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Biomedical subjects

William R Levis

Publications and source records attributed to William R Levis.

7 recordsLinked to original sources
PubMed2006

Haptens as drugs: contact allergens are powerful topical immunomodulators.

For the past 40 years, dermatologists have safely used contact sensitizers such as dinitrochlorobenzene (DNCB), diphenylcyclopropenone (DPCP), and squaric acid dibutylester (SADBE) for the treatment of warts, alopecia areata, and even skin cancers. Most of these studies have utilized these powerful topical immunomodulators in acetone, a volatile solvent that precludes development of contact sensitizers as products. We have overcome these problems and stabilized these topical immunomodulators in a non-volatile, nonirritating GRAS (generally regarded as safe) vehicle. The current review article covers the traditional use of contact sensitizers for a variety of benign and malignant conditions and discusses possible mechanisms in relation to developments in modem molecular immunodermatology.

Administration, Topical↗
PubMed2006

Topical diphenylcyclopropenone as a measure of immune competence in HIV-seropositive subjects.

BACKGROUND: CD4 T cell counts are recognized as the standard method for monitoring HIV-seropositive patients and, along with viral load, are clinically important as indicators for initiating highly active antiretrovival therapy (HAART). Skin reaction scores following topical application of diphenylcyclopropenone (DPC) also demonstrate diagnostic utility as a functional measure of immune competence. METHODS: We used low sensitizing doses of DPC in 40 patients applied in a non-volatile, non-irritating topical delivery system to assess immune competence in 40 HIV-seropositive subjects with a range of CD4 T cell counts. Standardized patch test reading scores were used, with 2+ or greater scores (erythema and induration) indicative of a positive response. The patch test scores were then compared with CD4 counts. RESULTS: Application of DPC in concentrations of 0.4% and 0.2% successfully resulted in 90% sensitivity skin reaction scores in subjects with >300 CD4 T cells/microL, following a single 0.1 mL application to the inner aspect of the arm. Lower DPC concentrations of 0.1% and 0.05% were too low for initial sensitization reactions. Three subjects with CD4 counts between 150 and 300 cells/microL showed positive skin reactions indicating that this DPC test gives the clinician information on cellular immunity beyond the CD4 count. CONCLUSION: We conclude that a single topical application of DPC at concentrations between 0.2% and 0.4% can serve as a measure of immune competence in HIV-seropositive patients. As a functional measure of immunocompetence, this DPC test provides information beyond a CD4 count, which is particularly relevant to HIV-positive subjects with CD4 counts between 200 and 350 cells/microL.

Administration, Cutaneous↗
PubMed2004

Platycodin D and D3 isolated from the root of Platycodon grandiflorum modulate the production of nitric oxide and secretion of TNF-alpha in activated RAW 264.7 cells.

Platycodon D (PD) and D3 (PD3) isolated from Platycodon grandiflorum has been previously reported to show anti-inflammatory activities in rats. In this study, the production of proinflammatory cytokines, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) was examined in a macrophage like cell line, RAW 264.7 cells, in the presence of PD and PD3, oligosaccharide derivatives of oleanolic acid. RAW 264.7 cells activated with lipopolysaccharide (LPS; 1 microg/ml) and recombinant interferon-gamma (rIFN-gamma; 50 U/ml) were treated with various doses of PD and PD3 for 24 h. Supernatants were analyzed for the production of NO and TNF-alpha using Griess reagent and enzyme-linked immunosorbent assay (ELISA), respectively. NO was inhibited in a dose-dependent manner by PD and PD3 (IC50 of platycodin D approximately 15 uM, IC50 PD3 approximately 55 uM). The expression of inducible NOS (iNOS) was inhibited by these compounds, as measured by Western blot analysis, as well as the expression of iNOS mRNA, as measured by Northern blot analysis. RAW 264.7 cells were treated at various times after LPS and activation with PD. Treatment with PD up to 8 h after activation showed significant inhibition of NO, indicating that early signal transduction of NOS synthesis may be inhibited by PD. In contrast to NO, secretion of TNF-alpha as well as expression of TNF-alpha mRNA was increased by PD and PD3. TNF-alpha secretion from RAW 264.7 cells was measured at various times after LPS and rIFN-gamma activation. Secretion of TNF-alpha was also increased up to 8 h postactivation, suggesting that PD may stimulate TNF-alpha synthesis or inhibit degradation of TNF-alpha mRNA. Oleanolic acid was without effect on both the production of NO and secretion of TNF-alpha. These data suggest a dichotomous regulation of these important proinflammatory mediators by PD and PD3.

Animals↗
PubMed2002

Reversal reaction to Hansen's disease.

A 25-year-old man with a history of mid-borderline (BB) Hansen's disease developing a reversal reaction after starting dapsone and rifampin therapy is presented. His clinical features included erythematous, edematous plaques and peripheral neuropathy. Reversal reactions are caused immunologically by enhanced cell-mediated (Th-1) immunity to Mycobacterium leprae, resulting in inflammation of infected tissues, such as skin and nerves. Acute neuritis can lead to permanent nerve damage and necessitate prompt treatment with prednisone and/or clofazamine.

Adult↗