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Biomedical subjects

W C Koff

Publications and source records attributed to W C Koff.

43 records · Page 3Linked to original sources

Inhibition of dengue virus replication by amantadine hydrochloride.

The effect of amantadine hydrochloride (1-adamantanamine hydrochloride) on dengue virus replication was examined in vitro. Amantadine decreased the titers of all four types of dengue viruses grown in LLC-MK2 cells by greater than 90% at concentrations of 50 micrograms/ml. There was no evidence for any cytopathic effect of the drug at concentrations less than 100 micrograms/ml. Studies of the time of addition showed that the antiviral effect was maximal when drug was added to virus cultures immediately after the viral adsorption period. In addition, amantadine caused a marked reduction in the growth of dengue virus type 2 in both human and rhesus peripheral blood leukocytes without affecting cell viabili ty. These findings demonstrate that amantadine significantly inhibits the replication of dengue viruses in vitro and indicate a need to determine the efficacy of this drug against dengue virus infections in vivo.

Amantadine↗

Inhibition of lymphocyte proliferative responses by ribavirin.

When added to cultures of human peripheral blood lymphocytes, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibited antigen- and mitogen-induced proliferative responses as determined by [3H]thymidine incorporation. Dose-dependent suppressive effects were obtained when concentrations of 5 to 60 microgram of ribavirin per ml were added at culture initiation or up to 96 h thereafter. Ribavirin inhibited [3H]uridine and [3H]leucine incorporation by concanavalin A-activated and normal lymphocytes although not as severely as deoxyribonucleic acid synthesis. The capacity of ribavirin to interfere with lymphoproliferative responses was entirely reversed by guanosine and, to a lesser extent, by adenosine and xanthosine. These studies demonstrate that ribavirin is a reversible inhibitor of lymphocyte nucleic acid synthesis and suggest that the drug may be immunosuppressive when administered in vivo.

Cells, Cultured↗

Inhibition of in vitro proliferative responses of human lymphocytes by rimantadine hydrochloride.

Rimantadine hydrochloride (alpha-methyl-1-adamantanemethylamine hydrochloride) inhibits the in vitro proliferative response of human peripheral blood lymphocytes to mitogenic and antigenic stimulation. Addition of drug (25 micrograms/ml) at the initiation of 5-day cultures suppressed the responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A by 25, 65, and 90%, respectively. Similarly, responses to streptokinase-streptodornase, tetanus toxoid, and A2/Aichi influenza vaccine were significantly inhibited at concentrations as low as 10 micrograms of rimantadine per ml. Viability studies on 5-day cultures using trypan blue exclusion showed no significant difference between drug-treated and untreated controls. Furthermore, addition of drug on day 3 of 8-day cultures, at a time when the majority of cells had undergone blastogenesis, greatly suppressed the responses to these mitogens. These studies suggest that, in addition to its antiviral action, rimantadine interferes with the generation of cellular immune responses.

Adamantane↗

Inhibition of influenza virus uncoating by rimantadine hydrochloride.

In freeze-thaw lysates of MDCK cells infected with 32P-labeled influenza virus A/WSN in the presence of added RNase, acid-precipitable radioactivity diminished to about 50% of initial values within 90 min after a 1-h virus adsorption period. A similar preparation containing rimantadine at a concentration of 50 micrograms/ml exhibited only a 10% reduction in acid-precipitable radioactivity. These findings suggest that rimantadine interferes with uncoating of influenza virus in infected cells.

Adamantane↗

The role of mucosal immunity in development of an acquired immunodeficiency syndrome (AIDS) vaccine: workshop summary.

As the AIDS pandemic spreads, the importance of developing effective vaccines against the human immunodeficiency virus (HIV) assumes increasing importance. Since prevention of any disease is a preferred goal, extensive efforts are being devoted to development of an effective vaccine capable of preventing HIV infection and/or disease. Although many investigators are studying the systemic immune response to HIV, relatively little is known about the mucosal immune response to HIV. A workshop was held to identify the basic research issues in mucosal immunity which need to be addressed in order to rationally design an effective vaccine against HIV. This summary emphasizes the salient points of the papers presented and identifies the unanswered questions.

Acquired Immunodeficiency Syndrome↗