tumor necrosis factor-alpha or interferon-gamma mediated interferon regulatory factor-1 gene transcription. Iron was not essential, however, for the association of interferon regulatory factor-1 mRNA with polyribosomes, suggesting iron was not essential for interferon regulatory factor-1 protein translation. Through such inhibitory regulation on pro-inflammatory transcription factors, iron chelators may serve as anti-inflammatory agents.

Cells, Cultured↗
PubMed2002

Chronic pruritus associated with Helicobacter pylori.

BACKGROUND: Helicobacter pylori is an established cause of gastritis and has been implicated in extradigestive diseases. OBJECTIVE: To investigate the role of H. pylori in patients with unexplained refractory pruritus. METHODS: Ten patients with severe pruritus unresponsive to conventional therapy were evaluated for active H. pylori infection by H. pylori serology followed by either esophagogastroduodenoscopy (EGD) or urea breath test. Of the 10 patients, 8 were found to have active infection. All 10 received anti-H. pylori antibiotic therapy and were reevaluated for relief of pruritus. RESULTS: Of 8 patients with active H. pylori infection, 87.5% (7/8) had some type of pruritus relief after triple therapy. Of these, 62.5% (5/8) had complete relief and 25% (2/8) had temporary relief of pruritus. The remaining 12.5% (1/8) did not respond. Two control patients without active H. pylori infection had no relief of pruritus with therapy. CONCLUSIONS: We have identified a population of patients with refractory pruritus and active H. pylori infection whose pruritus resolved after eradication of H. pylori.

Adult↗
PubMed2002

Keratoelastoidosis marginalis.

BACKGROUND: Keratoelastoidosis marginalis is a rare disease that is a variant of solar elastosis. Long-term ultraviolet radiation exposure and chronic trauma secondary to manual labor are considered to be inciting factors. OBJECTIVE: To outline the clinical and histological features of this disorder. METHODS: We report two cases and review the literature. RESULTS: Both patients had persistence of their disease despite multiple topical treatment regimens. CONCLUSION: Keratoelastoidosis marginalis is a chronic and progressive disease that is difficult to treat. The differential includes focal acral hyperkeratosis and acrokeratoelastoidosis.

Female↗