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S H Pincus

Publications and source records attributed to S H Pincus.

111 records · Page 7Linked to original sources

Variable regions of antibodies to synthetic polypeptides--III. Antibodies arising in response to administration of anti-idiotope.

Antibodies elicited by the synthetic polypeptide antigen (T,G)-A-L are directed against two distinct epitopes. The majority of antibodies bind to a GT containing epitope and bear an idiotope defined by monoclonal antibodies I7 and I9. In this study, we have examined the effect of in vivo administration of the I7 and I9 antibodies to mice. Administration of anti-idiotope elicits anti-(T,G)-A-L antibodies in all strains of mice tested, including genetic non-responders to (T,G)-A-L. These antibodies bind to GT and express the idiotope. Additionally, idiotope expressing antibodies that fail to bind to antigen are also produced. Monoclonal anti-(anti-idiotope) antibodies were made. One antibody bound to (T,G)-A-L, the other did not. Sequence analysis was performed and the V-regions of (T,G)-A-L binding antibodies were compared to those of the antibody that failed to bind antigen. Both sets of antibodies are derived from the same germline V-genes as the anti-(T,G)-A-L antibodies. These results have implications for understanding the nature of network regulation of the immune system and for those attempting idiotypic vaccination.

Amino Acid Sequence↗

Efficacy and safety of azelaic acid and glycolic acid combination therapy compared with tretinoin therapy for acne.

We conducted a 12-week, multicenter, randomized, double-masked, parallel-group study of the efficacy, safety, and tolerability of azelaic acid 20% cream and glycolic acid lotion compared with tretinoin 0.025% cream and a vehicle lotion to treat mild-to-moderate facial acne vulgaris. Patients treated with azelaic/glycolic acid experienced a significantly greater reduction in the number of papules, as well as a greater reduction in the number of inflammatory lesions, than those treated with tretinoin. Overall global improvement was approximately 25% in both groups. In the physician evaluations, treatment with azelaic/glycolic acid was found to cause significantly less dryness, scaling, and erythema than tretinoin. Patients also reported significantly less dryness, redness, and peeling with azelaic/glycolic acid. Significantly more patients in the azelaic/glycolic acid group than the tretinoin group reported that they felt attractive. The combination of azelaic acid and glycolic acid is a useful alternative to tretinoin, being at least as efficacious as the latter, while offering a superior tolerability and patient approval profile.

Acne Vulgaris↗

Influence of endosome-destabilizing peptides on efficacy of anti-HIV immunotoxins.

The effects on immunotoxin efficacy of fusogenic peptides derived from influenza virus hemagglutinin have been studied. These peptides have an amphipathic nature and change conformation from random at pH 7 to helical at pH 5. Fusogenic peptides are reported to destabilize endosomal membranes, resulting in the release of contents into the cytoplasm. The use of two related fusogenic peptides to enhance the efficacy of anti-HIV immunotoxins is described. The direct toxicity of the peptides was tested on HIV-infected H9/NL4-3 cells. Peptide HA24 was considerably more toxic than HA23. The peptides were mixed with two different immunotoxins. Immunotoxin action was enhanced by both peptides, with HA24 providing greater enhancement than HA23. Immunotoxins were then constructed by coupling HA23 or HA24 to the targeting antibody with disulfide-containing linkers. Peptide HA23 enhanced the activity of the immunotoxin 4-5-fold. Surprisingly, HA24 significantly inhibited immunotoxin activity. Coupling the peptides to the immunotoxin had no effect on antigen binding characteristics or the activity of the toxic moiety. Bafilomycin A1, an agent that inhibits vacuolar acidification, markedly potentiated the effects of all immunotoxins. These results demonstrate that amphipathic peptides can influence the efficacy of immunotoxins, but in sometimes unpredictable ways.

Alkaline Phosphatase↗