PubMed Health⌕ Search

Biomedical subjects

P Epstein

Publications and source records attributed to P Epstein.

28 records · Page 2Linked to original sources
PubMed1977

The aggregation of basic polypeptide residues bound to heparin.

The molecular basis for heparin interactions with proteins has been explored with L-lysine copolymer : heparin complexes, measuring the conformational change and charge neutralization which accompany the complexation, using optical methods. Previous studies had shown that the basic homopolypeptides (poly-L-lysine, poly-L-arginine) assume alpha-helical conformation upon interaction with numerous glycosaminoglycans (including heparin). Thus, the unique specificity for heparin in the anticoagulation system (which involves two or more lysine residues on the antithrombin molecule) is not paralleled by the findings with the basic homopolymers. Results with mixed polypeptides, poly(lysine : tyrosine, 1 : 1) and poly(lysine : phenylalanine, 1.4 : 1), show that these protein models assume different conformational forms upon complexation with heparin, the former shows a poly-L-lysine-like beta-structure circular dichroism spectrum and the latter an alpha-helical structure. The change in circular dichroism spectra increases with the addition of heparin until the ratio of positive to negative charge is about one. Dye-binding studies of the two copolymer systems reveal that the charged groups of both reactants are largely blocked in the polypeptide complexes at a calculated charge ratio equal to one. The data indicate that heparin interaction with the cationic polypeptides causes them to assume either the alpha-helical or beta-structure depending upon the nature of the neighboring uncharged amino acid and its proclivity for alpha-helix or beta-structure.

Chemical Phenomena↗
PubMed1974

Investigation of huge negative circular dichroism spectra of some nucleoproteins.

Under certain conditions of preparation, DNA, whether free or complexed with polylysine or histone KAP (I, fl), produce huge negative circular dichroism (CD) spectra with maxima at about 270nm. In order to investigate the cause of these spectra, reconstituted polylysine-DNA complex was used as a model system. It was found that the CD change of DNA in the complex is not a linear function of the fraction of base pairs bound. Such a CD spectrum is not changed despite dilution up to 128 folds for as long as 12 hours. Difference CD spectra taken between free DNA and any of the complexes are qualitatively the same, and are similar to those of free DNA and nucleohistone KAP (Fasman et al., Biochemistry 9, 2814-2822, 1970), free DNA and direct mixed polylysine-DNA complexes, or free DNA in high salt (Chang et al., Biochemistry12, 3028-3032, 1973). The suggestion is made that this CD spectrum might be caused by specific conformational changes in DNA, perhaps belonging to the family of B to C transitions followed by a further structural distortion of DNA due to aggregation of the nucleoprotein molecules.

Animals↗
PubMedDate not supplied

Immune responses to a recombinant human immunodeficiency virus type 1 (HIV-1) gpl60 vaccine among adults with advanced HIV infection. Massachusetts gp160 Working Group.

OBJECTIVE: To assess immunogenicity of recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccine (rgp160) in late HIV infection. STUDY DESIGN/METHODS: HIV-infected volunteers (n = 142), with CD4+ T lymphocyte counts of <400/mm3, were enrolled in a dose-comparison, open-label trial with stratification by CD4+ cell count, randomization to a primary series at two dose levels, and a sub-group receiving interferon-gamma (IFN-gamma) as an adjuvant. Subjects received booster doses of vaccine over a follow-up period of 18-28 months. RESULTS: At 6 and 12 months, 36% and 38% of participants, respectively, had new or augmented antibody titers (> or =4-fold increase) against one or more gpl60 epitopes (C1, V3, C41, 448C). Delayed-type hypersensitivity (DTH) to intradermal gpl60, initially not present in any participant, developed after immunization in 41%, with higher prevalence in participants receiving the lower dose of vaccine. Both antibody and skin test responses occurred in 20-25% of vaccine recipients. Virtually all antibody and skin test responses occurred in participants with initial CD4+ cell counts of >100 cells/mm3. IFN-gamma had no significant effect on immune response. Immunization was well tolerated. Trends in CD4+ cell count, clinical events, and laboratory findings correlated with baseline CD4+ T lymphocyte count stratum and not with immunization regimen. Opportunistic conditions occurred at expected rates. Viral load trends (p24 antigen in all participants and viral RNA by reverse transcription-polymerase chain reaction in a subset of 26 participants) did not correlate with immunization regimen. CONCLUSION: Immunization of patients with advanced HIV infection with rgpl60 resulted in new and augmented humoral and DTH responses, without unexpected significant adverse events or evident clinical benefits attributable to immunization.

AIDS Vaccines↗