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S Pincus

Publications and source records attributed to S Pincus.

64 records · Page 4Linked to original sources

Characterization of the effect of aphidicolin on adenovirus DNA replication: evidence in support of a protein primer model of initiation.

Adenovirus DNA replication is inhibited by aphidicolin but the inhibition clearly has different parameters than the inhibition of purified DNA polymerase alpha. In adenovirus infected Hela cells, 10 micrograms/ml of aphidicolin reduced viral DNA synthesis by 80%. Cellular DNA synthesis was inhibited by 97% at 0.1 microgram/ml. 10 micrograms/ml of drug had no effect on virus yield or late protein synthesis though higher concentrations of drug (50 micrograms/ml) caused an abrupt cessation of late protein synthesis and 100 micrograms/ml reduced virus yield by 3 logs. Concentrations of the drug from 0.5 microgram/ml to 10 micrograms/ml were found to dramatically slow the rate of DNA chain elongation in vitro but not stop it completely, so that over a long period of time net incorporation was reduced only slightly compared to the control. 50 micrograms/ml or 100 micrograms/ml of drug completely inhibited incorporation in vitro. Initiation of viral DNA replication - covalent attachment of dCMP to the preterminal protein - occurs in vitro. This reaction was found to be insensitive to inhibition by aphidicolin. We thus conclude that aphidicolin exerts its effect on adenovirus DNA chain elongation, but not on the primary initiation event of protein priming.

Aphidicolin↗

Azelaic acid 20% cream in the treatment of facial hyperpigmentation in darker-skinned patients.

This multicenter, randomized, double-masked, parallel-group study assessed the efficacy, safety, and tolerability of azelaic acid 20% cream compared with those of its vehicle for the treatment of facial hyperpigmentation in darker-skinned patients (phototypes IV to VI). Following a 24-week treatment period, azelaic acid produced significantly greater decreases in pigmentary intensity than did vehicle as measured by both an investigator's subjective scale (P = 0.021) and a chromometer analysis (P = 0.039). There was a significantly greater global improvement with azelaic acid than with vehicle at week 24 (P = 0.008). Azelaic acid produced a slightly but significantly greater amount of burning (weeks 4 and 12, P < or = 0.046) and stinging (week 4, P = 0.002) than did vehicle. At the end of the study, more patients treated with azelaic acid than with vehicle reported having much smoother skin and being very satisfied or satisfied with their treatment. Also, more patients treated with azelaic acid than with vehicle rated their medication as being more effective or the same as past treatments. Thus azelaic acid is an effective and well-tolerated treatment for hyperpigmentation in darker-skinned patients.

Adult↗

HTLV-associated diseases: human retroviral infection and cutaneous T-cell lymphomas.

An array of neurologic, oncologic, and autoimmune disorders are associated with infection with the human pathogenic retroviruses human T-cell leukemia virus types I and II (HTLV-I, II), as well as the human immunodeficiency viruses (HIV). The cutaneous T-cell lymphomas, mycosis fungoides (MF) and its hematogenous variant Sezary Syndrome (SS), share similar clinical and pathological features to HTLV-I-associated adult T-cell leukemia (ATL) and speculation of a retroviral link to MF and SS, especially in areas non-endemic for ATL, has lead to an intensified search for HTLV- and HIV-like agents in these diseases. To further explore a potential role for human retroviruses in MF and SS, skin biopsy-derived or peripheral blood mononuclear cell-derived DNA from 17 patients (MF, n = 7; erythrodermic MF (EMF), n = 5; SS, n = 5) from the North Eastern United States were screened using gene amplification by PCR and a liquid hybridization detection assay. Previously published primers and probes for HTLV-I (LTR, gag, pol, env, and pX), and our own primers and probes for HTLV-I (gag, pol, and env), HTLV-II (pol and env) and HIV-I (gag and pol) were employed. Serum antibodies to HTLV-I were negative in all but one EMF patient. The single HTLV-I seropositive patient carrying a diagnosis of EMF generated positive amplified signals for all of the eight HTLV-I regions tested. Ultimately, this individual evolved to exhibit clinical manifestations indistinguishable from ATL. The other 16 patients were negative for all 12 HTLV and HIV retroviral regions. Our findings suggest that none of the known prototypic human retroviruses are associated with seronegative MF and SS. The uniformly positive results for HTLV-I in the seropositive patient suggests that this patient initially presented with a smoldering form of ATL and illustrates the difficulty that sometimes may be encountered in the differential diagnosis of MF, SS, and ATL based solely on clinical and histopathological criteria.

Adult↗