Biomedical subjects

Robert S Root-Bernstein

Publications and source records attributed to Robert S Root-Bernstein.

7 recordsLinked to original sources

PubMed2006

Ascorbate enhancement of H1 histamine receptor sensitivity coincides with ascorbate oxidation inhibition by histamine receptors.

Ascorbate has previously been shown to enhance both alpha(1)- and beta(2)-adrenergic activity. This activity is mediated by ascorbate binding to the extracellular domain of the adrenergic receptor, which also decreases the oxidation rate of ascorbate. H1 histamine receptors have extracellular agonist or ascorbate binding sites with strong similarities to alpha(1-) and beta(2)-adrenergic receptors. Physiological concentrations of ascorbate (50 microM) significantly enhanced histamine contractions of rabbit aorta on the lower half of the histamine dose-response curve, increasing contractions of 0.1, 0.2, and 0.3 microM histamine by two- to threefold. Increases in ascorbate concentration significantly enhanced 0.2 microM histamine (5-500 microM ascorbate) and 0.3 microM histamine (15-500 microM ascorbate) in a dose-dependent manner. Histamine does not measurably oxidize over 20 h in oxygenated PSS at 37 degrees C. Thus the ascorbate enhancement is independent of ascorbate's antioxidant effects. Ascorbate in solution oxidizes rapidly. Transfected histamine receptor membrane suspension with protein concentration at >3.1 microg/ml (56 nM maximum histamine receptor) decreases the oxidation rate of 392 microM ascorbate, and virtually no ascorbate oxidation occurs at >0.0004 mol histamine receptor/mol ascorbate. Histamine receptor membrane had an initial ascorbate oxidation inhibition rate of 0.094 min.microg protein(-1).ml(-1), compared with rates for transfected ANG II membrane (0.055 min.microg protein(-1).ml(-1)), untransfected membrane (0.052 min.microg protein(-1).ml(-1)), creatine kinase (0.0082 min.microg protein(-1).ml(-1)), keyhole limpet hemocyanin (0.00092 min.microg protein(-1).ml(-1)), and osmotically lysed aortic rings (0.00057 min.microg wet weight(-1).ml(-1)). Ascorbate enhancement of seven-transmembrane-spanning membrane receptor activity occurs in both adrenergic and histaminergic receptors. These receptors may play a significant role in maintaining extracellular ascorbate in a reduced state.

Amino Acid Sequence↗

PubMed2005

Molecular shielding of electric field complex dissociation.

We have previously demonstrated the ability of electric fields to dissociate ascorbate and catecholamines and shown that the electric field generated by cell membranes is sufficient to produce dissociation of these complexes up to 8 nm from the cell membrane. We show here that this process is applicable to a wide range of biological complexes including small molecules (norepinephrine-morphine sulfate), protein-protein complexes (insulin-glucagon), and small molecule-protein complexes (epinephrine-bovine serum albumin). The extrapolation of the slope of the electric field dependence to zero electric field can be used to estimate the log of the dissociation constant (K(D)) of a complex and, by multiplying the log(K(D)) by -2.303RT, the association energy (E) of the complex. The slope of the electric field dependence is inversely related to the molecular radii, with the best fit of the slope related to E*(1/r1 + 1/r2), where r is the estimated radius of each molecule in the complementary pair. This indicates that the binding site of the pair is shielded by the remaining parts of the molecules, and the larger the molecule the greater the shielding. When the slope of the electric field dependence goes to 0 as r goes to infinity and 1/r goes to 0, the molecular shielding constant is 7.04 x 10(-8) cm2/V. Very large complexes will be minimally affected by the electric field due to molecular shielding and reduced electric field as their radius restricts approach to the membrane. Large protein receptors will deflect the membrane electric field and allow agonist binding.

Animals↗

PubMed2005

Vaccination markers: designing unique antigens to be added to vaccines to differentiate between natural infection and vaccination.

Some important vaccines, including ones against tuberculosis (Tb) and foot-and-mouth disease (FMD), are not used in many developed countries because there is no simple way to differentiate between vaccine-induced immunity and infection. Eliminating major protein antigens has not succeeded in the cases of Tb, FMD and some other vaccine preparations. Instead of eliminating antigens, novel antigens can be added to vaccines in order to induce a unique immunological response proving that the vaccine has been delivered. Methods for producing such unique antigens are presented and preliminary test results reported. The technique may also be useful for immunologically "branding" animals.

Amino Acid Sequence↗

PubMed2005

HIV may produce inhibitory microRNAs (miRNAs) that block production of CD28, CD4 and some interleukins.

It is well-known that HIV-1 infection results in a gradual decline of the CD4+ T-lymphocytes, but the underlying mechanism of this decline is not completely understood. Research has shown that HIV-1 infection of CD4+ T cells results in decreased CD28 expression, but the mechanism of this repression is unknown. There is also substantial evidence demonstrating regulatory involvement of microRNA (miRNA) during protein expression in plants and some animals, and reports have recently been published confirming the existence of viral-encoded miRNAs. Based on these findings, we hypothesize that viral-encoded miRNA from HIV-1 may directly alter T cell, macrophage and dendritic cell activity. To investigate a potential correlation between the genomic complementarity of HIV-1 and host cell protein expression, a local alignment search was performed to assess for regions of complementarity between the HIV-1 proviral genome and the mRNA coding sequence of various proteins expressed by CD+ T cells and macrophages. Regions of complementarity with strong correlations to the currently established criteria for miRNA:target mRNA activity were found between HIV-1 and CD28, CTLA-4 and some interleukins, suggesting that HIV-1 may produce translational repression in host cells.

Base Sequence↗

PubMed2004

Antigenic complementarity among AIDS-associated infectious agents and molecular mimicry of lymphocyte proteins as inducers of lymphocytotoxic antibodies and circulating immune complexes.

BACKGROUND: People at risk for acquired immunodeficiency syndrome (AIDS) have high rates of cofactor infections in addition to HIV, including cytomegalovirus, hepatitis viruses, Mycobacteria, Mycoplasmas, and Staphylococcus aureus. Most people with AIDS also develop lymphocytotoxic antibodies (LCTA) and circulating immune complexes (CIC). While HIV proteins mimic HLA antigens, many cofactor agents mimic CD4 antigens. It has therefore been proposed that cofactor infections may interact with HIV by producing complementary antigens that induce LCTA and CIC, and that the resulting immunological dysfunction is part of AIDS pathogenesis. OBJECTIVES: To test (1) whether HIV and its cofactor infections elicit complementary (idiotype-anti-idiotype) antibodies, and (2) if any of these antibodies mimic anti-lymphocyte antibodies. STUDY DESIGN: Two immunological methods are employed to test for antibody complementarity: (1) double antibody diffusion, a modification of Ouchterlony immunodiffusion, in which antibodies are tested for their ability to precipitate each other; (2) double-antibody ELISA, in which an antibody against one infectious agent is adsorbed to an ELISA plate and an antibody against a second agent is used to detect the first. RESULTS: Data on over a thousand double antibody diffusion (DAD) and about 70 DA-ELISA experiments are reported. These show that only specific pairs of antibodies are complementary: HIV-CMV; HIV-HBV; HIV-tuberculosis; HIV-mycoplasmas; HIV-S. aureus; and CMV-mycoplasmas. In addition, HIV antibodies precipitate CD4 antibodies; CMV antibodies precipitate HLA-DR antibodies; while mycobacteria and mycoplasma antibodies precipitate macrophage antibodies. CONCLUSIONS: Antibodies elicited by HIV infection can interact with antibodies elicited by cofactor infections to form CIC, and some of these antibodies mimic lymphocyte antibodies so that they may function as LCTA. Since LCTA and CIC are associated with increased lymphocyte death in AIDS, the immune response against cofactors in HIV may play a significant role in AIDS pathogenesis. The fact that both HIV and cofactors elicit antibodies with LCTA characteristics may pose problems for vaccine development.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Breaking faith.

Explore the source record for details and available documents.

Attitude↗

PubMedDate not supplied

Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review.

This paper reviews the three major theories of peptide receptor evolution: (1) Dwyer's theory that peptide receptors evolved from self-aggregating peptides; (2) Root-Bernstein's theory that peptide receptors evolved from functionally and structurally complementary peptides; and (3) Blalock's theory that receptors evolved from hydropathically complementary sequences encoded in the antisense strand of the DNA encoding each peptide. The evidence to date suggests that the co-yevolution of peptides and their receptors is strongly constrained by one or more of these physicochemically based mechanisms, which argues against a random or frozen accident' model. The data also suggest that structure and function are integrally related from the earliest steps of receptor-ligand evolution so that peptide functionality is non-random and highly conserved in its origin. The result is a molecular paleontology' that reveals the evolutionary constraints that shaped the interaction of structure and function.

Amino Acid Sequence↗