Lee R. Katz

The anti-herpes simplex virus activity of n-docosanol includes inhibition of the viral entry process

n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1/2 of approximately 3 h. Reduced expression of viral genes in n-docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins--an immediate post entry event--was indicated by a 75% reduction in the expression of beta-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate--early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-docosanol.

Topical application of docosanol‐ or stearic acid‐containing creams reduces severity of phenol burn wounds in mice

Because of their reported antiviral and anti‐inflammatory activities, cream formulations containing n‐docosanol (docosanol) or stearic acid were tested for effects on chemically‐induced burns in mice. In this model, injury was induced by painting the abdomens of mice with a chloroform solution of phenol. This was followed by the topical application of test substances 0.5, 3, and 6 h later. Progression of the wounds was assessed by a single evaluator after 8 h, using a numerical score of gross morphology. Docosanol‐ and stearic acid‐containing creams substantially and reproducibly lessened the severity and progression of skin lesions compared to untreated sites with a 76% and 57% reduction in mean lesion scores, respectively. Untreated wounds appeared red and ulcerated; docosanol cream‐treated wounds showed only slight erythema.

A rapid, semi-automated counting procedure for enumeration of antibody-forming cells in gel and nucleated cells in suspension.

A commercially available bacterial colony counter has been modified to permit rapid, highly accurate, semi-automated enumeration of antibody-producing plaque forming cells in semi-solid support medium as well as enumeration of nucleated cells in suspension on a standard hemacytometer chamber. This apparatus should therefore serve as an enormous time-conserving accessory to most modern laboratories involved in immunological research.

Haplotype preference in lymphocyte differentiation: II. F1 hybrid helper T cells generated with antigen-bearing parental macrophages can cooperate with B lymphocytes of either parent

Abstract Carrier-specific helper T cells were generated in F 1 hybrid mice by either conventional immunization procedures or by repeated immunizations with antigen-bearing macrophages derived from either F 1 or parental donors. The F 1 helper T cells generated in these various ways were then analyzed for their capacities to help hapten-primed B lymphocytes derived from each of the two parental strains as well as from F 1 donors in the development of secondary anti-hapten antibody responses. These analyses were conducted using two different types of in vivo assay systems as well as a totally in vitro system. Under all circumstances, helper T cells from F 1 mice, primed either in conventional fashion or with antigen bearing parental or F 1 macrophages, were capable of interacting effectively with B lymphocytes of each parent and of F 1 origin. Moreover, in the case of F 1 helper cells primed with antigen-bearing parental macrophages, there was no evidence of preferential helper activity for parental B lymphocytes corresponding to the type of macrophage used for sensitization; this was true irrespective of whether in vivo or in vitro assay systems were employed. The relevance of these findings and others which are either similar to, or discordant with, them to the general question of genetic restrictions in macrophage-T lymphocyte interactions is discussed.